zk1516398.htm
 
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
 
WASHINGTON, D.C. 20549
 
FORM 20-F
 
¨
REGISTRATION STATEMENT PURSUANT TO SECTION 12(b) OR (g) OF THE SECURITIES EXCHANGE ACT OF 1934
 
OR
 
x           ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
 
FOR THE FISCAL YEAR ENDED DECEMBER 31, 2014
 
OR
 
¨
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
 
OR
 
¨
SHELL COMPANY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
 
DATE OF EVENT REQUIRING THIS SHELL COMPANY REPORT __________
 
COMMISSION FILE NO. 000-30902
 
____________________________________________________
 
Compugen Ltd.
(Exact name of registrant as specified in its charter and translation of registrant's name into English)
 
___________________________________________________________________
 
 
Israel
(Jurisdiction of incorporation or organization)
72 Pinchas Rosen Street, Tel Aviv, 6951294 Israel
(Address of principal executive offices)
 
________________________________________________
 
Ari Krashin, Chief Financial Officer
Phone: +972-3-765-8585, Fax: +972-3-765-8555
72 Pinchas Rosen Street, Tel Aviv, 6951294 Israel
(Name, Telephone, E-mail and/or Facsimile number and Address of Company Contact Person)
 
________________________________________________
 
Securities registered or to be registered pursuant to Section 12(b) of the Act:

Title of each class
Name of each exchange on which registered
Ordinary shares, par value NIS 0.01 per share
The NASDAQ Stock Market LLC
(The NASDAQ Global Market)
 
 
 
 
 
Securities registered or to be registered pursuant to Section 12(g) of the Act:
 
 None
 
 (Title of Class)
 
Securities for which there is a reporting obligation pursuant to Section 15(d) of the Act:
 
None
 
Indicate the number of outstanding shares of each of the issuer's classes of capital or common stock as of the close of the period covered by the annual report:
 
50,254,492 Ordinary Shares
 
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act.
 
¨  Yes   x  No
 
If this report is an annual or transition report, indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
 
¨  Yes   x  No
 
Indicate by check mark whether the registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days:
 
x  Yes   o  No
 
Indicate by check mark whether the registrant has submitted electronically and posted on its corporate Web site, if any, every Interactive Data File required to be submitted and posted pursuant to Rule 405 of Regulation S-T (232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit and post such files).
 
x  Yes   o  No
 
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, or a non-accelerated filer. See definition of “accelerated filer and large accelerated filer” in Rule 12b-2 of the Exchange Act. (Check one):
 
Large accelerated filer o   Accelerated filer x   Non-accelerated filer o
 
Indicate by check mark which basis of accounting the registrant has used to prepare the financial statements included in this filing:
 
U.S. GAAP  x
 
International Financial Reporting Standards as issued by the International Accounting Standards Board  ¨
 
Other  ¨
 
If “Other” has been checked in response to the previous question, indicate by check mark which financial statement item the registrant has elected to follow.
 
Item 17  ¨                 Item 18  ¨
 
If this is an annual report, indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act).
 
o Yes   x No
 
 
 
 
 
TABLE OF CONTENTS
 
CAUTIONARY STATEMENT REGARDING FORWARD-LOOKING STATEMENTS
 
PART I.
1
  1
  1
  24
  39
  39
  52
  67
  69
  70
  72
  85
  85
 
PART II.
    
  86
  86
  86
  87
  87
  87
  87
  88
  88
  88
  88
  88
 
PART III
   
  89
  89
  89

 
i 
 
 
CAUTIONARY STATEMENT REGARDING
 
FORWARD-LOOKING STATEMENTS
 
This annual report on Form 20-F includes “forward-looking statements” within the meaning of Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. These statements include words such as “may”, "assume", “expect”, “anticipate”, “could”, “project”, “estimate”, “possible”, “potential”,  “believe”, “suggest”, and “intend”, and describe opinions about future events. We have based these forward-looking statements on information available to us as of the date hereof, and on our current assumptions, intentions, beliefs, expectations and projections about future events. We assume no obligation to update any such forward-looking statements. These forward-looking statements involve known and unknown risks and uncertainties that may cause the actual results, performance or achievements of Compugen to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Factors that could cause our actual results to differ materially from those projected in the forward-looking statements include, without limitation, the risk factors set forth under “Item 3. Key Information. Risk Factors”, the information about us set forth under “Item 4. Information about the Company” and information related to our financial condition under “Item 5. Operating and Financial Review and Prospects”.
 
------------
 
All references in this annual report on Form 20-F to “Compugen,” the “Company,” “we,” “us,” “our,” or similar references refer to Compugen Ltd. and our wholly owned subsidiary Compugen USA, Inc., except where the context otherwise requires or as otherwise indicated.
 
------------
 
We have prepared our consolidated financial statements in United States dollars and in accordance with generally accepted accounting principles in the United States, or U.S. GAAP. All references herein to “dollars” or “$” are to United States dollars, and all references to “Shekels” or “NIS” are to New Israeli Shekels.
 
 
ii 
 
 
PART I.
 
ITEM 1.                IDENTITY OF DIRECTORS, SENIOR MANAGEMENT AND ADVISERS
 
Not applicable.
 
ITEM 2.               OFFER STATISTICS AND EXPECTED TIMETABLE
 
Not applicable.
 
ITEM 3.                KEY INFORMATION
 
A.  SELECTED CONSOLIDATED FINANCIAL DATA
 
The following selected consolidated financial data are derived from our audited consolidated financial statements which have been prepared in accordance with U.S. GAAP. The selected consolidated financial data as of December 31, 2014 and 2013 and for the years ended December 31, 2014, 2013 and 2012 have been derived from our audited consolidated financial statements and notes thereto included elsewhere in this annual report. The selected consolidated financial data as of December 31, 2012, 2011 and 2010 and for the years ended December 31, 2011 and 2010 have been derived from audited consolidated financial statements not included in this annual report. The selected consolidated financial data set forth below should be read in conjunction with and are qualified by reference to "Item 5. Operating and Financial Review and Prospects” and our consolidated financial statements and notes thereto included elsewhere in this annual report.
 
Selected Financial Data
 
   
Year ended December 31,
  
 
  
2010
    
2011
    
2012
    
2013
    
2014
  
   
(US$ in thousands, except share and per share data)
  
Consolidated Statement of Operations Data
                              
Revenues
   $ 1,115     $ -     $ 242     $ 3,549     $ 12,367  
Cost of revenues
     224       -       201       2,509       3,344  
Total operating expenses (1)
     8,769       11,979       13,583       18,083       21,360  
Operating loss
     (7,878 )     (11,979 )     (13,542 )     (17,043 )     (12,337 )
Financial and other income (expenses), net
     675       (25 )     (86 )     3,460       1,758  
Equity loss
     -       -       -       -       (155 )
Losses before tax expenses
     (7,203 )     (12,004 )     (13,628 )     (13,583 )     (10,734 )
Income taxes
     -       -       -       (500 )     (360 )
Net loss
     (7,203 )     (12,004 )     (13,628 )     (14,083 )     (11,094 )
Realized and unrealized gain (loss) on Investment in Evogene and from foreign currency derivative contracts
     2,334       (2,141 )     1,103       (739 )     (3,406 )
Total comprehensive loss
     (4,869 )     (14,145 )     (12,525 )     (14,822 )     (14,500 )
Basic net loss per share
   $ (0.22 )   $ (0.35 )   $ (0.38 )   $ (0.36 )   $ (0.23 )
Weighted average number of ordinary shares used in computing basic net loss per share
       33,284,017         34,276,697         35,844,496         38,869,438         47,808,855  
Diluted net loss per share
   $ (0.22 )   $ (0.35 )   $ (0.38 )   $ (0.36 )   $ (0.26 )
Weighted average number of ordinary shares used in computing diluted net loss per share
       33,284,017         34,276,697         36,249,262         38,869,438         48,387,063  
 
(1)         Includes stock based compensation – see Note 9 to our 2014 consolidated financial statements.
 
 
1
 
 

 
   
As of December 31,
  
 
  
2010
    
2011
    
2012
    
2013
    
2014
  
   
(US$ in thousands)
  
Consolidated Balance Sheet Data
      
Cash and cash equivalents, short-term bank deposits and restricted cash
   $ 22,508     $ 22,463     $ 19,685     $  46,920     $  73,186  
Receivables from funding arrangement
     5,000       -       -       -       -  
Investment in Evogene
     6,227       4,093       5,196       4,565       1,054  
Long-term bank deposits
     -       -       -       -       35,026  
Total assets
     36,458       29,081       28,909       56,711       114,986  
Deferred Revenues
     -       -       -       6,772       1,789  
Research and development funding arrangements and others
     4,037       6,434       7,872       13,189       421  
Accumulated deficit
     (168,487 )     (180,491 )     (194,119 )     (208,202 )     (219,296 )
Total shareholders' equity
   $ 28,285     $ 19,581     $ 17,672     $ 31,888     $ 106,116  
 
For additional financial information, please see “Item 5. Operating and Financial Review and Prospects – A. Operating Results”.
 
B.  CAPITALIZATION AND INDEBTEDNESS
 
Not applicable.
 
C.  REASONS FOR THE OFFER AND USE OF PROCEEDS
 
Not applicable.
 
D. RISK FACTORS
 
Many factors could affect our financial condition, cash flows and results of operations. We are subject to various risks including all the risks which are inherent in pharmaceutical discovery and development and those risks resulting from changing economic, political, social, industry, business and financial conditions in Israel and the major market countries. If we do not successfully, or cannot, address the risks to which we are subject, we could experience a material adverse effect on our business, results of operations and financial condition, which could include the need to limit or even discontinue our business operations, and accordingly our share price, may decline. We can give no assurance that we will successfully address any of these risks. The principal risks we face are described below.
 
 
2
 

Risks Related to our Business, Financial Results and Financing Needs
 
We cannot provide assurance that our business model will succeed in generating substantial revenues.
 
Our business model is primarily based on receiving revenues in the form of fees, research revenues, milestone payments, royalties and other revenue sharing payments from commercialization of products by third parties based on product candidates (i) discovered by us and then licensed to such third parties, and/or (ii) discovered pursuant to various forms of collaborations with such third parties whereby our discovery platforms or other discovery capabilities target areas of mutual interest. In 2010, we initiated a program to predict and select novel molecules in specific areas of high interest in both oncology and immunology. Therapeutic product candidates resulting from this effort are validated and advanced forward in the preclinical stage, and in selected cases to possible clinical evaluation stages, prior to licensing or other collaborations (our “Pipeline Program”).  To date, third party arrangements have only been entered into at early validation or pre-clinical stages which have an inherent risk of high failure rate. The inability to derive adequate revenues from our business model would materially harm our business, financial condition and results of operations and could result in the need to limit or even discontinue our business operations.
 
We have a history of losses, we expect to incur future losses and we may never achieve or sustain profitability.
 
As of December 31, 2014, we had an accumulated deficit of approximately $219.3 million and had incurred net losses of approximately $13.6 million in 2012, approximately $14.1 million in 2013, and approximately $11.1 million in 2014. In addition, we expect to continue to incur net losses in the future due to the costs and expenses associated with our expanding research and development activities, including significantly increasing Pipeline Program activities, our increase in activities in the United States, and the development, validation and integration of additional discovery platforms. To date, we have entered into only one commercial arrangement with respect to our Pipeline Program molecules under which we have received to date a total amount of $17.2 million. Otherwise, we have received only minimal revenues from limited commercialization efforts with respect to molecules discovered during our infrastructure building period. We cannot be certain that we will enter into additional arrangements for our Pipeline Program candidates or other discoveries or capabilities, or that such additional arrangements will provide sufficient revenues to achieve profitability. Even if we do achieve profitability, we may not be able to sustain or increase profitability.
 
We may need to raise additional funds in the future, and if we are unable to raise such additional funds, we may need to curtail or cease operations. To the extent any such funding is based on the sale of equity, our existing Shareholders would experience dilution of their shareholdings.
 
We believe that our existing cash and cash equivalents, short-term and long-term bank deposits will be sufficient to fund our operations for at least the next 24-36 months. However, we cannot predict with any degree of certainty when, or even if, we will achieve profitability and therefore may need additional funds to continue financing our discovery, validation, development and commercialization activities. In addition, we may seek additional capital due to favorable market conditions or strategic considerations even if we believe we have sufficient funds for our current or future operating plans.
 
Additional funds, including proceeds from commercialization agreements, or from other financings, may not be available to us when needed, on acceptable terms, or at all. In addition, the terms of any financing may adversely affect the holdings or the rights of our existing Shareholders. For example, if we raise additional funds by issuing equity securities, our existing Shareholders would experience dilution of their shareholdings. Debt financing, if available, may involve restrictive covenants that could limit our flexibility in conducting future business activities. If we are unable to obtain funding on a timely basis, we may be required to significantly curtail one or more of our research or development programs. We also could be required to seek funds through arrangements with collaborators or others that may require us to enter into arrangements on terms that would otherwise not be acceptable to us. Any failure to raise capital when needed would materially harm our business, financial condition and results of operations.
 
 
3
 
 
We are currently pursuing our business model primarily in the fields of oncology and immunology and this limitation may not yield sufficient revenues to support our increasing level of activities.
 
Following establishment and validation of a sufficiently broad and integrated infrastructure of our individual predictive discovery capabilities, we initiated our Pipeline Program to predict and select novel molecules in specific areas of high interest in both oncology and immunology. To date, we have entered into only one commercial arrangement, with Bayer Pharma AG ("Bayer"), with respect to our Pipeline Program molecules (the “Bayer Collaboration”), under which we have received to date a total amount of $17.2 million. We cannot be certain this focus of our discovery efforts to the fields of oncology and immunology and decision to advance selected programs at our own expense will generate a stable or significant revenue stream. The inability to derive adequate revenues within our initial fields of focus would materially harm our business, financial condition and results of operations and could result in the need to limit or even discontinue our business operations.
 
Our Pipeline Program will require additional resources that may not be available.
 
In 2010 we initiated our Pipeline Program pursuant to which we are both (i) substantially increasing the number of predicted and selected therapeutic candidates being evaluated by us, and (ii) taking certain therapeutic candidates beyond their validation stage (of either drug target expression profile for monoclonal antibody (“mAb”) targets and antibody-drug conjugate ("ADC") targets or disease animal model for Fc fusion proteins) into disease animal models for therapeutic mAbs against the targets, and in selected cases, possibly clinical evaluation, and to preclinical activities for Fc fusion proteins. Assuming a similar level of success as we experienced in the past in the initial validation stages, this may result in multiple product candidates reaching more costly stages of research and development in parallel. If we are not able to secure the funding or the technologies required for these more advanced activities, we may be required to abandon, postpone, or attempt to license out certain molecules at an earlier than anticipated stage, which may result in a substantial reduction in the potential returns from the Pipeline Program, or even result in the inability to have some or all of such successful “proof of concept” therapeutic candidates further developed and commercialized.
 
We operate in a rapidly developing field and will be required to allocate substantial additional funds in the future to our research activities.
 
Our drug and diagnostic product candidate discovery capabilities rely on a proprietary infrastructure of predictive models, algorithms and other computational tools incorporating proprietary knowledge of key biological phenomena. Life science today is a rapidly changing field with substantial research being undertaken on a worldwide basis by both academia and industry. In order to maintain our competitive position in predictive discovery, we must continue to allocate resources to broadening and deepening our scientific infrastructure. Any inability to allocate such resources when needed could materially harm our future business, financial condition and results of operations.
 
We have a limited operating history with respect to the commercialization aspects of our business model upon which investors can base an investment decision or upon which to predict future revenues.
 
Our ability to generate revenues from collaboration and licensing activities for current and future product candidate discoveries, primarily in the form of fees, research revenues, milestone payments, royalties and other revenue sharing payments has had limited success to date. In 2013, we entered into the Bayer Collaboration, our first collaboration with respect to our Pipeline Program activities, under which we have received to date a total amount of $17.2 million, and have received only minimal revenues from our earlier collaborations based on discoveries made during our infrastructure building. We recognized $12.4 million in revenue in 2014, $3.5 million in revenue in 2013, and $242,000 in 2012. Furthermore, only in 2010 did we implement our Pipeline Program pursuant to which we are advancing certain therapeutic product candidates past disease animal model proof of concept or other validation studies. We therefore have very limited experience with respect to the financial terms that may be available for our candidates at later stages of validation and development, and financial terms for agreements by other companies, to the degree disclosed, vary greatly. Accordingly, our operating history with respect to the commercialization aspects of our business model provides a limited basis to assess our ability to generate significant fees, research revenues, milestone payments, royalties or other revenue sharing payments from the licensing and commercialization of our product candidate discoveries, or from research and development collaborations.
 
 
4
 
 
Risks Related to our Discovery and Development Activities
 
We are focusing our discovery and development activities on mAb drug targets, mAb therapeutics, and Fc fusion proteins, for uses in oncology and immunology. If we fail to continue to discover and develop product candidates of industry interest in these fields, or to focus our Pipeline Program efforts on the most promising of such discoveries and candidates, our business will likely be materially harmed.
 
Since late 2010 we have chosen to focus our broadly applicable predictive discovery capability in the areas of oncology and immunology, including both auto-immune and inflammatory conditions, and more specifically on mAb therapeutics and Fc fusion proteins to address unmet needs in these fields. We have also chosen immune checkpoints as the objective for our first focused discovery program, and more recently we have initiated our second focused program for discovery of targets for antibody-drug-conjugate (ADC) therapy. The result of our decision in 2010 to focus on our Pipeline Program is that we are not undertaking internal development in other areas, including those where we previously demonstrated discovery capabilities, such as diagnostic products (other than biomarker discovery for selected internal checkpoint programs) and peptide based drugs, and intend to pursue such opportunities only in collaboration with third parties. With respect to checkpoint proteins, although there have been positive clinical results reported by others with respect to a small number of products based on certain checkpoint proteins, resulting in substantial industry, academic and medical interest, with some products gaining FDA approval based on this positive data, there can be no assurance that our checkpoints, which currently are the basis for the majority of candidates in our Pipeline Program, will provide similar clinical advantages or interest, that no long term adverse effects will be seen, or that a different class of molecules will not be discovered with comparable or superior attributes. In the event of any of these occurrences, the actual and/or perceived value of a substantial portion of our Pipeline Program would likely be reduced in which case our business may be harmed. Additionally, although certain of our initial candidates based on Compugen discovered checkpoint proteins are generating interest from potential partners, to date we have signed only one collaboration involving two such discoveries and all such candidates are at early stages of development. There is no assurance that we will be able to consummate additional collaborations or agreements on reasonable terms, if at all. In addition, if we fail to continue to discover product candidates of industry interest in our fields of focus, or to pursue validation and development efforts in our Pipeline Program on the most promising discoveries, our business will likely be materially harmed. There are many risks associated with this decision of focusing on these areas that include, among others:
 
 
•
not utilizing all of our discovery capabilities;
 
 
•
choosing therapeutic areas with a very high degree of competition;
 
 
•
choosing therapeutic areas of great complexity and with very high failure rates in product development;
 
 
•
failing to successfully focus our discovery infrastructure to discover novel product candidates in our chosen therapeutics areas;
 
 
•
having insufficient relevant knowledge in our chosen therapeutic areas to select the right unmet needs or candidates, or to properly and efficiently further them in development; and  
 
 
•
the inherent risk of high program failure rate in early stage therapeutic development.
 
In each case, our failure could be due to lack of experience or applying the wrong criteria, with the possible result that no selected candidates result in licensed or marketable products in these fields. If any of these risks should materialize, our business, financial condition and results of operations would be materially harmed.
 
 
5
 
 
Our predictive discovery capabilities remain unproven with respect to yielding marketable products. If in further development and clinical evaluation, all, or a larger percentage than typically seen in industry experience, of our product candidates fail to prove sufficiently safe and effective for regulatory approval and marketing, our business will be significantly harmed.
 
Our in silico (by computer) predictive approach to drug discovery remains unproven with respect to yielding marketable products, and to date, our validation efforts for our initial discoveries have been limited to in vitro testing and in vivo testing using animal disease models. These discovery capabilities, which are designed to predict and select potential product candidates in many different therapeutic and diagnostic areas of interest, rely on the modeling, by our scientists, of complex biological processes, both physiological and pathological. This modeling is partial and may prove insufficient to result in true predictions of the biological processes as they occur naturally. If in further development and clinical evaluation, all, or a larger percentage than typically seen in industry experience, of our initial product candidates fail to prove sufficiently safe and efficacious for regulatory approval and marketing, our business will be significantly harmed.
 
Our in silico predictive approach to drug discovery typically results in a significant number of putative discoveries of interest with each discovery program. If we or our partners fail to select the right candidates to validate and/or progress, due to either lack of experience or applying the wrong criteria or experimental methodology, the selected candidates may never result in marketable products and our business, financial condition and results of operations will be materially harmed.
 
Our in silico predictive approach to drug discovery typically results in a significant number of putative discoveries of interest with each discovery program. Following each such discovery run, we assess which of such putative discoveries to move forward with initiation of validation based on various scientific and business criteria, and this assessment continues on an on-going basis. In addition, since our research and development resources are limited we are able to progress with only a fraction of our discoveries in parallel. If at any stage in such assessment, we or our partners fail to select the right candidates to validate and/or progress, due to either lack of experience or applying the wrong criteria or experimental methodology, the selected candidates may never result in marketable products, and our business, financial condition and results of operations may be materially harmed.
 
The large number of product candidates in our Pipeline Program may dilute the required resources on each individual candidate and thus result in significant delays.
 
Our predictive in-silico methodology results in a large number of candidates entering our Pipeline Program. Prosecuting multiple product candidates limits the resources available to each of the individual candidates and might create delays. If such delays become significant this can make product candidates less competitive or even obsolete as competing products advance or significantly reduce their value due to shorter patent term protection. Therefore, such delays may significantly harm these product candidates and our business.
 
If either the predictive discovery approach in general, or our “therapeutics needs (market) driven” approach, does not prove to be successful, our business will be significantly harmed.
 
Our method of discovering novel product candidates involves first selecting either on our own or with a partner company an unmet therapeutic need where we believe our predictive capabilities would be relevant, or could be modified to be relevant. In this “therapeutics needs (market) driven” approach, our goal is to harness all of our relevant capabilities in order to address the specific unmet need, rather than obtaining product candidates resulting from the development, validation or initial runs of a single discovery platform, as was the case prior to initiation of our Pipeline Program. After selection of the unmet need we wish to address, we then focus all of our relevant discovery platforms, algorithms and other computational biology capabilities to predict in silico (by computer) sequences for a typically large number of possible product candidates. Next we utilize proprietary algorithms and tools and other methodologies to select, from this large number of possibilities, those novel candidates that we believe have the highest probability of success. Selected product candidates are then produced and undergo in vitro and/or in vivo validation testing. Although our initial “therapeutics needs (market) driven” approach has resulted in the discovery of a number of novel product candidates in an area of significant industry interest, all of these product candidates are in very early stages of development. Therefore, we cannot predict whether this “therapeutics needs (market) driven” approach will continue to yield product candidates or that any of our existing discoveries or future discoveries will be suitable for final development into therapeutic products. If either the predictive discovery approach in general does not prove to be successful, or this “therapeutics needs (market) driven” approach does not lead to successful product candidates, our business will be significantly harmed.
 
Our focus on the Pipeline Program has resulted in a substantial increase in activities, certain of which we will undertake for the first time and may result in product candidate failures, or fewer molecules being available for commercialization.
 
Until recently, our in vitro and in vivo validation studies concluded with disease animal model or drug target expression profile analysis. Upon completion of such activities, or earlier, we initiated our efforts to enter into collaborations for such molecules. This is at an earlier stage than is typical for licensing in the pharmaceutical industry. Pursuant to the Pipeline Program initiated in 2010, and with the increase in our R&D activities, we are both advancing more molecules in parallel, and intend to advance certain molecules further towards pre-clinical activities, with the possibility of selected molecules entering clinical evaluation in the future. This decision to advance further with certain molecules requires the company to undertake certain activities for the first time and may result in product candidate failures during such additional activities, either due to our lack of expertise, unsupportive findings, or lack of an appropriate technology. Furthermore, due to our limited resources, we must choose which Pipeline Program molecules to advance further in pre-clinical development, and in selected cases possibly clinical development in the future. This could result in fewer molecules being available for commercialization, due to our available resources being insufficient to further advance all programs. In addition, if we fail to select the right product candidates to advance further, due to either lack of experience or applying wrong criteria or experimental methodology, the selected candidates may never result in a marketable product. If any of these risks materialize, our business, financial condition and results of operations may be materially harmed.
 
 
6
 
 
We have limited experience in the development of therapeutic product candidates.
 
Our experience in the development of therapeutic product candidates is very limited. In order to successfully develop and commercialize therapeutic products, we must either access such expertise via collaborations or service providers, or improve our internal expertise, capabilities and facilities. We may not be able to hire the scientists with the required expertise in a timely manner, if at all, and/or engage any or all of the service providers or other experts that we need in order to do so. If we fail to have available, at the appropriate times, the required experience and expertise for the further development and commercialization of our therapeutic product candidates, we may be unsuccessful in these activities, or these activities may be significantly delayed and as a result our business would be materially harmed.
 
Our establishment of our own therapeutic mAb research and development capabilities contains a number of risks.
 
In 2012, we announced that we had established our own therapeutic mAb development capabilities in our U.S. based, wholly owned subsidiary, Compugen USA, Inc., in order to develop mAb therapeutics against the target candidates that we discovered. The establishment of such in-house capabilities contains a number of risks, including, without limitation, the need for additional resources and funding in order to maintain such capabilities or to acquire additional technologies, and the need to identify additional qualified employees and consultants in order to further advance these capabilities. Furthermore, although the scientists we have hired have prior experience with other organizations in the field of therapeutic mAb research and development, we have limited experience as a company in this field and limited experience in managing a site in a different geographic location. Therefore, as a result, if we are unsuccessful in any of these required undertakings, our business could be materially harmed. In addition, the chairperson of Compugen USA, Inc. has additional occupations in the field of mAb discovery, which although not at present directly competitive, could present, in the future, potential conflict of interest issues.
 
There are risks that are inherent in the development and commercialization of therapeutic products, and if these risks materialize, our business and financial results may be materially harmed.
 
We and our collaborators face a number of risks of failure that are inherent in the process of developing and commercializing novel therapeutic products. These risks, which typically result in very high failure rates even for successful biopharma companies, include, among others, the possibility that:
 
 
•
our mAb targets will prove to be inappropriate targets for mAb therapeutics;
 
 
•
our product candidates will be found to be therapeutically ineffective;
 
 
•
our  product candidates will be found to be toxic or to have other unacceptable side effects;
 
 
•
our  product candidates will not show added value compared to competing products;
 
 
•
we or our collaborators will fail to receive required regulatory approvals;
 
 
•
we will not be able to generate product candidate differentiation between some of our product candidates;
 
 
•
we or our collaborators will fail to manufacture our product candidates in the quantity or quality needed for preclinical studies or clinical trials on a large scale and in a cost effective manner;
 
 
•
our early stage commercialization efforts may provoke competition by potential partners;
 
 
•
the commercialization of our product candidates may infringe third party intellectual property rights;
 
 
•
the development, marketing or sale of our product candidates will fail because of our inability or failure to protect or maintain our own intellectual property rights;
 
 
•
once a product is launched on the market, there will be little or no demand for it for a number of possible reasons, including lack of acceptance by the medical community or by patients, lack of or insufficient coverage and payment by third party payors, or as a result of there being more attractive, less risky or less expensive, products available for the same use; and
 
 
7
 
 
 
•
the product will be withdrawn from the market, or sales limited due to side effects observed in clinical practice
 
If one or more of these risks or any similar risks should materialize, our business and financial results may be materially harmed.
 
Risks Related to Development, Manufacturing, Clinical Trials and Government Regulation
 
We or our collaborators may be unable to obtain regulatory approval for any product that we or a collaborator may develop.
 
Any therapeutic product that we or our collaborators may attempt to develop, manufacture or market in the United States will be subject to extensive governmental regulations, including those relating to development, preclinical testing, performance of clinical trials, manufacturing and post-approval commercialization. Preclinical testing, clinical trials and manufacturing, among other activities, will be subjected to an extensive review process before a new therapeutic product may be sold in the United States. Satisfaction of these and other regulatory requirements is costly, time consuming, uncertain and subject to unanticipated delays. The time required to obtain U.S. Food and Drug Administration, or FDA, approval, and any other approvals for therapeutic products is unpredictable but typically requires several years.
 
Any therapeutic product that we or our collaborators may wish to develop, manufacture or market in countries other than the United States will also be subject to numerous regulatory requirements governing the conduct of clinical trials, manufacturing and marketing, pricing and third-party reimbursement among other things in such countries. The foreign regulatory approval process includes all of the risks and uncertainties associated with FDA approval described above as well as risks attributable to the satisfaction of local regulations in such foreign jurisdictions.
 
It is possible that none of the therapeutic products we or our collaborators may develop will obtain the approvals necessary for us or our collaborators to sell them either in the United States or any other country. Furthermore, approval by the FDA of a therapeutic product does not assure approval by regulatory authorities outside the United States or vice versa. Even if approval for a therapeutic product is obtained, such approval may be subject to limitations on the indicated uses or appropriate patient population that could result in a significantly reduced potential market size for the product.
 
If we or our collaborators fail to obtain the appropriate regulatory approvals necessary for us or our collaborators to sell our products, or if the approvals are more limited than those that we intend to seek, our business, financial condition and results of operations would be materially harmed.
 
It may be difficult to manufacture therapeutic products based on our technologies.
 
Our Pipeline Program is focused on mAbs and protein therapeutics in the fields of oncology and immunology and such therapeutic types can be difficult to manufacture. Should it prove to be difficult to manufacture any therapeutics based on our technologies in sufficient quantities, meeting the required quality standards or in an economical manner to conduct clinical trials and to commercialize any approved therapeutic candidate, our business, financial condition and results of operations would be materially harmed.
 
If we or any of our collaborators, or third-party manufacturers, fail to comply with regulatory requirements, we or they could be subject to enforcement actions, which could affect the marketability of Compugen-discovered therapeutics and may significantly harm our financial status and/or reputation.
 
If we or any of our collaborators or third-party manufacturers with which we may enter into agreements in the future fail to comply with applicable federal, state or foreign laws or regulations, we or they could be subject to enforcement actions. These enforcement actions may include:
 
 
•
warning letters;
 
 
•
recalls, product seizures or medical product safety alerts;
 
 
•
data lock, for failure to comply with applicable privacy and data security laws;
 
 
•
restrictions on, or prohibitions against, marketing such tests or products;
 
 
8
 
 
 
•
restrictions on importation of such tests or products;
 
 
•
suspension of review or refusal to accept or approve new or pending applications;
 
 
•
withdrawal of product approvals;
 
 
•
injunctions;
 
 
•
civil and criminal penalties and fines; or
 
 
•
debarment or other exclusions from government programs.
 
