COMPUGEN LTD [CGEN] Filings

   

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We have a history of losses and we expect to incur future losses and may never achieve or sustain profitability.

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We may need to raise additional funds in the future, and if we are unable to raise such additional funds, we may need to limit, 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.

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We cannot provide assurance that our business model will succeed in generating substantial revenues.

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In the near term, we are highly dependent on the success of COM701, COM902 and COM503. We may not be able to advance our internal clinical stage programs through clinical development or manufacturing or successfully partner or commercialize them, or obtain marketing approval, either alone or with a collaborator, or may experience significant delays in doing so.

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Clinical trials of any product candidates that we, or any current or future collaborators may conduct, may fail to satisfactorily demonstrate safety and/or efficacy, and we, or any collaborator, may incur additional costs or experience delays in completing, or ultimately be unable to complete the development and commercialization of these product candidates.

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Clinical development involves a lengthy and expensive process, with an uncertain outcome. We may encounter substantial delays or even an inability to begin clinical trials for any specific product or may not be able to conduct or complete our trials on the timelines we expect.

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From time to time we publicly disclose preliminary data from our ongoing clinical trials. As more patient data become available the data and the interpretation of the data may change.

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We rely and expect to continue to rely on third parties to conduct our clinical trials. These third parties may not successfully or professionally carry out their contractual duties, comply with regulatory requirements or meet expected deadlines, and we may experience significant delays in the conduct of our clinical trials as well as significant increased expenditures.

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Serious adverse events or undesirable side effects or lack of efficacy, may emerge in clinical trials conducted by other companies running clinical trials investigating the same target as us, which could adversely affect our development programs or our capability to enroll patients or partner the program for further development and commercialization.

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We are subject to certain manufacturing risks, any of which could either result in additional costs or delays in completing, or ultimately make us unable to complete, the development and commercialization of our product candidates.

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From time to time, we may also publish preliminary biomarker data from our ongoing clinical trials. As more patient data become available the data and the interpretation of the data may change.

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Our current and future relationships, and/or the relationships of our collaborators through which we may market, sell, and distribute our products, with healthcare professionals, physicians and other parties in the United States and elsewhere may be subject, directly or indirectly, to applicable anti-kickback, fraud and abuse, false claims, physician payment transparency, health information and general privacy and security and other healthcare laws and regulations, which could expose us to adverse consequences.

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There are risks that are inherent in the development and commercialization of new therapeutic products.

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We have limited experience in the development of therapeutic product candidates, and we may be unable to implement our business strategy.

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Our approach to the discovery of therapeutic products is based on our predictive computational discovery capabilities that are not yet fully proven clinically, and we do not know whether we will be able to discover and develop additional potential product candidates or products of commercial value.

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We are focusing our discovery and therapeutic development activities on therapeutic product candidates for uses in immuno-oncology. Our current candidates may fail, and we may fail to continue to discover and develop therapeutic product candidates of industry interest in this field.

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We depend significantly on third parties to carry out the research, development and commercialization of our therapeutic product candidates. If we are unable to maintain our existing agreements or to enter into additional agreements with such third parties, mainly collaborators, in the future, our business will likely be materially harmed.

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Our dependence on collaboration agreements with third parties presents number of risks.

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Our existing partnership agreement with Gilead is subject to many risks.

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We operate in a highly competitive and rapidly changing industry which may result in others discovering, developing or commercializing competing products ahead of us or more successfully than we do.

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Given our level of managerial, operational, financial and other resources, our current activities and future growth may be limited.

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Our information technology systems, or those of the third parties upon whom we rely, including our cloud providers, CROs or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of our pipeline and our business, as well as to regulatory investigations or actions; litigation; fines and penalties; reputational harm; loss of revenue and other adverse consequences.

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We are subject to stringent and changing obligations related to data privacy and security. Failure or perceived failure to comply with current or future obligations could lead to government enforcement actions (which could include civil or criminal penalties), private litigation, and/or adverse publicity and could negatively affect our operating results and business.

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If the scope of any patent protection we obtain is not sufficiently broad, or if we lose any of our patent protection, our ability to prevent our competitors from commercializing similar or identical product candidates would be adversely affected.

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We may need to obtain additional licenses of third-party technology or other rights that may not be available to us or are available only on commercially unreasonable terms, and which may cause us to operate our business in a more costly or otherwise adverse manner that was not anticipated.

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We, or potential collaborators and licensees, may infringe third-party rights and may become involved in litigation, which may materially harm our business.

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We may become involved in lawsuits to protect or enforce our patents or other intellectual property, which could be expensive, time consuming and unsuccessful.

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Conditions in Israel and in the Middle East may adversely affect our operations.

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Our results of operations may be adversely affected by the exchange rate fluctuations between the dollar and the New Israeli Shekel.

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We may not be able to meet the continued listing standards of Nasdaq, which require a minimum closing bid price of $1.00 per share, which could result in our delisting and negatively impact the price of our ordinary shares and our ability to access the capital markets.

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Future sales of our ordinary shares or securities convertible or exchangeable for our ordinary shares may depress our share price.

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If we sell ordinary shares in future financings, shareholders may experience immediate dilution and, as a result, our share price may decline.

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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.

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If we are a passive foreign investment company, or PFIC, our U.S. shareholders may be subject to adverse U.S. federal income tax consequences.

