TIGIT

AstraZeneca has recently initiated a Phase III clinical trial for Rilvegostomig, a PD-1/TIGIT dual antibody, in a head-to-head comparison against Pembrolizumab (known as K drug) for treating non-squamous non-small cell lung cancer (NSCLC). This trial is particularly noteworthy as it targets a promising yet troubled TIGIT pathway, which has yet to yield a successful drug. A Bold Move by AstraZeneca As the K drug continues to dominate the oncology market, AstraZeneca's decision to conduct this head-to-head trial signals a significant challenge to the status quo. The PD-1/TIGIT dual antibody aims to leverage the immune checkpoint molecules PD-1 and TIGIT, with the latter being widely expressed across various solid tumors and dubbed the "next PD-1." However, the journey for TIGIT-targeted therapies has been fraught with setbacks, leading to major pharmaceutical companies withdrawing their involvement. Rilvegostomig is currently the fastest-developing drug in this area, with ongoing Phase III trials for cholangiocarcinoma and NSCLC, and further studies in gastric cancer and head and neck squamous cell carcinoma. The Quest to Break the "Unachievable" Spell The significance of this trial extends beyond TIGIT's potential; it could reshape the future of PD-1/TIGIT dual antibody development. AstraZeneca's commitment to proving TIGIT's viability is evident as they aim to replicate the success of Evorisumab, which recently outperformed K drug in clinical trials, triggering a surge in business development (BD) deals in the PD-(L)1/VEGF dual antibody space. Despite the challenges facing TIGIT-targeted therapies, several companies are still pursuing this avenue. AstraZeneca's efforts, alongside those of Roche and others, highlight a shared determination to explore this promising target. Industry Movements and Future Prospects The recent struggles faced by TIGIT-targeted therapies, including failures from major players like Merck and Roche, have raised questions about the target's viability. However, AstraZeneca and others remain optimistic, with multiple Phase III trials underway that could potentially shift the narrative around TIGIT. In conclusion, while the path for TIGIT has been rocky, the ongoing commitment from key players like AstraZeneca offers hope for breakthroughs in this promising area of cancer therapy. The industry eagerly awaits results from the Rilvegostomig trial, which could transform perceptions of TIGIT and related therapies.

- Multiple TIGIT clinical data readouts anticipated throughout 2025, including >400 patients from two Phase 2 trials and one Phase 1/2 assessing belrestotug + dostarlimab in 1L NSCLC and 1L HNSCC - EOS-984 Phase 1 monotherapy and PD-1 combination data anticipated in 2H25 - EOS-215, a potential best-in-class anti-TREM2 monoclonal antibody, IND submission anticipated in 1Q25 - Cash balance and investment balance of $683.9 million as of September 30, 2024 expected to provide runway through 2027 WATERTOWN, Mass. and GOSSELIES, Belgium, Jan. 10, 2025 (GLOBE NEWSWIRE) -- iTeos Therapeutics, Inc. (Nasdaq: ITOS), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients, today outlined business updates and strategic priorities for 2025. “As iTeos enters 2025, we are well-positioned to emerge as a leading oncology company by advancing therapies with first- or best-in-class potential that target resistance mechanisms within the tumor microenvironment. Starting in the second quarter, this year will feature robust TIGIT datasets in both non-small cell lung cancer and head and neck cancer, aiming to highlight the differentiation with our unique TIGIT:PD-1 doublet, belrestotug + dostarlimab. We are also excited about EOS-984 and EOS-215, our early-stage programs which demonstrate our track record of designing and developing innovative and differentiated therapies,” said Michel Detheux, Ph.D., president and chief executive officer of iTeos. “We look forward to a pivotal year for our company, with multiple data readouts and continued progress across our oncology portfolio.” Program Highlights Belrestotug (EOS-448/GSKFF28849A): IgG1 anti-TIGIT monoclonal antibody in development for the first-line treatment of locally advanced or metastatic PD-L1-high non-small cell lung cancer (NSCLC) and for the first-line treatment of PD-L1 positive recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) in collaboration with GSK. GALAXIES Lung-301 Enrollment ongoing globally in randomized, double-blind Phase 3 registrational study assessing belrestotug + dostarlimab versus placebo + pembrolizumab in patients with first-line advanced, unresectable, or metastatic PD-L1 high NSCLCFood and Drug Administration (FDA) and The National Medical Products Administration (NMPA) granted clearance to advance belrestotug 400mg + dostarlimab as the recommended Phase 3 dose, allowing for the activation of clinical sites in the U.S. and China, respectively. GALAXIES Lung-201 Topline interim data from Phase 2 platform study assessing belrestotug + dostarlimab doublet and a triplet with GSK’s investigational anti-CD96 antibody, nelistotug, in first-line advanced / metastatic PD-L1 high NSCLC anticipated in 2Q25 to include safety, ORR, and ctDNA data from >240 patients, with pembrolizumab monotherapy ORR for 30 patients and PFS data from initial 124 patients treated. Data are expected to be submitted for presentation at a scientific congress in 2H 2025. GALAXIES