If we or our collaborators become subject to such enforcement actions, these enforcement actions, could affect the ability to successfully develop, market and sell therapeutic products based on our discoveries and could significantly harm our financial status and/or reputation and lead to reduced acceptance of such products by the market.
 
If we do not comply with laws regulating the use of human tissues or other human biological samples or the conduct of experiments involving animals, our business could be adversely affected.
 
We use human tissue samples or other human biological samples and conduct experiments involving animals for the purpose of development and validation of our technologies and product candidates. Our access to and use of human tissue samples or other human biological samples and the conduct of experiments involving animals are subject to government regulation in the United States, Israel and elsewhere and may become subject to additional regulation. For example, the Israeli Ministry of Health requires, among other things compliance with the principles of the Helsinki Declaration, the Public Health Regulations (Clinical Trials in Human Subjects) 5740-1980, the Genetic Information Law, 5761-2000, the provisions of the Israel Ministry of Health Guidelines for Clinical Trials in Human Subjects and the provisions of the current Harmonized Tripartite Guideline for Good Clinical Practice. Our use of clinical data related to any tissue or other human biological samples must comply with a applicable local, national and international privacy law. Our use of animal models for pre-clinical research must comply with the U.S. Animal Welfare Act, the United States Public Health Service Policy on Humane Care and Use of Laboratory Animals, and applicable state and local laws.Our failure to comply with these or similar regulations could negatively impact our business and results of operations.
 
If we do not comply with laws regulating the protection of the environment and health and human safety, our business could be adversely affected.
 
Our research and development activities involve the use of hazardous materials and chemicals, and we maintain quantities of various flammable and toxic chemicals in our facilities. Although we believe our safety and other procedures for storing, handling and disposing these materials in our facilities comply with applicable governmental regulations and guidelines, the risk to our employees or others of accidental contamination or injury from these materials cannot be eliminated. If an accident occurs, we could be held liable for resulting damages, which could be substantial. We are also subject to numerous environmental, health and workplace safety laws and regulations, including those governing laboratory procedures, exposure to blood-borne pathogens and the handling of biohazardous materials. We may incur substantial costs to comply with, these laws and regulations and substantial fines or penalties if we violate any of these laws or regulations.
 
Risks Related to Our Dependence on Third Parties
 
We depend significantly on third parties to carry out the development and commercialization of our product candidates. If we are unable to maintain our existing agreements or to enter into additional agreements with such third parties in the future, our business will likely be materially harmed.
 
Our primary strategy for the development and commercialization of products based on our product candidates depends on third parties to carry out and/or finance development and commercialization of such products, principally pharmaceutical, and biotechnology companies and other healthcare related organizations. To date, we have entered into one collaboration with Bayer with respect to two programs from our Pipeline Program, and a number of other small collaborations relating to development and commercialization rights with respect to certain of our discovery stage product candidates, and established a JV with Merck-Serono for the discovery and development of biomarkers for the prediction of drug-induced hepatotoxicity. None of the product candidates subject to such agreements have advanced beyond the discovery and early pre-clinical stages or beyond early biomarker development stage and we cannot be sure that any of these agreements will result in the successful development or commercialization of any products. Further, we cannot assure you that we will succeed in identifying additional suitable parties or entering into any other additional agreements on satisfactory terms or at all for the discovery, development and/or commercialization of our product candidates. If we are unable to identify such additional suitable parties or enter into new agreements on satisfactory terms, our business will likely be materially harmed.
 
 
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Our dependence on collaboration agreements with third parties presents a number of risks, and if one or more of these risks materialize, our business may be materially harmed.
 
The risks that we face in connection with our existing collaborations, licenses and other business alliances as well as those that we may enter into in the future include, among others, the following:
 
 
•
we may be unable to reach mutually agreeable terms and conditions with respect to potential new collaborations;
 
 
•
we may be unable to comply or fully comply with our obligations under collaboration agreements into which we enter, and as a result, we may not generate royalties or milestone payments from such agreements, and our ability to enter into additional agreements may be harmed;
 
 
•
our obligations under existing or future collaboration agreements may harm our ability to enter into additional collaboration agreements;
 
 
•
our collaborators have significant discretion in electing whether to pursue any of the planned activities and the manner in which it will be done, including the amount and nature of the resources to be devoted to the development and commercialization of our product candidates;
 
 
•
our collaborators have significant discretion in terminating the collaborations for scientific, business or other reasons;
 
 
•
if our collaborators breach or terminate the agreement with us, the development and commercialization of our product candidates could be adversely affected because at such time we may not have sufficient financial or other resources or capabilities to successfully develop and commercialize these therapeutics on our own or find other partners;
 
 
•
our collaborators may fail to design and implement appropriate preclinical and/or clinical trials;
 
 
•
our collaborators may fail to manufacture our product candidates needed for either clinical trials or for commercial purposes on a sufficiently large scale , in the required quality and/or in a cost effective manner;
 
 
•
our collaborators may fail to develop and market products based on our discoveries due to various regulatory restrictions;
 
 
•
our collaborators may fail to develop and market products based on our discoveries prior to the successful marketing of competing products by others or prior to expiry of the patents protecting such products;
 
 
•
changes in a collaborator’s business strategy may negatively affect its willingness or ability to complete its obligations under its arrangement or to continue with its collaboration with us;
 
 
•
ownership of the intellectual property generated under or incorporated in our collaborations may be disputed;
 
 
•
our ownership of rights in any intellectual property or products that may result from our collaborations may depend on additional investment of money that we may not be able or willing to make;
 
 
•
prospective collaborators may pursue alternative products or technologies, by internally developing them or by preferring those of our competitors;
 
 
•
disagreements between us and our collaborators may lead to delays in, or termination of, the collaboration;
 
 
•
our collaborators may fail to develop or commercialize successfully any products based on discoveries or product candidates to which they have obtained rights from us; and
 
 
•
our collaboration partners may be acquired by, acquire, or merge with, another company, and the resulting entity may have different priorities or competitive products to the collaboration product being developed previously by our partner.
 
If any of these risks should materialize, our business, financial condition and results of operations may be materially harmed.
 
 
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To date we have entered into only one collaboration agreement with respect to our Pipeline Program candidates, and this agreement with Bayer is subject to many risks. If such agreement is terminated by Bayer, particularly prior to our signing additional collaboration agreements, our business and financial condition may be materially harmed.
 
In August 2013, we entered into a Research and Development Collaboration and License Agreement with Bayer for the research, development, and commercialization of antibody-based therapeutics for cancer immunotherapy against two novel, Compugen-discovered immune checkpoint regulators – CGEN 15001T and CGEN 15022. This is our first collaboration arrangement for any of our Pipeline Program candidates.
 
The collaboration with Bayer is subject to all of the risks as set forth above with respect to our dependence in general on collaboration agreements with third parties. In addition, since this is our first collaboration involving our Pipeline Program candidates, and specifically covering Compugen-discovered immune checkpoint regulators, until such time as we have additional agreements, the effect of any event related to this collaboration will likely have a significantly greater effect on our business and financial condition than otherwise would be the case.
 
Bayer may terminate the agreement, at any time with or without cause either in whole or only with respect to one of the two programs, and in each case also on a product-by-product and/or country-by country basis, upon prior written notice. Upon any termination of the agreement, depending upon the circumstances, the parties have varying rights and obligations with respect to the continued development and commercialization of any products and or various payment and royalty obligations in the event of such continuation of the development and commercialization. If significant adverse unforeseen events occur in the Bayer collaboration or the agreement is terminated, in whole or in part, particularly prior to our signing additional collaboration agreements, our business and financial condition may be materially harmed.
 
Our reliance on third parties for the performance of key research, validation and development activities heightens the risks faced by our business.
 
We invest significant efforts and resources into outsourcing certain key functions with third parties, including certain research, validation and development activities, manufacturing operations, and others. We do not control the third parties to whom we outsource these functions, but we depend on them to undertake activities and provide results or materials which may be significant to us. If these third parties fail to properly perform these activities, or provide us with incorrect or incomplete results, or fail to produce and/or provide certain materials this could lead to significant delays in the program or even program failure, along with significant additional costs. In addition, should any of these third parties fail to comply with the applicable laws and regulations and/or research and development or manufacturing accepted standards in the course of their performance of services for us, there is a risk that we could be held responsible for such violations of law as well. Any such failures by third parties could have a material adverse effect on our business, financial condition or results of operations. Additionally we have entered into an agreement to obtain access to a highly diverse human phage display antibody library to generate antibodies against its novel targets for its Pipeline Program. This agreement terminates in June 2015, unless we pay certain renewal fees. In addition, if we fail to comply with the other provisions of this agreement, the third party from which we have obtained license to this library may terminate our rights to use the library, which could harm our business, financial condition or results of operations.
 
We rely on the services of various third party service providers. If we fail to identify and obtain quality services from such third parties, our discovery, validation and development activities may be harmed.
 
In carrying out discovery, validation and development activities for our product candidates, we and our partners rely on advice, services and results obtained from various third party service providers, such as contract research organizations, or CROs, contract manufacturing organizations, or CMOs, technology providers, academic institutions and other consultants. This includes, without limitation, production of certain biological reagents and performance of certain in vitro and in vivo validation of our discoveries and product candidates. We do not always independently verify the results obtained by such third parties and in some cases, rely upon the data provided by the third party. If we fail to identify and obtain accurate and quality services technologies and/or data from such third parties, or if the contractual demands of such third parties become unreasonable and we are not able to reach satisfactory agreements with such third parties, we may not be able to obtain the required services and/or technologies, in which event we may lose our investment in these services, fail to receive the expected benefits from our discoveries, and our validation and development capabilities or activities, may be significantly harmed or delayed.
 
 
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We have limited experience and capabilities in conducting, managing or sponsoring preclinical evaluation of therapeutic drug candidates.
 
During 2010, we began to focus our discovery efforts primarily in the fields of oncology and immunology, and initiated the Pipeline Program to both substantially increase the number of molecules in our validation pipeline and to increase the value of certain of our candidates by advancing selected molecules to pre-clinical studies and in selected cases, possibly clinical evaluation. We have limited experience and capabilities in conducting, managing or sponsoring the work and efforts required beyond the proof of concept experimental validation stage towards preclinical evaluation, and by doing so we will need to rely on our consultants and third party service providers. If we fail to identify the right consultants or service providers, if the consultants or service providers fail in providing the required services or if we fail to take the necessary steps towards preclinical evaluation, for these or other reasons, our business may be harmed.
 
We have no experience in conducting or managing clinical trials for potential therapeutic products, and rely on third parties to conduct such trials on our behalf. If these third parties are not successful in carrying out their duties our development of potential products may be delayed.
 
We have no experience in conducting or managing the clinical trials necessary to obtain regulatory approvals for any product, and we intend to rely on our collaborators or third parties, such as CROs, medical institutions and clinical investigators to perform these functions. Our reliance on third parties for clinical development activities reduces our control over these activities. Third-party contractors may not complete activities on schedule, or may not conduct clinical trials in accordance with regulatory requirements or our trial design. If these third parties do not successfully carry out their contractual duties or meet required performance standards or expected deadlines, we might be required to replace them, or the data that they provide could be rejected, all of which may result in a delay of the affected trial and additional program costs.
 
We rely on access to public and commercial databases to feed our discovery capabilities, including our individual discovery platforms. If we are denied access to these databases, if the quality of available information is poor, or if the quantity of the available information is insufficient, our operations and business may be harmed.
 
In the development and validation of our discovery platforms and other tools, as well as in connection with the resulting therapeutic and diagnostic product candidates, we rely on our ability to access and use public and commercially available databases. The quality of our platforms, tools and discoveries is in part dependent on the quality and quantity of the data in these databases. If we are denied access to these databases, if we are granted access to such databases on terms which are not commercially reasonable, if the quality of data available from those databases is poor, or if the quantity of the available information is insufficient, each of which has occurred in the past, our business and our results of operations may be materially harmed.
 
We rely on access to high-quality biological samples supported by detailed clinical records to conduct parts of our discovery and validation activities. If we fail to identify and purchase or otherwise obtain such samples, if the quality of available biological samples is poor, or if the quantity of the available biological samples is insufficient, which has occurred in the past, our discovery and validation capabilities may be harmed.
 
In carrying out our discovery and validation of product candidates, we rely on our ability to access and use commercially available biological samples. The quality of our discoveries is in part dependent on the quality and quantity of available biological samples. If we fail to identify and purchase or otherwise obtain such samples for any reason, if the quality of available biological samples is poor, if the samples have not been obtained and made available for secondary use in accordance with applicable law, or if the quantity of the available biological samples is insufficient, which has occurred in the past, our discovery and validation capabilities may be harmed.
 
 
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Risks Related to Competition and Commercialization
 
Our business model is at an early stage of implementation and to date has not yielded significant revenues.
 
The success of our business model relies on providing, through licensing agreements and other forms of collaboration, product candidates for commercialization by third parties, principally pharmaceutical and biotechnology companies. In all cases, our objective is that these collaborations will be “product oriented”, with us having the right to receive fees, research revenues, milestones, royalties and other revenue-sharing payments from products developed and commercialized based on our product candidates. Additionally, our business model includes research and discovery collaborations either aimed at harnessing our infrastructure capabilities towards the partners’ discovery needs, or pursuant to which we can license out our various non-focus specific discoveries of interest. Potential revenue sources in these types of transactions could include fees, research revenues, milestone payments, royalties and other revenue sharing payments. Our commercialization efforts are at an early stage of implementation. To date, we have entered into one collaboration with respect to molecules from our Pipeline Program, established a JV with Merck-Serono for the discovery and development of biomarkers for the prediction of drug-induced hepatotoxicity and have entered into a number of other small collaboration agreements, none of which, other than the Bayer Collaboration, has to date provided significant revenues. There can be no assurance that such agreements will be successful in the future or that we will be able to enter into additional arrangements with respect to other existing or future discoveries. If we are unable to achieve success, primarily by entering into additional license agreements or other collaboration arrangements related to our product candidates, our business will be materially harmed.
 
In addition, most of our programs are in the discovery, research and validation or early preclinical stage. The data generated so far may not be sufficient for prospective collaborators, and may not fit their strategy. A limited number of companies are interested in early stage collaborations, and some of them will require more data before they enter into a significant collaboration. We are therefore dependent on the fit of the stage of our programs to pharma strategy and we may not be able to identify additional partners interested in programs at the stage we are in. This may adversely affect our ability to enter into additional agreements for the research, development and commercialization of our product candidates, and as a result may harm our business.
 
Additionally, an initial industry trend towards drug combinations in the field of cancer immunotherapy, mainly immune modulating agents such as immune checkpoints, may result in a situation under which our immune checkpoint candidates will serve as a combination product and may therefore be entitled to only a fraction of the anticipated product revenues.
 
The agreement cycle for potential collaborations is complex and lengthy and as a result, we may expend substantial funds and management resources with no assurance of success.
 
In general, each potential license agreement or other form of collaboration we may enter into will require negotiating with our potential partner a large number of scientific, legal and business terms and conditions that can vary significantly in each instance due to the specific product candidate or candidates involved, and the potential partner’s licensing, development and business operations and strategy. The accommodation of these requirements mandates a thorough consideration of both the scientific and business aspects of each transaction. Furthermore, the diversity and wide applicability of our discovery capabilities and our product candidates, together with the fact that we are mainly located in Israel, adds additional levels of complexity to our business development efforts. As a result, the process of preparing and negotiating our licensing and other agreements may take more than 12 months and will require the input and substantial time and effort of our key scientific and management personnel. Accordingly, we will need to expend substantial funds and substantial key personnel time and effort into these business development activities with no assurance of successfully entering into agreements with potential collaborators and this could harm our business.
 
The trend towards consolidation in the pharmaceutical, diagnostic and biotechnology industries may adversely affect us.
 
There is a trend towards consolidation in the pharmaceutical, diagnostic and biotechnology industries. Although this consolidation trend is diminishing, it may still result in the remaining companies having greater financial resources and discovery and technological capabilities, thus intensifying competition in these industries. This trend may also result in fewer potential collaborators or licensees for our therapeutic and diagnostic product candidates. Also, if a consolidating company is already doing business with our competitors, we may lose existing or potential licensees or collaborators as a result of such consolidation. In addition, if a consolidating company is already doing business with us, we may lose the interest of the consolidating parties in our discovery capabilities or individual discoveries as a result of a modified strategy and new priorities of such consolidated entity. This trend may adversely affect our ability to enter into agreements for the development and commercialization of our product candidates, and as a result may harm our business.
 
 
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The biotechnology and pharmaceutical industries are highly competitive, and we may be unable to compete effectively.
 
The biotechnology and pharmaceutical industries in general, and the immune checkpoints field in particular, are highly competitive. Numerous entities in the United States, Europe and elsewhere compete with our efforts to discover, validate and partner with licensees and/or collaborators to commercialize therapeutic and diagnostic products or product candidates. Our competitors include pharmaceutical and biotechnology companies, academic and research institutions and governmental and other publicly funded agencies. We face, and expect to continue to face, competition from these entities to the extent they develop products that have a function similar or identical to the function of our therapeutic product candidates in the fields of oncology and immunology that may attract our potential collaborators or that may reach the market sooner. We also face, and expect to continue to face, competition from entities that seek to develop technologies that enable the discovery of novel targets, antibodies and Fc fusion proteins in the fields of oncology and immunology. Many of our competitors have one or more of the following:
 
 
•
much greater financial, technical and human resources than we have at every stage of the discovery, development, manufacture and commercialization process;
 
 
•
more extensive experience in preclinical testing, conducting clinical trials, obtaining regulatory approvals, and in manufacturing and marketing diagnostics and therapeutics;
 
 
•
more extensive experience in oncology and immunology and in the fields of mAb therapy and fusion protein therapeutics;
 
 
•
products that have been approved or are in late stages of development; and
 
 
•
collaborative arrangements in our target markets with leading companies and research institutions.
 
Since we are a small company with limited human and financial resources, we are not able to work with a large number of collaborators in parallel and/or advance a large number of molecules in parallel. Our competitors may develop or commercialize products with significant advantages over any therapeutic products we, our collaborators or third-party licensees may develop. They may also obtain patents and other intellectual property rights before us and thereby prevent us from pursuing the development and commercialization of our discoveries. Our competitors may therefore be more successful in developing and/or commercializing products than we, our collaborators, or third party licensees are, which could adversely affect our competitive position and business. If we are unable to compete successfully against existing or potential competitors, our financial results and business would be materially harmed.
 
Changes in healthcare policy could increase our expenses, decrease our revenues and impact sales of, and reimbursement for, our products.
 
Our ability to commercialize our future product candidates successfully, alone or with collaborators, will depend in part on the extent to which coverage and reimbursement for these product candidates will be available from government health programs, such as Medicare and Medicaid in the United States, private health insurers and other third-party payors. At present, significant changes in healthcare policy, in particular the continuing efforts of the U.S. and other governments, insurance companies, managed care organizations and other payors to contain or reduce health care costs are being discussed, considered and proposed.
 
For example, in the United States, there have been several initiatives implemented to achieve these aims. The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Affordability Reconciliation Act (collectively, the “ACA”), substantially changes the way health care is financed by both governmental and private insurers. The ACA contains a number of provisions that are expected to impact our business and operations, including those governing enrollment in federal healthcare programs and reimbursement changes which will impact existing government healthcare programs and will result in the development of new programs.
 
 
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In addition to the ACA, there will continue to be proposals by legislators at both the federal and state levels, regulators and third-party payors to keep these costs down. In general, it is too early to predict specifically what effect these acts and their implementation or any future healthcare reform legislation or policies in the United States or other countries will have on our business, including our ability to set prices for our product candidates which we believe are fair, and therefore our ability to generate revenues and achieve and maintain profitability. Yet, current and future healthcare reform legislation and policies could have a material adverse effect on our business and financial condition.
 
Risks Related to our Operations
 
We may move to new facilities in the fourth quarter of 2015. This move could lead to disruptions in our business operations.
 
The current lease for our laboratories and headquarters in Tel-Aviv, Israel, expires on December 31, 2015, and we are currently exploring other options including the extension of the current lease, or a relocation of our laboratories and headquarters to new facilities during the fourth quarter of 2015. There is a risk that if we elect to move our laboratories and headquarters and new facilities, this physical move could lead to damage to equipment or other business assets or the loss of important data, or delays that may affect our commitment to our collaborators or delays in achieving our yearly goals or that we could encounter problems with our new facilities.
 
Such a move also includes, among others, the following risks:
 
•  unanticipated additional costs connected to such move;
 
•  employee attrition;
 
•  delay in the completion of the new facilities;
 
•  delay in receipt of required approvals and/or permits; and
 
•  logistical and operational  issues arising from the move.
 
Any of these factors could disrupt or delay our business operations.
 
Our operations including research and development are centralized at two sites without significant redundancies. Physical or environmental damages or other reasons making one or both sites non-operational may significantly affect our business  
 
Our company has two major sites, in Tel Aviv, Israel and South San Francisco. Damage to either or both of these sites (or to the new site if we elect to move our headquarters and laboratories) due to natural calamities or other reasons can significantly disrupt our business, delay our business operations, jeopardize our ability to meet contractual obligations or patent prosecution deadlines and result in significant harm to our business.
 
We may be unable to hire or retain key personnel or sufficiently qualified employees, in which case our business may be harmed.
 
Our business is highly dependent upon the continued services of our senior management and key scientific and technical personnel. While members of our senior management and other key personnel have entered into employment or consulting agreements and non-competition and non-disclosure agreements, they can terminate their employment agreements with us at any time without cause. We cannot be sure that these key personnel and others will not leave us or compete with us, which could harm our business activities and operations. It is difficult to find suitable and highly qualified personnel in certain aspects of our industry.
 
It can also be difficult for us to find employees with appropriate experience for our business. During the year 2014 we significantly increased our number of employees, and our plans to further increase our R&D budget and activities during the year 2015 will require increased efforts to attract the required personnel with the required expertise and experience. We require a multidisciplinary approach and some of our researchers require an understanding in both exact and biological sciences. Our business may be harmed if we are unable to retain our key personnel, or to attract, integrate or retain other highly qualified personnel in the future.
 
 
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We may be unable to safeguard the integrity, security and confidentiality of our data or third parties’ data, and if we are unable to do so, our business may be harmed.
 
We rely heavily on the use and manipulation of large amounts of data and on the secure and continuous use of our internal computers, communication networks and software and hardware systems. We have implemented and maintain physical and software security measures to preserve and protect our computers and communication, hardware and software systems as well as our data and third parties’ data. However, these methods may not fully protect us against fire, storm, flood, power loss, earthquakes, telecommunications failures, physical or software break-ins or similar events. In addition, these measures may not be sufficient to prevent unauthorized access, use or publication of such proprietary data. A party who is able to circumvent our security measures could misappropriate or destroy (partially or completely) proprietary information or cause interruptions in our operations. In addition, a party, including an employee or a contractor, who obtains unauthorized access to our proprietary data or breaches a confidentiality agreement with us could publish or transfer large portions or all of our proprietary data. Some of our proprietary data is maintained in secured cloud services that may also be subject to security breach, including by employees of the cloud services provider. Such publication of proprietary data could materially harm our intellectual property position, thereby seriously harming our competitive position. Such security breaches, if significant, could materially harm our operations and even cause our business to cease.
 
If we are unable to manage the challenges associated with our bi-national operations, the growth of our business could be limited.
 
In addition to our operations in Israel, our wholly owned subsidiary, Compugen USA, Inc., operates in South San Francisco, California. We are subject to a number of risks and challenges that specifically relate to these bi-national operations. Our combined operations may not be successful if we are unable to meet and overcome these challenges, which could limit the growth of our business and may have a material adverse effect on our business and operating results. These risks include:
 
 
•
difficulty managing and coordinating operations in multiple locations, which could adversely affect the progress of our research and development programs and business prospects;
 
 
•
local regulations or intellectual property requirements that may restrict or impair our ability to conduct pharmaceutical and biotechnology-based research and development; foreign protectionist laws and business practices that favor local competition;
 
 
•
laws and regulations governing U.S. immigration and entry into the United States that may restrict free movement of our employees between Israel and the United States and employment of Israeli citizens in our U.S. facilities; and
 
 
•
fluctuations in foreign currency exchange rates that may increase the U.S. dollar cost of our operations in either country.
 
Risks Related to Intellectual Property
 
We may not be able to obtain or maintain patent protection for our inventions and if we fail to do so, our business will likely be materially harmed.
 
We have applied for patents covering therapeutic and diagnostic product candidates as well as aspects of some of our technologies, and the success of our business depends, to a large extent, on our ability to obtain and maintain such patents and any additional patents covering our future product candidates. As of February 1, 2015 we had a total of 54 issued and allowed patents, of which 35 are U.S. patents, six are Australian patents, four are Israeli patents, five are European patents, one is Canadian patent and three are Japanese patents. Our issued patents expire between 2020 and 2029. We also have 132 pending patent applications, which as of February 1, 2015, included 24 patent applications that have been filed in the United States, 18 patent applications that have been filed in Europe, 23 patent applications that have been filed in Israel, 11 patent applications that have been filed in Australia, 9 patent applications that have been filed in Canada, 9 patent applications that have been filed in Japan, 5 patent applications that have been filed in India, 5 patent applications that have been filed in China, 3 patent applications that have been filed in Brazil, 3 patent applications that have been filed in Korea, 3 patent applications that have been filed in New Zealand, 3 patent applications that have been filed in the Russian Federation, 3 patent applications that have been filed in Singapore, 3 patent applications that have been filed in Mexico, 3 patent applications that have been filed in South Africa, 3 patent applications that have been filed in Hong Kong, two patent applications that have been filed in Egypt and two applications that have been filed under the Patent Cooperation Treaty for which we have not yet designated the countries of filing. We plan to continue to apply for patent protection for our therapeutic and diagnostic inventions, but we cannot be sure that any of our patent applications will be accepted, or that they will be accepted to the extent that we seek. Additionally, we file for patent protection in selected countries and not in all countries of the world. Therefore, we are exposed to competition in those countries in which we have no patent protection. Also, due to our early stage business model, we may be required to seek patent protection at a very early stage. This may cause issuance of a patent at an earlier stage creating a shorter commercialization period under patent protection, possibly enabling others to compete with us. Delays in filing patents may preclude us from obtaining protection on some or all of our product candidates due to others filing ahead of us.
 
 
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The process of obtaining patents for inventions that cover our products is uncertain for a number of reasons, including but not limited to:
 
 
•
the patenting of our inventions involves complex legal issues, many of which have not yet been settled;
 
 
•
legislative and judicial changes, or changes in the examination guidelines of governmental patent offices may negatively affect our ability to obtain molecule-based patents;
 
 
•
in view of the finite number of human proteins, we face competition from other biotechnology and pharmaceutical companies who have already sought patent protection relating to proteins and protein based products, as well as therapeutic and diagnostic antibodies specifically binding these proteins, and their utility based discoveries that we may intend to develop and commercialize; such prior patents may negatively affect our ability to obtain protein-based and antibody-based patents, may hinder our ability to obtain sufficiently broad patent claims for our inventions, and/or may limit our freedom to operate;
 
 
•
publication of gene and gene products data by non-commercial and commercial entities may hinder our ability to obtain sufficiently broad patent claims for our inventions;
 
 
•
even if we succeed in obtaining patent protection, such protection may not be sufficient to prevent third parties from using our patented inventions;
 
 
•
even if we succeed in obtaining patent protection, we may face FTO issues;
 
 
•
even if we succeed in obtaining patent protection, our patents could be partially or wholly invalidated, including by our competitors;
 
 
•
there are significant costs that may need to be incurred in registering and filing patents;
 
 
•
our data may support others in strengthening their patents;
 
 
•
seeking patent protection at an early stage may prevent us from providing comprehensive data supporting the patent claims and may prevent allowance of the patent or limit the scope of patent coverage; and
 
 
•
we may not be able to supply data to support our patents, on time or by the required quality, in order to support our patent positions and this may harm our ability to get appropriate protection or protection at all.
 
The U.S. Supreme Court, or the Court, has also issued decisions for which the full impact is not yet understood. On June 13, 2013, in Association for Molecular Pathology v. Myriad Genetics, Inc. the Court held that claims to isolated genomic DNA were not patentable subject matter, but claims to complementary DNA (cDNA) molecules were patentable subject matter. The USPTO Examination Guidelines, issued in March 2014, introduced new procedure for determining subject matter eligibility of claims post Myriad, and they include specific questions and factors that weigh against or for patent eligibility of other isolated natural products. On March 20, 2012, in Mayo Collaborative Services, DBA Mayo Medical Laboratories, et al. v. Prometheus Laboratories, Inc., the Court held that several claims drawn to measuring drug metabolite levels from patient samples and correlating them to drug doses were not patentable subject matter. The decision has created uncertainty around the ability to patent certain biomarker-related method patents. In the recent decision in Abbvie Deutschland v. Janssen Biotech and Centorcor Biologics, Fed. Cir. July 1, 2014, the jury found both Abbvie’s patents on fully humanized antibodies to IL-12 invalid as failing the written description requirement. There are no clear rules regarding the number of species that must be disclosed to describe a genus claim, as this number necessarily changes with each invention, and it changes with progress in the field. Although it is well-settled that the written description requirement does not require actual reduction to practice of the representative species, a patentee must provide a clear correlation between common structural elements and function across the whole genus. These decisions have increased the uncertainty with regard to our ability to obtain patents in the future as well as the value of current and future patents, once obtained. Depending on decisions by the U.S. federal courts and the Patent Office, the interpretation of laws and regulations governing patents could change in unpredictable ways that could weaken our ability to obtain new patents or to enforce our existing patents, all of which could have a material adverse effect on our business.
 
 
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If we do not succeed in obtaining patent protection for our inventions to the fullest extent for which we seek protection, our business and financial results could be materially harmed.
 
We may not be able to protect our non-patented proprietary data, technologies or discoveries, and that may materially harm our business.
 
Aside from our patented information, we also rely on our proprietary know-how and trade secrets that we develop and that are not protectable or protected by patents. The protective measures that we employ may not provide adequate protection for our trade secrets and know-how. Our business collaborators, licensees, employees, advisers and consultants may disclose our proprietary know-how or trade secrets in violation of their obligations to us. We may not be able to meaningfully protect our rights in our proprietary know-how or trade secrets against such unauthorized disclosure and any consequent unauthorized publication.
 