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the successful clearance of IND for COM503;

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the successful clinical trial design (and implementation thereof) and results;

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inability to generate sufficient preclinical, toxicology, or other data to support the initiation of clinical trials;

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lack of authorization from regulators or institutional review boards, or IRBs, or ethics committees to allow us or our investigators to amend a clinical trial or commence a clinical trial or conduct a clinical trial at a prospective trial site or continue such clinical trial;

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delays in sufficiently developing, characterizing, or controlling a manufacturing process suitable for clinical trials;

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inability to generate sufficient quantities or quality of our drug substance or drug product to support the initiation or continuation of clinical trials;

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delays in reaching a consensus with collaborators or regulatory agencies on trial design or trial amendment;

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delays in reaching agreement on acceptable terms with prospective CROs, and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical trial sites;

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imposition of a temporary or permanent clinical hold by the FDA, or a similar delay imposed by foreign regulatory agencies for a number of reasons, including after review of an IND, other application or amendment; (i) as a result of a new safety finding that presents unreasonable risk to clinical trial participants; (ii) a negative finding from an inspection of our clinical trial operations or trial sites; (iii) developments on trials conducted by competitors for related technology that raises FDA concerns about risk to patients of the technology broadly; or (iv) if FDA finds that the investigational protocol or plan is clearly deficient to meet its stated objectives;

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clinical trials of any product candidates may fail to show safety or efficacy, produce negative or inconclusive results and we may decide, or regulators may require us, to conduct additional preclinical studies or clinical trials or we may decide to abandon product development programs;

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difficulty collaborating with patient groups and investigators;

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failure by our CROs, other third parties, or us to adhere to clinical trial and related regulatory requirements;

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failure to perform in accordance with the FDA’s Good Clinical Practice, or GCP, requirements, or similar applicable regulatory guidelines in other countries;

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failure to perform in accordance with the FDA’s Good Manufacturing Practice, or GMP, requirements, or similar applicable regulatory guidelines in other countries;

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the number of patients required for clinical trials of any product candidates may be larger than we anticipate or can financially support, enrollment in these clinical trials may be slower than we anticipate, or participants may drop out of these clinical trials or fail to return for post-treatment follow-up at a higher rate than we anticipate;

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delays in having patients complete their participation in a trial or return for post-treatment follow-up;

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occurrence of adverse events associated with the product candidate that are viewed to outweigh its potential benefits;

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changes in regulatory requirements and guidance that require amending or submitting new clinical protocols;

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changes in the standard of care or in the regulatory landscape on which a clinical development plan was based, which may require new or additional trials;

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the cost of clinical trials of our product candidates being greater than we anticipate;

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clinical trials of our product candidates producing negative or inconclusive results, or early results that will not be repeated in larger or future cohorts or randomized studies, which may result in our deciding, or regulators requiring us, to conduct additional clinical trials or abandon product development programs;

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choosing the wrong dosing regimen and/or the wrong drug combination;

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delays or failure to secure supply agreements with suitable reagent suppliers, or any failures by suppliers to meet our quantity or quality requirements for necessary reagents; and

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delays in manufacturing, testing, releasing, validating, or importing/exporting sufficient stable quantities of our product candidates for use in clinical trials or the inability to do any of the foregoing.

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warning letters;

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recalls, product seizures or medical product safety alerts;

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data lock or order to destroy or not use personal data;

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restrictions on, or prohibitions against, marketing such products;

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restrictions on importation of such products;

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suspension of review or refusal to accept or approve new or pending applications;

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withdrawal of product approvals;

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injunctions;

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civil and criminal penalties and fines; or

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debarment or other exclusions from government programs.

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we will not be able to discover additional drug targets;

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our new target candidates will prove to be inappropriate for treatment of cancer;

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our new target candidates will prove to be inappropriate targets for therapeutic product candidates;

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our new target candidates will prove to be inappropriate targets for immunotherapy;

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we will not succeed in choosing the appropriate drug modality for these targets;

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our therapeutic product candidates will fail to progress to preclinical studies or clinical trials;

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our therapeutic product candidates will be found to be therapeutically ineffective;

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our therapeutic product candidates will be found to be toxic or to have other unacceptable side effects or negative consequences;

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our therapeutic product candidates will be inferior, or not show added value, compared to competing products or the standard of care;

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our early-stage development efforts may provoke competition by others or may face competition by others;

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our early-stage development efforts will bear significant delays in the development of additional preclinical stage programs;

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our products covered by our collaborations may face internal competition from our partners’ internal pipeline;

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we or our collaborators will fail to receive required regulatory approvals;

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we or our collaborators will fail to manufacture our therapeutic product candidates in the quantity or quality needed for preclinical studies or clinical trials on a large or commercial scale, on time or in a cost-effective manner or with the drug stability required;

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the discovery of drug targets and the discovery, development or commercialization of our therapeutic product candidates will infringe third-party intellectual property rights;

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the development, marketing or sale of our therapeutic product candidates will fail because of our inability or failure to protect or maintain our own intellectual property rights;

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once a product is commercially available, 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, inefficient or insufficient marketing and sales activities or as a result of there being more attractive, less risky or less expensive, products available for the same use; and

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not being able to discover new drug targets in this field;

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not having chosen the right therapeutic area;

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having chosen a therapeutic area with a very high degree of competition;

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industry interest in this area or in specific classes/families of drug targets within this area of focus would decrease over time;

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the checkpoint inhibitors field is facing fatigue;

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having chosen a therapeutic area of great biological complexity and with very high failure rates in product development;

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not choosing the appropriate drug modality;

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having insufficient knowledge, expertise, personnel or capabilities in our chosen therapeutic area to identify the right unmet medical needs, or drug targets, or to timely, properly and efficiently validate the targets and/or select the appropriate mAb for further development as therapeutic product candidates, or to timely, properly or efficiently further them in development; and

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the inherent risk of high program failure rate throughout therapeutic development.