H&N-202 Interim data from Phase 2 platform study assessing belrestotug + dostarlimab doublet and triplet with nelistotug in first-line patients with PD-L1 positive recurrent/metastatic HNSCC anticipated in 2025 to include safety and ORR from >150 patients. TIG-006 HNSCC Topline data from the TIG-006 study in cohorts 2C & 2D assessing belrestotug + dostarlimab doublet in first-line PD-L1 positive advanced / metastatic HNSCC anticipated in 2025 to include safety, ORR, and PFS from a total of 42 patients. EOS-984: Potential first-in-class small molecule in oncology inhibiting ENT1, a dominant transporter of adenosine involved in T cell metabolism, expansion, effector function, and survival. APT-008 Topline data assessing EOS-984 as a monotherapy and in combination with pembrolizumab in patients with advanced solid tumors anticipated in 2H25. EOS-215: Potential best-in-class anti-TREM2 with a novel mechanism of action blocking monoclonal antibody targeting tumor-associated macrophages to reprogram the tumor microenvironment. TRM-010 Investigative New Drug (IND) application for EOS-215 anticipated in 1Q25. Financial Updates Cash Position: The Company’s cash and cash equivalent position was $683.9 million as of September 30, 2024, inclusive of a $35.0 million milestone received relating to the dosing of the first patient in the GALAXIES Lung-301 clinical trial. The Company expects its cash balance to provide runway through 2027, which includes the potential initiation of multiple Phase 3 registrational trials assessing belrestotug + dostarlimab doublet. About iTeos Therapeutics, Inc.iTeos Therapeutics is a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients. iTeos Therapeutics leverages its deep understanding of tumor immunology and immunosuppressive pathways to design novel product candidates with the potential to restore the immune response against cancer. The Company’s innovative pipeline includes three clinical-stage programs targeting novel, validated immunosuppressive pathways designed with optimized pharmacologic properties for improved clinical outcomes. iTeos Therapeutics is headquartered in Watertown, MA with a research center in Gosselies, Belgium. About Belrestotug (EOS-448/ GSK4428859A)Belrestotug is an Fc active human immunoglobulin G1, or IgG1, monoclonal antibody (mAb) targeting T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT), an important inhibitory receptor which contributes to the suppression of adaptive and innate immune responses against cancer. As an optimized high-affinity, potent anti-TIGIT mAb, belrestotug is designed to enhance the antitumor response through a multifaceted immune modulatory mechanism by engaging with TIGIT and FcγR, a key regulator of immune responses which induces cytokine release and antibody dependent cellular cytotoxicity (ADCC). The therapeutic candidate is progressing in multiple indications in collaboration with GSK. About EOS-984EOS-984 is a potential first-in-class small molecule targeting equilibrative nucleoside transporter 1 (ENT1) designed to inhibit the immunosuppressive activity of adenosine and restore immune cell proliferation. The therapeutic candidate has the potential to fully reverse the profound immunosuppressive action of adenosine on T and B cells and is in Phase 1 development. About EOS-215EOS-215 is a potential best-in-class monoclonal antibody which blocks ligand binding to triggering receptor expressed on myeloid cells 2 (TREM2), switching off multiple tumor growth and survival promoting activities of tumor resident macrophages and effectively “reprogramming” the macrophages to allow for T cell activation. The therapeutic candidate has shown activity in both in vitro and in vivo highly immune resistant models and is currently in IND-enabling studies. Forward-Looking Statements This press release contains forward-looking statements. Any statements that are not solely statements of historical fact are forward-looking statements. Words such as “believe,” “anticipate,” “plan,” “expect,” “will,” “may,” “intend,” “prepare,” “look,” “potential,” “possible” and similar expressions are intended to identify forward-looking statements. These forward-looking statements include statements relating to the potential benefits of our product candidates; iTeos being well-positioned to emerge as a leading oncology company by advancing therapies with first- or best-in-class potential that target resistance mechanisms within the tumor microenvironment; our plans and expected milestones, including having topline interim data from GALAXIES Lung-201 in 2Q25 that includes safety, ORR, and ctDNA data from > 240 patients, with pembrolizumab monotherapy ORR for 30 patients and PFS data from initial 124 patients treated, our expectation to submit data from GALAXIES Lung-201 for presentation at a scientific congress in 2H 2025, having interim data from GALAXIES H&N-202 in 2Q25 that include safety and ORR from a total of >150 patients, our expectation to submit the GALAXIES H&N-202 data for presentation at a scientific congress in 2H25, having topline data from the first portion of TIG-006 study in cohorts 2C & 2D in 2HQ25 that include safety, ORR, and PFS from a total of 40 patients, having topline data from EOS-984 in 2H25, our expectation to submit an IND for EOS-215 in 1Q25; and our expectation that 2025 will be a pivotal year, with multiple data readouts and continued progress across our