If we are not able to adequately protect our proprietary know-how and trade secrets, competitors may be able to develop technologies and resulting discoveries and inventions that are the same or similar to our own discoveries and inventions. That could erode our competitive advantage and materially harm our business.
 
The existence of third party intellectual property rights may prevent us from developing our discoveries or require us to expend financial and other resources to be able to continue to do so.
 
In selecting a therapeutic product candidate for development, we take into account, among other considerations, the existence of third party intellectual property rights that may hinder our right to develop and commercialize that product candidate. The human genomic pool is finite. To our knowledge, third parties, including our competitors, have been filing wide patent applications covering an increasing portion of the human genomic pool and the proteins and peptides expressed therefrom. As a result of the existence of such third party intellectual property rights, we have been and may be further required to:
 
 
•
forgo the research, development and commercialization of certain therapeutic product candidates that we discover, notwithstanding their promising scientific and commercial merits;  or
 
 
•
invest substantial management and financial resources to either challenge or in-license such third party intellectual property, and we cannot be sure that we will succeed in doing so on commercially reasonable terms, if at all.
 
We do not always have available to us, in a timely manner, information of the existence of third party intellectual property rights related to our own discoveries. The content of U.S. and other patent applications remains unavailable to the public for a period of approximately 18 months from the filing date. In some instances, the content of U.S. patent applications remains unavailable to the public until the patents are issued. As a result, we can never be certain that programs that we commence will be free of third party intellectual property rights. If we become aware of the existence of third party intellectual property rights only after we have commenced a particular program, we may have to forgo such project after having invested substantial resources in it.
 
We may infringe third party rights and may become involved in litigation, which may materially harm our business.
 
If a third party accuses us of infringing its intellectual property rights or if a third party commences litigation against us for the infringement of patent or other intellectual property rights, we may incur significant costs in defending such action, whether or not we ultimately prevail. Typically, patent litigation in the pharmaceutical and biotechnology industry is expensive and prolonged. Costs that we incur in defending third party infringement actions would also result in the diversion of management’s and technical personnel’s time. In addition, parties making claims against us may be able to obtain injunctive or other equitable relief that could prevent us or our collaborators and licensees from further developing our discoveries or commercializing our products. In the event of a successful claim of infringement against us, we may be required to pay damages or obtain one or more licenses from the prevailing third party, which may not be available to us on commercially reasonable terms, if at all. If we are not able to obtain such a license or not able to obtain such a license at a reasonable cost, we could encounter delays in product introductions and loss of substantial resources while we attempt to develop alternative products. Defense of any lawsuit or failure to obtain any such license could prevent us or our partners from commercializing available products and could cause us to incur substantial expenditures.
 
 
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Patent reform and other legislative changes in the U.S. and other countries may affect our ability to obtain and enforce our patents.
 
In 2011, the United States passed comprehensive patent reform laws in the “America Invents Act,” or the “Act.” These changes may affect our ability to obtain and enforce patents in a number of ways. First, the Act provides for a period of ex parte post-grant review with expanded grounds for challenging validity of a patent for nine months after grant of a patent. If the validity of one of our U.S. patents is successfully challenged, some or all of the claims may be invalidated, such that we could not enforce the patent and hence may not be able to protect one or more of our therapeutic product candidates. Other countries may also pass legislative changes to their patent laws which could materially affect – and even invalidate – one or more of our already filed patent applications, or even granted patents.
 
Increased progress in our scientific and technological environment may reduce our chances of obtaining a patent.
 
In order to obtain a patent to protect one of our therapeutic product candidates, we must show that the underlying invention (that is, the candidate itself or its use) is inventive. As an increasing amount of scientific knowledge is becoming available regarding genes, proteins and biological mechanisms, the bar is increasingly raised to show sufficient inventiveness, as inventiveness is judged against all publicly available information available prior to filing of the patent application (the exact date may vary by country or due to other circumstances). We were initially pioneers in a largely unexplored field, but now there are many others working in our area. We may not be able to obtain patents for our product candidates due to the increased information published in this area. Collective patent applications, in which a large number of candidates are included in one patent application, are also challenged due to the raised bar for information that must be included in a patent application, as well as due to the availability of other publications. Our own published patent applications and other publications also serve as prior art against our new inventions and patent applications, and may prevent us from obtaining new patents.
 
We may become subject to claims for remuneration or royalties for assigned service invention rights by our employees, which could result in litigation and adversely affect our business
 
We enter into assignment of invention agreements with our employees pursuant to which such individuals agree to assign to us all rights to any inventions created in the scope of their employment or engagement with us. A significant portion of our intellectual property has been developed by our employees in the course of their employment for us. Under the Israeli Patent Law, 5727-1967, or the Patent Law, inventions conceived by an employee due to and during his or her employment with a company are regarded as “service inventions,” which belong to the employer, absent a specific agreement between the employee and employer giving the employee service invention rights or waiver of such rights by employer. The Patent Law also provides that if there is no agreement with respect to whether the employee is entitled to remuneration for his or her service invention, to what extent and under what conditions, such entitlement and terms shall be determined by the Israeli Compensation and Royalties Committee, or the Committee, a body constituted under the Patent Law. Recent decisions by the Committee and Israeli courts have created some uncertainty in this area. Although our employees have agreed to assign to us service invention rights, we may face claims demanding remuneration in consideration for assigned inventions. As a consequence of such claims, we could be required to pay additional remuneration or royalties to our current and/or former employees, or be forced to litigate such claims, which could negatively affect our business.
 
Confidentiality agreements with employees and others may not adequately prevent disclosure of trade secrets and other proprietary information.
 
In addition to patents, we rely on trade secrets, know-how and technology, not protected by patents, to maintain our competitive position. In order to protect our proprietary technology and processes, we rely in part on confidentiality agreements with our collaborators, employees, consultants, outside scientific collaborators and sponsored researchers and other advisors. These agreements may not effectively prevent disclosure of confidential information and may not provide an adequate remedy in the event of unauthorized disclosure of confidential information. In addition, others may independently discover trade secrets and proprietary information, and in such cases we could not assert any trade secret rights against such party. Costly and time-consuming litigation could be necessary to enforce and determine the scope of our proprietary rights, and failure to obtain or maintain trade secret protection could adversely affect our competitive business position.
 
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Risks Related to Operations in Israel
 
Conditions in the Middle East and in Israel may harm our operations.
 
Our headquarters and part of our research and development facilities are located in Israel. Accordingly, political, economic and military conditions in Israel may directly affect our operations. Since the establishment of the State of Israel in 1948, a number of armed conflicts have taken place between Israel and its Arab neighbors, as well as incidents of civil unrest, military conflicts and terrorist actions. Future armed conflicts or political instability in the region, as recently seen in Egypt, Syria and other neighboring countries, may negatively affect business conditions and adversely affect our results of operations. In addition, Iran has threatened to attack Israel and is suspected of developing nuclear weapons. Iran is also believed to have a strong influence among extremist groups in the region. These situations may potentially escalate in the future and turn violent which could affect Israel and us.
 
Furthermore, several countries, principally in the Middle East, restrict doing business with Israel and Israeli companies, and additional countries may impose restrictions on doing business with Israel and Israeli companies if hostilities in the region continue or intensify. Parties with whom we do business have sometimes declined to travel to Israel during periods of heightened unrest or tension, forcing us to make alternative arrangements when necessary. In addition, the political and security situation in Israel may result in parties with whom we have agreements involving performance in Israel claiming that they are not obligated to perform their commitments under those agreements pursuant to force majeure provisions in the agreements. Additionally, some of our employees, including key employees, perform annual military reserve duty and may be called to active military services for extended periods of time which could adversely affect our operations.
 
Our insurance does not cover losses that may occur as a result of events associated with the security situation in the Middle East. Although the Israeli government is currently committed to covering the reinstatement value of direct damages that are caused by terrorist attacks or acts of war, there can be no assurance that such government coverage will be maintained, or if maintained, will be sufficient to compensate us fully for damages incurred. Any losses or damages incurred by us could have a material adverse effect on our business. Any armed conflicts or political instability in the region would likely negatively affect business conditions and could harm our results of operations.
 
Holders of our ordinary shares who are U.S. residents may be required to pay additional U.S.  income taxes if we are classified as a PFIC for U.S. federal income tax purposes.
 
There is a risk that we may be classified as a passive foreign investment company, or PFIC. Our treatment as a PFIC could result in a reduction in the after-tax return of U.S. holders of our ordinary shares and may cause a reduction in the value of our shares. For U.S. federal income tax purposes, we will generally be classified as a PFIC for any taxable year in which either: (i) 75% or more of our gross income is passive income or (ii) at least 50% of the average value (determined on a quarterly basis) of our total assets for the taxable year produce or are held for the production of passive income. Based on our analysis of our income, assets, activities and market capitalization, we do not believe that we were a PFIC for the taxable year ended December 31, 2014. However, there can be no assurances that the United States Internal Revenue Service (“IRS”) will not challenge our analysis or our conclusion regarding our PFIC status. There is also a risk that we were a PFIC for one or more prior taxable years or that we will be a PFIC in future years, including 2015. If we were a PFIC during any prior years, U.S. holders who acquired or held our ordinary shares during such years generally will be subject to the PFIC rules. The tests for determining PFIC status are applied annually and it is difficult to make accurate predictions of our future income, assets, activities and market capitalization, which are relevant to this determination. If we were determined to be a PFIC for U.S. federal income tax purposes, highly complex rules would apply to U.S. holders owning our ordinary shares and such U.S. holders could suffer adverse U.S. tax consequences. For more information please see “Item 10. Additional Information – E. Taxation - Certain Material U.S. Federal Income Tax Considerations – Passive Foreign Investment Company.”
 
 
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Our results of operations may be adversely affected by the devaluation of the dollar against the New Israeli Shekel.
 
We hold most of our cash, cash equivalents and short-term and long-term bank deposits in U.S. dollars but incur a significant portion of our expenses, principally salaries and related personnel expenses and administrative expenses for our Israeli based operations, in NIS. As a result, we are exposed to the risk that if the U.S. dollar devaluates against the NIS, our NIS denominated expenses will be greater than anticipated when reported in U.S. dollars. The U.S. Dollar devaluated against the NIS (by 2.3% and 7.0% in 2012 and 2013, respectively) and in 2014 the U.S. Dollar appreciated against the NIS by 12% and, as a result, our NIS denominated expenses were affected by these fluctuations. Inflation in Israel may compound the adverse impact of any devaluation by further increasing the amount of our Israeli expenses. We entered into foreign currency derivative contracts to hedge a portion of our anticipated NIS payroll and certain operation expenses. For more information, see Note 2u of our 2014 consolidated financial statements. Israeli inflation may also (in the future) outweigh the positive effect of any appreciation of the U.S. dollar relative to the NIS, if, and to the extent that, it outpaces such appreciation or precedes such appreciation. The Israeli rate of inflation (1.6% and 1.8% in 2012 and 2013, respectively) and in 2014 deflation of 0.2%, has not had a material adverse effect on our financial condition during 2012, 2013 or 2014.
 
We may not be entitled to certain tax benefits.
 
We may be entitled to benefit in the future from certain government programs and tax legislation, particularly as a result of the ‘Approved Enterprise’ status granted to some of our operations by the Investment Center in the Israeli Ministry of the Economy and the ‘Benefiting Enterprise’ status that resulted from our eligibility for tax benefits under the Israel Law for Encouragement of Capital Investments, 1959 (an “Approved Enterprise”, a “Benefiting Enterprise” and the “Investment Law”, respectively). The availability of these tax benefits, however, is subject to certain requirements under the Investment Law including, among other things, making specified investments in fixed assets and equipment. The tax benefits that we anticipate receiving under our current “Approved Enterprises” and “Benefiting Enterprises” programs may not be continued in the future at their current levels or at all. To date, we have not actually received any such tax benefits because we have not yet generated any taxable income.
 
It may be difficult to enforce a U.S. judgment against us, or our officers and directors or to assert U.S. securities law claims in Israel.
 
It may be difficult to obtain, within the United States, service of process upon us, since we are incorporated in Israel, and upon our directors and officers and our Israeli auditors, almost all of whom reside outside the United States. In addition, because substantially all of Compugen Ltd.'s assets and almost all of Compugen Ltd.'s directors and officers are located outside the United States, it may be difficult to enforce a judgment obtained in the United States against us or any of our directors and officers in United States or Israeli courts, including a judgment, based on the civil liability provisions of the U.S. federal securities laws. Also, it may be difficult to enforce civil liabilities under U.S. federal securities laws or to assert original actions instituted in Israel under such U.S. federal securities laws. Israeli courts may refuse to hear a claim based on an alleged violation of U.S. securities laws reasoning that Israel is not the most appropriate forum to bring such a claim. In addition, even if an Israeli court agrees to hear such a claim, it is not certain whether Israeli law or U.S. law will be applicable to the claim. If U.S. law is found to be applicable, the content of applicable U.S. law must be proven as a fact by expert witnesses, which can be a time consuming and costly process. Certain matters of procedure will also be governed by Israeli law. There is little binding case law in Israel that addresses the matters described above. As a result of the difficulty associated with enforcing a judgment against us in Israel, you may not be able to collect any damages awarded by either a U.S. or foreign court.
 
Provisions of Israeli law may delay, prevent or affect a potential acquisition of all or a significant portion of our shares or assets and therefore depress the price of our shares.
 
Israeli corporate law regulates mergers, requires that acquisitions of shares above specified thresholds be conducted through tender offers, requires special approvals for transactions involving directors, officers or significant shareholders and regulates other matters that may be relevant to these types of transactions.
 
In addition, Israeli tax considerations may also make potential transactions unappealing to us or to our Shareholders whose country of residence does not have a tax treaty with Israel exempting such Shareholders from Israeli tax or who are not exempt under the provisions of Israeli tax laws from Israeli capital gains tax on the sale of our shares.
 
 
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Furthermore, under the R&D Law, to which we are subject due to our receipt of grants from the OCS, a recipient of OCS grants such as us must report to the applicable authority of the OCS any change in the holding of the means of control of our Company as a result of which any non-Israeli citizen or resident or a non-Israeli entity becomes an interested party in our Company and the consideration available to our Shareholders in a transaction involving the transfer outside of Israel of technology or know-how developed with OCS funding (such as a merger or similar transaction) may be reduced by any amounts that we are required to pay to the OCS.
 
These and other similar provisions could delay, prevent or impede an acquisition of us or our merger with another company, even if such an acquisition or merger would be beneficial to us or to our Shareholders, and it may therefore limit the price that investors may be willing to pay in the future for our ordinary shares.
 
We received grants from the OCS that may restrict the transfer of know-how that we develop.
 
We have received research and development grants from the OCS. Therefore, even following full repayment of any OCS grants, we must nevertheless continue to comply with the requirements of the R&D Law. The transfer to third parties of know-how or technologies developed under the programs submitted to the OCS and as to which we received the grants, or manufacturing or rights to manufacture based on and/or incorporating such know-how to third parties, might require the consent of the OCS, and may require certain payments to the OCS. Although such restrictions do not apply to the export from Israel of the Company’s products developed with such know-how, they may prevent us from engaging in transactions with our affiliates, customers or other third parties outside Israel, involving product or other asset transfers, which might otherwise be beneficial to us.
 
Being a foreign private issuer exempts us from certain SEC and NASDAQ requirements.
 
We are a “foreign private issuer” within the meaning of rules promulgated by the SEC. As such, we are exempt from certain provisions applicable to U.S. public companies including:
 
 
•
the rules under the Exchange Act requiring the filing with the SEC of quarterly reports on Form 10-Q and current reports on Form 8-K;
 
 
•
the sections of the Exchange Act regulating the solicitation of proxies, consents or authorizations in respect of a security registered under the Exchange Act;
 
 
•
the provisions of Regulation FD aimed at preventing issuers from making selective disclosures of material information; and
 
 
•
the sections of the Exchange Act requiring insiders to file public reports of their stock ownership and trading activities and establishing insider liability for profits realized from any “short-swing” trading transaction (a purchase and sale, or sale and purchase, of the issuer’s equity securities within less than six months).
 
In addition, under the rules and regulations of The NASDAQ Stock Market, a foreign private issuer may follow its home country practice in lieu of certain NASDAQ listing requirements. For example, under NASDAQ’s rules a company traded on the NASDAQ market is required to select director nominees either by independent directors constituting a majority of the board of directors or by a nominations committee comprised solely of independent directors. Under Israeli law, there is no such requirement to have an independent nominating committee or to have the independent directors of a company select (or recommend for selection) director nominees. Consistent with Israeli law, we have elected that our Board of Directors handle this process. We are also not required to adopt a formal board resolution or charter addressing the director nominations process and such related matters as may be required under the U.S. federal securities laws, as NASDAQ requires for a U.S. issuer. In addition, pursuant to Israeli law, we seek Shareholder approval for all corporate actions requiring such approval under the requirements of the Israeli Companies Law, 5759-1999, as amended (the “Companies Law”), which are different from the requirements for seeking shareholder approval under NASDAQ Listing Rule 5635. For a description of certain transactions requiring shareholder approval under the Companies Law see “Item 10. Additional Information — B. Memorandum and Articles of Association — Conflict of interest”. Furthermore, consistent with Israeli law, generally a quorum for an adjourned general meeting of Shareholders of the Company, is any two Shareholders present in person, by proxy or by proxy card at such meeting. As such, the quorum requirements for an adjourned meeting are different from the NASDAQ requirement that an issuer listed on NASDAQ have a quorum requirement that in no case be less than 33 1/3% of the outstanding shares of the company’s common voting stock. Because of these SEC and NASDAQ exemptions, investors are not afforded the same protections or information generally available to investors holding shares in public companies organized in the United States.
 
 
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Your rights and responsibilities as a Shareholder will be governed by Israeli law which differs in some material respects from the rights and responsibilities of shareholders of U.S. companies.
 
The rights and responsibilities of the holders of our ordinary shares are governed by our Articles of Association which we refer to as our “Articles”, and by Israeli law. These rights and responsibilities differ in some material respects from the rights and responsibilities of shareholders in U.S.-based corporations. In particular, a shareholder of an Israeli company has a duty to act in good faith and in a customary manner in exercising its rights and performing its obligations towards the company and other shareholders, and to refrain from abusing its power in the company, including, among other things, in voting at a general meeting of shareholders on the following: amendments to a company’s articles of association, increases in a company’s authorized share capital, mergers and related party transactions requiring shareholder approval. In addition, a shareholder who is aware that it possesses the power to determine the outcome of a shareholder vote or to appoint or prevent the appointment of a director or other Office Holder (as such term is defined in the Companies Law, see “Item 6 - Directors, Senior Management and Employees – B. Compensation - Approval Required for Directors’”) in the company has a duty of fairness toward the company. There is limited case law available to assist us in understanding the nature of this duty or the implications of these provisions. These provisions may be interpreted to impose additional obligations and liabilities on holders of our ordinary shares that are not typically imposed on shareholders of U.S. corporations.
 
Risks Related to our Ordinary Shares
 
Sales under our existing shelf registration statement will dilute existing Shareholders.
 
On January 7, 2013, we filed a shelf registration statement on Form F-3 with the SEC under which we may offer and sell from time to time in one or more offerings, our ordinary shares, debt securities, rights, warrants and units having an aggregate offering price of up to $100 million (“the 2013 Shelf Registration”). This registration statement was declared effective by the SEC on January 16, 2013. Pursuant to this registration statement on March 5, 2014 we closed an underwritten public offering of 6,900,000 ordinary shares, including 900,000 shares sold pursuant to the full exercise of the underwriters’ option to purchase additional shares, at a price to the public of $10.50 per share. Gross proceeds to us from this offering were approximately $72.5 million before deducting the underwriting discounts and commissions and estimated offering expenses payable by us. We currently have approximately $27.5 million of securities remaining available for offering under the 2013 Shelf Registration. On August 26, 2014, we filed a shelf registration statement on Form F-3 with the SEC under which we may offer and sell from time to time in one or more offerings, our ordinary shares, debt securities, rights, warrants and units comprising any combination of these securities having an aggregate offering price of up to $200 million (“the 2014 Shelf Registration”). This registration statement was declared effective by the SEC on September 4, 2014. As of March 1, 2015 no securities have been issued pursuant to the 2014 Shelf Registration. While there is no assurance that we will sell any shares, including shares underlying securities convertible into, exchangeable for, exercisable for shares, under this shelf registration statement, any such sales in the future may result in dilution to existing Shareholders. In addition, we may seek additional capital by selling shares or other securities under these shelf registration statements due to favorable market conditions or strategic considerations even if we believe we have sufficient funds for our current or future operating plans.
 
Our ordinary shares are traded on more than one market and this may result in price variations.
 
In addition to being traded on The NASDAQ Global Market, our ordinary shares are also traded on the Tel Aviv Stock Exchange, or TASE. Trading in our ordinary shares on these markets take place in different currencies (U.S. dollars on NASDAQ and NIS on the TASE), and at different times (resulting from different time zones, trading days and public holidays in the United States and Israel). The trading prices of our ordinary shares on these two markets may differ due to these and other factors. Any decrease in the price of our ordinary shares on one market could cause a decrease in the trading price of our ordinary shares on the other market.
 
 
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Our share price and trading volume have been volatile and may be volatile in the future and that could limit investors’ ability to sell our shares at a profit and could limit our ability to successfully raise funds.
 
During the calendar years 2013 and 2014, our stock price on NASDAQ has traded from a low of $4.56 to a high of $14.32 and trading volume is volatile from time to time. The volatile price of our shares and periodic volatile trading volume may make it difficult for investors to predict the value of their investment, to sell shares at a profit at any given time, or to plan purchases and sales in advance. A variety of factors may affect the market price of our ordinary shares including:
 
 
•
global macroeconomic developments;
 
 
•
our success (or lack thereof) in entering into collaboration agreements and achieving certain research and developmental milestones thereunder;
 
 
•
our need to raise additional capital and our success or failure in doing so;
 
 
•
achievement or denial of regulatory approvals by us or our competitors;
 
 
•
announcements of technological innovations or new commercial products by our competitors;
 
 
•
developments concerning proprietary rights, including patents;
 
 
•
developments concerning our existing or new collaborations;
 
 
•
regulatory developments in the United States, Israel and other countries;
 
 
•
delay or failure by us or our partners in initiating, completing or analyzing pre-clinical or clinical trials or the unsatisfactory design or results of such trials;
 
 
•
period to period fluctuations in our results of operations;
 
 
•
changes in financial estimates by securities analysts;
 
 
•
changes in senior management or the board of directors;
 
 
•
our ability (or lack thereof) to disclose the commercial terms of, or progress under, our collaborations;
 
 
•
our ability (or lack thereof) to show and accurately predict revenues; and
 
 
•
transactions with respect to our ordinary shares by insiders or institutional investors.
 
We are not able to control many of these factors, and we believe that period-to-period comparisons of our financial results will not necessarily be indicative of our future performance.
 
In addition, the stock market in general, and the market for biotechnology companies in particular, have experienced extreme price and volume fluctuations that may be unrelated or disproportionate to the operating performance of individual companies. These broad market and industry factors may seriously harm the market price of our ordinary shares, regardless of our operating performance.
 
Furthermore, the market prices of equity securities of companies that have a significant presence in Israel may also be affected by the changing security situation in the Middle East and particularly in Israel. As a result, these companies may experience volatility in their stock prices and/or difficulties in raising additional financing required to effectively operate and grow their businesses. Thus, market and industry-wide fluctuations and political, economic and military conditions in the Middle East may adversely affect the trading price of our ordinary shares, regardless of our actual operating performance.
 
As a result of the volatility of our stock price, we could be subject to securities litigation, which could result in substantial costs and divert management’s attention and company resources from our business.
 
ITEM 4.          INFORMATION ON THE COMPANY
 
A.HISTORY AND DEVELOPMENT OF THE COMPANY
 
History
 
Our legal and commercial name is Compugen Ltd. We were incorporated on February 10, 1993 as an Israeli corporation. The legislative framework under which Compugen Ltd. operates is the Companies Law, which originally became effective on February 1, 2000, and the Israeli Companies Ordinance (New Version) 1983, as amended. Our principal offices are located at 72 Pinchas Rosen Street, Tel Aviv 6951294, Israel, and our telephone number is +972-3-765-8585. Our primary Internet address is www.cgen.com. None of the information on our website is incorporated by reference into this annual report.
 
We have a wholly owned subsidiary, Compugen USA, Inc., which was incorporated in Delaware in March 1997 and is qualified to do business in California. This subsidiary did not have any significant operations from 2008 to March 2012.
 
 
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Principal Capital Expenditures
 
In the years ended December 31, 2014, 2013 and 2012, our capital expenditures were  $2.2 million, $328,000, and $1.1 million,  respectively, and for the year 2014 were spent primarily on laboratory equipment, general computer software and hardware. We have no current significant commitments for capital expenditures.
 
B. BUSINESS OVERVIEW
 
Overview
 
Compugen is a leading drug discovery company focused on the discovery and development of monoclonal antibodies (mAbs) and therapeutic proteins to address important unmet needs in the fields of oncology and immunology. We utilize a broad and continuously growing integrated infrastructure of proprietary scientific understandings and predictive platforms, algorithms, machine learning systems and other computational biology capabilities for the in silico (by computer) prediction and selection of novel drug target candidates, which are then experimentally validated. Beginning in late 2010, we established the Pipeline Program, consisting of targets and product candidates for applications in oncology and immunology, based largely on novel immune checkpoint regulator candidates discovered by us during our first focused discovery program. The discovery and development of mAb therapeutic candidates against selected Compugen-discovered novel target candidates is performed at our wholly-owned U.S. subsidiary located in South San Francisco. Our business model includes entering into collaborations covering the further development and commercialization of product candidates at various stages from our Pipeline Program and various forms of research and discovery agreements, in both cases potentially providing us with milestones, royalties and other forms of revenue sharing payments.
 
Predictive Discovery Infrastructure: Our continuously growing discovery infrastructure, established over more than a decade of pioneering research with respect to predictive modelling of biological phenomena, consists of a multi-dimensional platform integrating proprietary scientific understandings and predictive models, algorithms, machine learning systems and other computational biology capabilities. Unlike traditional experimentally based discovery methodologies, our predictive methodology typically results in multiple novel candidates from each discovery effort, for example our first focused discovery program resulted in the discovery of 11 potential B7/CD28- like checkpoint protein candidates.
 
Initial Fields of Focus: Oncology and immunology are both areas of complex and challenging diseases with significant unmet medical needs. Therefore, these are areas of high industry interest with numerous efforts to identify novel therapeutic solutions. Our science-driven predictive capabilities are well suited for the identification of novel therapeutic candidates for these complex, multi-factorial and challenging therapeutic fields. During 2013 and 2014, we further focused our activities to be mainly in the field of immuno-oncology, an area of high medical promise and industry interest.
 
The Pipeline Program: In order to leverage our capability to predict multiple novel drug targets with each discovery effort, we established our Pipeline Program to allow the parallel validation and early development of multiple product candidates. Our Pipeline Program currently consists of drug targets and therapeutic product candidates at various stages ranging from target validation to pre-clinical studies in the fields of oncology and immunology, with a primary focus on immuno-oncology. The aim of the Pipeline Program is to advance the validation of Compugen-discovered mAb target candidates to generate therapeutic mAbs against such targets, or Fc fusion proteins derived from these target candidates and to further advance selected therapeutic candidates beyond their animal proof of concept stage. The newly discovered candidates enter the Pipeline Program when they begin experimental evaluation following their in silico prediction and selection. mAb target candidates undergo various experimental validation studies to confirm their therapeutic potential. The experimental validation studies are conducted at our facilities, or at external expert laboratories, selected specifically for each relevant field. This is followed by the generation of a therapeutic mAb to be used for in vitro and in vivo proof of concept studies in disease animal models. Therapeutic mAb candidates, either humanized or fully-human, then enter the stage of lead candidate selection and optimization, with a final lead to be advanced to investigational new drug application (IND) enabling studies. For specific mAb therapeutic candidates we intend to continue development into early clinical development. With respect to therapeutic protein product candidates that have either been or will be successfully validated in vitro, these candidates are further advanced to in vivo proof of concept studies in disease animal models and to mechanism of action studies to explore their novel biology.
 
 
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Pipeline Program
 
Overview
 
During 2010, we integrated our approach to drug target and drug discovery, moving from a “technology driven” individual platform based methodology to a “therapeutics needs (market) driven” approach. In this “therapeutics needs (market) driven” approach, we harness all of our relevant discovery platforms, systems and tools towards a selected unmet need in order to predict and validate novel candidates that we believe have the highest potential to be successful first-in-class drug candidates to address that particular need. In late 2010, we initiated our Pipeline Program, pursuant to which we have both (i) accelerated the number of predicted and selected product candidates being evaluated by us, primarily in our fields of focus, and (ii) taken certain product candidates further beyond their proof of concept into preclinical activities, and in selected cases, assuming continued preclinical success, we intend to take them into early clinical development. However, in view of the large number of early stage product candidates in our Pipeline Program, we expect that the majority will be pursued under collaborative and/or licensing arrangements of different types with third parties.
 
Our first focused discovery program under this therapeutics needs (market) driven approach was directed towards the discovery of novel members of the immune checkpoint regulators family of proteins, initially specifically focusing on B7/CD28 co-stimulatory/co-inhibitory proteins, which are of high interest to the industry and have therapeutic potential in both cancer and autoimmune diseases. As a result of this successful discovery effort, the primary focus of our Pipeline Program is mAb therapeutics targeting these potential B7/CD28 like checkpoint candidates for cancer immunotherapy, and to a lesser degree, protein therapeutics for autoimmune diseases based on these novel checkpoint candidates.  
 
Our initial results in identifying potential B7/CD28-like immune checkpoint candidates and the high industry interest in this class of proteins, led us to expand our discovery efforts during 2013 and 2014 to the identification of additional sets of immunomodulatory proteins beyond this family.  By extending our predictive discovery capabilities for immunotherapy, we developed a methodology designed to discover immunomodulators distinct from B7/CD28-like proteins by which we predicted four such potential target candidates.  During 2014, we demonstrated successful initial experimental results for one of these novel immunomodulatory candidates that had been predicted in silico. The other three candidates are in testing.  In addition, during 2013 we successfully undertook our second focused discovery effort in the area of targets for Antibody Drug Conjugate or ADC Technology, and during 2014 demonstrated positive initial experimental results for the first two of five in silico predicted targets for ADC cancer therapy.
 