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we may not be able to initiate or continue preclinical and clinical trials of products that are under development;

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we may experience significant disruption and delay to our clinical supply chain;

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we may experience significant adverse effect if we are unable to transfer the manufacturing process to a different third-party manufacturer in a timely and efficient manner;

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we may need to repeat clinical trials or stop our clinical trials;

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we may be delayed in submitting regulatory applications, or receiving regulatory approvals, for our product candidates;

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we may lose the cooperation of our collaborators;

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we may be required to cease distribution or recall some or all batches of our products; and

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ultimately, we may not be able to meet commercial demands for our products, if approved.

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we may be unable to reach mutually agreeable terms and conditions with respect to potential new collaborations;

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we or our current and/or future collaborators may be unable to comply or fully comply with the obligations under collaboration agreements to which we are (or will become) a party, and as a result, we may not generate milestone payments or royalties from such agreements, and our ability to enter into additional agreements may be harmed;

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our obligations under existing or future collaboration agreements may harm our ability to enter into additional collaboration agreements;

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collaborators generally 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;

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collaborators generally have significant discretion in terminating the collaborations for scientific, clinical, business or other reasons;

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if our current and/or future collaborators breach or terminate an agreement with us, the development and commercialization of our therapeutic product candidates could be adversely affected because at such time we may not have sufficient financial or other resources or capabilities or access to the other partner’s data and drug(s) to successfully develop and commercialize these therapeutics on our own or find other partners or enforce our rights under breached or terminated agreement;

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our current and/or future collaborators may require us changing or adopting the trial design to fit their business priorities, standards and other objectives;

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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;

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our current and/or future collaborators may terminate the program or the agreement and then compete against us in the development or commercialization of similar therapeutics;

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disagreements between us and our current and/or future collaborators may lead to delays in, or termination of, the collaboration;

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our current and/or future collaborations may face internal competition by their internal pipelines;

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prospective collaborators may hesitate to pursue collaborations on novel target candidates that lack robust validation to serve as a basis for the development of therapeutics; and

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our current and/or future collaborators 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 these collaborators.

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much greater financial, technical and human resources than we have at every stage of the discovery, development, manufacture and commercialization process;

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more extensive experience in computational discovery, preclinical testing, conducting clinical trials, obtaining regulatory approvals, and in manufacturing and marketing therapeutics;

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more extensive experience in oncology and immuno-oncology and in the fields of mAb therapeutics;

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access to and experience in the development of therapeutic modalities that are competitive to mAb therapeutics;

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more extensive experience in oncology and immuno-oncology and in the field of target discovery;

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more extensive experience in the research and development of biological or genetic markers to determine response of or responders to therapeutic agents or for patient selection;

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greater accessibility to data and proprietary data from patients;

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access to internally developed, proprietary technologies for the discovery, research, development, or manufacturing of therapeutic agents;

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greater resources and means to compete with us on target discovery and as well as in acquiring or generating technologies complementary to, or necessary for, our programs as well as in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites;

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products that have been approved or are in late stages of development and in many cases, PD-1 or PDL-1 inhibitors that are serving or will be serving as the backbone of cancer immunotherapy;

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reduced reliance on collaborations or partnerships with third parties in order to further develop and commercialize competitive therapeutic products; and

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collaborative arrangements in our target markets with leading companies and research institutions.

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the patenting of inventions involves complex legal issues relating to intellectual property laws, prosecution and enforcement of patent claims across a number or patent jurisdictions, many of which have not yet been settled;

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legislative and judicial changes, or changes in the examination guidelines of governmental patent offices may negatively affect our ability to obtain patent claims to certain biological molecules- and/or use of certain therapeutic targets;

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if we are not the first to file a patent application on one of our inventions, we may not be able to obtain a patent on our invention, and may not be able to protect one or more of our therapeutic product candidates;

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competition from other biotechnology and pharmaceutical companies who have already sought patent protection relating to proteins and protein based products, as well as therapeutic antibodies or other modulators 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 patent claims on antibodies or certain proteins or other biologic modulators, or may hinder our ability to obtain sufficiently broad patent claims for our inventions, and/or may limit our freedom to operate;

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publication of data on gene products or proteins by non-commercial and commercial entities may hinder our ability to obtain sufficiently broad patent claims for our inventions;

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even if we succeed in obtaining patent protection, such protection may not be sufficient to prevent third parties from circumventing our patent claims;

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even if we succeed in obtaining patent protection, we may face freedom to operate issues;

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even if we succeed in obtaining patent claims protecting our inventions and product candidates, our patents could be subject to challenge and litigation by our competitors, and may be partially or wholly invalidated as a result of such legal/judicial challenges and in connection with such challenges;

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significant costs that may need to be incurred in registering and filing patents;

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insufficient data to support our claims and/or may support others in strengthening their patents;

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seeking patent protection at an early stage may prevent us from providing comprehensive data supporting the patent claims and may prevent allowance of certain patent claims or limit the scope of patent claim coverage;

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we may not be able to supply sufficient data to support our claims, within the legally prescribed time following our initial filing in order to support our patent claims and this may harm our ability to get appropriate patent protection or protection at all;

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our claims may be too broad and not have sufficient enablement, in which case such claims might be rejected by patent offices or invalidated in court; and

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we might fail to demonstrate a unique technical feature for our antibodies as compared to existing prior art, in which case our claims might be rejected by the respective patent office, requiring superiority over prior art.