oncology portfolio. These forward-looking statements involve risks and uncertainties, many of which are beyond iTeos’ control. Actual results could materially differ from those stated or implied by these forward-looking statements as a result of such risks and uncertainties. Known risk factors include the following: the expected benefits and opportunities related to the agreement between iTeos and GSK may not be realized or may take longer to realize due to a variety of reasons, including any inability of the parties to perform their commitments and obligations under the agreement, challenges and uncertainties inherent in product research and development and manufacturing limitations; success in preclinical testing and early clinical trials does not ensure that later clinical trials will be successful, and early results from a clinical trial do not necessarily predict final results; interim and early data may change as more patient data become available and are subject to audit and verification procedures; the data for our product candidates may not be sufficient for obtaining regulatory approval to move into later stage trials or to commercialize products; iTeos may encounter unanticipated costs or may expend cash more rapidly or more slowly than currently anticipated due to challenges and uncertainties inherent in product research and development and biologics manufacturing; iTeos may not be able to execute on its business plans, including meeting its expected or planned regulatory milestones and timelines, research and clinical development plans, and bringing its product candidates to market, for various reasons, some of which may be outside of iTeos’ control, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved for in a timely manner, negative developments in the field of immuno-oncology, such as adverse events or disappointing results, including in connection with competitor therapies, and regulatory, court or agency decisions such as decisions by the United States Patent and Trademark Office with respect to patents that cover our product candidates; and those risks identified under the heading “Risk Factors” in iTeos’ Annual Report on Form 10-Q for the period ended September 30, 2024 filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by the Company which you are encouraged to review. Statements regarding the Company’s cash runway do not indicate when or if the Company may access the capital markets. Any of the foregoing risks could materially and adversely affect iTeos’ business, results of operations and the trading price of iTeos’ common stock. We caution investors not to place undue reliance on the forward-looking statements contained in this press release. iTeos does not undertake any obligation to publicly update its forward-looking statements other than as required by law. For further information, please contact: Investor Contact:Carl MauchiTeos Therapeutics, Inc.carl.mauch@iteostherapeutics.com Media Contact:media@iteostherapeutics.com

New approach to harness cytokine biology to treat cancer patients advances to the clinic First patient dosed with potential first-in-class anti-IL-18 binding protein antibody, COM503, licensed to Gilead Sciences, Inc. Phase 1 dose escalation and dose expansion trial to assess the safety and tolerability of COM503 as monotherapy and in combination for patients with advanced solid tumors Compugen responsible for running the Phase 1 trial HOLON, Israel, Jan. 8, 2025 /PRNewswire/ -- Compugen Ltd. (Nasdaq: CGEN) (TASE: CGEN), a clinical-stage cancer immunotherapy company and a pioneer in computational target discovery, today announced that the first patient was dosed in a Phase 1 clinical trial with COM503, a potential first-in-class antibody against IL-18 binding protein licensed by Compugen to Gilead. Compugen is responsible for running the Phase 1 trial. This Phase 1 multi-center dose escalation and dose expansion trial will evaluate the safety, tolerability, and pharmacokinetics of COM503 as monotherapy and in combination with Gilead's anti-PD1, zimberelimab in patients with advanced solid tumors. The trial was initiated in the fourth quarter of 2024 as planned. "We are delighted to advance COM503, our antibody that provides a new and potentially differentiated approach to harness cytokine biology for cancer therapeutics, quickly into the clinic," said Anat Cohen-Dayag, Ph.D., President, and CEO of Compugen. "Compugen's discovery engine Unigen™, identified that the tumors of patients with cancer express high levels of IL-18. However, the anti-tumor activity of IL-18 is blocked by an endogenous IL-18-binding protein, rendering it ineffective in fighting cancer. By blocking this endogenous IL-18 binding protein, COM503 presents a unique opportunity to release naturally occurring IL-18 locally within the tumors, where it can potentiate anti-tumor immune responses, thereby potentially overcoming the limitations of systemically administered cytokines." Manish Sharma, M.D., Co-Director of Clinical Research, at the START Center for Cancer Research-Midwest (START Midwest) in Grand Rapids, Michigan, added, "Having COM503 as an additional novel investigational treatment option with a unique mechanism of action to offer our cancer patients is exciting. We, at START Midwest, were delighted to be the first to dose a patient with COM503 and look forward to swiftly enrolling additional patients in this first