First Focused Discovery Program – Immune Checkpoints
 
Oncology and Immunology are two medical fields with significant unmet medical needs. Biologics have revolutionized patients’ treatment in these areas and have gained substantial commercial success. Compugen has therefore elected these areas as its initial areas of focus for its broadly applicable predictive capabilities. These therapeutic areas continue to grow. The top three best-selling drugs during 2013 were biologics, all indicated for the treatment of arthritis, and include Humira (adalimumab), Remicade (infliximab) and Rituxan/MabThera (rituximab). Biologics to treat cancer represented three of the top eight best-sellers in 2013, and included Rituxan, Herceptin and Avastin. Six of the top eight blockbuster biologicals are antibodies. The anti-TNF antibody Humira (adalimumab) is the top selling single brand of a recombinant biological with 2014 sales of $12.5 billion.
 
Modulation of the immune system has shown clinical success in several therapeutic applications, such as treating various types of cancer, inhibiting autoimmune diseases and prolonging graft survival in organ transplant recipients. This initial clinical significance is the basis for the increasing interest in the discovery and development of immunomodulators for therapeutic uses, and the rationale behind Compugen’s first therapeutic needs driven efforts: the identification of novel immune checkpoint protein candidates that can serve as targets for therapeutic mAb discovery or be engineered to produce therapeutic protein candidates. Data presented at the American Society of Clinical Oncology (ASCO) on checkpoint inhibitors for immuno-oncology is continuing to excite the industry, proposing a paradigm shift in cancer therapy, with excellent promise for patients’ long-term survival, though still only for a fraction of the patients. Despite the impressive efficacy observed with current immune checkpoint strategies, there still remains a significant unmet need to be addressed, e.g., by novel immune checkpoints.
 
 
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Immune checkpoints: Immune checkpoints are inhibitory receptors and their ligands, which are crucial for the maintenance of self-tolerance (that is, the prevention of autoimmunity) and for the protection of tissues from damage when the immune system is responding to pathogenic infection. In several autoimmune diseases, including for example multiple sclerosis and rheumatoid arthritis, self-reactive T cells escape immune checkpoints and autoimmune responses ensue. Therefore, restoring immunologic balance by activating immune checkpoints and regulatory immune cells is a promising avenue for the treatment of autoimmunity.
 
Immune checkpoints also play critical roles in cancer development as they are "highjacked" by tumors to block the ability of the immune system to destroy the tumor (“immune resistance”). Therapeutic blockade of immune checkpoints can boost anti-tumor immunity, enabling the patient’s immune system to recognize and attack the tumor cells, and mount durable anti-tumor responses and tumor destruction. Immune checkpoints have emerged as potential "game changers" and promising targets for cancer immunotherapy. Clinical studies employing mAb blockade of immune checkpoints, such as PD-1 and CTLA4, have shown durable responses. Antibodies targeting immune checkpoints have been thus termed “the next frontier" in the treatment of cancer and some refer to this approach as ‘the beginning of the end of cancer’ and even start talking about ‘cancer cure’. Cancer immunotherapy was selected by Science magazine as the Breakthrough of the Year 2013. It also came into high focus of the investment community, with multiple analyses, conferences, articles in leading business journals, and investments in new companies. Industry analysts estimate that the cancer immunotherapy market has a significant potential and annual sales’ projections of some of these analysts range between $28 billion and $35 billion.
 
There are currently three therapies approved for the treatment of cancer that target immune checkpoint proteins. Yervoy®, an antibody treatment targeting CTLA-4, was approved by the FDA in 2011 and registered 2013 sales of $960 million dollars, representing an increase of 36% over 2012 sales. In September 2014, Keytruda®, an antibody therapy targeting PD-1, received accelerated approval from the FDA for the treatment of advanced melanoma. This was followed by the approval in December 2014 of Opdivo®, an antibody therapy targeting PD-1, for the treatment of advanced melanoma. These therapies, along with many additional immune checkpoint targeting programs, are currently in advanced clinical trials in cancer indications with significant unmet need including: non-small-cell lung carcinoma (NSCLC), bladder cancer, head and neck cancer and renal cell carcinoma.  
 
Discovery of novel immune checkpoints for oncology and immunology: A key Compugen established capability in this field was the development and use of our Protein Family Members Discovery Platform for the discovery of novel protein members belonging to various known and clinically important protein families. This discovery platform incorporates two key Compugen proprietary infrastructure capabilities: LEADS and MED (described in more detail below). Specialized algorithms designed for identification of the unique characteristics of specific protein families, utilizing LEADS and MED, analyze the entire proteome to search for novel proteins belonging to a desired family. This platform concept was initially developed for the identification of novel immunomodulators which can serve as protein therapeutics for various pathological conditions, and more specifically, the B7/CD28 protein family of costimulators/coinhibitors. The reason we focused initially on this protein family is that B7/CD28 proteins are known to play key roles in regulating immune responses and serve as immune checkpoints. Also, there is a very low homology between these family members, which we believed we could overcome by using our unique approach. We believe new proteins of this family could have significant therapeutic potential in many pathological conditions, including oncology, infectious disease, and autoimmune diseases. Applying the Protein Family Members Discovery Platform resulted in the identification of 11 putative immune checkpoint B7/CD28-like protein candidates. The total number of B7-like immune checkpoint candidates, discovered to date by us is eleven, among those that we have disclosed are CGEN-15001T, CGEN-15022, CGEN-15049, CGEN-15027 CGEN-15052, and CGEN-15092.
 
In order to discover the immunomodulators distinct from B7/CD28-like proteins, we used a new discovery capability that incorporates the predictive modeling of two distinct biological phenomena related to the role of the immune system that are conceptually different from those employed in the discovery of Compugen’s B7/CD28-like candidates. The first biological phenomenon that was modeled exploits the interplay between the immune system and intruding pathogens. As a result of such interplay, some immune proteins tend to evolve differently from non-immune related ones. We devised an evolutionary model to detect such potential immune proteins, and this predictive algorithm was incorporated into our discovery infrastructure and integrated with our existing tools for the discovery of target candidates for cancer immunotherapy.
 
 
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The second biological phenomenon was modeled on the biology of tumor-associated macrophages (TAMs).  TAMs are an important component of the tumor microenvironment and play a major role in creating the immunosuppressive environment that enables tumor development. Proteins having the potential to modulate the tumor microenvironment may serve as potential targets for cancer immunotherapy. The modeling of this second biological phenomenon relies heavily on our MED Platform, which was employed to predict proteins that may play a role in the biology TAMs.  
 
Target characterization and validation and therapeutic discovery and development of our immune checkpoint candidates:
 
During 2014 we enhanced our target characterization and validation infrastructure, as well as our therapeutic discovery and development efforts, in order to be able to advance multiple immune checkpoint candidates in our Pipeline Program.  We added personnel, equipment, new experimental systems and technologies to increase expertise and workload throughput. Furthermore, in addition to our internal expansion efforts, we entered into new or expanded agreements with leading contract research organizations and academic research centers.
 
In December 2014, we signed a multi-year research collaboration with Johns Hopkins University, School of Medicine, under the direction of Prof. Drew Pardoll and Dr. Charles Drake. Prof. Pardoll and Dr. Drake, members of Compugen’s Scientific Advisory Board, are pioneers in the field of immuno-oncology. The collaboration will focus on further evaluation of selected novel B7/CD28-like immune checkpoint candidates discovered by us for the potential treatment of cancer. This evaluation will include the candidates’ differentiation profile with respect to known checkpoints and their potential to serve either for monotherapy or in combination with other cancer treatments. This collaborative research will expand our ongoing assessment of the biology and mechanism of actions of our novel B7/CD28-like immune checkpoint candidates, and provide access to the world-class immuno-oncology research tools and expertise at Johns Hopkins University. 
 
Immune checkpoint target candidates:
 
Our first validated target, CGEN-15001T, is expressed on numerous types of solid cancers and hematological malignancies, such as prostate cancer, melanoma, Hodgkin's lymphoma and Non-Hodgkin's lymphoma. A second target, CGEN-15022, is expressed in numerous types of epithelial cancers with significant unmet clinical needs, such as liver, colorectal, lung and ovarian cancers. The different expression profiles of CGEN-15022 and CGEN-15001T not only provide important differentiating characteristics between these two novel targets, but also offer promising potential to utilize these proteins as mAb targets to treat a broad set of key cancer indications with significant unmet medical needs. In August 2013, we signed a research and discovery collaboration and license agreement with Bayer for the development and commercialization of antibody-based therapeutics for cancer immunotherapy against CGEN-15001T and CGEN-15022.
 
In September 2013, we disclosed experimental data for CGEN-15049, a novel immune checkpoint target candidate. This experimental data demonstrated CGEN-15049's expression in a wide variety of cancers and its functional effects on the activities of different types of immune cells that play critical roles in the immune system's response against the tumor. In October 2014, we disclosed additional results from studies further confirming CGEN-15049 as a promising target candidate for cancer immunotherapy. These studies evaluated the function of CGEN-15049 on immune cells derived from the tumor environment of melanoma patients, and in these experimental studies, CGEN-15049 continued to demonstrate the potential to inhibit the immune system’s ability to attack cancer cells. More specifically, these studies have shown that overexpression of CGEN-15049 in human melanoma cells inhibits the activity of tumor antigen-specific cytotoxic T cells (CTLs) derived from melanoma patients’ tumors. These effector immune cells, also referred to as tumor infiltrating lymphocytes (TILs), infiltrate tumors and are known to play a major role in anti-tumor immune responses. The results suggest that CGEN-15049 may inhibit the activity of the immune system in the tumor microenvironment through its impact on TILs, which would otherwise fight the tumor. Additionally, initial experimental data from a mouse tumor model further support expression of CGEN-15049 on suppressive immune cells within the tumor microenvironment. Together with the previously reported expression on a wide variety of cancers, and combined with the immunomodulatory activity of CGEN-15049 on immune cells involved in tumor progression, these data support a potential role for this drug target in suppressing anti-tumor immune responses. Therefore, blockade of CGEN-15049 activity by mAb therapy has the potential to result in the stimulation of an anti-tumor immune response, leading to tumor elimination. Based on the experimental results to date, CGEN-15049, is being advanced in our Pipeline Program, with ongoing therapeutic antibody development activities against this novel target.
 
 
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In June 2014, we disclosed promising experimental results for CGEN-15052, a novel immune checkpoint target candidate, which demonstrated in several experimental settings robust inhibition of T cell activation, both as a membrane protein and as an Fc fusion protein. Initial testing of human cancer tissue samples with a polyclonal antibody indicated that CGEN-15052 is expressed in multiple epithelial cancers, with particularly high expression in lung cancer samples. We believe these positive findings support CGEN-15052’s involvement in tumor immunology and its potential as a target for cancer immunotherapy.
 
In October 2014, we disclosed successful experimental data for CGEN-15027, a novel immune checkpoint target candidate. The experimental results disclosed include the checkpoint target expression in the cancer microenvironment, both on cancer cells derived from lung, breast, and liver cancer patients, and on tumor infiltrating immune cells. In addition, the disclosed data demonstrate CGEN-15027’s inhibitory effect on cancer-specific immune cells. These results suggest that CGEN-15027 has strong potential to serve as a target for mAb cancer therapy with a mechanism of action that is potentially distinct from previously-disclosed Compugen checkpoint target candidates.
 
The immune checkpoint mAb targets’ respective fusion proteins were genetically engineered as recombinant proteins consisting of the extracellular region of the immune checkpoint membrane proteins fused to an Fc antibody domain. CGEN-15001 was the first of these predicted candidates to undergo extensive in vitro and in vivo validation, demonstrating robust efficacy in animal models of multiple sclerosis and rheumatoid arthritis, pointing to its therapeutic potential for treatment of multiple autoimmune diseases. Data for additional proteins demonstrating beneficial effects in animal models of autoimmune diseases was later disclosed, such as for CGEN-15021, CGEN-15091, CGEN-15031 and CGEN-15051. In 2013, we disclosed additional results for CGEN-15001 in disease animal models of type 1 diabetes and psoriasis. In addition, we disclosed in 2013 that CGEN-15001 was highly effective in preventing graft rejection in a bone marrow transplantation animal model, suggesting that this drug candidate acts through an induction of immune tolerance. In comparison to current therapeutic approaches that generally suppress the immune system, tolerance induction would provide a sustained resolution of the disease without compromising the immune system’s capacity to fight infections and malignancies. In 2014, we have significantly expanded our activities in the field of immuno-oncology and committed a higher portion of our resources to oncology rather than immunology. During this year, within the field of immunology we focused on CGEN-15001 in further elucidating its unique mechanism of action and in studying its translational potential using biological samples from autoimmune patients.  We announced and presented experimental results supporting CGEN-15001’s induction of long-term autoimmune disease remission in disease animal models. We have further presented animal model data indicating that the durable therapeutic response to CGEN-15001 treatment is potentially maintained via regulatory T cells (Tregs), a type of immune cells known to play critical roles in the maintenance of immune tolerance.
 
Second Focused Discovery Program – Targets for Antibody Drug Conjugate Technology
 
Antibody-drug conjugate (ADC) cancer therapy destroys cancer cells by delivering high-potency cytotoxic agents, called the payload, directly to the cancer cells. The principle underlying ADC therapy is to impact only the cancer cells by linking the cytotoxic agent payload to an antibody or antibody fragment that specifically binds to a protein that is present on cancer cells and expressed at lower levels in healthy cells. When administered to the patient, the antibody with the payload specifically targets this protein, and is internalized into the cells, where the toxic payload is released and activated. Thus, unlike traditional chemotherapies, ADCs are designed to specifically destroy only cells displaying the cancer target protein. ADCs against a number of targets, both in solid and hematologic tumors, have already demonstrated clinical success, with two ADC products gaining FDA approval since 2011.
 
Fueled by the success of recent FDA approvals, ADC cancer therapy is an area of increased focus and activity and there are approximately 40 ADCs currently in clinical testing. ADC therapeutics generated over $500 million of sales in 2013 and the ADC market is forecast to grow to $10.4 billion dollars by 2024 (Roots Analysis 2014). Additionally, in recent years the ADC field has been characterized by a very active partnering landscape amongst pharmaceutical and biotech companies, signifying the high unmet clinical need in cancer treatment and the high level of interest in developing novel ADC therapies.
 
Arming antibodies or antibody fragments with cytotoxic agents can be viewed as a means of enhancing tumor cell killing while sparing normal cells. ADCs represent a potential approach to enhance the efficacy of mAbs, by harnessing the mAb specificity to target the delivery of a cytotoxic agent to the tumor. Cancer therapy through ADCs addresses an area of high unmet medical need and is of great interest to the pharma industry. The lack of suitable ADC targets with superior characteristics compared to the known ones is a major challenge, which provides an opportunity for Compugen to serve as a key source of such potential targets.
 
 
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Compugen’s ADC target discovery program, which was initiated in 2013, utilizes our underlying predictive discovery infrastructure which was also used in our earlier immune checkpoint program, with the addition of certain algorithms and other computational capabilities specifically developed for this effort. The additional algorithms enable prediction of membrane proteins having the potential to internalize, which are both expressed on cancer cells and have low expression on healthy cells, in order to allow the ADC drug to selectively attack the tumor and spare healthy tissues. It was additionally enhanced to identify targets associated with advanced cancer stages and poor clinical outcome, in order to provide potential superior first-in-class treatment to patient populations with limited therapeutic options and high unmet need.
 
The initial results from our second focused in silico discovery program were announced at the end of 2013 with the predictive discovery and selection of five potential candidate targets for ADC cancer therapy. In January 2015, we announced that two of the five in silico predicted targets for ADC cancer therapy demonstrate low expression levels in normal critical tissues, such as heart and liver, and higher expression in multiple cancer types, such as colorectal and prostate cancers, for which there is high unmet medical need. These results suggest that these two target candidates may serve for the development of ADC therapy in oncology. Initial validation of the remaining three candidates, and further testing of these two candidates, is ongoing. It is expected that a therapeutic antibody discovery program against a selected ADC target will commence later during the year 2015. 
 
Monoclonal Antibody Therapy
 
Monoclonal antibody (mAb) therapy relates to a class of biological drugs that bind with high specificity to target cells or proteins. Due to the versatility and specificity of this approach, mAb therapies are being intensively researched and developed as treatments for numerous serious diseases with the belief that they have the potential to be more effective and have fewer side effects compared to traditional chemical drugs. During the past two decades, mAbs have emerged as an important and rapidly growing drug class, with over 20 mAbs already approved for therapeutic use in the U.S. for various clinical indications, including oncology, chronic inflammatory diseases, transplantation, infectious diseases and cardiovascular diseases. For cancer therapy, a mAb may inhibit cellular processes critical for tumor growth, stimulate the patient's immune system to attack the target cancerous cells, or be used for targeted delivery of chemotherapy specifically to the cells identified by the antibodies (known ADC technology). Moreover, according to an analysis by Tufts University, the rate of success for mAb therapeutics from first use in humans to regulatory approval is more than double that of traditional chemical drugs.
 
Although significant progress has been made in recent years in mAb therapeutics, numerous challenges still remain. One of the main challenges in this extremely promising field is the identification of novel targets for mAb therapy. To this end, we have developed several proprietary target discovery platforms through focusing and integrating of various aspects of our unique predictive discovery capabilities to identify novel drug targets for mAb therapies.
 
The Pipeline Program consists of mAb targets discovered by using our predictive discovery methodologies. While our computational capabilities can enable target discovery in any number of areas, we have focused our antibody pipeline efforts on two main target classes: immune checkpoints and targets for ADC technology. Immune checkpoint target candidates disclosed by Compugen include CGEN-15001T, CGEN-15022, CGEN-15049, CGEN-15027, CGEN-15092 and CGEN-15052. These targets have shown initial successful biological validation. Additional undisclosed immune checkpoint candidates are undergoing target validation.
 
Compugen has secured access to a highly diverse human phage display antibody library to generate antibodies against its novel targets for its Pipeline Program. We are using this library to screen for antibodies that bind to a given target with high specificity and affinity. Those antibodies are then tested for desired activities, such as the ability to stimulate anti-tumor immune response, or induce tumor cell killing when coupled with a toxin. Lead candidates are to be selected based on in vitro activity or efficacy in animal-based tumor studies, to be further advanced towards clinical development.
 
In additional to phage display technologies, we also use traditional hybridoma approaches for antibody discovery.  This is done in specific cases to broaden the diversity of candidate antibodies for a given program, and to take advantage of the natural evolution of antibody affinity that occurs following immunization of an animal. All hybridoma efforts are carried out through select contract research organizations (CROs) who have a dedicated expertise in this area.
 
 
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Antibodies for Antibody Drug Conjugate Technology
 
We have a number of potential ADC targets that will serve as the basis for future antibody development programs. Additionally, antibody development efforts have been initiated against a protein previously discovered by Compugen that demonstrates desired ADC target features. Antibodies that bind specifically to the target are tested for their ability to internalize following binding on the cell surface, and cell killing is assessed using commercially available reagents commonly used for in vitro ADC testing. For proof of concept testing in animal models, future candidate antibodies will be conjugated with linkers and toxins that are widely used and well defined in the industry, and used to treat mice bearing tumors that express the target on the cell surface. Lead candidates will be chosen based on their ability to induce tumor destruction, together with biophysical properties that are consistent with use in a therapeutic setting.
 
Therapeutic Proteins for Immunology in the Pipeline Program
 
Therapeutic proteins are large biological molecules usually produced by recombinant technologies. Therapeutic proteins are clinically used to treat a wide range of diseases including cancer, autoimmune diseases, infectious diseases, blood-related disorders and others. Potential therapeutic proteins for immunology disclosed by Compugen include CGEN-15001, CGEN-15021, CGEN-15091, CGEN-15031 and CGEN-15051. These are based on novel B7/CD28-like immune checkpoint candidates discovered using the Company’s Protein Family Members Discovery Platform. These therapeutic protein candidates were created by fusing the extracellular domain of the newly discovered immune checkpoints to an Fc fragment of an antibody. This class of therapeutic proteins, known as Fc fusion proteins, has achieved significant clinical and commercial success as exemplified by the anti-rheumatic biologics ENBREL® (etanercept) with sales of about $8.89 billion in 2013, and ORENCIA® (abatacept) with about $1.4 billion in sales in 2013. The therapeutic potential of Compugen’s Fc fusion drug candidates for immunology was demonstrated in animal models of autoimmune diseases. CGEN-15001, Compugen’s leading Fc fusion program and the current Fc fusion therapeutics focus of the company, was successfully tested in disease models of multiple sclerosis, rheumatoid arthritis, psoriasis, type 1 diabetes and bone marrow transplantation. In these disease models, CGEN-15001 provided sustained long-term therapeutic effect and showed immune tolerance induction in the transplantation model. The promise of this class of therapeutic candidates based on immune checkpoints is to potentially affect immunological processes underlying autoimmunity, thereby potentially providing long-term therapeutic solutions for patients.
 
Our Discovery Infrastructure
 
Our proprietary underlying and growing predictive discovery infrastructure has been shown to be applicable for the discovery of product candidates in multiple therapeutic and diagnostic areas. This infrastructure incorporates predictive understandings of numerous biological phenomena at the molecular level. These predictive understandings were obtained during a decade-long and ongoing research effort at Compugen and are based on the integration and sophisticated analyses of large amounts of data of various types, such as genetic, molecular, structural, clinical, biological pathways and others. This effort is performed on an ongoing basis by an experienced multidisciplinary research team of scientists, who on average have been employed by Compugen Ltd. for approximately 7.5 years and over time have generated more than 70 peer reviewed publications of certain of our findings and capabilities in scientific journals.
 
A key aspect of our capabilities is the increasing set of building block algorithms and other proprietary technologies for the accurate integration of the enormous amount of data from different sources, which form the basis for our infrastructures, such as our core discovery infrastructure platforms, LEADS, MED and NexGen as described below. This has resulted in the ability to utilize this discovery infrastructure to provide output in the form of meaningful biological information, in addition to continuing the development and enhancement of the infrastructure itself. A further requirement of our discovery capabilities is the development of a set of query algorithms specifically designed for the prediction and selection of molecules that should address specific areas or needs. Such query algorithms are different for each of our growing list of individual discovery capabilities.
 
 
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Following the prediction and selection of potential product candidates through use of this infrastructure, which is accomplished entirely by computer, the resulting predicted candidates are validated utilizing well-accepted laboratory experimental procedures, which in addition to providing validation of the candidates, also provide key information for further refining the query algorithms and other aspects of the infrastructure. For example, during 2014 we predicted two additional B7/CD28-like immune checkpoint candidates, increasing the total number of such Compugen-discovered candidates to 11, through the utilization of the same predictive models and algorithms that led to the identification of nine novel candidates in our earlier discovery efforts, but following enhancement of these models and algorithms through incorporation of additional information obtained from such earlier efforts.
 
Infrastructure Platforms
 
An important aspect of our infrastructure development efforts was the creation of our three key infrastructure platforms, LEADS, MED and NexGen, which integrate our scientific understandings and predictive models. These infrastructure platforms serve as key components first in the development of our individual discovery platforms described in the following section, and then in allowing us to approach unmet clinical needs through their integrated use with the discovery platforms and other computational systems and tools developed by us.
 
LEADS provides a comprehensive in silico view of the human transcriptome, proteome, and peptidome and serves as a rich infrastructure for the discovery of novel genes, transcripts and proteins. This was the first infrastructure platform developed by us and it has been enhanced and improved for over a decade. LEADS provides precise gene, transcript, protein and peptide prediction through modeling of various biological phenomena such as alternative splicing, antisense, fusion gene, RNA editing and polymorphisms. LEADS serves as a rich and accurate database of thousands of proprietary and novel genes and proteins. The infrastructure is based on mapping of messenger RNAs, or mRNAs, and expressed sequence tags (ESTs) to the genome, followed by clustering of the sequences and assembly of the gene structure and all possible mRNA transcripts and resulting proteins, through a multistep predictive analysis process. LEADS includes proprietary algorithms developed at Compugen and public and proprietary input data. This combination of proprietary algorithm tools and data, public and proprietary, allows us to identify previously unknown proteins and transcripts.
 
MED is an in silico disease expression database integrating more than 70,000 microarray experiments which are grouped into approximately 1,400 sets. Each set is a unification of different experiments of tissues with the same clinical relevance (i.e. normal tissues, malignant tissues, tissues from drug treated patients). In contrast to a commonly used single experiments analysis approach, the results from all 70,000 microarray experiments are integrated by MED via a sophisticated procedure that we developed, and they are then unified into a "virtual" or in silico chip. The “virtual” chip allows us to analyze simultaneously the expression of genes across all 1,400 conditions and tissues based on the results from the 70,000 experiments. This integrated analysis allows a broad view of the expression profile of a single gene over thousands of experiments and multiple tissue types. It also allows the identification and elimination of exceptional expression results obtained from various data sources, resulting in a system with an improved signal-to-noise ratio and thus superior accuracy. The fact that the platform integrates data from many sources and experiments gives robust results. MED’s in silico discoveries have been experimentally validated repeatedly over the years with expression data obtained in-house by a quantitative expression assay system, qRT-PCR, on established controlled and independent mRNA tissue panels.
 
NexGen is designed to allow the incorporation into our infrastructure and integrated analysis of Next Generation Sequencing data which is now beginning to be generated worldwide through RNA-Seq methodology. RNA-Seq is a new and powerful ultra-high throughput approach to provide raw data for transcriptome analysis and expression profiling. Although this new approach provides a massive amount of data in the form of very short partial transcript sequences, it also creates an extremely challenging environment for obtaining meaningful and accurate information. Our NexGen Platform, which incorporates advanced algorithms and other proprietary tools, is designed to efficiently and accurately integrate and analyze this vast amount of short sequence data. The integration of this capability with our discovery infrastructure, mainly our predictive transcriptome and proteome, is expected to provide us with both enhanced identification of novel genes and splice variants, and a broader view of the expression levels of RNA transcripts, facilitating new associations to pathological or healthy conditions. These new integrated capabilities should provide us with further substantial advantages in predictive discovery of potential drugs and drug targets, and also in the discovery of potential diagnostic product candidates.
 
 
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Discovery Platforms
 
Each of our individual discovery platforms targets a specific area or type of molecule and consists of three modules: prediction, selection and validation. The first two modules are accomplished by computer, while the third module involves laboratory based in vitro and in vivo experimental validation of selected candidates. In general, the prediction and selection modules utilize our discovery infrastructure to predict putative product candidates for a defined unmet need.
 
Our current key individual discovery capabilities are:
 
 
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mAb Target Discovery: This platform relies on both the LEADS and MED infrastructure platforms and utilizes query algorithms focused on the discovery of targets suitable for mAb technology based on statistical analysis of expression data provided by these platforms. Compugen’s mAb Target Discovery capability has been expanded beyond the initial focus on various solid tumors such as lung, ovarian, breast, colorectal and hematological cancers. New field extension modules have been added, which are now enabling the discovery of drug targets involved in drug response, metastatic stage cancer, and additional cancers such as melanoma, renal, liver, and pancreatic.
 
 
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Protein Family Members Discovery Platform: This platform incorporates both LEADS and MED infrastructure capabilities for the discovery of novel protein members belonging to various known and clinically important protein families. Since most traditional approaches for identifying such novel members are largely based on sequence homology, we first identify other types of characteristics that are shared between known members of the family of interest, and then the specialized algorithms select proteins from the LEADS proteome that share these characteristics and therefore could potentially be unknown family members.
 
 
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Antibody-Drug Conjugate Cancer Therapy Discovery Platform: Compugen’s discovery infrastructure was expanded by incorporating additional algorithms that enable prediction of membrane proteins having the potential to internalize, that are both expressed on cancer cells and have low expression on healthy cells, in order to allow the ADC drug to selectively attack the tumor and spare healthy tissues. It was additionally enhanced to identify targets associated with advanced cancer stages and poor clinical outcome, in order to provide potential superior first-in-class treatment to patient populations with limited therapeutic options.
 
 
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Other Immunomodulator Discovery Approaches: In order to discover other types of immunomodulators we used a new discovery capability that incorporates the predictive modeling of two distinct biological phenomena. The first biological phenomenon that was modeled exploits the interplay between the immune system and intruding pathogens. As a result of such interplay, some immune proteins tend to evolve differently from non-immune related ones. We devised an evolutionary model to detect such potential immune proteins, and this predictive algorithm was incorporated into our discovery infrastructure and integrated with our existing tools for the discovery of target candidates for cancer immunotherapy. The second biological phenomenon which was modeled in the role of tumor-associated macrophages (TAMs).  TAMs are an important component of the tumor microenvironment and play a major role in creating the immunosuppressive environment that enables tumor development. Proteins having the potential to modulate the tumor microenvironment may serve as potential targets for cancer immunotherapy. The modeling of this second biological phenomenon relies on our MED Platform, which was employed to predict proteins that play a role in the biology of TAMs.  
 
 
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Biomarker Discovery Approaches: Compugen has developed various biomarker discovery approaches based on specialized algorithms for the discovery of various type of biomarkers. The key approaches relate to the discovery of drug-induced toxicity biomarkers as demonstrated by our successful discovery activities for Neviah Genomics, our joint venture with Merck Serono, and for the discovery of potential biomarkers for our selected immune checkpoint target candidates.
 
Commercialization
 
Therapeutic Needs (Market Driven) Discoveries
 
Although our predictive discovery infrastructure has broad applicability and is not limited to a certain indication or therapeutic field, beginning in 2010, we focused our activities upon drug target and drug discovery in the fields of oncology and immunology. In addition, we transitioned from a “technology driven” individual platform capability approach to a “therapeutics needs (market) driven” approach. In this “therapeutics needs (market) driven” approach we harness all of our relevant infrastructure and discovery platforms, systems and tools towards a selected unmet need in order to predict and validate novel molecules that we believe have the highest potential to be successful first-in-class drug candidates for that need.
 
 
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In late 2010, we also initiated our Pipeline Program, which is now focused on mAbs and protein therapeutics in the fields of oncology and immunology and is largely based on novel immune checkpoint regulator candidates discovered by us.
 
Our business model includes collaborations covering the further development and commercialization of product candidates at various stages from our Pipeline Program and various forms of research and discovery agreements. We are currently primarily focusing on exploring collaboration opportunities with respect to our Pipeline Program product candidates, in which we may be more involved in the further development of the partnered candidates. In addition, we selected two immuno-oncology target programs for internal advancement towards future clinical trials. However, as additional experimental data becomes available we may decide to focus more resources on one such Program. Potential revenue sources in line with our business model could include fees, research revenues, milestones payments, royalties and other revenue sharing payments.  
 
Additionally, we intend to seek research and discovery collaborations aimed at harnessing our infrastructure capabilities towards the partners’ discovery needs. In these arrangements we would combine our discovery approaches to identify and prioritize novel proteins and/or targets according to the specific unmet need of the therapeutic approach and our partner. Potential revenue sources in these types of transactions could include upfront fees, research funding, option exercise and license fees, milestone payments, royalties and other revenue sharing payments.
 