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forgo the research, development and commercialization of certain drug target candidates and product candidates that we discover, notwithstanding their promising scientific and commercial merits; or

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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.

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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;

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the sections of the Exchange Act regulating the solicitation of proxies, consents or authorizations in respect of a security registered under the Exchange Act, including extensive disclosure of compensation paid or payable to certain of our highly compensated executives as well as disclosure of the compensation determination process;

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the provisions of Regulation FD aimed at preventing issuers from making selective disclosures of material information; and

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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).

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global or regional macroeconomic developments;

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general market, political and economic conditions in the countries in which Compugen operates, including Israel and the effect of the evolving nature of the recent “Swords of Iron” war in Israel;

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the spread, and resulting actions, of COVID-19 or other global or regional health pandemics or epidemics;

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clinical data disclosed by us or our competitors;

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massive sell of our shares by a large shareholder;

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our success (or lack thereof) in entering into collaboration agreements and achieving certain research and developmental milestones thereunder;

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our need to raise additional capital and our success or failure in doing so;

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our ability (or lack thereof) to disclose key discoveries or developments due to competitive concerns or need to secure our intellectual property position;

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achievement or denial of regulatory approvals by us or our competitors;

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announcements of technological innovations or new commercial products by our competitors;

 

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developments concerning material proprietary rights, including material patents;

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developments concerning our existing or new collaborations;

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regulatory developments in the United States, Israel and other countries;

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changes in the structure of healthcare payment systems;

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delay or failure by us or our partners in initiating, completing or analyzing preclinical or clinical trials or the unsatisfactory design or results of such trials;

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period to period fluctuations in our results of operations;

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changes in estimates by securities analysts;

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changes in senior management or the board of directors or changes in the size or structure of the company;

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our ability (or lack thereof) to disclose the commercial terms of, or progress under, our collaborations;

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our ability (or lack thereof) to show and accurately predict revenues; and

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transactions with respect to our ordinary shares by insiders or institutional investors.

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We integrate our cutting-edge computational capabilities with our ground-breaking immuno-oncology research and drug development expertise to discover novel drug targets and biological pathways with the potential to address the unmet need of patients non-responsive to current cancer immunotherapies

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We harness these capabilities to inform our drug development process; and

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We identify drug combinations and design biomarker strategy for potential future patient selection.

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COM701 is our internal lead immuno-oncology pipeline program. COM701 is a humanized antibody that binds with high affinity to PVRIG, a novel immune checkpoint target candidate discovered by us that blocks the interaction with its ligand, PVRL2. Our data suggests that the PVRIG pathway is parallel and complementary to TIGIT, an immune checkpoint discovered computationally by us in 2009. These two pathways intersect with DNAM-1, a costimulatory receptor on T cells and NK cells. The PD-1 pathway also intersects with DNAM-1. In certain tumors, and in certain patient populations, the simultaneous blockade of these pathways may be required to stimulate an antitumor immune response. Phase 1 trials for COM701 were initiated in September 2018.

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COM902 is a high affinity, fully human antibody developed by us, targeting TIGIT, an immune checkpoint. COM902 blocks the interaction of TIGIT with PVR, its ligand. As part of the DNAM-1 axis signaling, in certain tumors, and in certain patient populations, the simultaneous blockade of TIGIT, PVRIG and PD-1 may be required to stimulate an antitumor immune response. Phase 1 trials for COM902 were initiated in March 2020.

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Rilvegostomig is a novel PD-1/TIGIT bispecific antibody with a TIGIT component that is derived from COM902 and is being developed by AstraZeneca pursuant to an exclusive license agreement with AstraZeneca. AstraZeneca initiated its Phase 3 ARTEMIDE-Bil01 trial as adjuvant therapy for biliary tract cancer after resection in combination with chemotherapy at the end of 2023 dosing its first patient in such trial in December 2023. In addition, AstraZeneca is also running several Phase 1 and 2 trials with rilvegostomig in additional indications.

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COM503 is a potential first-in-class high affinity antibody, which blocks the interaction between IL-18 binding protein and IL-18, thereby freeing natural IL-18 in the tumor microenvironment to inhibit cancer growth. “interleukin-18 binding protein and interleukin-18 complex” is a potential dominant immunosuppressive mechanism which is used by tumors to escape the immune system. The inflammasome-induced pro-inflammatory cytokine, interleukin-18, is present at high levels in the tumor microenvironment, where it is expected to naturally activate anti-tumor effector cells, such as T and NK cells. But IL-18 is one of the rare cytokines that is naturally blocked by an endogenous high affinity inhibitor, called IL-18 binding protein.