Bayer Collaboration
 
On August 5, 2013, Compugen and Bayer entered into the Bayer Collaboration for the research, development, and commercialization of antibody-based therapeutics against two novel, Compugen-discovered immune checkpoint regulators, CGEN 15001T and CGEN 15022.
 
Under the terms of the Bayer Collaboration, we received an upfront payment of $10 million, and we are eligible to receive an aggregate of over $500 million in potential milestone payments for both programs, not including aggregate preclinical milestone payments of up to $30 million during the research programs. Additionally, we are eligible to receive mid- to high single digit royalties on global net sales of any approved products under the collaboration. During the year 2014, we achieved the first and second pre-clinical milestones with respect to one of the immune checkpoint regulators licensed to Bayer and received a total of $7.2 million in milestone payments.  
 
Under the Bayer Collaboration, Compugen and Bayer will jointly pursue a preclinical research program with respect to each of the two immune checkpoint regulators. A joint steering committee consisting of representatives from each party is responsible for overseeing and directing each such research program pursuant to an agreed upon workplan. Following the completion of each such research program, Bayer will have full control over further clinical development of any cancer therapeutic product candidates targeting the Compugen-discovered immune checkpoint regulators and will have worldwide commercialization rights for any approved products.
 
Bayer may terminate the Bayer Collaboration, either in whole or only with respect to one of the programs, and in each case also on a product-by-product and/or country-by country basis, at any time without cause, upon prior written notice. Either party may also terminate the Bayer Collaboration, either in whole or with respect to only one of the programs, if the other party is in material breach and such breach has not been cured within the applicable cure period. Upon any termination of the Agreement, depending upon the circumstances, the parties have varying rights and obligations with respect to the continued development and commercialization of any products and certain payment and royalty obligations.
 
Validation Based (Technology Driven) Discoveries
 
A result of the more than decade long and continuing establishment of our discovery infrastructure was the validation of each of our discovery platforms described above. This validation, and in some cases the initial runs of the discovery platform, resulted in the “technology driven” discovery of multiple novel molecules in a broad range of therapeutic and diagnostic fields, such as oncology, immunology, cardiovascular, ocular diseases and more.
 
 
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In view of the wide applicability of our predictive biology capabilities, we have in the past formed, or participated in the formation, of companies to utilize certain of these capabilities in other fields. We have also entered into other arrangements for the further development and commercialization of various non-focus area specific discoveries of interest, most of which resulted from our infrastructure development and validation activities. In all such cases, these arrangements provide the potential for future financial gain to Compugen without any further financial commitment for either development or commercialization from us. This commercialization pathway is anticipated to be of lesser importance in the future.
 
In 2012, we entered into two such arrangements: (i) the joint establishment of a new Israeli company, Neviah Genomics Ltd., (“Neviah”) with Merck Serono, a division of Merck, Darmstadt, Germany, in the field of toxicity biomarkers, and (ii) a financing arrangement with a United States investment company to allow the further development of Keddem Bioscience Ltd., previously a wholly owned, but inactive, subsidiary of Compugen, in the field of small molecule drugs.
 
In January 2015 Neviah announced that it had discovered and experimentally validated a set of biomarkers for the early detection of chronic drug-induced liver toxicity. Based on these results, Neviah is moving toward the further development of its PropheTox™ Bioassay, targeting 2016 for its commercial introduction. MS Ventures and Compugen recently agreed to jointly finance the further validation of the assay and remaining product development costs, for more information see Note 2v to our 2014 consolidated financial statements.
 
Competition
 
The biotechnology and pharmaceutical industries are highly competitive. Numerous entities in the United States and elsewhere compete with our efforts to make discoveries and out-license them to pharmaceutical and biotech companies. Our competitors include biotechnology companies, the research and discovery groups of pharmaceutical companies, academic and research institutions and governmental and other publicly funded agencies.
 
We face, and expect to continue to face, competition from entities that discover and develop products that have a function similar or identical to the function of our therapeutic product candidates or a product that acts in a different, but successful, manner addressing the same unmet need. With respect to our therapeutic product candidates, our potential competitors are comprised of companies that discover and develop novel targets for monoclonal antibody therapy and/or therapeutic proteins. Specifically in the immune checkpoint field for cancer immunotherapy, there are several leading pharmaceutical and biotechnology companies as well as smaller biotechnology companies and academic institutions that are developing biological therapies to enhance immune response towards tumors. The product candidates being developed by the smaller companies and/or academic institutions are expected to compete with our product candidates on licensing and collaboration opportunities. If approved, such cancer immunotherapy products would compete with our approved products in the respective field.
 
Our discovery program depends, in large part, on our discovery platforms and other technologies and our proprietary data to make inventions and establish intellectual property rights in genes and gene-based products, including mRNAs and proteins. There are a number of other means by which such inventions and intellectual property can be generated. We believe that our computational technologies, and specifically our discovery platforms, provide us with a competitive advantage in the field of predicting gene-based products. We believe that this advantage is made possible by building an infrastructure for predictive discovery based on the incorporation of ideas and methods from exact sciences into biology, and by the modeling of significant biological phenomena and the resultant better research capabilities that we have developed, as well as our unique team of predictive discovery scientists from both biology and exact sciences disciplines who have worked together for approximately 12 years on average.
 
Many of our potential competitors, either alone or with their collaborative partners, have substantially greater financial, technical and human resources than we do and significantly greater experience in the discovery and development of therapeutics, obtaining FDA and other regulatory approvals, and commercialization. Accordingly, our competitors may be more successful than we may be in identifying product candidates, protecting them with patent applications, developing them, accelerating their development process, obtaining FDA and other regulatory approvals and achieving widespread market acceptance. We anticipate that we will face intense and increasing competition as advanced technologies become available.
 
 
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Intellectual Property Rights
 
Our intellectual property assets are our principal assets. These assets include the intellectual property rights subsisting in our proprietary know-how and trade secrets underlying our predictive biology capabilities and discovery platforms, our patents and patent applications, particularly with respect to Compugen discovered molecules and utilities, and the copyrights subsisting in our software and related documentation. We seek to vigorously protect our rights and interests in our intellectual property. We expect that our commercial success will depend on, among other things, our ability to obtain commercially valuable patents, especially for our product candidates, maintain the confidentiality of our proprietary know-how and trade secrets, and otherwise protect our intellectual property. We seek patent protection for certain promising inventions that relate to our product candidates. As of February 1, 2015, we had a total of 54 issued and allowed patents, of which 35 are U.S. patents, six are Australian patents, four are Israeli patents, five are European patents, one is Canadian patent and three are Japanese patents. Our issued patents expire between 2020 and 2029. We also have 132 pending patent applications, which as of February 1, 2015, included 24 patent applications that have been filed in the United States, 18 patent applications that have been filed in Europe, 23 patent applications that have been filed in Israel, 11 patent applications that have been filed in Australia, 9 patent applications that have been filed in Canada, 9 patent applications that have been filed in Japan, 5 patent applications that have been filed in India, 5 patent applications that have been filed in China, 3 patent applications that have been filed in Brazil, 3 patent applications that have been filed in Korea, 3 patent applications that have been filed in New Zealand, 3 patent applications that have been filed in the Russian Federation, 3 patent applications that have been filed in Singapore, 3 patent applications that have been filed in Mexico, 3 patent applications that have been filed in South Africa, 3 patent applications that have been filed in Hong Kong, two patent applications that have been filed in Egypt and two applications that have been filed under the Patent Cooperation Treaty for which we have not yet designated the countries of filing.
 
Our general policy is to continue patent filings and maintenance for our product candidates, only with respect to candidates or projects that are being actively pursued internally or with partners, or that we believe to have future commercial value. We routinely abandon patent applications and may choose to abandon maintenance of patents supporting candidates or projects that do not meet these criteria.
 
We also seek protection for our proprietary know-how and trade secrets that are not protectable or protected by patents, by way of safeguarding them against unauthorized disclosure. This is done through the extensive use of confidentiality agreements and assignment agreements with our employees, consultants and third parties as well as by technological means. We use license agreements both to access third party technologies and to grant licenses to third parties to exploit our intellectual property rights.
 
Manufacturing
 
We currently intend to rely on contract manufacturers or our collaborative partners to produce materials and drug substances for drug products required for our research and development activities. We plan to continue to rely upon contract manufacturers and collaboration partners to manufacture commercial quantities of these materials for any approved therapeutic products.
 
Government Regulation
 
Environmental Regulation
 
Some of our research and development activities involve the controlled use of biologic and chemical materials, a small amount of which could be considered to be hazardous. We are subject to laws and regulations in the U.S. and Israel governing the use, storage, handling and disposal of all these materials and resulting waste products. We store relatively small amounts of biologic and chemical materials. To our knowledge, we substantially comply with these laws and regulations. However, the risk of accidental contamination or injury from these materials cannot be entirely eliminated. In the event of an accident, we could be held liable for any resulting damages, and any liability could exceed our resources.
 
Regulation of Use of Human Tissue
 
We need to access and use various human or non-human tissue samples for the purpose of development and or validation of some of our product candidates. Our access and use of these samples is subject to government regulation, in the United States, Israel and elsewhere and may become subject to further regulation. The use of clinical data associated with human tissue samples is also heavily regulated in the United State, Israel and elsewhere.  United States and other governmental agencies may also impose restrictions on the use of data derived from human or other tissue samples. To our knowledge, we substantially comply with these regulatory requirements.
 
 
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Regulations Concerning the Use of Animals in Research
 
We also are subject to various laws and regulations regarding laboratory practices and the use of animals in our research. In the United States, the FDA regulations describe good laboratory practices, or GLPs, for various types of nonclinical laboratory studies that support or are intended to support applications for research or marketing permits for products regulated by the FDA, including investigational new drug applications, or INDs. Preclinical animal studies conducted by us or third parties on our behalf may be subject to the U.S. Animal Welfare Act, the U.S. Public Health Service Policy on Humane Animal Care and Use, U.S. Department of Agriculture regulations for certain animal species. In Israel, the Council on Animal Experimentation has regulatory and enforcement powers, including the ability to suspend, change or withdraw approvals, among other powers. To our knowledge, the Company and the third party service providers we work with, as applicable, substantially comply with these regulatory requirements.
 
Regulation of Products Developed with the Support of Research and Development Grants
 
For a discussion of regulations governing products developed with research and development grants from the Government of Israel, see “Item 5. Operating and Financial Review and Prospects. C - Research and Development, Patents and Licenses – The Office of the Chief Scientist.”
 
Regulation of Therapeutic Product Candidates
 
In the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act, or FDCA, and biologics under the FDCA and the Public Health Service Act, and implementing regulations. The process of obtaining regulatory approvals and the subsequent compliance with applicable federal, state and local statutes and regulations require the expenditure of substantial time and financial resources. Failure to comply with the applicable United States requirements at any time during the product development process, approval process or after approval, may subject an applicant to administrative or judicial sanctions. The process required by the FDA before a drug may be marketed in the United States generally involves the following:
 
 
•
completion of preclinical laboratory tests and animal studies in compliance with the FDA’s GLP or other applicable regulations;
 
 
•
submission to the FDA of an IND, which must become effective before human clinical trials may begin;
 
 
•
performance of adequate and well-controlled human clinical trials in accordance with Good Clinical Practices, or GCPs, to establish the safety and efficacy of the proposed drug for its intended use;
 
 
•
submission to the FDA of a new drug application, or NDA if the drug is a small molecule, or a biologics license application, or BLA, if the drug is a biologic;
 
 
•
satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug or biologic is produced to assess compliance with current Good Manufacturing Practice, or cGMP, to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity; and
 
 
•
FDA review and approval of the NDA or BLA.
 
Once a pharmaceutical candidate is identified for development it enters the preclinical testing stage. Preclinical tests include laboratory evaluations of product chemistry, toxicity and formulation, as well as animal studies. An IND sponsor must submit the results of the preclinical tests, together with manufacturing information and analytical data, among other things, to the FDA as part of the IND. The sponsor will also include a protocol detailing, among other things, the objectives of the first phase of the clinical trial, the parameters to be used in monitoring safety, and the effectiveness criteria to be evaluated, if the first phase lends itself to an efficacy evaluation. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, places the clinical trial on a clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. Clinical holds also may be imposed by the FDA at any time before or during studies due to, among other things, safety concerns or non-compliance.
 
 
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All clinical trials must be conducted under the supervision of one or more qualified investigators in accordance with GCPs. An IRB at each institution participating in the clinical trial must review and approve the study plan for any clinical trial before it commences at that institution. An IRB considers, among other things, whether the risks to individuals participating in the trials are minimized and are reasonable in relation to anticipated benefits. The IRB also approves the information regarding the trial, advertisements, participant recruiting materials and the consent form that must be provided to each trial subject or his or her legal representative and must monitor the trial until completed.
 
Each new clinical protocol must be submitted to the FDA, and to the IRBs. Protocols detail, among other things, the objectives of the study, dosing procedures, subject selection and exclusion criteria, and the parameters to be used to monitor subject safety.
 
Human clinical trials are typically conducted in three sequential phases that may overlap or be combined:
 
  •
Phase 1: The drug is initially introduced into healthy human subjects and tested for safety, dosage tolerance, absorption, metabolism, distribution and excretion. In the case of some products, usually for severe or life-threatening diseases, especially when the product may be too inherently toxic to ethically administer to healthy volunteers, the initial human testing may be conducted in patients.
 
  •
Phase 2: Involves studies in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage.
 
  •
Phase 3: Involves studies undertaken to further evaluate dosage, clinical efficacy and safety in an expanded patient population at geographically dispersed clinical study sites. These studies are intended to establish the overall risk-benefit ratio of the product and provide an adequate basis for product labeling and approval.
 
Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and safety reports must be submitted to the FDA and the investigators for serious and unexpected adverse events. The FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the applicable regulations, IRB’s requirements or if the drug has been associated with unexpected serious harm to patients.
 
Concurrent with clinical trials, companies usually complete additional nonclinical studies and must also finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the drug within required specifications and, among other things, the manufacturer must develop methods for testing the identity, strength, quality and purity of the final drug. Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the drug does not undergo unacceptable deterioration over its shelf life.
 
United States Review and Approval Processes
 
The results of product development, preclinical studies and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted on the chemistry of the drug, proposed labeling, and other relevant information are submitted to the FDA as part of an NDA or BLA requesting approval to market the product for one or more indications. The FDA initially reviews all NDAs or BLAs submitted to ensure that they are sufficiently complete for substantive review before it accepts them for filing. The FDA may request additional information rather than accept an NDA or BLA for filing. Once the submission is accepted for filing, the FDA begins an in-depth substantive review. The FDA may refer the NDA or BLA to an advisory committee for review, evaluation and recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendation of an advisory committee.
 
The review process is lengthy and the FDA may refuse to approve an NDA or BLA if the applicable regulatory criteria are not satisfied or may require additional clinical or other data and information. Even if such data and information are submitted, the FDA may ultimately decide that the NDA or BLA does not satisfy the criteria for approval.
 
 
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If a product receives regulatory approval, the approval may be limited to specific diseases and dosages or the approved indications for use may otherwise be limited, which could restrict the commercial value of the product. In addition, the FDA may require a company to conduct post-approval testing and clinical trials, to further assess a drug’s safety and effectiveness after NDA or BLA approval, and may require testing and surveillance programs to monitor the safety of approved products which have been commercialized including Risk Evaluation and Mitigation Strategy (REMS) to ensure that the benefits of a drug outweigh its risks.
 
Post-approval Requirements
 
Approved drugs and biologics are subject to extensive and continuing regulation by the FDA, including, among other things, cGMP compliance, record-keeping requirements, reporting of adverse experiences with the drug, providing the FDA with updated safety and efficacy information, and complying with FDA promotion and advertising requirements. After an approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements is not maintained or if serious problems occur after the product reaches the market. Drugs may be promoted for use only for the approved indication or indications and in accordance with the provisions of the approved label. The FDA and other federal and state agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to criminal and civil penalties.
 
Non-U.S. Regulations
 
In addition to regulations in the United States, drugs are subject to a variety of foreign laws and regulations governing clinical trials and commercial sales and distribution before they may be sold outside the United States. Whether or not we obtain FDA approval for a product, we must obtain the necessary approvals by the comparable regulatory authorities of foreign countries before we can commence clinical trials or marketing of the product in those countries. The approval process varies from country to country and the time may be longer or shorter than that required for FDA approval. The requirements governing the conduct of clinical trials, the approval process, product licensing, pricing and reimbursement vary greatly from country to country.
 
C.  ORGANIZATIONAL STRUCTURE
 
We were incorporated under the laws of the State of Israel on February 10, 1993 as Compugen Ltd., which is both our legal and commercial name. Compugen USA, Inc., a wholly owned subsidiary, was incorporated in Delaware in March 1997 and is qualified to do business in California.
 
 D.  PROPERTY, PLANTS AND EQUIPMENT
 
We currently lease an aggregate of approximately 15,380 square feet of office and biology laboratory facilities in Tel Aviv, Israel, under a lease that expires on December 31, 2015, and we are currently exploring other options including the extension of the current lease, or a move of our laboratories and headquarters to new facilities. In addition, Compugen USA, Inc. currently subleases 12,560 square feet of office and biology laboratory facilities in South San Francisco, California, under a sublease that expires on May 30, 2018. We believe that the facilities that we currently lease in the US and will lease under the new lease agreement in Israel are sufficient for our current needs. There are no encumbrances on our rights in these leased properties or on any of the equipment that we own.
 
If we elect to move our facilities, we expect that we will be required to expend approximately $1.5 million in order to expand, construct and improve the new facilities for this move. We will obtain these amounts from our current resources. If we elect to move our facilities, this move is expected to take place in the fourth quarter of 2015.
 
To our knowledge, there are no environmental issues that affect our use of the properties that we lease.
 
ITEM 4A.             UNRESOLVED STAFF COMMENTS
 
None
 
ITEM 5.                OPERATING AND FINANCIAL REVIEW AND PROSPECTS
 
The following discussion of our critical accounting policies and our financial condition and operating results should be read in conjunction with our consolidated financial statements and related notes, prepared in accordance with U.S. GAAP as of December 31, 2014, and with any other selected financial data included elsewhere in this annual report.
 
 
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Background
 
Compugen is a leading drug discovery company focused on the discovery and development of monoclonal antibodies (mAbs) and therapeutic proteins to address important unmet needs in the fields of oncology and immunology. We utilize a broad and continuously growing integrated infrastructure of proprietary scientific understandings and predictive platforms, algorithms, machine learning systems and other computational biology capabilities for the in silico (by computer) prediction and selection of novel drug target candidates, which are then experimentally validated. Beginning in late 2010, we established the Pipeline Program, consisting of targets and product candidates for applications in oncology and immunology, based largely on novel immune checkpoint regulator candidates discovered by us during our first focused discovery program. The discovery and development of mAb therapeutic candidates against selected Compugen-discovered novel target candidates is performed at our wholly-owned U.S. subsidiary located in South San Francisco. Our business model includes entering into collaborations covering the further development and commercialization of product candidates at various stages from our Pipeline Program and various forms of research and discovery agreements, in both cases potentially providing us with milestones, royalties and other forms of revenue sharing payments.
 
A.  OPERATING RESULTS
 
Overview
 
Since our inception, we have incurred significant losses and, as of December 31, 2014, we had an accumulated deficit of $219.3 million. We expect to continue to incur net losses for the foreseeable future.
 
Prior to 2010, we focused a significant portion of our research and discovery efforts on the creation of area specific discovery platforms intended to identify novel drug and diagnostic product candidates and in earlier years, had also commercialized certain of our computational biology software products.  By year-end 2010 we had (i) largely integrated the various area specific discovery platforms and other computational biology tools and systems into a multi-dimensional and broadly applicable predictive discovery infrastructure, (ii) selected oncology and immunology as our areas of focus, (iii) selected the field of checkpoint proteins as our first focused discovery program, and (iv) initiated our Pipeline Program to advance selected candidates beyond their research proof of concept stage. In 2012 we initiated activities in Compugen USA, Inc. for mAb discovery and development against certain targets we had discovered.  In 2013, we entered into our first collaboration based on our Pipeline Program candidates with Bayer. Beginning in late 2013 we significantly increased our research activities in the field of immuno-oncology in order to allow for a larger number of checkpoint target and product candidates for cancer immunotherapy to move forward in parallel. Later in 2014 we decided to select one or more immuno-oncology target programs for internal advancement towards future clinical trials.
 
We incurred net losses of approximately $13.6 million in 2012, approximately $14.1 million in 2013 and approximately $11.1 million in 2014. We expect to continue to incur net losses for the foreseeable future due in part to the costs and expenses associated with our research, development and discovery activities. Our business model primarily involves collaborations covering the further development and commercialization of our discovered product candidates and various forms of research and discovery agreements, in both cases providing us with potential milestone payments and royalties on product sales or other forms of revenue sharing payments.
 
Our net research and development expenses are expected to be our major operating expense in 2015, accounting for more than 70% of our expected total 2015 operating expenses. Our research and development expenditures have always comprised a significant portion of our total cash expenditures, and are budgeted to increase by more than 40% in 2015 compared to 2014.
 
We currently have sufficient working capital in order to sustain our operations for at least the next 12 months.  For a detailed description of our cash and cash equivalents position, see “Item 5. Operating and Financial Review and Prospects – B. Liquidity and Capital Resources”.
 
Critical Accounting Policies
 
The preparation of our consolidated financial statements and other financial information appearing in this annual report requires our management to make estimates and judgments that affect the reported amounts of assets, liabilities, revenues and expenses, and related disclosure of contingent assets and liabilities. We evaluate on an on-going basis these estimates, mainly related to share based payments, embedded derivatives and fair value measurements related to research and development funding arrangements, revenue recognition and commitments and contingencies.
 
 
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We base our estimates on our experience and on various assumptions that we believe are reasonable under the circumstances. The results of our estimates form the basis for our management’s judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions.
 
Share Based Payments
 
We account for stock-based compensation in accordance with ASC 718, “Compensation – Stock Compensation” (“ASC 718”), which requires companies to estimate the fair value of equity-based payment awards on the date of grant using an option-pricing model. The value of the portion of the award that is ultimately expected to vest is recognized as an expense over the requisite service periods in our consolidated statement of comprehensive loss.
 
We primarily selected the Black-Scholes-Merthon model, which is the most common model in use in evaluating stock options.  This model evaluates the options as if there is a single exercise point, and thus considers expected option life (expected term).  The input factored in this model is constant for the entire expected life of the option.
 
We recognize compensation expenses for the value of awards which have graded vesting based on the straight line method over the requisite service period of each of the awards, net of estimated forfeitures.  ASC 718 requires forfeitures to be estimated at the time of grant and revised, if necessary, in subsequent periods if actual forfeitures differ from those estimates.
 
The computation of expected volatility is based on historical volatility of our stock.  The risk-free interest rate assumption is the implied yield currently available on United States treasury zero-coupon issues with a remaining term equal to the expected life term of the options.  We determined the expected life of the options based on historical experience, representing the period of time that options granted are expected to be outstanding.
 
We apply ASC 505-50, "Equity-Based Payments to Non-Employees" (“ASC 505-50”) with respect to options and warrants issued to non-employees. ASC 505-50 requires the use of option valuation models to measure the fair value of the options and warrants at the measurement date.
 
Share-based compensation expense recognized under ASC 718 and ASC 505-50 were approximately, $2.5 million $3.5 million and $3.6 million for the years ended December 31, 2012, 2013 and 2014, respectively.
 
Embedded Derivatives and Fair Value Measurements related to research and development funding arrangements
 
In accordance with ASC 730-20, "Research and Development Arrangements" and ASC 815, "Derivative and Hedging" we considered the Participation Rights issued in the funding arrangements with Baize Investments (Israel) Ltd. ("Baize") to be a research and development arrangement (the "Research and Development Component") coupled with embedded derivatives (that are the Conversion Alternative and the Participation Rights) as those instruments do not have fixed settlement provisions.
 
Consequently, we determined that the embedded derivatives in the Research and Development Component should be accounted for as a liability to be measured at fair value at inception. The embedded derivatives will be re-measured to fair value at each reporting period until their exercise or expiration with the change in such calculated value reported in the statement of operations (as part of financial income or expenses). As a result, the fair value of those embedded derivatives would be bifurcated out of the amount to be allocated to the Research and Development Component.
 
We have further determined that the Detachable Warrants issued to Baize should be accounted for and classified as an equity component since the warrants have fixed settlement provisions.
 
The Research and Development Component was calculated as residual between the payments received and the embedded derivatives (as mentioned above), recorded at cost and has been amortized over the period in which the development is being provided in connection with the relevant designated product candidates as deduction from research and development expenses in the consolidated statements of comprehensive loss. For a detailed description of Embedded Derivatives and Fair Value Measurements related to the research and development funding arrangements, see “Item 5. Operating and Financial Review and Prospects – B. Liquidity and Capital Resources- Funding Agreements” and Note 7 to our 2014 consolidated financial statements.
 
 
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The above approached to valuation uses estimations, which are consistent with the plans, and estimates that we use to manage our business. There is inherent uncertainty in making these estimates.
 
Revenue recognition
 
We currently generate revenue mainly from the Bayer Collaboration. The revenues are derived mainly from the upfront license payment, research and development services and contingent payments related to milestones achievements.
 
We apply ASC 605-25, "Multiple-Element Arrangements" pursuant to which each required deliverable is evaluated to determine whether it qualifies as a separate unit of accounting based on whether the deliverable has "stand-alone value". The arrangement’s consideration that is fixed or determinable is then allocated to each separate unit of accounting based on the relative selling price of each deliverable which is not contingent based on its vendor specific objective evidence (''VSOE'') if available, third party evidence (''TPE'') if VSOE is not available, or estimated selling price (''ESP'') if neither VSOE nor TPE is available.
 
Revenues from upfront license payments and research and development services are recognized according to the proportional performance method along the research and development services period in accordance with ASC 605-10, "Revenue Recognition".
 
Contingent payments related to milestone achievements and royalties are recognized immediately upon the accomplishment of futures events, in accordance with ASC 605-28, "Revenue Recognition – Milestone Method".
 
On June 27, 2014, and October 14, 2014 we achieved the first and second substantive milestones with respect to one licensed program, under the Bayer Collaboration according to which we recognized revenues in total amount of $7.2 million in accordance with the criteria prescribed under ASC 605-28.
 
See Note 12 to our 2014 consolidated financial statements.
 
Selected Financial Data
 
The following discussion and analysis is based on and should be read in conjunction with our audited consolidated financial statements, including the related notes, contained in “Item 18 – Financial Statements” and the other financial information appearing elsewhere in this annual report.
 
 
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Year ended December 31,
  
 
  
2012
    
2013
    
2014
  
   
(US$ in thousands, except share and per share data)
  
Consolidated Statements of Operations Data
                  
                   
Revenues
   $ 242     $ 3,549     $ 12,367  
Cost of revenues
     201       2,509       3,344  
Gross profit
     41       1,040       9,023  
                         
Research and development expenses, net
     9,442       12,275       15,074  
Marketing and business development expenses
     684       962       838  
General and administrative expenses
     3,457       4,846       5,448  
Total operating expenses (*)
     13,583       18,083       21,360  
Operating loss
     (13,542 )     (17,043 )     (12,337 )
Financial income (loss), net
     (86 )     3,460       1,758  
Equity loss
     -       -       (155 )
Loss before income tax
     (13,628 )     (13,583 )     (10,734 )
Income tax expenses
     -       (500 )     (360 )
Net loss
   $ (13,628 )   $ (14,083 )   $ (11,094 )
                         
Unrealized gain (loss) arising during the period on the investment in Evogene
     1,103       2,972       (1,202 )
Realized gain arising during the period on the investment in Evogene
     -       (3,711 )     (2,345 )
Unrealized gain from foreign currency derivative contracts
     -       -       141  
Total comprehensive loss
   $ (12,525 )   $ (14,822 )   $ (14,500 )
Basic net loss per share
     (0.38 )     (0.36 )     (0.23 )
Weighted average number of shares used in computing basic net loss per share
      35,844,496       38,869,438       47,808,855  
Diluted net loss per share
     (0.38 )     (0.36 )     (0.26 )
Weighted average number of shares used in computing diluted net loss per share
      36,249,262       38,869,438       48,387,063  
 
(*)       Includes stock based compensation – see Note 9 to our 2014 consolidated financial statements.
 
 
43
 
 
   
As of December 31,
  
   
2012
    
2013
    
2014
  
   
(US$ in thousands)
  
Consolidated Balance Sheet Data:
                  
Cash and cash equivalents, short-term bank deposits and restricted cash
   $ 19,685     $ 46,920     $ 73,186  
                         
Investment in Evogene
     5,196       4,565       1,054  
Other accounts receivable and pre-paid expenses
     690       1,731       858  
Long-term bank deposits
     -       -       35,026  
Total assets
     28,909       56,711       114,986  
Research and development funding arrangements and others
     7,872       13,189       421  
Deferred revenues
     -       6,772       1,789  
Accumulated deficit
     (194,119 )     (208,202 )     (219,296 )
Total shareholders' equity
     17,672       31,888       106,116  
 
 Years Ended December 31, 2014 and 2013
 
Revenues. Revenues totaled approximately $12.4 million in 2014 and $3.5 million in 2013. The increase in revenues for 2014 is attributable to the receipt in 2014 of the first and second pre-clinical milestone payments, in a total amount of $7.2 million with respect to one of the immune checkpoint target candidates licensed to Bayer, and an increase in the recognized portion of the non-refundable upfront license fee received under the Bayer Collaboration.
 
Cost of Revenues. Cost of revenues attributable to product candidate research and collaboration agreements totaled approximately $3.3 million for 2014 and $2.5 million for 2013. The increase in the cost of revenues in 2014 is primarily due to an increase in expenses attributed to the Bayer Collaboration.
 
Research and Development Expenses, Net. Research and development expenses, net increased by 23%, to approximately $15.1 million for 2014, from approximately $12.3 million for 2013. The increase was primarily due to the increasing levels of activities in support of our Pipeline Program, including a substantial increase in activities relating to the research and development of mAb therapeutic candidates at our U.S. subsidiary and a substantial increase in professional research and development headcount to support these activities. Research and development expenses, net, as a percentage of total operating expenses, were 71% in 2014 compared to 68% in 2013.
 
Marketing and Business Development Expenses. Marketing and business development expenses decreased by 13% to approximately $838,000 in 2014 compared to approximately $962,000 in 2013. The decrease was primarily due to higher level of expenses in 2013 in connection with the Bayer Collaboration. Marketing and business development expenses, as a percentage of total operating expenses, were 4% in 2014 compared to 5% in 2013.
 
General and Administrative Expenses. General and administrative expenses increased by 12% to approximately $5.4 million for 2014 from approximately $4.8 million for 2013. The increase was attributed mainly to increased activity of our operations and related activities, resulting in higher salary and compensation expenses. In addition we had higher level of expenses related to professional services, including our scientific advisory board established late 2013. General and administrative expenses, as a percentage of total operating expenses, were 25% in 2014 and 27% in 2013.
 
Financial Income (loss), Net. Financial income, net decreased by 49% to approximately $1.8 million in 2014 from approximately $3.5 million in 2013. This decrease was attributed to lower realized gain from the sale of a portion of our holdings of Evogene Ltd. (“Evogene”) ordinary shares in the amount of $2.3 million in 2014 compared to $3.7 million in 2013.
 
Equity loss. Equity loss was $155,000 in 2014. This loss is attributed to the amount provided to Neviah as part of a convertible loan arrangement.
 
Income tax expenses. Income tax expenses were $360,000 in 2014 compared with $500,000 in 2013. These expenses were attributed to withholding tax related to the Bayer Collaboration.
 
 
44
 
 
Years Ended December 31, 2013 and 2012
 
Revenues. Revenues totaled approximately $3.5 million in 2013 and $242,000 in 2012. The increase in revenues for 2013 is due to the portion of the non-refundable upfront payment received under the Bayer Collaboration that was recognized in 2013 in accordance with revenue recognition policy over the performance period in which the research and development service are provided.
 
Cost of Revenues. Cost of revenues attributable to product candidate research and collaboration agreements totaled approximately $2.5 million in 2013 and $201,000 in 2012. The increase in the cost of revenues in 2013 is primarily due to an increase in expenses attributed to the Bayer Collaboration.
 
Research and Development Expenses, Net. Research and development expenses, net increased by 31%, to approximately $12.3 million in 2013, from approximately $9.4 million in 2012. The increase was primarily due to the increasing levels of activities in support of our Pipeline Program, including a substantial increase in activities relating to the research and development of mAb therapeutic candidates at our U.S. subsidiary. Research and development expenses, net, as a percentage of total operating expenses, were 68% in 2013 compared to 70% in 2012.
 
Marketing and Business Development Expenses. Marketing and business development expenses increased by 41% to approximately $962,000 in 2013 from approximately $684,000 in 2012. The increase was primarily due to payments made in connection with the Bayer Collaboration. Marketing and business development expenses, as a percentage of total operating expenses, were 5% for both 2013 and 2012.
 
General and Administrative Expenses. General and administrative expenses increased by 37% to approximately $4.8 million in 2013 from approximately $3.5 million in 2012. The increase was primarily due to legal fees related to the Bayer Collaboration, an increase in non-cash expense related to stock based compensation and the expenses related to the establishment of our scientific advisory board in 2013.  General and administrative expenses, as a percentage of total operating expenses, were 27% in 2013 and 25% in 2012.
 
Financial Income (loss), Net. Financial income, net was $3.5 million in 2013 compared to a financial loss, net of approximately $86,000 in 2012. The increase was attributed to the realized gain from the sale of a portion of our holdings in Evogene ordinary shares in the amount of $3.7 million in 2013.
 
Income tax expenses. Income tax expenses were $500,000 in 2013. These expenses were attributed to withholding tax related to the Bayer Collaboration.
 
Governmental Policies that Materially Affected or Could Materially Affect Our Operations
 
Our income tax obligations consist of those of Compugen Ltd. in Israel and of Compugen USA, Inc. in its taxing jurisdictions.
 
The corporate tax rate in Israel effective as of January 1, 2015, is 26.5%, unchanged from 2014 and compared with 25% in 2013. In the future, if and when we generate taxable income, our effective tax rate will be primarily influenced by: (a) the split of taxable income between the various tax jurisdictions; (b) the availability of tax loss carry forwards and the extent to which valuable allowance has been recorded against deferred tax assets; (c) the portion of our income which is entitled to tax benefits pursuant to the Investment Law; and (d) the changes in the exchange rate of the U.S. dollar to the NIS. We may benefit from certain government programs and tax legislation, particularly as a result of the Approved Enterprise status granted to some of our operations by the Investment Center in the Israeli Ministry of Economy and the Benefiting Enterprise status that resulted from our eligibility for tax benefits under the Investment Law. To be eligible for these benefits, we need to meet certain conditions. Should we fail to meet such conditions, these benefits could be cancelled and we might be required to refund the amount of the benefits previously received, if any, in whole or in part, together with interest and linkage differences to the Israeli CPI, or other monetary penalty. We also benefit from a Government of Israel program under which we receive grants from the OCS.  For more information please see “Item 5 Operating and Financial Review and Prospects– C. Research and Development, Patents and Licenses - Research and Development Grants; The Office of the Chief Scientist”. There can be no assurance that these programs and tax legislation will be continued in the future or that the available benefits will not be reduced.
 
 
45
 
 
The termination or curtailment of these programs or the loss or reduction of benefits under the Investment Law could have a material adverse effect on our business, financial condition and results of operations.
 
Currently we have two Approved Enterprises and two Benefiting Enterprises programs under the Investment Law. The tax benefits period with respect to all of these programs has not yet begun as we have not yet generated any taxable income. These benefits should result in income recognized by us being tax exempt or taxed at a lower rate for a specified period of time after we begin to report taxable income and exhaust any net operating loss carry-forwards. However, these benefits may not be applied to reduce the U.S. federal tax rate for any income that our U.S. subsidiary may generate.
 
We have elected the alternative benefits route under the Investment Law with respect to our Approved Enterprises. Under this route we waived government grants in return for a tax exemption on undistributed income. Due to the geographic location of our facilities, such tax exemption on undistributed income will apply for a limited period of two years. In the event that such tax exempt income is thereafter distributed as a dividend or a deemed dividend, we will be required to pay the applicable corporate tax that would otherwise have been payable on such income. During the remainder of the benefits period applicable to us, a corporate tax rate not exceeding 25% will apply.
 
In April 2005, substantive amendments to the Investment Law came into effect. Under these amendments, eligible investment programs of the type in which we participated prior to the amendment were eligible to qualify for substantially similar benefits as a ‘Benefiting Enterprise’, subject to meeting certain criteria. This replaced the previous terminology of ‘Approved Enterprise’, which required pre-approval from the Investment Center of the Ministry of the Economy of the State of Israel. As a result of these amendments, tax-exempt income generated from Benefiting Enterprises under the provisions of the amended law will, if distributed upon liquidation or if paid to a Shareholder for the purchase of his or her shares, be deemed distributed as a dividend and will subject the Company to the applicable corporate tax that would otherwise have been payable on such income. Therefore, a company may be required to record deferred tax liability with respect to such tax-exempt income, which would have an adverse effect on its results of operations.
 
Additional amendments to the Investment Law became effective in January 2011 and were further amended in August 2013 (the “2011 Amendment”). Under the 2011 Amendment, income derived by ‘Preferred Companies’ from ‘Preferred Enterprises’ (both as defined in the 2011 Amendment) would be subject to a uniform rate of corporate tax for an unlimited period as opposed to the incentives prior to the 2011 Amendment that were limited to income from Approved or Benefiting Enterprises during their benefits period. According to the 2011 Amendment, the uniform tax rate on such income, referred to as ‘Preferred Income’, would be 10% in areas in Israel that are designated as Development Zone A and 15% elsewhere in Israel during 2011-2012, 7% and 12.5%, respectively, in 2013, and 9% and 16%, respectively, thereafter. Income derived by a Preferred Company from a ‘Special Preferred Enterprise’ (as defined in the Investment Law) would enjoy further reduced tax rates for a period of ten years of 5% in Development Zone A and 8% elsewhere. As of January 1, 2014, dividends distributed from Preferred Income would subject the recipient to a 20% tax (or lower, if so provided under an applicable tax treaty), which would generally be withheld by the distributing company, provided however that dividends distributed from ‘Preferred Income’ from one Israeli corporation to another, would not be subject to tax. Under the transitional provisions of the 2011 Amendment, companies may elect to irrevocably implement the 2011 Amendment with respect to their existing Approved and Benefiting Enterprises while waiving benefits provided under the legislation prior to the 2011 Amendment or keep implementing the legislation prior to the 2011 Amendment. Should a company elect to implement the 2011 Amendment with respect to its existing Approved Enterprises and Benefiting Enterprises prior to June 30, 2015 dividends distributed from taxable income derived from Approved or Benefiting Enterprises to another Israeli company would not be subject to tax. We have not elected to implement the 2011 Amendment and we do not currently have any Preferred Enterprises. While a company may incur additional tax liability in the event of distribution of dividends from tax exempt income generated from its Approved and Benefiting Enterprises, as previously described, no additional tax liability will be incurred by a company in the event of distribution of dividends from Preferred Income.
 
As of December 31, 2014, our net operating loss carry-forwards for Israeli tax purposes amounted to approximately $167.3 million. Under Israeli law, these net operating losses may generally be carried forward indefinitely and offset against certain future taxable income.
 
As of December 31, 2014, the net operating loss carry-forwards of our U.S. subsidiary for federal income tax purposes amounted to approximately $14.5 million. These losses are available to offset any future U.S. taxable income of our U.S. subsidiary and will expire between the years 2019 and 2032.
 
 
46
 
 
Use of our U.S. net operating losses may be subject to substantial annual limitation due to the “change in ownership” provisions of the Internal Revenue Code of 1986 and similar state provisions. The annual limitation may result in the expiration of net operating losses before utilization.
 
For a description of Israel government policies that affect our research and development expenses, and the financing of our research and development, see “Item 5. Operating and Financial Review and Prospects -C - Research and Development, Patents and Licenses - Research and Development Grants; The Office of the Chief Scientist”.
 
B.  LIQUIDITY AND CAPITAL RESOURCES
 
Public Offering of Ordinary Shares
 
On March 5, 2014 we closed an underwritten public offering of 6,900,000 ordinary shares, including 900,000 shares sold pursuant to the full exercise of the underwriters’ option to purchase additional shares, at a price to the public of $10.50 per share (the “2014 Offering”).
 
Gross proceeds to Compugen from the 2014 Offering were approximately $72.5 million, before deducting the underwriting discounts and commissions and estimated offering expenses payable by us.
 
The 2014 Offering was made pursuant the effective shelf registration statement on Form F-3 (File No. 333-185910), which was filed with the Securities and Exchange Commission (the “Commission”) on January 7, 2013 and declared effective by the Commission on January 16, 2013.
 
Jefferies LLC acted as the sole bookrunner for the 2014 Offering.  JMP Securities LLC, Oppenheimer & Co. Inc. and Chardan Capital Markets acted as co-managers.
 
Funding Agreements
 
Baize Research and Development Funding Agreements
 
On December 29, 2010, we entered into a Funding Agreement (the “Original Pipeline Funding Agreement”) with Baize, pursuant to which Baize provided the Company with $5.0 million in support of the Company’s therapeutic product candidates in research and development.  On December 20, 2011, we also entered into a mAb Funding Agreement with Baize, pursuant to which Baize agreed to invest $8.0 million in connection with certain research funding for certain  mAb product candidates.  This agreement was amended on July 24, 2012 and December 27, 2012 (as amended, the “mAb Funding Agreement”).
 
On April 21, 2013, we entered with Baize into an amendment to the funding agreements, pursuant to which the mAb Funding Agreement was terminated and the Original Pipeline Funding Agreement was amended (the “Amended Pipeline Funding Agreement”) as follows.

 
·
Until June 30, 2015, Baize had the right to receive 10% of the cash consideration received by us or our affiliates from third parties, less certain pass-through amounts, with respect to the “Combined Program Initial Candidates” (“Amended Initial Participation Rights”). The Combined Program Initial Candidates included (i) the five designated product candidates from the Original Pipeline Funding Agreement and (ii) all mAb product candidates to be developed against the eight specified Targets from the mAb Funding Agreement.
 
 
·
Not later than June 30, 2015 or, if later, 30 days following the receipt by Baize from Compugen of the annual report for 2014 containing a status report with respect to the Combined Program Initial Candidates Baize was required to select five product candidates from the Combined Program Initial Candidates, as “Selected Products.”
 
 
·
Beginning July 1, 2015 through December 31, 2030, Baize was to have the right to receive 10% of the cash consideration received by Compugen or its affiliates from third parties, less certain pass-through amounts, with respect to the five Selected Products (the “Amended Final Participation Rights”, together with the Amended Initial Participation Rights, the "Amended Participation Rights").
 
 
·
Baize had the right at any time until June 30, 2015 to exchange the Amended Participation Rights for a number of Compugen’s ordinary shares to be calculated as the quotient of (i) $13 million less 50% of any cash consideration paid to Baize as Amended Participation Rights, divided by (ii) the average closing price of Compugen’s ordinary shares during the twenty (20) trading days prior to the Actual Exchange Date (the “Exchange Price”); provided however that the Exchange Price was not to be lower than $3.00 per share, and was not to exceed $12.00 per share.
 
 
·
The warrant granted to Baize to purchase up to 500,000 of Compugen’s ordinary shares under the Original Pipeline Funding Agreement was terminated, and Compugen had issued Baize a new warrant (the “2013 Warrant”) to purchase up to 500,000 of the Compugen’s ordinary shares, exercisable at $7.50 per share through June 30, 2015.
 
 
47
 
 
On August 20, 2014, we entered with Baize into the Termination and Equity Conversion Agreement (the “2014 Baize Agreement”) pursuant to which:
 
 
·
The Amended Pipeline Funding Agreement, including all rights to receive the Amended Participation Rights and all rights to receive information concerning the Combined Program Initial Candidates, has been terminated.
 
 
·
The 2013 Warrant has been terminated.
 
 
·
We issued to Baize 1,600,000 of our ordinary shares, par value NIS 0.01 per share.
 
 
·
Until December 31, 2015, Baize has the right to receive 5% of the cash consideration received by Compugen or its affiliates from third parties, less certain pass-through amounts, with respect to the Combined Program Initial Candidates.
 
Cantor Sales Agreement
 
On August 30, 2011, we entered into a sales agreement with Cantor Fitzgerald & Co. (the “Cantor Sales Agreement”), which enabled us to offer and sell an aggregate of up to 6,000,000 of our ordinary shares, from time to time, through Cantor, as our sales agent. The gross proceeds from all sales made pursuant to the Cantor Sales Agreement could not exceed $40.0 million in the aggregate. Sales of our ordinary shares under the Cantor Sales Agreement were made in sales deemed to be “at-the-market” equity offerings as defined in Rule 415 promulgated under the Securities Act of 1933, as amended.  On January 21, 2014, the registration statement on Form F-3 under which we had been selling ordinary shares pursuant to the Cantor Sales Agreement terminated.  Prior to the termination of the registration statement, we had sold through the Cantor Sales Agreement an aggregate of 4,174,120  of our ordinary shares, and received gross proceeds of approximately $30.8 million, before deducting issuance expenses, including 363,090 ordinary shares for gross proceeds of $3.9 million in January 2014. Cantor received a commission of 3.0% of gross sales in connection with the sale of these ordinary shares.
 
Cash resources
 
In 2014, our primary sources of cash were:
 
 
·
Proceeds from 2014 Offering;
 
 
·
Cash generated from the sale and issuance of ordinary shares under the  Cantor Sales Agreement;
 
 
·
pre-clinical milestones payments under the Bayer Collaboration;
 
 
·
exercise of employee stock options; and
 
 
·
sales of Evogene shares
 
We used these funds primarily to finance our business operations.
 
We expect that our sources of cash for 2015 will include cash held in our bank accounts, and may include proceeds generated from license, collaborative and/or research agreements, proceeds from possible sale of Evogene shares and proceeds from issuance of ordinary shares as a result of the exercise of stock options or from financing transactions.
 
Net Cash Used in Operating Activities
 
Net cash used in operating activities was approximately $10.8 million in 2012, approximately $6.4 million in 2013 and approximately $11.1 million in 2014. The increase in 2014 as compared to 2013 was mainly attributed to the substantial increase in research and development expenses between the periods related primarily to the continuation of the growth in the activities at our U.S.-based operation and increased activities under our Pipeline Program.
 
 
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Net Cash Provided By (Used In) Investing Activities
 
Net cash used in investing activities was approximately $11.6 million in 2013 and approximately $64.1 million in 2014; net cash provided by investing activities was approximately $12.3 million in 2012. Changes in net cash during 2014 as compared to 2013 were primarily attributed to the substantial increase in investment in short-term and long-term bank deposits mainly of the proceeds from the 2014 Offering partially offset by proceeds from maturity of short-term bank deposits.
 
Net Cash Provided by Financing Activities
 
Net cash provided by financing activities was approximately $9.1 million in 2012 approximately $30.4 million in 2013 and approximately $72.1 million in 2014.  The principal sources of cash provided by financing activities in 2014 were proceeds received from sale and issuance of ordinary shares in the 2014 Offering  and in an “at the market” under the Cantor Sales Agreement and proceeds received from the issuance of ordinary shares as a result of the exercise of stock options.
 
Net Liquidity
 
Liquidity refers to the liquid financial assets available to fund our business operations and pay for near-term obligations. These liquid financial assets mostly consist of cash and cash equivalents as well as short-term bank deposits. As of December 31, 2014, we had total cash and cash equivalents, short-term bank deposits of approximately $72.6 million, not including the market value of the Evogene ordinary shares owned by us and long-term bank deposits. We believe that our existing cash and cash equivalents, and short-term and long-term bank deposits will be sufficient to fund our operations for at least the next 24-36 months.
 
On January 7, 2013, we filed a shelf registration statement on Form F-3 with the SEC under which we may offer and sell from time to time in one or more offerings, our ordinary shares, debt securities, rights, warrants and units having an aggregate offering price of up to $100.0 million.  This registration statement was declared effective by the SEC on January 16, 2013.  We sold 6,900,000 ordinary shares for gross proceeds of approximately $72.5 million under this registration statement in the 2014 Offering. On August 26, 2014, we filed a shelf registration statement on Form F-3 with the SEC under which we may offer and sell from time to time in one or more offerings, our ordinary shares, debt securities, rights, warrants and units having an aggregate offering price of up to $200.0 million.  This registration statement was declared effective by the SEC on September 4, 2014. We may seek additional capital due to favorable market conditions or strategic considerations even if we believe we have sufficient funds for our current or future operating plans.
 
C.  RESEARCH AND DEVELOPMENT, PATENTS AND LICENSES
 
We invest heavily in research and development. Research and development expenses, net, were our major operating expenses representing approximately 70% of total operating expenses for each of   2014, 2013 and 2012. Our research and development expenses, net, were approximately $15.1 million in 2014, compared to approximately $12.3 million in 2013, and approximately $9.4 million in 2012. As of December 31, 2014, 68 of our employees were engaged in research and development on a full-time basis. This represents approximately 82% of our entire work force.
 
We focus our research efforts on the development of our discovery platforms and related technologies, and the discovery validation and early stage development of our mAb therapy and therapeutic proteins product candidates. During 2010 we initiated the Pipeline Program to substantially expand the number of product candidates undergoing in vitro and in vivo validation and to significantly enhance the commercial value of our product candidate pipeline by advancing certain candidates beyond the successful animal disease model proof of concept stage, towards pre-IND studies. We expect that in 2015 our research and development expenses, will continue to be our major operating expense, representing more than 70% of our total operating expenses.
 
We believe that our future success will depend, in large part, on our ability to discover promising therapeutic product candidates and to successfully advance the research and development of certain of our product candidates under our internal Pipeline Program towards pre-IND studies and to successfully license such product candidates to pharmaceutical companies.  In addition, we expect to continue to expand our inventory of proprietary algorithms, predictive models and discovery infrastructure and platforms which provide opportunities for the discovery of promising therapeutic candidates for inclusion in our Pipeline Program and pursuant to research and discoveries collaborations.
 
 
49
 
 
Research and Development Grants
 
We have participated in programs offered by the OCS that support research and development activities, and by the European Community, under the European Union’s 6th Framework Program (“European Union”) and under the Israel-U.S. Binational Industrial Research and Development Foundation (“BIRD Foundation”). We also received certain investment amounts under a funding agreement with Baize. We received grants from the OCS and BIRD Foundation as well as other forms of consideration from Baize accounted as reduction from the research and development expenses over the research period. See note 2n to our 2014 consolidated financial statement. We did not apply for additional grants from the OCS for research and technological development in 2014.
 
The Office of the Chief Scientist
 
We received or may receive grants from the OCS for several projects. Under the terms of these grants, we will be required to pay royalties ranging between 3% to 5% of the revenues we generate from our products developed with funds received from the OCS, beginning with the sale of the first product developed with funds received from the OCS and ending when 100% of the dollar value of the grant is repaid (plus LIBOR interest applicable to grants received on or after January 1, 1999). As of December 31, 2014, our contingent obligation for royalties, based on royalty-bearing government grants, net of royalties already paid, totaled approximately $9.0 million.
 
The R&D Law requires that the manufacture of products developed with government grants will be carried out in Israel, unless the OCS provides its approval to the contrary. This approval, if provided, is generally conditioned on an increase in the total amount to be repaid to the OCS, to up to 300% of the dollar value of the grant plus applicable interest. The specific increase within this ceiling would depend on the extent of the manufacturing to be conducted outside of Israel. Transfer of the know-how developed with funds received from the OCS and any right derived therefrom to third parties is prohibited, unless conducted in accordance with the restrictions set forth under Israeli law. Approval for such transfer outside of Israel, if provided, is generally conditioned on a redemption payment which is calculated according to a formula set forth in the R&D Law and regulations promulgated thereunder up to an amount equal to six (6) times the total amount of grants received under the R&D Law and from the OCS in general plus applicable interest. Therefore, our flexibility in commercializing some of our technologies may be reduced. We believe that this restriction does not apply to the commercialization through licensing of product candidates that we discover by using our knowhow developed with funds received from the OCS.
 
D.  TREND INFORMATION
 
Trend towards consolidation
 
There is a trend towards consolidation in the pharmaceutical, diagnostic and biotechnology industries, which may negatively affect our ability to enter into agreements and may cause us to lose existing licensees or collaborators as a result of such consolidation. This trend often involves larger companies acquiring smaller companies, and this may result in the larger companies having greater financial resources and technological capabilities. This trend towards consolidation in the pharmaceutical, diagnostic and biotechnology industries may also result in there being fewer potential companies to license our products and services.
 
Trend towards reduction of in-house research and development programs within major pharmaceutical companies.
 
Recently, a number of major pharmaceutical companies have announced cutbacks in their in-house research and development programs.  The effects of these cutbacks on our business opportunities could be positive or negative, and are likely to vary on a company by company basis.
 
Trend towards reliance by major pharmaceutical companies on smaller company’s product candidates to support their pipelines.
 
There appears to be a trend towards larger companies relying on smaller companies’ product candidates.  However, this trend usually applies to product candidates that have reached a further stage of development than our candidates.  However, in certain fields, pharmaceutical and biotechnological companies are becoming more open to in-licensing product candidates at earlier stages of development, including at early pre-clinical stages. As a result, there may be more interest in entering into agreements with us for further development and commercialization of our early stage product candidates.
 
However, if this is not correct we may be required to invest a substantial amount of money and other resources to advance each of our product candidates prior to licensing, without assurance that any such product candidates will be commercialized, and limiting the number of product candidates that we are able to so advance, while reducing resources available for our discovery activities, due to resource constraints.
 
 
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If, consistent with our strategy for commercialization of our therapeutic product candidates, we are successful in commercializing our product candidates at an early stage, our licensees may propose terms that we may not consider commercially desirable and the consideration that we may receive for each individual product may be relatively low. The consideration that we would expect to receive for commercializing our product candidates increases commensurately with the number of such products commercialized and the stage of development that we attain for them.  Furthermore, considerations regarding our willingness to advance the product candidate at our risk would likely be of much less importance in research and discovery collaborations.
 
E.  OFF-BALANCE SHEET ARRANGEMENTS
 
We entered into forward contracts to hedge against the risk of overall changes in future cash flow from payments of salaries and related expenses as well as other expenses denominated in NIS. As of December 31, 2014, we had outstanding forward contracts in the notional amount of $5.6 million. These contracts were for a period of nine months ended September 30, 2015.
 
F.  TABULAR DISCLOSURE OF CONTRACTUAL OBLIGATIONS
 
The table below summarizes our contractual obligations as of December 31, 2014, and should be read together with the accompanying comments that follow.
 
   
Payments due by period
(US$ in thousands)
  
   
Total
    
Less than 1 year
    
1-3 years
    
3-5 years
    
More than 5 years
  
Operating Lease Obligations(1)
   $ 2,330     $ 908     $ 1,153     $ 269     $ -  
Accrued Severance Pay, net(2)
     257       -       -       -       -  
Total
   $ 2,587     $ 908     $ 1,153     $ 269     $ -  
 
(1) Consists of operating leases for our facilities and for motor vehicles.
 
(2) Severance pay obligations to our Israeli employees, for more information please see “Item 6. Directors, Senior Management and Employees – D. Employees.
 
The above table does not include royalties that we may be required to pay to the OCS or to Baize under the 2014 Baize Agreement. For more information, see “Item 5. Operating and Financial Review and Prospects – C. Research and Development, Patents and Licenses”.
 
The above table also does not include contingent contractual obligations or commitments that may crystallize in the future, such as contractual undertakings to pay royalties subject to certain conditions occurring.
 
 
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ITEM 6.
DIRECTORS, SENIOR MANAGEMENT AND EMPLOYEES
 
A.  DIRECTORS AND SENIOR MANAGEMENT
 
The following table sets forth information with respect to Compugen Ltd.'s directors and Compugen’s senior management as of March 1, 2015:
 
Name
  
Age
  
Positions
Prof. Yair Aharonowitz(1)(2)
  
74
  
Director
Prof. Ruth Arnon
  
80
  
Director
Anat Cohen-Dayag, Ph.D.
  
48
  
President and Chief Executive Officer, Director
Martin S. Gerstel
  
73
  
Chairman of the Board of Directors
Dov Hershberg
  
75
  
Director
Arie Ovadia, Ph.D. (1)(2)
  
65
  
Director (Chairman of the Audit Committee)
Prof. Joshua Shemer(1)(2)
  
67
  
Director (Chairman of the Compensation Committee)
Ari Krashin
  
42
  
Chief Financial Officer
John Hunter
  
52
  
Vice President Antibody Research and Development
Zurit Levine
  
47
  
Vice President Research and Discovery
 
____________________
 
(1)      An external director pursuant to the Israeli Companies Law
 
(2)      Member of our Audit Committee and our Compensation Committee
 
Prof. Yair Aharonowitz joined Compugen’s Board of Directors as an external director in July 2007 and was reappointed as an external director in April 2010 and in April 2013.  He is a Professor (Emeritus) of Microbiology and Biotechnology at Tel Aviv University (TAU). He was a visiting scientist at Oxford University, an Alberta Heritage Fellow at the University of Alberta, Edmonton, and a visiting professor at the Karolinska Institute and at the University of British Columbia. Professor Aharonowitz’s research interests include the molecular genetics and biosynthesis of antibiotics, molecular biology of microbial pathogens and the development of new targets for new antibiotics. He served as TAU Vice President and Dean for R&D (1997-2001), Chairman of the Department of Microbiology and Biotechnology and Chairman of the Institute of Biotechnology and served as a member of the TAU Executive Council. He served as the Chairman of Ramot Fund for Applied Research, as a member of TAU committee for strategic planning, on the TAU patent committee and was a member of the National Committee for Biotechnology. He is a Fellow of the American Academy of Microbiology.
 
Prof. Ruth Arnon joined Compugen’s Board of Directors in May 2007. Formerly the Vice-President of the Weizmann Institute of Science (1988-1997), she is a noted immunologist, having joined the Institute in 1960.  She served as Head of the Department of Chemical Immunology, Dean of the Faculty of Biology and Director of the Institute's MacArthur Center for Molecular Biology of Tropical Diseases. Prof. Arnon has made significant contributions to the fields of vaccine development, cancer research and to the study of parasitic diseases. Along with Prof. Michael Sela, she developed Copaxone® a drug for the treatment of multiple sclerosis which is presently marketed worldwide.  Prof. Arnon is a member of the Israel Academy of Sciences and presently serves as its President. She is an elected member of the European Molecular Biology Organization, served as President of the European Federation of Immunological Societies and as Secretary-General of the International Union of Immunological Societies. Her awards include the Robert Koch Prize in Medical Sciences, Spain's Jiminez Diaz Memorial Prize, France's Legion of Honor, the Hadassah World Organization's Women of Distinction Award, the Wolf Prize for Medicine, the Rothschild Prize for Biology, the Israel Prize and she received an Honorary Doctorate from Ben-Gurion University and from Tel Aviv University. In addition, Prof. Arnon is the incumbent of the Paul Ehrlich Chair in Immunochemistry at the Weizmann Institute.
 
 
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Anat Cohen-Dayag, Ph.D. At its meeting held on February 10, 2014, the Board of Directors appointed Dr. Anat Cohen-Dayag as a member of the Board of Directors, effective as of such date, to hold office until the 2014 annual general meeting of Shareholders and was reelected by the Shareholders at the 2014 annual general meeting. Dr. Anat Cohen-Dayag joined Compugen in 2002 as Director of Diagnostics, a position she held until 2005 at which time she became Vice President Diagnostic Biomarkers, a position she held until January 2007. From January 2007 until November 2008, Dr. Cohen-Dayag served as Compugen’s Vice President, Biomarkers and Drug Targets, at which point she was appointed Vice President, Research and Development. In June 2009, Dr. Cohen-Dayag was appointed, together with Mr. Martin Gerstel, as co-Chief Executive Officer of Compugen. In March 2010, upon Mr. Gerstel’s election as Chairman of the Board of Directors, Dr. Cohen-Dayag was appointed as Compugen’s President and CEO. Prior to joining Compugen, she was head of research and development and member of the Executive Management at Mindsense Biosystems Ltd. Prior to Mindsense Biosystems Ltd., Dr. Cohen-Dayag served as a scientist at the R&D department of Orgenics Ltd. Dr. Cohen-Dayag holds a B.Sc. in Biology from the Ben-Gurion University, Israel, and an M.Sc. in Chemical Immunology and a Ph.D. in Cellular Biology, both from the Weizmann Institute of Science, Israel. Additionally, Dr. Cohen-Dayag is a director of Ramot at Tel Aviv University Ltd., and a director of the IATI (Israeli Advanced Technologies Industries).
 