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COM701 - a therapeutic antibody targeting PVRIG

Furthermore, our data show that, PVRIG is expressed in stem-like memory T cells (TSCM) and PVRL2 is expressed in both dendritic cells and tertiary lymphoid structures, as well as in PD-L1 low less inflamed tumors. TSCM cells, dendritic cells and tertiary lymphoid structures have all been shown to be important in clinical response to checkpoint inhibitors and this unique expression pattern might enable PVRIG blockade to be active in patients with less inflamed tumors. In addition, expression studies showed that PVRIG, TIGIT, and their respective ligands, are expressed in a broad variety of tumor types, such as breast endometrial and ovarian. These two pathways intersect with DNAM-1, a costimulatory receptor on T cells and NK cells. The PD-1 pathway also intersects with DNAM-1. In certain tumors, and in certain patient populations, the simultaneous blockade of these pathways may be required to stimulate an antitumor immune response. COM701 is in a Phase 1 clinical trial in patients with advanced solid tumors, to evaluate in combination therapy with PD-1 inhibitor + TIGIT inhibitor.

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COM701 in combination with nivolumab induced preliminary anti-tumor activity and TME immune-modulation in patients with MSS-CRC typically not responsive to approved checkpoint inhibitors

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PVRIG has a unique dominant expression on early differentiated T like stem cells (Tscm) and its ligand, PVRL2, is expressed on dendritic cells (DCs)

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Spatial transcriptomic analysis showed that Tscm and DCs preferentially localize to Tertiary Lymphoid Structures (TLS) regions while exhausted T cells localize to the tumor

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PVRIG is dominantly expressed on CD8+ T cells in TLS region

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PVRIG blockade may enhance Tscm activation by DCs in lymph-nodes and TLS, a mechanism which potentially could lead to increased T cell expansion and infiltration into cold tumors

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COM701+ nivolumab combination is well tolerated with a favorable safety profile

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ORR 2/22 (9%) higher than ORR (1-2%) reported for standard of care - regorafenib or TAS-102

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Encouraging preliminary antitumor activity in the subset of MSS-CRC patients with liver metastases, ORR 2/17 (12%), compared to 0% ORR historically for other immunotherapies in a U.S. patient population

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Translational data demonstrated potent TME immune activation, in the majority of patients based on 13 paired biopsies, most notable in responders and consistent with COM701 mechanism of action. Such modulation is not typical of checkpoint inhibitors in cold indications

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In 20 patients who had exhausted all standard therapies, with a median number of 6 prior therapies, the dual combination demonstrated:

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Encouraging overall response rate of 10%, with 2 partial responses and 1 ongoing at the data cut-off date

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Disease control rate of 45% (2 confirmed partial responses, 7 stable disease)

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Translational assessment of peripheral blood, showed a pharmacodynamic activation of the immune system

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One patient with a partial response supported by increased infiltration of CD8 cells into the tumor microenvironment, had high grade serous adenocarcinoma, 7 prior lines of treatment including best response of progressive disease on the combination of nivolumab and lucitanib (an investigational agent)

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Most frequent treatment related adverse events grade 1/2, no grade 4/5 adverse events

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65% of the patients had high-grade serous adenocarcinoma, including the two responders

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Metastatic breast cancer adds to previous indications in which COM701 combinations show clinical benefit in tumors typically not responding to immunotherapy

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Presentation of new data from the metastatic breast cancer cohort expansion study of patients treated with COM701 and nivolumab, another indication showing clinical benefit in patients typically not responding to immunotherapy with initial data showing that baseline PVRL2 levels are higher in patients with clinical benefit supporting the findings in platinum resistant ovarian cancer patients (see below finding in platinum resistant ovarian cancer patients)

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In 20 patients who had exhausted all standard therapies, with a median number of 4 prior therapies, the triple combination demonstrated:

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Encouraging overall response rate of 20%, with 4 confirmed partial responses, out of which 3 are responding for at least 9 months. All 4 responders are still on study treatment at the data cut-off date, therefore median duration of response has not been reached

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Disease control rate of 45% (4 confirmed partial responses, 5 stable disease)

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Low pre-treatment PD-L1 expression in 2 of the responders (CPS <1 and 3), analysis of the other responders is still ongoing

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Translational assessment of peripheral blood, including profiling of cytokines and circulating immune cells, showed a pharmacodynamic activation of the immune system

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Most frequent treatment related adverse events grade 1/2, no grade 4/5 treatment related adverse events

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COM701 in combination with nivolumab and BMS-986207 (anti-TIGIT) resulted in encouraging confirmed durable partial responses (overall response rate 22% (2/9) and disease control rate 44%) with a favorable safety profile

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Partial response reported in a patient on study treatment for almost 7 months who was previously refractory to standard of care lenvatinib and pembrolizumab

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Greater peripheral immune activation seen in patients experiencing clinical benefit

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Data further support potential of COM701 in hard-to-treat tumors including those refractory to immune checkpoint inhibitors

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COM701 + nivolumab + BMS-986207 (anti-TIGIT) resulted in clinically meaningful durable partial responses > 16 months in platinum resistant ovarian cancer patients

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COM701 dual and triple combinations mediated clinical benefit in platinum resistant ovarian cancer patients, independent of baseline inflammatory status and was associated with an increase in T cell infiltration to the tumor

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PVRL2, the PVRIG ligand, identified as potential predictive biomarker to help enrich for patients who may derive benefit from COM701 combinations for certain indications

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COM902 - a therapeutic antibody targeting TIGIT

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Rilvegostomig - a therapeutic PD-1/TIGIT bi-specific antibody with a TIGIT component that is derived from our COM902

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Bapotulimab (formerly known as BAY1905254) – a therapeutic antibody targeting CGEN-15001T/ILDR2

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completion of preclinical laboratory tests and animal studies in compliance with the FDA’s GLP or other applicable regulations;

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submission to the FDA of an IND, which must become effective before human clinical trials may begin;

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performance of adequate and well-controlled human clinical trials in accordance with GCPs to establish the safety and efficacy of the product for its intended use;

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submission of annual reports to regulatory authorities;

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submission to the FDA of a biologics license application, or BLA;

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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 product’s identity, strength, quality and purity; and

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FDA review and approval of the BLA.

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cash at hand and yield on investment of such cash balances; and

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proceeds from ordinary shares sold through the Sales Agreement with Leerink.

		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)			1,436				690				746				-				-
Accrued Severance Pay, net(2)			421				-				-				-				421
Total			1,857				690				746				-				421

Name		Age		Positions
Paul Sekhri(3)		65		Chairman of the Board of Directors (Chairman of the Nomination and Corporate Governance Committee)
Anat Cohen-Dayag, Ph.D.		57		President and Chief Executive Officer, Director
Mathias Hukkelhoven, Ph.D.		70		Director
Gilead Halevy(2)		57		Director (Chairman of the Audit Committee)
Kinneret Livnat Savitzky, Ph.D.(1)(3)		56		Director
Eran Perry(1)(2)		53		Director
Sanford (Sandy) Zweifach(1)(2)(3)		67		Director (Chairman of the Compensation Committee)
Alberto Sessa		61		Chief Financial Officer
Henry Adewoye, MD(4)		59		Senior Vice President and Chief Medical Officer
Zurit Levine, Ph.D.		56		Senior Vice President, Technology Innovation
Yaron Turpaz, Ph.D.		53		Senior Vice President and Senior Advisor, Data and Informatics Solutions
Eran Ophir, Ph.D.		46		Chief Scientific Officer
Pierre Ferre, Ph.D.		47		Vice President, Preclinical Development

Information Regarding the Covered Office Holders		Compensation for Services(2)
Name and Principal Position(1)		Base Salary ($)				Benefits and Perquisites ($)(3)				Stock-Based Compensation ($) (4)				Total ($)
Dr. Anat Cohen-Dayag President & Chief Executive Officer			479,234				461,150				524,064				1,464,448
Dr. Henry Adewoye Senior Vice President and Chief Medical Officer			425,000				131,067				271,502				827,569
Dr. Pierre Ferre Vice President, Preclinical Development			211,521				238,439				120,440				570,400
Dr. Eran Ophir Senior Vice President, Research and Drug Discovery			195,677				161,131				183,835				540,643
Dr. Zurit Levine Senior VP, Technology Innovations			188,631				167,207				176,426				532,264

(a)

Audit Committee - $2,500 for a member, or $5,000 for the chairperson;

(b)

Compensation Committee - $2,000 for a member, or $4,000 for the chairperson; and

(c)

Nomination and Governance Committee - $1,000 for a member, or $3,000 for the chairperson.

•

a breach of duty of care to us or to another person;

•

a breach of duty of loyalty to us, provided that the Office Holder acted in good faith and had reasonable grounds to assume that such act would not prejudice our interests;

•

monetary liabilities or obligations imposed upon him or her in favor of another person;

•

A payment which the Office Holder is obligated to make to an injured party as set forth in Section 52(54)(a)(1)(a) of the Securities Law, and expenses that the Office Holder incurred in connection with a proceeding under Chapters H’3, H’4 or I’1 of the Securities Law, including reasonable litigation expenses, including attorney’s fees, or in connection with Article D of Chapter Four of Part Nine of the Companies Law; and

•

Expenses incurred by the Office Holder in connection with a proceeding under Chapter G’1, of the Israel Restrictive Trade Practices Law, 5748-1988, or Restrictive Trade Law, including reasonable litigation expenses, including attorney’s fees.

•

For any monetary liabilities or obligations imposed on our Office Holder in favor of another person pursuant to a court judgment, including a compromise judgment or an arbitrator’s decision approved by a court;

•

For any payments which our Office Holder is obligated to make to an injured party as set forth in Section 52(54)(a)(1)(a) of the Israeli Securities Law and expenses the Office Holder incurred in connection with a proceeding under Chapters H’3, H’4 or I’1 of the Israeli Securities Law, including reasonable litigation expenses, including attorney’s fees, or in connection with Article D of Chapter Four of Part Nine of the Companies Law;

•

For reasonable litigation expenses, including attorney’s fees, incurred by the Office Holder in consequence of an investigation or proceeding instituted against the Office Holder by an authority that is authorized to conduct such investigation or proceeding, and which was concluded without filing of an indictment against the Office Holder and without imposing on the Office Holder a financial obligation in lieu of criminal proceedings, or which was concluded without filing of an indictment against the Office Holder but with imposing on such Office Holder a financial obligation in lieu of criminal proceedings in respect of an offense that does not require proof of criminal intent or in connection with a financial sanction; For the purposes hereof: (i) “a proceeding that concluded without filing an indictment in a matter in respect of which an investigation was conducted”; and (ii) “financial obligation in lieu of a criminal proceeding”, shall have the meanings specified in Section 260(a)(1A) of the Companies Law;