Martin S. Gerstel has served as a member and as the Chairman of the Board of Directors of Compugen since 1997, other than from February 2009 to February 2010, during which time he served as either CEO or co-CEO and, in both cases, as a member of the Board of Directors. Prior to Compugen, Mr. Gerstel was co-chairman and CEO of ALZA Corporation, which he helped found in 1968. Mr. Gerstel is the Chairman of Evogene Ltd., Keddem Bioscience Ltd., the co-founder and co-chairman of Itamar Medical Ltd., and serves as a director of Yissum Ltd., Yeda Ltd. and the U.S. Foundation for the National Medals of Science and Technology. He is a member of the Board of Governors and the Executive Committee of the Weizmann Institute of Science and the Board of Governors of The Hebrew University of Jerusalem, and is an advisor to the board of the BIRD Foundation. Mr. Gerstel holds a B.S. from Yale University and an MBA from Stanford University.
 
Dov Hershberg joined Compugen’s Board of Directors in February 2009, prior to which he served as a consultant to the Board of Directors. From February 2009 through February 2010, Mr. Hershberg served as Chairman of the Board of Directors.  Mr. Hershberg previously managed the BIRD Foundation from 1997 through 2006.  Mr. Hershberg is a founder and a former CEO, management team and board member of Powermat Technologies Ltd., a wireless electricity company.  Prior to joining the BIRD Foundation, Mr. Hershberg held various senior management positions in software development, marketing and sales. He was the founder and CEO, with colleagues from Stanford University, of Molecular Applications Group which created software in biomedical research. Mr. Hershberg spent eleven years at Digital Equipment Corporation in various senior management positions in product development, marketing and sales and worked as a mathematician in the Israeli Aircraft Industry.  Mr. Hershberg holds graduate degrees in Mathematics, from the Hebrew University in Jerusalem, Israel and in Applied Mathematics and Operations Research from Columbia University in New York City. 
 
Arie Ovadia, Ph.D. joined Compugen’s Board of Directors as an external director in July 2007 and was reappointed as an external director in April 2010 and in April 2013. He advises major Israeli companies on finance, accounting and valuations, and is a member of the Board of Directors of several corporations, including Strauss Ltd., Israel Petrochemical Industries Ltd., Bazan Ltd., Maxtech Technologies Ltd., and Elron Electronic Industries Ltd. He has taught at New York University, Temple University and, in Israel, at Tel Aviv and Bradford Universities and The College of Management. Dr. Ovadia served as a member of the Israeli Accounting Board, and is a 14-year member of the Israel Securities Authority. Dr. Ovadia holds an undergraduate degree and an MBA from Tel Aviv University, and earned his Ph.D. in economics from the Wharton School at the University of Pennsylvania.
 
Prof. Joshua Shemer joined Compugen’s Board of Directors as an external director in July 2007 and was reappointed as an external director in April 2010 and in April 2013.  Prof. Shemer is Full Professor of Medicine at the Tel Aviv University. In addition, Prof. Shemer is the Chairman of Assuta Medical Centers in Israel and a member of the Board of Directors of Maccabi Healthcare Services in Israel. Prof. Shemer is a director of the Israeli center for medical technology assessment in healthcare in Gertner Institute, Tel Hashomer.  Prof. Shemer is an Associate Editor at IMAJ and Harefuah, and a member of the Editorial Board of the International Journal of Technology Assessment in Health Care. Prof. Shemer teaches Medical Technology Management at the Faculty of Medicine at Tel Aviv University.  He was a member and former chairman of the National Public Committee for Updating the National List of Health Services in Israel and the National Council for Trauma of the Israeli Ministry of Health. Prof. Shemer was the Director-General of Maccabi Healthcare Services. Prof. Shemer was formerly Director-General of the Ministry of Health and Surgeon General of the Israel Defense Forces Medical Corps. Prof. Shemer has published five books and more than 200 peer reviewed articles. Additionally, Prof. Shemer is an external director of El-Al Airlines Ltd. Prof. Shemer is a graduate of the Hebrew University and Hadassah School of Medicine and Board certified in Internal Medicine in Israel, and board certified in health adminstration in Israel.
 
 
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Ari Krashin was appointed Chief Financial Officer of Compugen in September, 2014. Mr. Krashin has over 15 years of experience in capital markets, finance and business development. He served as a chief financial officer for both public and private companies the most recent being AnyClip Media and Spacenet Inc. Mr. Krashin was also the CFO of Gilat Satellite Networks (Nasdaq: GILT) where he led the company's global finance and related operations, including business development, M&A activities, investor relations and administration. Mr. Krashin is a certified public accountant and began his professional career with Kesselman and Kesselman, PWC, Israel.
 
John Hunter, Ph.D joined Compugen in 2012 as Site Head at our U.S. subsidiary, Compugen USA, Inc., and VP Antibody Research and Development. Dr. Hunter has worked for 18 years on different aspects of oncology drug development. Following graduation from UCSF, from 1996 to 2003, Dr. Hunter worked for Millennium Pharmaceuticals Inc., where he employed genomic approaches to identify novel drug targets in lung cancer. As a founding member of Millennium’s Translational Medicine group he worked to develop clinical biomarkers for their Aurora kinase small molecule inhibitors.  Following Dr. Hunter's employment at Millennium, Dr. Hunter joined Xenogen Corp., where he worked as Senior Scientist in Oncology from 2004 to 2005. Dr. Hunter later joined XOMA Ltd., where from 2005 to 2012 he managed early stage antibody discovery for multiple therapeutic programs in oncology and inflammation.  Dr. Hunter currently leads therapeutic antibody research and development efforts for Compugen’s portfolio of novel oncology targets.
 
Zurit Levine, Ph.D. joined Compugen in 1999 and has held several positions in Compugen’s Research & Development department. In 2004, she was appointed Director of Therapeutic Selection & Validation, which position she held until 2007 when she was appointed Director of Therapeutic Discovery. In 2009, she was appointed Executive Director of Research & Development. From January 2010 to August 2011, she held the position of Vice President, Research and Development. In August 2011 she was appointed Vice President, Research and Discovery. Dr. Levine holds a B.Sc. in Biology, an M.Sc. in Biochemistry and a Ph.D. in Biochemistry, all from the Tel Aviv University, Israel.
 
Arrangements Involving Directors and Senior Management
 
There are no arrangements or understandings of which we are aware pursuant to which any of our directors or executive officers have been selected for their positions with our Company. In addition, there are no family relationships among any of our directors and executive officers.
 
B.  COMPENSATION
 
Aggregate Compensation of Officers
 
The aggregate compensation paid or accrued by us to all persons who were, at any time during 2014, Office Holders (as defined below in “- Approval Required for Directors’ and Officers’ Compensation”) of the Company in respect of the fiscal year ended December 31, 2014 (16 persons, two of whom are no longer Office Holders as of December 31, 2014) was approximately $4.2 million. This amount includes approximately $478,000 set aside or accrued to provide pension, severance, retirement or similar benefits.
 
During 2014, we granted a total of 565,000 options to purchase ordinary shares to persons who are currently, or who were at any time during 2014 Office Holders, as a group. These options are exercisable at a range between $7.79 and $10.07 per share, and generally expire ten years after their respective dates of grant. As of December 31, 2014, there were a total of 3,672,267 outstanding options to purchase ordinary shares that were held by persons who are currently, or who were at any time during 2014, Office Holders.
 
Individual Compensation of Covered Executives
 
The table below outlines the compensation granted to our five most highly compensated Office Holders with respect to the year ended December 31, 2014. All amounts reported in the table reflect the cost to the Company, as recognized in our financial statements for the year ended December 31, 2014. We refer to the five individuals for whom disclosure is provided herein as our “Covered Executives.”
 
 
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Information Regarding the Covered Executives
        
Compensation for Services
  
Name and Principal Position(1)
  
Base Salary($)
    
Benefits and Perquisites ($)(2)
    
Annual Cash Bonus ($)(3)
    
Other ($)(4)
    
Stock-Based Compensation($)(5)
    
Total($)
  
Dr. Anat Cohen-Dayag
President & CEO
     264,945       87,202       30,806       116,000       444,721       943,674  
John Hunter
VP Antibody Development
     205,833       36,415       69,000       -       192,678       503,926  
Zurit Levine
VP Research and Discovery
     167,193       56,231       26,377       -       157,909       407,710  
Eyal Neria
VP R&D, Planning and Control
     144,219       48,248       9,855       -       203,721       406,043  
Martin Gerstel
Chairman of the Board of Directors
     140,362       19,464       15,683       59,000       195,395       429,904  
 
1)
All Covered Executives listed in the table other than Mr. Martin Gerstel are full-time employees of the Company. Cash compensation amounts denominated in currencies other than the U.S. dollar were converted into U.S. dollars at an exchange rate of NIS 3.5779 = $1.00, which reflects the average conversion rate for 2014.
 
2)
Amounts reported in this column include benefits and perquisites, including those mandated by applicable law. Such benefits and perquisites may include, to the extent applicable to the Covered Executives, payments, contributions and/or allocations for savings funds, pension, severance, vacation, car or car allowance, medical insurances and benefits, risk insurance (e.g., life, disability, accident), phone, convalescence pay, payments for social security, tax gross-up payments and other benefits and perquisites consistent with the Company’s policies.
 
3)
Amounts reported in this column refer to the annual cash bonuses for 2014, approved by our Compensation Committee and Board of Directros which have been provided for in the Company’s financial statements for the year ended December 31, 2014 but which will be paid during 2015. They do not include bonuses paid during 2014 which were provided for in the Company’s financial statements for previous years.
 
4)
Amounts reported in this column refer to the payment of special cash bonuses in connection with the Bayer Collaboration paid to Dr. Cohen-Dayag and Mr. Gerstel which pursuant to the Companies Law required the approval by our Shareholders which was granted at the 2014 Annual General Meeting, following the approval of our Compensation Committee and Board of Directors. Any such bonuses for other executive officers were provided for in the Company’s financial statements for 2013.
 
5)
Amounts reported in this column represent the expense recorded in our financial statements for the year ended December 31, 2014 with respect to options to purchase our ordinary shares granted to our Covered Executives. Assumptions and key variables used in the calculation of such amounts are discussed in Note 9 to our 2014 consolidated financial statements set forth elsewhere in this report.
 
 
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Approval Required for Directors’ and Officers’ Compensation
 
Pursuant to an amendment to the  Companies Law which became effective on December 12, 2012 (the “2012 Amendment”), the Company was required to adopt a compensation policy regarding the terms of office and employment of its Office Holders (as such term is defined below), including exemption and release of the Office Holder from liability for breach of his or her duty of care to the Company, an undertaking to indemnify the Office Holder, post factum indemnification or insurance; any grant, payment, remuneration, compensation, or other benefit provided in connection with termination of service; and any benefit, other payment or undertaking to provide any payment as aforesaid (“Terms of Office and Employment”). On September 17, 2013, our Shareholders adopted a compensation policy with respect to the Terms of Office and Employment of the Company’s Office Holders (the “Compensation Policy”).
 
The term "Office Holder" as defined in the Companies Law includes a general manager, chief executive officer, executive vice president, vice president, any other person fulfilling or assuming any of the foregoing positions without regard to such person’s title, as well as a director or a manager directly subordinate to the general manager or the chief executive officer ("Office Holder"). In addition to each person listed in the table under “Item 6. Directors, Senior Management and Employees – A. Directors and Senior Management”, Ms. Dikla Czaczkes Axselbrad, who was our CFO until May 12, 2014, and Mr. Avihai Shen who was our interim CFO until September 9, 2014, the Company considers four other individuals to have been Office Holders in 2014.
 
Pursuant to the Companies Law, arrangements with respect to the Terms of Office and Employment of Office Holders must generally be approved by the compensation committee and the board of directors, and be consistent with the compensation policy. However, under certain circumstances and conditions, the compensation committee and board of directors may approve an arrangement that deviates from the compensation policy, provided that such arrangement is approved by the company's shareholders by a simple majority, provided that (i) such majority includes a majority of the votes cast by shareholders who are not controlling shareholders and who do not have a personal interest in the matter, present and voting (abstentions are disregarded), or (ii) the votes cast by shareholders who are not controlling shareholders and who do not have a personal interest in the matter who were present and voted against the policy, constitute two percent or less of the voting power of the company (such majority determined in accordance with clause (i) or (ii), the “Compensation Majority”).
 
The Terms of Office and Employment of directors, including a chief executive officer who is also a director, further require the approval of the shareholders by a simple majority; with respect to a chief executive officer who is not a director, shareholder approval is also required, provided it is approved by the Compensation Majority. In addition, under certain circumstances, a company may be exempt from receiving shareholder approval with respect to the Terms of Office and Employment of a candidate for chief executive officer.
 
In special circumstances, to the extent the Terms of Office and Employment of Office Holders (who are not directors) are not approved by the shareholders (where such approval is required), the compensation committee and the board of directors may subsequently override the resolution of the shareholders following a new discussion of the matter and for specified reasons. Amendment of Terms of Office and Employment of Office Holders (who are not directors) requires the approval of the compensation committee only, if the committee determines that the amendment is not material. Under the Companies Law and regulations promulgated pursuant thereto, the compensation payable to external directors and independent directors is subject to certain further limitations. See “Item 6 – Directors, Senior Management and Employees – C. Board Practices – External Directors and Independent Directors under the Companies Law”
 
Compensation to our Non-Management Directors
 
Under arrangements previously approved by the Audit Committee, the Board of Directors and the Shareholders, and ratified and approved by the Compensation Committee, the Board of Directors and the Shareholders with the approval of the Compensation Policy and consistent therewith, each of our current directors and each additional or other director who may be appointed from time to time in the future and who is not, or who ceases to be, an employee of the Company and who does not, or ceases to, hold a management position with the Company or provide services to the Company in addition to his or her office as a director (each a “non-management director”) is compensated as of April 22, 2013, as follows:
 
(i) an annual fee of NIS 36,452 and an additional annual amount of NIS 17,985 to be paid to non-management directors who serve on one or more committees of the Board of Directors (the“Annual Fees”) (approximately $9,191 and $4,535, respectively, according to the representative rate of exchange on March 1, 2015, of $1.00 = NIS 3.966);
 
 
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(ii) a per meeting fee of NIS 3,597 (approximately $907  according to the representative rate of exchange on March 1, 2015, of $1.00 = NIS 3.966) for participation in any Board of Directors and/or committee meetings (the "Participation Compensation"), provided that (a) if such participation is by means of communication pursuant to Section 101 of the Companies Law, then such “per meeting” fee shall be 60% of the Participation Compensation; (b) in the event a resolution is adopted by the Board of Directors without a meeting pursuant to Section 103 of the Companies Law, then  such “per meeting” fee shall be 50% of the Participation Compensation;
 
(iii) the Annual Fees and the Participation Compensation are adjusted bi-annually to reflect changes in the Israeli Consumer Price Index in the manner provided in the regulations promulgated pursuant to the Companies Law governing the terms of compensation payable to external directors (the “Compensation Regulations”);
 
(iv) the Annual Fees are paid in four equal installments, and the Participation Compensation is  remitted to such directors on a quarterly basis, in each case at the beginning of each calendar quarter with respect to the previous quarter, all as provided for in the Compensation Regulations; and
 
(v) a grant of options to purchase 10,000 of the Company’s ordinary shares on July 31 of each calendar year to each non-management director then serving on the Board of Directors, at an exercise price equal to the closing price on the date of such grant on the principal securities exchange on which the Company's shares are then traded and subject (other than as described herein) to the terms and conditions of the Company’s 2010 Share Incentive Plan (the “2010 Plan”) or any other equity-based incentive plan the Company may adopt in the future and pursuant to which these equity awards would be granted. 3,333 of such options will vest on each of the first two anniversary dates of such grant and 3,334 on the third anniversary date. Notwithstanding the terms of the relevant plan, all options granted to non-management directors shall be fully vested immediately upon the completion of one or more of the following events, whether by way of a consolidation, merger or reorganization of the Company or otherwise: (a) a sale of all or substantially all of Company’s issued share capital or assets to any other company, entity, person or a group of persons, or (b) the acquisition of more than 50% of Company’s equity or voting power by any Shareholder or group of Shareholders. Notwithstanding the terms of the relevant plan, all options granted which shall be vested as of the date of final termination of office as a non-management director of the Company may be exercised within one year following such termination of office. To the extent legally available and applicable, such equity-based awards will be granted to the non-management directors through a trustee under Section 102 of the Israel Income Tax Ordinance [New Version], 5721-1961 (the "Tax Ordinance"), under the capital gains route.
 
VAT is added to the above compensation in accordance with applicable law.
 
Effective as of February 1, 2015, after adjustment in accordance with the Compensation Regulations, including as a result of a change in the Company’s Shareholders Equity, the Annual Fees to each non-management director stood at NIS 52,685, the additional payment to be paid to non-management directors who serve on one or more committees of the Board of Directors stood at NIS 18,311.62; and the Participation Compensation to each non-management director stood at NIS 3,662.32 (approximately $13,284. $4,617 and $923 respectively according to the representative rate of exchange on March 1, 2015, of $1.00 = NIS 3.966).
 
Compensation to our External Directors
 
Under arrangements previously approved by the Audit Committee, the Board of Directors and the Shareholders of the Company, and ratified and approved by the Compensation Committee, the Board of Directors and the Shareholders with the approval of the Compensation Policy and consistent therewith, in accordance with the Companies Law and the Compensation Regulations, each of our external directors shall be entitled to receive fees in connection with their service as external directors and their participation in Board of Directors meetings as well as meetings of committees of the Board of Directors equivalent to the compensation payable to other non-management directors, and shall also be eligible to receive options to purchase ordinary shares on an annual basis equal to the number of ordinary shares subject to the options being granted to each non-management director on terms substantially similar to those described above, provided however that the compensation paid to the Company's external directors shall be no less than the minimum amount that must be paid to external directors of the Company in accordance with the Compensation Regulations. According to the Compensation Regulations, the minimum amounts are adjusted twice annually based on the Israeli Consumer Price Index and are a function of the Company's Shareholders' equity.
 
 
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In addition, under arrangements previously approved by the Audit Committee, the Board of Directors and the Shareholders of the Company, and ratified and approved by the Compensation Committee, the Board of Directors and the Shareholders, with the approval of the Compensation Policy and consistent therewith, in accordance with the Companies Law and the Compensation Regulations, in the event that, during their term as external directors, the Company increases the remuneration payable, whether the annual payment or the participation compensation, to any ‘other directors’, as such term is defined in the Compensation Regulations, or grants additional options to purchase ordinary shares or other stock-based remuneration to ‘other directors’, each external director will be entitled, without further approval, to receive additional remuneration, if necessary, so that his or her annual compensation and/or compensation for participation in meetings, as the case may be, will be equivalent to the average compensation payable to such ‘other directors’ as annual payment or as participation compensation, respectively, or be granted additional options to purchase such number of additional ordinary shares as is equal to the average number of additional ordinary shares subject to the options being granted to such ‘other directors’ and on substantially similar terms, or receive such other stock-based remuneration required in order to align their compensation with the average compensation payable, including average stock-based remuneration awarded, to ‘other directors’, as applicable.
 
Compensation to our Active Chairman of the Board of Directors
 
Mr. Martin Gerstel, who serves as our Active Chairman of the Board of Directors, is not entitled to receive the above cash or equity based compensation granted to non-management directors. Effective as of March 1, 2010, and following the approval of our Audit Committee, Board of Directors and Shareholders, we entered into an employment agreement with Mr. Gerstel, pursuant to which he serves as Active Chairman of the Board of Directors. Generally, any change to such terms will be subject to the approval process and other conditions set forth in the Companies Law following the 2012 Amendment, as described above under “-Approval Required for Directors’ and Officers’ Compensation.
 
Pursuant to Mr. Gerstel's employment agreement he is entitled to a gross monthly salary of NIS 42,000 (approximately $10,590 according to the representative rate of exchange on March 1, 2015, of $1.00=NIS 3.966) which will remain at NIS 42,000 regardless of exchange rate fluctuations but which is subject to adjustment from time to time in accordance with periodic cost of living increases, and certain other employment terms customary in Israel. Consistent with our Compensation Policy, our Compensation Committee and Board of Directors approved an adjustment to the monthly salary of Mr. Gerstel, effective as of January 1, 2015. This salary increase is subject to the approval of our Shareholders and will be brought for their approval at the Company's 2015 annual meeting of Shareholders. The employment agreement may be terminated by either party by providing 90 days prior written notice.
 
Consistent with our Compensation Policy, our Shareholders approved at the 2014 Annual General Meeting, following the approval of the Compensation Committee and Board of Directors  the payment of a special cash bonus to Mr. Gerstel for, among other accomplishments, his contribution and efforts in connection with the Bayer Collaboration, in a total amount of $59,000.
 
Our Shareholders further approved, at our 2014 Annual General Meeting following the approval of the Compensation Committee and the Board of Directors and consistent with our Compensation Policy, the annual target cash bonuses with respect to the years 2014, 2015 and 2016 for Mr. Gerstel and the related objectives and terms thereof.

Consistent with the Shareholders’ approval the Compensation Committee and the Board of Directors approved an annual cash bonus in the amount of NIS 56,110 (approximately $15,683 according to an exchange rate of $1.00=NIS 3.5779 which reflects the average conversion rate for 2014) to be paid to Mr. Gerstel with respect to 2014.
 
 
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As of December 31, 2014 Mr. Gerstel held options to purchase a total of 797,500 ordinary shares, of which options to purchase 50,000 ordinary shares were granted during 2014. Out of the options to purchase 797,500 ordinary shares (i) options to purchase 687,500 ordinary shares, with a weighted average exercise price of $1.64 per share, were exercisable as of December 31, 2014; and (ii) options to purchase 110,000 ordinary shares, with a weighted average exercise price of $7.55 per share, had not vested as of December 31, 2014. Of the unvested options at December 31, 2014, options to purchase 60,000 ordinary shares are expected to vest during 2016; options to purchase the remaining 50,000 ordinary shares are expected to vest during 2017. These options were granted under the Company's 2000 Option Plan and under the Company's 2010 Plan. Notwithstanding the terms of the relevant plan, the options granted to Mr. Gerstel have terms substantially similar to non-management directors as described above. For additional information on Mr. Gerstel's holdings see “Item 6. Directors, Senior Management and Employee – E. Share Ownership - Share Ownership by Directors and Other Office Holders”.
 
Compensation to our President and Chief Executive Officer
 
Dr. Anat Cohen-Dayag, the Company's President and Chief Executive Officer has been employed by the Company since September 2, 2002, and served as the Company's President and co-Chief Executive Officer from June 2009 to March 2010, and as President and Chief Executive Officer since March 2010. Dr. Cohen-Dayag is not entitled to receive the above cash or equity-based compensation granted to non-management directors and is not entitled to any compensation in addition to that being paid to her as the President and Chief Executive Officer of the Company.
 
Pursuant to Dr. Anat Cohen-Dayag's employment agreement as the President and Chief Executive Officer of the Company she is entitled to a gross monthly salary of NIS 82,500 (approximately $20,802 according to the representative rate of exchange on March 1, 2015, of $1.00=3.966)), adjusted from time to time in accordance with periodic cost of living increases, which shall be reviewed annually. Dr. Cohen-Dayag is also entitled to certain benefits and perquisites customary in Israel, including those mandated by applicable law. In addition, Dr. Anat Cohen-Dayag is eligible for consideration of equity based grants by the Board of Directors on an annual basis subject to receipt of all approvals required by applicable law and to an annual cash bonus based upon achievement of objectives determined by the Company subject to receipt of all approvals required by applicable law. The Company’s Shareholders approved at the Company’s 2014 Annual General Meeting the annual target cash bonuses with respect to the years 2014, 2015 and 2016 for Dr. Anat Cohen-Dayag and the related objectives and terms thereof. Consistent with our Compensation Policy, the Compensation Committee and Board of Directors approved an adjustment to the monthly base salary of Dr. Cohen-Dayag effective as of January 1, 2015. This salary increase is subject to the approval of our Shareholders and will be brought for their approval at the Company's 2015 annual meeting of Shareholders.
 
Consistent with our Compensation Policy, our Shareholders approved at the 2014 Annual General Meeting, following the approval of the Compensation Committee and Board of Directors, the payment of a special cash bonus to Dr. Cohen-Dayag, for among other accomplishments, her contribution and efforts in connection with the Bayer Collaboration, in a total amount of $116,000.
 
Consistent with our Shareholders’ approval, the Compensation Committee and Board of Directors approved an annual cash bonus in the amount of NIS 110,220 (approximately $30,806 using exchange rate of $1.00=NIS 3.5779 which reflects the average conversion rate for 2014)  to be paid to Dr. Cohen-Dayag with respect to 2014.
 
Dr. Anat Cohen-Dayag's employment agreement may generally be terminated by either party by providing six (6) months advance written notice, provided that in the event of termination by the Company for “justifiable cause” (as such term is defined in her employment agreement as shall be in effect from time to time) the Company may terminate Dr. Cohen-Dayag's employment without advance notice and that Dr. Cohen-Dayag may resign with advance notice of only two (2) months in the event of resignation for “good reason” (as such term is defined in her employment agreement as shall be in effect from time to time). Upon termination, Dr. Anat Cohen-Dayag will be entitled to receive certain payments associated with termination.
 
In the event of termination of her employment by the Company other than for “justifiable cause” or resignation by Dr. Cohen-Dayag for “good reason” (hereinafter, referred together as “Dismissal”), Dr. Cohen-Dayag will also be entitled to an additional one-time payment equal to six (6) monthly salaries (the “Adaptation Payment”) and upon Dismissal within one year following certain “change of control” events (as defined in her employment agreement as shall be in effect from time to time), Dr. Cohen-Dayag will be entitled to a special termination payment (in addition to the Adaptation Payment) in an amount equal to six (6) monthly salaries.
 
 
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In addition, upon Dismissal, all outstanding unvested options granted to Dr. Cohen-Dayag as of such time will be accelerated and become immediately exercisable as of the effective date of such termination and Dr. Cohen-Dayag will be entitled to exercise all outstanding vested options (including those vested as a result of such accelerated vesting) for a period of one (1) year from the date of termination of employment, provided that such period does not extend beyond ten (10) years from the date of grant. In the event of a “change of control”, all non-vested options granted to Dr. Anat Cohen-Dayag as of such time will become fully vested. Upon termination of Dr. Cohen-Dayag’s employment by the Company other than with “justifiable cause” or by Dr. Cohen-Dayag, in each case within one year following a “change of control”, Dr. Cohen-Dayag will be entitled to exercise all outstanding vested options (including those vested as a result of such accelerated vesting) for a period of one (1) year from the date of such termination or resignation, provided that such period does not extend beyond ten (10) years from the date of grant.
 
As of December 31, 2014 Dr. Cohen-Dayag held options to purchase a total of 1,029,771 ordinary shares, of which options to purchase 100,000 ordinary shares were granted during 2014. Out of the options to purchase 1,029,771 ordinary shares: (i) options to purchase 689,771 ordinary shares, with a weighted average exercise price of $3.20 per share, were exercisable as of December 31, 2014; and (ii) options to purchase 340,000 ordinary shares, with a weighted average exercise price of $6.09 per share, had not vested as of December 31, 2014. Of the unvested options at January 1, 2015, options to purchase 120,000 ordinary shares are expected to vest during 2015, options to purchase 120,000 ordinary shares are expected to vest during 2016 and options to purchase the remaining 100,000 ordinary shares are expected to vest during 2017. These options were granted under the Company's 2000 Option Plan and the Company's 2010 Plan. For additional information on Dr. Cohen-Dayag's holdings see “Item 6. Directors, Senior Management and Employee – E. Share Ownership - Share Ownership by Directors and Other Office Holders”.
 
Indemnification, Exemption and Insurance
 
Our Compensation Committee, the Board of Directors and the Shareholders have resolved, consistent with our Compensation Policy, (i) to ratify and approve the purchase and the periodic renewal, at the expense of the Company of insurance coverage in respect of the liability of the Company’s Office Holders currently in office and any additional or other Office Holders as may be appointed from time to time in the future, including external directors, without the need for further act or approval, to the maximum extent permitted by law, that will provide for up to $15 million in coverage and will include coverage with respect to any public offering of shares or other securities of the Company; (ii) to exempt and release to the maximum extent permitted by law all of the directors and the chief executive officer of the Company currently in office, and any additional or other directors and chief executive officer(s) as may be appointed from time to time in the future, including external directors, without the need for further act or approval, from and against all liability for monetary or other damages due to, or arising or resulting from, a breach of their duty of care to the Company, including, with respect to directors, in their capacity as officers of the Company to the extent they also serve as officers of the Company, and to provide them with letters in this regard; and (iii) to undertake in advance to indemnify all directors and the chief executive officer of the Company currently in office, and any additional or other directors and chief executive officer(s) as may be appointed from time to time in the future, including external directors, without the need for further act or approval, to the extent, and for such matters, costs and expenses as set forth in a letter of indemnification and exemption and release approved for issuance to them.
 
Following the adoption of the Compensation Policy, and consistent therewith, the Compensation Committee and the Board of Directors resolved to similarly undertake in advance to indemnify all Office Holders of the Company (in addition to the directors and the Chief Executive Officer of the Company) currently in office and any additional or other Office Holders (in addition to the Directors and the Chief Executive Officer of the Company) as may be appointed from time to time; and to similarly exempt and release to the maximum extent permitted by law all such other Office Holders of the Company currently in office and any additional or other Office Holders of the Company (in addition to the directors and the chief executive officer of the Company) as may be appointed from time to time in the future, from and against all liability for monetary or other damages due to, or arising or resulting from, a breach of their duty of care to the Company and to provide them with letters in this regard.
 
 
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Consistent with our Compensation Policy and pursuant to the Companies Law and regulations promulgated thereunder, our Compensation Committee approved an increase of the insurance coverage in respect of the liability of our Office Holders and any additional or other Office Holders as may be appointed from time to time in the future, that will provide for up to $25 million in coverage.
 
C.  BOARD PRACTICES
 
We are incorporated in Israel, and, therefore, are subject to various corporate governance practices under Israeli law such as with respect to external directors, independent directors, audit committee, compensation committee and an internal auditor. These matters are in addition to the requirements of the NASDAQ Global Market and other relevant provisions of U.S. securities laws applicable to us. Under the NASDAQ Listing Rules of the NASDAQ Stock Market, which we refer to as the NASDAQ Listing Rules, a foreign private issuer may generally follow its home country practices for corporate governance in lieu of the comparable NASDAQ Global Market requirements, except for certain matters such as composition and responsibilities of the audit committee and the SEC-mandated standards for the independence of its members. For U.S. domestic companies, the NASDAQ Listing Rules specify that the majority of the members of the board of directors must be independent.  We currently comply with this requirement. In addition, under the Companies Law, we are required to appoint at least two external directors, with which we comply, as described below under “External Directors”.
 