•

For reasonable litigation expenses, including attorney’s fees, incurred by the Office Holder or which the Office Holder is ordered to pay by a court, in a proceeding filed against the Office Holder by the Company or on its behalf or by another person, or in a criminal action of which the Office Holder is acquitted, or in a criminal action in which the Office Holder is convicted of an offense that does not require proof of criminal intent;

•

For expenses incurred by our Office Holder in connection with a proceeding under Chapter G’1, of the Restrictive Trade Law, including reasonable litigation expenses, including attorney’s fees; and

•

For any other liability, obligation or expense indemnifiable or which our Officer Holders may from time to time be indemnifiable by law.

•

a breach by the Office Holder of his or her duty of loyalty, except that the company may enter into an insurance contract or indemnify an Office Holder if the Office Holder acted in good faith and had a reasonable basis to believe that the act would not prejudice the company;

•

a breach by the Office Holder of his or her duty of care if such breach was intentional or reckless, but unless such breach was solely negligent;

•

any act or omission done with the intent to derive an illegal personal benefit; or

•

any fine, civil fine, financial sanction or monetary settlement in lieu of criminal proceedings imposed on such Office Holder.

 

Board Diversity Matrix as of February 20, 2024
Total Number of Directors	7
	Female	Male	Non-Binary	Did Not Disclose Gender
Part I: Gender Identity
Directors	2	4		1
Part II: Demographic Background
African American or Black
Alaskan Native or Native American
Asian
Hispanic or Latinx
Native Hawaiian or Pacific Islander
White	2	3
Two or More Races or Ethnicities		1
LGBTQ+	1
Did Not Disclose Demographic Background	1

•

information regarding the business advisability of a given action brought for the Office Holder’s approval or performed by the Office Holder by virtue of his or her position; and

•

all other information of importance pertaining to the aforesaid actions.

•

refrain from any act involving a conflict of interest between the fulfillment of his or her position in the company and the fulfillment of any other position or his or her personal affairs;

•

refrain from any act that is competitive with the business of the company;

•

refrain from exploiting any business opportunity of the company with the aim of obtaining a personal gain for himself or herself or for others; and

•

disclose to the company all relevant information and provide it with all documents relating to the company’s affairs which the Office Holder obtained due to his or her position in the company.

	December 31, 2023	December 31, 2022	December 31, 2021
Research & Development	46	46	51
Administration, Accounting and Operations	21	21	21
Marketing and Business Development	1	2	1
Total	68	69	73

Beneficial Owner		Amount Owned				Percent of Class
Anat Cohen-Dayag(1)			1,026,122				1.1	%
All directors and executive officers as a group (13 persons)(2)			3,143,964				3.4	%

(1)

Includes (i) 56,122 shares held by Dr. Cohen-Dayag, and (ii) 970,000 shares subject to options that are exercisable within 60 days after February 20, 2024, with a weighted average exercise price of $6.47 per share, and which expire between March 2024 and March 2032.

(2)

Includes (i) a total of 76,259 ordinary shares held by directors and executive officers, and (ii) a total of 3,067,705 shares subject to options that are beneficially owned by directors and executive officers that are exercisable within 60 days after February 20, 2024, with a weighted average exercise price of $5.48 per share and which expire between February 2024 and November 2032.

Reporting Beneficial Owner		Number of Ordinary Shares Beneficially Owned				Percent of Ordinary Shares Beneficially Owned(1)
Bristol-Myers Squibb Company(2)			4,757,058				5.3	%

(1)

Based upon 89,530,193 ordinary shares issued and outstanding as of February 20, 2024.

(2)

Based upon information provided by the shareholder in its Form 13G filed with the SEC on November 19, 2021. With respect to the ordinary shares reported in its Schedule 13G, Bristol-Myers Squibb Company, indicated as having (i) sole voting power and dispositive power with respect to 4,757,058 ordinary shares, and (ii) no shared voting power nor shared dispositive power with respect to ordinary shares. Furthermore, in such filing BMS indicated aggregate beneficial ownership of 4,757,058 ordinary shares. The address of the principal business office of BMS is 430 East 29th Street, New York, NY 10016.

•

at least 75% of its gross income is passive income, or

•

at least 50% of the value (determined on the basis of a quarterly weighted average) of its total assets for the taxable year is attributable to assets that produce or are held for the production of passive income.

		2023				2022
Audit Fees		$	163,000			$	163,000
Audit Related Fees		$	65,000			$	10,000
Tax Fees		$	4,500			$	4,500
All Other Fees		$	2,500			$	2,500
Total		$	235,000			$	180,000

Exhibit Number	Description
1.1	Amended and Restated Articles of Association of Compugen, as amended (incorporated by reference to Exhibit B to Exhibit 99.1 to Compugen’s report on Form 6-K filed with the SEC on August 7, 2023 (File No. 000-30902)).
1.2	Memorandum of Association of Compugen, as amended (incorporated by reference to Annex A2 of Exhibit 99.4 to Compugen’s report on Form 6-K filed with the SEC on August 5, 2019 (File No. 000-30902)).
2.1*	Description of Securities.
4.1	Compugen Ltd. 2021 Employee Share Purchase Plan (incorporated by reference to Exhibit 10.1 to Compugen’s Registration Statement on Form S-8 filed with the SEC on December 12, 2020 (File No. 333-251263)).
4.2	Compugen Ltd. 2010 Share Incentive Plan, as amended (incorporated by reference to Exhibit 4.1 to Compugen’s Registration Statement on Form S-8, filed with the SEC on July 30, 2020 (File No.333-240182)).
4.3	Amended and Restated Form of Indemnification Undertaking and Exemption and Release between Compugen Ltd. and its directors and office holders (incorporated by reference to Exhibit 4.8 to Compugen’s Annual Report on Form 20-F/A for the year ended December 31, 2021, filed with the SEC on February 28, 2022 (File No. 000-30902)).
4.4	Office Lease Agreement (“Holon Lease”), dated March 2015, by and between Kanit Hashalom Investments Ltd. and Compugen Ltd. (incorporated by reference to Exhibit 99.2 to Compugen’s Form 6-K filed with the SEC on May 5, 2015 (File No. 000-30902)).
4.5	Amendment to Holon Lease made and entered into on November 26, 2015, by and between Kanit Hashalom Investments Ltd. and Compugen Ltd. (incorporated by reference to Exhibit 4.10 to Compugen’s Annual Report on Form 20-F for the year ended December 31, 2015, filed with the SEC on March 7, 2016 (File No. 000-30902)).
4.6	Addendum to Holon Lease made and entered into on October 14, 2020 by and between Kanit Hashalom Investments Ltd. and Compugen Ltd. (incorporated by reference to Exhibit 4.11 to Compugen’s Annual Report on Form 20-F for the year ended December 31, 2020, filed with the SEC on February 25, 2021 (File No. 000-30902))
4.7@	License Agreement, between the Company and MedImmune Limited (“MedImmune”), entered into as of March 30, 2018 (incorporated by reference to Exhibit 10.1 to Compugen’s Form 6-K, filed with the SEC on May 9, 2018 (File No. 000-30902)).
4.8@	Amendment No. 1 to the License Agreement, between the Company and MedImmune, dated May 9, 2018 (incorporated by reference to Exhibit 10.1 to Compugen’s Form 6-K, filed with the SEC on August 1, 2018 (File No. 000-30902)).
4.9	Amendment No. 2 to the License Agreement, between the Company and MedImmune, dated September 16, 2020 (incorporated by reference to Exhibit 4.14 to Compugen’s Annual Report on Form 20-F for the year ended December 31, 2020, filed with the SEC on February 25, 2021 (File No. 000-30902)).

4.10#	Amendment No. 3 to the License Agreement, between the Company and MedImmune, dated August 4, 2021 (incorporated by reference to Exhibit 4.15 to Compugen’s Annual Report on Form 20-F/A for the year ended December 31, 2021, filed with the SEC on February 28, 2022 (File No. 000-30902)).
4.11*#	License Agreement, between Compugen Ltd. and Gilead Sciences, Inc., dated December 18, 2023.
8.1*	Subsidiaries.
12.1*	Certification by Principal Executive Officer pursuant to Rule 13a-14(a)/Rule 15d-14(a) under the Exchange Act and Section 302 of the Sarbanes-Oxley Act of 2002.
12.2*	Certification by Principal Financial Officer pursuant to Rule 13a-14(a)/Rule 15d-14(a) under the Exchange Act and Section 302 of the Sarbanes-Oxley Act of 2002.
13.1*	Certification by Principal Executive Officer and Principal Financial Officer pursuant to Rule 13a-14(b)/Rule 15d-14(b) under the Exchange Act and 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.
15.1*	Consent of Kost Forer Gabbay & Kasierer, a member firm of Ernst & Young Global.
97.1*	Compugen’s Policy for Recovery of Erroneously Awarded Compensation.
101*	The following financial information from Compugen Ltd.’s Annual Report on Form 20-F for the year ended December 31, 2023, formatted in Inline XBRL (eXtensible Business Reporting Language): (i) Consolidated Statements of Operations for the years ended December 31, 2023, 2022 and 2021; (ii) Consolidated Balance Sheets as of December 31, 2023 and 2022; (iii) Consolidated Statements of Changes in Shareholders’ Equity for the years ended December 31, 2023, 2022 and 2021; (iv) Consolidated Statements of Cash Flows for the years ended December 31, 2023, 2022 and 2021; and (v) Notes to Consolidated Financial Statements.

101.INS	Inline XBRL Instance Document
101.SCH	Inline XBRL Taxonomy Extension Schema Document
101.PRE	Inline XBRL Taxonomy Extension Presentation Linkbase Document
101.CAL	Inline XBRL Taxonomy Calculation Linkbase Document
101.LAB	Inline XBRL Taxonomy Label Linkbase Document
101.DEF	Inline XBRL Taxonomy Extension Definition Linkbase Document
104	Cover Page Interactive Data File (Formatted as Inline XBRL and contained in Exhibit 101).

*	Filed herewith.

@	Confidential treatment has been granted by the Securities and Exchange Commission as to certain portions.

#	Portions of this exhibit (indicated by asterisks therein) have been omitted as these portions are both not material and private or confidential.