Board of Directors
 
Compugen Ltd.'s Board of Directors consists of seven members, three of whom were elected as external directors under the provisions of the Companies Law (discussed below). Other than our three external directors, who are elected for a fixed term of three years, our directors are elected by our Shareholders by a simple majority of the voting power present and voting at an annual general meeting of Shareholders for a term of approximately one year, ending at the annual general meeting immediately following the annual general meeting at which they were elected and until their successors have been duly elected or until any such directors' term of office terminates as provided in the Companies Law or due to any of the circumstances set forth in our Articles. Our Articles, provide that we may have no less than five, nor more than fourteen directors.
 
None of our directors is party to a service contract with us that provides for any severance or similar benefits upon termination of his or her service other than our active Chairman of the Board of Directors, Mr. Martin Gerstel, and our president and Chief Executive Officer, Dr. Anat Cohen-Dayag, with each of whom we have entered into an employment agreement, according to which they are entitled to employment terms required by Israeli law and as provided for in the agreements, including severance payments. For additional information on the employment agreement entered into with Mr. Gerstel and with Dr. Cohen-Dayag, please see “Item 6 – Directors, Senior Management and Employees – B. Compensation - Compensation to our Active Chairman of the Board of Directors; - Compensation of our President & Chief Executive Officer.”
 
Directors under the Companies Law - General
 
A nominee for service as a director in a public company may not be elected without submitting a declaration to the company, prior to his or her election, specifying that he or she has the requisite qualifications to serve as a director, an external director or an independent director, as applicable, and the ability to devote the appropriate time to performing his or her duties as such.
 
A director, including an external director or an independent director, who ceases to meet the statutory requirements to serve as a director, external director or independent director, as applicable, must notify the company to that effect immediately and his or her service as a director will expire upon submission of such notice.
 
External Directors and Independent Directors under the Companies Law
 
Under the Companies Law and the regulations promulgated pursuant thereto, Israeli public companies are required to have on their board of directors at least two external directors meeting certain independence criteria, all as provided under Israeli law. External directors are elected for a term of three years at the general meeting of shareholders by a disinterested majority of the shareholders (and cannot be appointed by the board of directors), and may be re-elected to additional terms of three years each, subject to certain conditions; each committee of a company’s board of directors that has the authority to exercise powers of the board of directors must include at least one external director, and its audit committee and remuneration committee, must include all external directors.
 
 
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Among other requirements, a person may not be elected as an external director of a company if such person, his or her relative, partner, employer, anyone to whom he or she is directly or indirectly subordinate, or any entity under his or her control, has or had, on or within the two years preceding the date of his or her election, any ‘affiliation’ (as defined in the Companies Law) with the company, any controlling shareholder of the company, a relative of a controlling shareholder, or any entity controlled by the company or by a controlling shareholder of the company; and if the company has no controlling shareholder or a shareholder holding 25% or more of the company’s voting rights, also with the chairman of the board of directors, the chief executive officer or the most senior financial officer of the company, or with a shareholder holding 5% or more of the outstanding shares or voting rights of the company. The term affiliation includes an employment relationship, a business or professional relationship, maintained on a regular basis, or control, as well as service as an Office Holder.
 
Pursuant to the Companies Law an external director is required to have either accounting and financial expertise or professional qualifications according to criteria set forth under the Companies Law and regulations promulgated thereunder, and generally, at least one of the external directors is required to have accounting and financial expertise. The board of directors must make the determinations as to the financial and accounting expertise, and as to the professional qualifications, of a director taking into consideration those criteria and matters set forth in the regulations. In addition, the boards of directors of publicly traded companies are required to make a determination as to the minimum number of directors who must have financial and accounting expertise as aforesaid based, among other things, on the type of company, its size, the volume and complexity of the company’s activities and the number of directors. Our Board of Directors has determined that the minimum number of directors with financial and accounting expertise is one and that Dr. Arie Ovadia, one of the Company's external directors, qualifies as such. 
 
Professor Yair Aharonowitz, Dr. Arie Ovadia and Professor Joshua Shemer currently serve as our external directors, each of whom is also independent under the NASDAQ Listing Rules. The initial election of each of Professor Yair Aharonowitz, Dr. Arie Ovadia and Professor Joshua Shemer for a term of three years was approved by our Shareholders at our annual general meeting of Shareholders held on July 31, 2007. They were each re-elected by our Shareholders on April 15, 2010 and again on April 22, 2013 for an additional three year-term that expires on April 21, 2016.
 
Under the Companies Law, an 'independent director' is either an external director or a director appointed or classified as such who meets the same non-affiliation criteria as an external director, as determined by the company’s audit committee, and who has not served as a director of the company for more than nine consecutive years. For these purposes, ceasing to serve as a director for a period of two years or less would not be deemed to sever the consecutive nature of such director’s service. A company, such as the Company, whose shares are listed for trading on specified exchanges outside of Israel, including the Nasdaq Global Market, may also classify directors who qualify as independent directors under the relevant non-Israeli rules relating to independence standards and who meet certain non-affiliation criteria, as ‘independent directors’ under the Companies Law, all as provided under regulations promulgated under the Companies Law.
 
External directors and independent directors may receive compensation solely as provided for in the Companies Law and the Compensation Regulations.  In addition, the Companies Law includes specific provisions with respect to the manner in which external directors and independent directors may be dismissed from office.  Following termination of service, external directors and independent directors and their relatives are generally subject to certain restrictions with respect to receipt of benefits, service as an Office Holder, employment and provision of professional services to the company, a controlling shareholder thereof or any entity controlled by a controlling shareholder.
 
Independent Directors under the NASDAQ Listing Rules
 
In addition to the requirements of the Companies Law as described above, since our shares are listed on the NASDAQ Global Market, pursuant to the NASDAQ Listing Rules, a majority of our directors must be independent (as defined under the NASDAQ Listing Rules). We comply with such NASDAQ independence requirement, as five of the seven members of our Board of Directors - Professor Yair Aharonowitz, Dov Hershberg, Dr. Arie Ovadia, Professor Joshua Shemer and Professor Ruth Arnon- have been determined by our Board of Directors to meet the NASDAQ independence requirements.
 
 
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Board Committees
 
Audit Committee
 
The Companies Law requires public companies such as ours to appoint an audit committee comprised of at least three directors. The audit committee must include all of the external directors, one of whom shall serve as the chairman of the committee, the majority of its members must be independent directors (as described above under “- Independent Directors under the Companies Law”) and may not include certain directors. Generally, any person who is not entitled to be a member of the audit committee may not attend the audit committee's meetings.
 
Under the NASDAQ Listing Rules, we are required to maintain an audit committee that operates under a formal written charter and has certain responsibilities and authority, including being directly responsible for the appointment, compensation, retention and oversight of the work of our independent auditors. According to the NASDAQ Listing Rules, the audit committee is required to consist of at least three members, all of whom must be financially literate and also meet the independence requirements established by the SEC under Rule 10A-3 of the Exchange Act and the independence criteria set forth in the NASDAQ Listing Rules. The NASDAQ Listing Rules also require that at least one member of the audit committee be financially sophisticated (as defined in such listing rules).
 
The responsibilities of the Audit Committee include among other things: (i) identifying flaws in the management of the Company’s business and making recommendations to the Board of Directors as to how to correct them, and providing for arrangements regarding employee complaints with respect thereto (ii) reviewing and considering certain related party transactions and certain actions involving conflicts of interest, (iii) reviewing the internal auditor’s work program performance and examining the company’s internal control structure and processes (iv) examining the external auditor’s scope of work as well as the external auditor’s fees and providing its recommendations to the appropriate corporate organ, and (viii) overseeing the accounting and financial reporting processes of the Company.
 
 In carrying out its duties, the Audit Committee meets with management at least once in each fiscal quarter at which time, among other things, it reviews, and either approves or disapproves, the financial results of the Company for the immediately preceding fiscal quarter and conveys its conclusions in this regard to the Board of Directors. The Audit Committee also generally monitors the services provided by the Company’s external auditors to ensure their independence, and reviews all audit and non-audit services provided by them. The Company’s external and internal auditors also report regularly to the Audit Committee at its meetings and the Audit Committee discusses with the Company’s external auditors the quality, not just the acceptability, of the accounting principles, the reasonableness of significant judgments and the clarity of disclosures in the Company’s financial statements, as and when it deems it appropriate to do so.
 
Under the NASDAQ Listing Rules the audit committee is directly responsible for the appointment, compensation, retention and oversight of the work of the Company’s independent auditors, among other things. However, under Israeli law and our Articles, the appointment of independent auditors requires the approval of the Shareholders and their compensation requires the approval of our Board of Directors.  In addition, pursuant to the Companies Law, the Audit Committee is required to examine the independent auditors’ scope of work as well as the external auditors’ fees and to provide its recommendations with respect thereto to the appropriate corporate organ. Accordingly, the appointment of the independent auditors will be required to be approved and recommended to the Shareholders by the Audit Committee and approved by the Shareholders. The compensation of the independent auditors for audit services and non-audit services will be required to be approved by the Audit Committee and recommended to the Board of Directors and approved by the Board of Directors.
 
We have an Audit Committee consisting of three independent directors, all of whom are financially literate and one of whom has accounting or related financial management expertise and is financially sophisticated. The members of the Audit Committee are Dr. Arie Ovadia, who serves as the chairman of our Audit Committee, Professor Yair Aharonowitz, and Professor Joshua Shemer. All of the members of our Audit Committee qualify as independent directors under the NASDAQ Listing Rules and are external directors under the Companies Law. We have adopted a charter for the Audit Committee, which sets forth the purpose and responsibilities of such committee under the above-described legal requirements.
 
 
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Compensation Committee
 
The Companies Law requires public companies such as the Company to appoint a compensation committee comprised of at least three directors. The compensation committee must include all of the external directors, one of whom will serve as the chairman of the committee and may not include certain directors. All other members of the compensation committee, who are not external directors, must be directors who receive compensation that is in compliance with the Companies Law and the Compensation Regulations. Generally, any person who is not entitled to be a member of the compensation committee may not attend the compensation committee’s meetings.
 
The responsibilities of our Compensation Committee include, among others: (i) reviewing and making recommendations to the Board of Directors with respect to the Company’s policy regarding the Terms of Office and Employment of its Office Holders, (ii) reviewing and considering arrangements with respect to the Terms of Office and Employment of Office Holders, and (iii) overseeing, subject to applicable law, the administration of the Company’s various compensation plans and arrangements, including, incentive compensation and equity based plans. In carrying out these duties, the Compensation Committee meets on an ad hoc basis (usually several times in each fiscal year). Under the Companies Law, the Compensation Committee may need to seek the approval of the Board of Directors and the Shareholders for certain compensation-related decisions, (see “Item 6 - Directors, Senior Management and Employees – B. Compensation - Approval Required for Directors’ and Officers’ Compensation”).  Each member of our compensation committee is an ‘independent director’ in accordance with the NASDAQ listing standards.  Prof. Yair Aharonowitz, Dr. Arie Ovadia and Prof. Joshua Shemer are the current members of the Compensation Committee, with Prof. Joshua Shemer serving as its chairman. Each of them is an external director under the Companies Law and an independent director in accordance with the NASDAQ Listing Rules. We have adopted a charter for the Compensation Committee, which sets forth the purpose and responsibilities of such committee.
 
Nominating Committee
 
Our Board of Directors does not maintain a nominating committee. The functions of such committee are performed by the full Board of Directors.  This practice is compliant with Israeli law and, as a foreign private issuer, we have elected, pursuant to NASDAQ Listing Rule 5615(a) (3), to follow Israeli practice, in lieu of compliance with the NASDAQ Listing Rule 5602(e).
 
Internal Auditor
 
Under the Companies Law, the board of directors must appoint an internal auditor, recommended by the audit committee. The role of the internal auditor is to examine, among other matters, whether the company's actions comply with the law and orderly business procedures. Under the Companies Law, an interested party or an Office Holder of a company, or a relative of an interested party or of an Office Holder of a company, as well as the company's independent auditors or any one on behalf of the independent auditors may not serve as a company's internal auditor. The internal auditor’s tenure cannot be terminated without his or her consent, nor can he or she be suspended from such position unless the board of directors has so resolved after hearing the opinion of the audit committee and after providing the internal auditor with the opportunity to present his or her position to the board of directors and to the audit committee. An interested party is defined in the Companies Law as a holder of 5% or more of the company's outstanding shares or voting rights, any person or entity who has the right to designate one or more directors or the chief executive officer of the company or any person who serves as a director or as a chief executive officer of the company.
 
On February 8, 2010, our Board of Directors appointed Hila Barr of Brightman Almagor Zohar & Co., a member company of Deloitte Touche Tohmatsu, as its internal auditor.  Hila Barr is not an employee, affiliate or Office Holder of the Company, or affiliated with the Company's independent auditors.
 
 
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D.  EMPLOYEES
 
The following table sets out the number of our employees engaged in specified activities, at the end of the fiscal years 2014, 2013 and 2012 (the numbers include employees of our wholly owned U.S. subsidiary Compugen USA, Inc.:
 
   
December 31, 2014
    
December 31, 2013
    
December 31, 2012
  
Research & Development
     68       42       *38  
Administration, Accounting and Operations
     13       13       *12  
Marketing and Business Development
     2       2       2  
Total
     83       57       52  
 
* includes one employee on a part-time basis
 
In April 2012 we established a new monoclonal antibody (mAb) research and development operation in South San Francisco, California. For the year ended December 31, 2012, 43 of our employees were located in Israel and nine were located in the U.S, for the year ended December 31, 2013, 48 of our employees were located in Israel and nine were located in the U.S, and for the year ended December 31, 2014, 60 of our employees were located in Israel and 23 were located in the U.S.
 
We consider our relations with our employees to be satisfactory and we have not experienced a significant labor dispute or strike. We are not a party to any collective bargaining agreement with respect to our Israeli employees. However, we are subject to certain labor related statutes and to certain provisions of collective bargaining agreements between the Histadrut (General Federation of Labor in Israel) and the Coordinating Bureau of Economic Organizations and/or the Industrialists’ Association, which are applicable to our Israeli employees by virtue of expansion orders of the Israeli Minister of the Economy. These statutes and provisions cover a wide range of subjects and provide certain minimum employment standards, including the length of the work day and work week, minimum wages, travel expenses, contributions to a pension fund, insurance for work-related accidents, procedures for dismissing employees, determination of severance pay, annual and other vacations, sick pay and other conditions of employment. We generally provide our employees with benefits and working conditions beyond the required minimum. An additional provision applicable to all employees in Israel under collective bargaining agreements and expansion orders is the automatic adjustment of wages in relation to increases in the Israeli CPI. The amount and frequency of these adjustments are modified from time to time; however, no such adjustments have been made in recent years pursuant to expansion orders.

Our severance pay liability to our Israeli employees, based upon the number of years of service and the latest monthly salary, is in the large part covered by regular deposits with recognized pension funds, deposits with severance pay funds and purchases of insurance policies. Pursuant to Section 14 of the Israeli Severance Pay Law 5723-1963, certain of our liabilities for employee severance rights upon termination are covered by regular contributions to defined contribution plans so that upon termination of employment of the relevant employees, we are only required to release the payments made by us to such funds on account of severance and by doing so are deemed to have complied with all of our severance payment obligations relating to the service of applicable employees with respect to the period during which the provisions of such section apply.  For information concerning our liability for severance pay, see Note 2o to our 2014 consolidated financial statements.
 
Our employees are not represented by a labor union. We have written employment contracts with each of our employees.
 
 
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E.  SHARE OWNERSHIP
 
Share Ownership by Directors and Other Office Holders
 
All of the persons listed above under the caption “Directors and Senior Management” own ordinary shares of the Company and/or options to purchase ordinary shares of the Company. Except as set forth in the table below, none of the directors or executive officers beneficially owns ordinary shares and/or ordinary shares underlying options amounting to 1% or more of the outstanding ordinary shares. The following table sets forth certain information as of March 1, 2015, regarding the beneficial ownership by our directors and executive officers. All numbers quoted in the table are inclusive of options to purchase shares that are exercisable within 60 days after March 1, 2015. The information in this table is based on 50,372,492 ordinary shares outstanding as of March 1, 2015.
 
Beneficial Owner
  
Amount Owned
    
Percent of Class
  
Martin S. Gerstel (1)
     2,541,268       4.98 %
Anat Cohen-Dayag (2)
     729,771       1.43 %
All directors and Office
Holders as a group (15 persons) (3)
     4,175,901       7.94 %
 
___________________
 
 
 (1)
Includes (i) 119,240 shares held by Mr. Gerstel, (ii) 500,000 shares held by Shomar Corporation, an affiliate of Mr. Gerstel, (iii) 619,033 shares held by Merrill Lynch IRA for Martin S. Gerstel, of which Mr. Gerstel is the beneficiary, and (iv) 615,495 shares held in a trust for which Mr. Gerstel is trustee and a member his immediate family is the beneficiary.  Also includes 687,500 shares subject to options that are currently exercisable or that become exercisable within 60 days after March 1, 2015 with a weighted average exercise price of $1.64 per share and which expire between January 2019 and July 2022.
 
 
 (2)
Consists of 729,771 shares subject to options that are exercisable within 60 days after March 1, 2015 with a weighted average exercise price of $3.21 per share, and which expire between March 2016 and August 2022.
 
 
 (3)
See Notes 1 and 2 above, Also includes (i) a total of 833,198 shares subject to options that are beneficially owned by directors and other Office Holders that are exercisable within 60 days after January 31, 2014 with a weighted average exercise price of $3.65 per share and which expire between March 2016 and July 2023 and (ii) a total of 71,664 ordinary shares held by directors.
 
Share Option Plans
 
We maintain one active share option plan, plus one additional share option plan under which prior grants remain outstanding, for our employees, directors and consultants. In addition to the discussion below, see Note 9 to our 2014 consolidated financial statements.
 
Our Board of Directors administered our share option plans until February 2014 and as of such date subject to applicable law (including with respect to the required approval procedure of compensation to Office Holders under the Companies Law (for additional information on the approval procedure of compensation to Office Holders, see “Item 6. Directors, Senior Management and Employees – B. Approval Required for Directors' and Officers' Compensation”), the Compensation Committee administers our share option plans and has the authority to designate terms of the options granted under our plans including the grantees, exercise prices, grant dates, vesting schedules and expiration dates, which may be no more than ten years after the grant date. Options may not be granted with an exercise price of less than the fair market value of our ordinary shares on the date of grant, unless otherwise determined by our Board of Directors.
 
Compugen Share Option Plan (2000)
 
The Compugen Share Option Plan (2000), or the “2000 Option Plan”, enabled granting options for up to an aggregate of 10,191,511 ordinary shares of the Company to our and our subsidiaries' employees, directors and consultants. No further options are being granted under this plan following a July 25, 2010 decision of our Board of Directors which resolved to cancel the shares then remaining available for grant under the 2000 Option Plan. As of December 31, 2014, options to purchase 2,189,205 ordinary shares at a weighted average exercise price of approximately $2.56 per share were outstanding (i.e., were granted but not canceled, expired or exercised) under the 2000 Option Plan. Options to purchase 5,493,599 ordinary shares under the plan have previously been exercised at a weighted average exercise price of approximately $2.83.
 
 
 
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Compugen 2010 Share Incentive Plan
 
On July 25, 2010, our Board of Directors adopted the Compugen 2010 Share Incentive Plan or the “2010 Plan”. The adoption of the 2010 Plan was approved by our Shareholders on May 12, 2011. In addition, the Board of Directors and Shareholders resolved that the options available for grants under the 2000 Option Plan, at such time, as well as any options that may return to such pool in connection with terminated options, will be made available for future grants under the 2010 Plan. 1,953,851 shares were initially reserved for the grant under the 2010 Plan. The Shareholders approved at our 2014 Annual General Meeting to authorize and reserve for purposes of and for issuance under the 2010 Share Incentive Plan an additional 3,000,000 ordinary shares.  In keeping with our Board of Directors’ and Shareholders' resolution any shares subject to options granted under the 2000 Option Plan prior to the adoption of the 2010 Plan which terminate unexercised, will also be made available for future grants under the 2010 Plan. On August 6, 2012 our Board of Directors adopted certain amendments to the 2010 Plan which, among other things, provided for additional types of awards, namely restricted share and restricted share unit awards.
 
If a grantee leaves his or her employment or other relationship with us, or if his or her relationship with us is terminated without cause (and other than by reason of death or disability, as defined in the 2010 Plan), the term of his or her unexercised options will generally expire in 90 days, unless determined otherwise by our Board of Directors. As of December 31, 2014, options to purchase 4,541,665 ordinary shares at a weighted average exercise price of approximately $5.78 per share were outstanding (i.e., were granted but not canceled, expired or exercised) under the 2010 Plan. Options to purchase 318,387 ordinary shares under the plan have previously been exercised at a weighted average exercise price of approximately $4.67. Options to purchase 3,925,677 ordinary shares remain available for future grant as of December 31, 2014.
 
Administration of our Share Options Plans
 
Our Board of Directors has elected the “Capital Gains Track” (as defined in Section 102(b) (2) of the Tax Ordinance for the grant of options to Israeli grantee.
 
Pursuant to Section 102 of the Tax Ordinance, and pursuant to an election made by the Company thereunder, gains derived by employees (which term includes directors) in Israel arising from the sale of shares acquired pursuant to the exercise of options granted to them through a trustee under Section 102 of the Tax Ordinance after January 1, 2003, will generally be subject to a flat capital gains tax rate of 25%, although these gains may also include a salary income component.  As a result of this election under Section 102, the Company will not, in the case of equity awards made on or after January 1, 2003, be allowed to claim as an expense for tax purposes in Israel the amounts credited to the employee as capital gains, although it will generally be entitled to do so in respect of the salary income component (if any) of such awards when the related tax is paid by the employee.
 
ITEM 7.             MAJOR SHAREHOLDERS AND RELATED PARTY TRANSACTIONS
 
A.  MAJOR SHAREHOLDERS
 
Based on a review of required SEC filings, we are not aware of any person or entity that is the beneficial owner of more than 5% of our outstanding ordinary shares as of march 1, 2015.  As of March 1, 2015, there were a total of 57 holders of record of our ordinary shares, of which 37 were registered with addresses in the United States. Such United States holders were, as of such date, the holders of record of approximately 96.6% of the outstanding ordinary shares. Our ordinary shares are traded on the NASDAQ Global Market in the United States and on the TASE in Israel. A significant portion of our shares are held in street name, therefore we cannot determine who our Shareholders are, their geographical location or how many shares a particular Shareholder owns.
 
Significant Changes in Share Ownership
 
The following table shows changes over the last three years in the percentage ownership by major Shareholders:

   
Ordinary Shares
Owned as of
February 28, 2013
    
Ordinary Shares
Owned as of
February 28, 2014
    
Ordinary Shares
Owned as of
March 1, 2015
  
   
Number of shares
    
Percentage of ownership
    
Number of shares
    
Percentage of ownership
    
Number of shares
    
Percentage of ownership
  
Martin Gerstel
     2,385,015       6.31 %     2,499,604       5.94 %     2,541,268       4.98 %
Clearbridge Advisors LLC (2)
     1,273,245       3.55 %      (1 )      (1 )      (1 )      (1 )
 
 
(1)
Number and percentage of shares outstanding as of such date is unknown, but is less than 5%.
 
 
(2)
Percentage of shares outstanding as of February 28, 2013 is based solely on a Schedule 13G/A filed with the SEC on February 14, 2013.
 
 
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B.  RELATED PARTY TRANSACTIONS
 
Other than as set forth below and transactions related to compensation of our officers and directors as described under “Item 6.  Directors, Senior Management and Employees—B.  Compensation,” since January 1, 2014, we have not entered into any related party transactions.
 
Keddem Bioscience Ltd.
 
In 1999, we established a chemistry division to carry out a research program in which we integrated the disciplines of organic chemistry with physics and advanced computational technologies for the development of a method to substantially increase the predictability and success rates of small molecule drug discovery. These operations were subsequently transferred in 2004 to our then wholly owned subsidiary Keddem Bioscience Ltd (“Keddem”), where such operations were later suspended for financial reasons in 2007. On November 19, 2012 we signed an agreement with a private U.S.-based investment company pursuant to which up to $15 million in milestone related equity financing will be made available to Keddem. This financing will be used to further develop and commercialize Keddem's unique technology platform.  Under the agreement, the new investor will obtain a majority equity interest in Keddem, with Compugen maintaining a minority interest and certain future preferential access rights to utilize the Keddem technology with Compugen discovered drug targets.  Martin Gerstel, our Chairman of the Board of Directors is also Chairman of the Board of Keddem, and as of the date of this annual report, we owned 36% of the outstanding securities of Keddem.
 
See also Note 2v to our 2014 consolidated financial statements.
 
Neviah Genomics Ltd.
 
In June 2012, we established together with Merck KGaA and Merck Holdings Netherlands B.V. (collectively, "Merck") a new start-up company, Neviah, which is focused on the discovery and development of novel biomarkers for the prediction of drug-induced toxicity. Neviah operates out of the Merck Serono Israel Bioincubator. Pursuant to our agreement, Merck is providing the initial funding for Neviah and its expertise in the validation and development of biomarkers into a diagnostic test, and we are utilizing certain proprietary predictive discovery technologies and receiving research revenues for our efforts. The agreement provides Compugen with an equity ownership in the new company and a right to royalties from potential future sales. In 2014, we received $212,000 in research revenues under this agreement. In December 2014, we invested together with Merck an amount in addition to Merck’s original investment in order to finance the further validation of the assay and remaining product development costs, for more information see Note 2v to our 2014 consolidated financial statements. Dr. Zurit Levine our VP Research and Discovery, and Dr. Eyal Neria our VP R&D, Planning and Control are directors in Neviah on behalf of the Company. Until January 11, 2014, Adv. Tami Fishman Jutkowitz our general counsel was a director in Neviah. Adv. Tami Fishman Jutkowitz was replaced on January 11, 2014 by Dr. Eyal Neria.
 
As of the date of this annual report, we owned 25.12% of the outstanding securities of Neviah.
 
See also Note 2v and Note 14 to our 2014 consolidated financial statements.
 
Indemnification of Our Directors and Officers
 
Compugen releases its Office Holders from liability and indemnifies them to the fullest extent permitted by law and its Articles, and provides them with letters of indemnification and exemption and release for this purpose, in the form approved at a special Shareholders meeting which took place at September 2013. Under the letters of indemnification and exemption and release, (i) Compugen’s undertaking to indemnify each Office Holder for monetary liabilities or obligations imposed by a court judgment (including a settlement or an arbitrator’s award approved by a court) shall be limited to matters that result from or are connected to those events or circumstances set forth therein, and (ii) the indemnification that the Company undertakes towards all persons whom it resolved to indemnify for the matters and circumstances described therein, jointly and in the aggregate, shall not exceed $5 million. Under Israeli law, indemnification is subject to other limitations, including those described below. Subject to applicable law, we may also indemnify our Office Holders following specific events.
 
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Compugen’s Office Holders are also covered by directors’ and officers’ liability insurance. The Companies Law provides that a company may not exempt or indemnify an Office Holder, or enter into an insurance contract, which would provide coverage for any liability incurred as a result of any of the following: (i) a breach by the Office Holder of his or her duty of loyalty except, with respect to insurance coverage or indemnification, due to a breach of his or her duty of loyalty to the company committed in good faith and with reasonable grounds to believe that such act would not prejudice the interests of the company; (ii) a breach by the Office Holder of his or her duty of care to the company committed intentionally or recklessly (other than if solely done in negligence); (iii) any act or omission done with the intent of unlawfully realizing personal gain; or (iv) a fine, monetary sanction, forfeit or penalty imposed upon an Office Holder. In addition, the Companies Law provides that Office Holders can only be exempted in advance with respect to liability for damages caused as a result of a breach of their duty of care to the company (but not for such breaches committed intentionally or recklessly, as noted above, or in connection with a distribution (as defined in the Israeli Companies Law)). For more information see “Item 6.  Directors, Senior Management and Employees—B.  Compensation-Indemnification, Exemption and Insurance”.
 
C.  INTERESTS OF EXPERTS AND COUNSEL
 
Not applicable.
 
ITEM 8.             FINANCIAL INFORMATION
 
A.  CONSOLIDATED STATEMENTS AND OTHER FINANCIAL INFORMATION
 
Consolidated Financial Statements
 
Our consolidated financial statements are included beginning on page F-1 of this annual report.  See also “Item 18.  Financial Statements.”
 
Legal Proceedings
 
Currently, we are not a party to any legal or arbitration proceedings, including governmental proceedings that are pending or known to be contemplated, that our management believes, individually or in the aggregate, may have, or have had in the recent past, a significant effect on our financial position or profitability, nor are we party to any material proceeding in which any director, member of our senior management or affiliate is a party adverse to us or our subsidiaries or has a material interest adverse to us or our subsidiaries.
 
Dividend Distribution Policy
 
We have never paid any cash dividends on our ordinary shares, and we do not intend to pay cash dividends on our ordinary shares in the foreseeable future. Our current policy is to retain earnings for use in our business.
 
In the event that we decide to pay a cash dividend from income that is tax exempt under our Approved Enterprises and/or Benefiting Enterprises programs, we would be required to pay the applicable corporate tax that would otherwise have been payable on such income which would be in addition to the tax payable by the dividend payee. See Note 10 to our 2014 consolidated financial statements and “Item 10. Taxation.”
 
B.  SIGNIFICANT CHANGES
 
Not applicable.
 
 
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ITEM 9.             THE OFFER AND LISTING
 
A.  OFFER AND LISTING DETAILS
 
Our ordinary shares were listed on The NASDAQ Global Market through June 16, 2009.  On June 17, 2009, we transferred the listing of our ordinary shares from The NASDAQ Global Market to The NASDAQ Capital Market, and on January 27, 2014 we transferred the listing of our ordinary shares from The NASDAQ Capital Market back to The NASDAQ Global Market. The high and low sales prices per share of our ordinary shares for the periods indicated are set forth below:
 
Year Ended
  
High
    
Low
  
December 31, 2010                                                                                
   $ 5.32     $ 3.04  
December 31, 2011                                                                                
   $ 5.80     $ 3.32  
December 31, 2012
   $ 6.47     $ 2.96  
December 31, 2013                                                                                
   $ 11.92     $ 4.56  
December 31, 2014
   $ 14.32     $ 6.27  
                 
Quarter Ended
                
March 31, 2013                                                                                
   $ 6.32     $ 4.84  
June 30, 2013                                                                                
   $ 6.60     $ 4.56  
September 30, 2013                                                                                
   $ 10.60     $ 5.04  
December 31, 2013                                                                                
   $ 11.92     $ 7.92  
March 31, 2014                                                                                
   $ 14.32     $ 8.76  
June 30, 2014                                                                                
   $ 11.55     $ 7.58  
September 30, 2014                                                                                
   $ 10.02     $ 8.19  
December 31, 2014                                                                                
   $ 9.09     $ 6.27  
                 
Month Ended