dose escalation part of the trial with a focus on evaluating the safety and pharmacokinetics of COM503 monotherapy." About the COM503 Phase 1 trial: The primary objectives of this trial are to assess the safety and tolerability of COM503 as a monotherapy and in combination with zimberelimab in patients with advanced solid tumors and to identify the maximum tolerated dose /maximum administered dose and/or the recommended dose of COM503 as monotherapy and in combination with zimberelimab. For more information about the Phase 1 clinical trial, visit clinicaltrials.gov, NCT06759649. About the Compugen-Gilead license agreement In December 2023, Compugen and Gilead entered into a license agreement, pursuant to which Gilead was granted exclusive rights to develop and commercialize anti-IL-18 binding protein antibodies, including the COM503 drug candidate. Compugen managed the preclinical development of COM503 and is responsible for the Phase 1 trial evaluating the safety and tolerability of COM503. Thereafter, Gilead will have sole right to develop and commercialize COM503. Gilead paid Compugen $60 million as upfront payment and $30 million as COM503 IND clearance milestone. Compugen is eligible to receive up to an additional $758 million in future development, regulatory and commercial milestone payments, with a total deal value of up to $848 million. Compugen is also eligible to receive single-digit to low double-digit tiered royalties on worldwide net sales. About Compugen Compugen is a clinical-stage therapeutic discovery and development company utilizing its broadly applicable predictive computational discovery platform (Unigen™) to identify new drug targets and biological pathways for developing cancer immunotherapies. Compugen has two proprietary product candidates in Phase 1 development: COM701, a potential first-in-class anti-PVRIG antibody and COM902, a potential best-in-class antibody targeting TIGIT for the treatment of solid tumors. Rilvegostomig, a PD-1/TIGIT bispecific antibody where the TIGIT component is derived from Compugen's clinical stage anti-TIGIT antibody, COM902, is in Phase 3 development by AstraZeneca through a license agreement for the development of bispecific and multispecific antibodies. COM503, a potential first-in-class, high affinity anti-IL-18 binding protein antibody, which is in Phase 1 development is licensed to Gilead. In addition, the Company's therapeutic pipeline of early-stage immuno-oncology programs consists of programs aiming to address various mechanisms of immune resistance. Compugen is headquartered in Israel, with offices in San Francisco, CA. Compugen's shares are listed on Nasdaq and the Tel Aviv Stock Exchange under the ticker symbol CGEN. Compugen Forward-Looking Statements This press release contains "forward-looking statements" within the meaning of the Securities Act of 1933 and the Securities Exchange Act of 1934, as amended, and the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements are based on the current beliefs, expectations, and assumptions of Compugen. Forward-looking statements can be identified using terminology such as "will," "may," "expects," "anticipates," "believes," "potential," "plan," "goal," "estimate," "likely," "should," "confident," and "intends," and similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements include, but are not limited to, statement regarding our belief that by blocking IL-18 binding protein, COM503 presents a unique opportunity to release naturally occurring IL-18 locally within the tumors, where it can potentiate anti-tumor immune responses, thereby potentially overcoming the limitations of systemically administered cytokines. 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. Among these risks: the clinical trials of any product candidates that Compugen, or any current or future collaborators, may develop may fail to satisfactorily demonstrate safety and efficacy to the FDA, and Compugen, or any collaborators, may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of these product candidates; Compugen's business model is substantially dependent on entering into collaboration agreements with third parties and Compugen may not be successful in generating adequate revenues or commercializing aspects of its business model; Compugen's approach to the discovery of therapeutic products is based on its proprietary computational target discovery infrastructure, which is unproven clinically; general market, political and economic conditions in the countries in which Compugen operates, including Israel; the effect of the evolving nature of the recent war in Gaza; and Compugen does not know whether it will be able to discover and develop additional potential product candidates or products of commercial value. These risks and other risks are more fully discussed in the "Risk Factors" section of Compugen's most recent Annual Report on Form 20-F as filed with the Securities and Exchange Commission (SEC) as well as other documents that may be subsequently filed by Compugen from time to time with the SEC. In addition, any forward-looking statements represent Compugen's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. Compugen does not assume any obligation to update any forward-looking statements unless required by law. Company contact: Yvonne Naughton, Ph.D. VP, Head of Investor Relations, and Corporate Communications Email: ir@cgen.com Tel: +1 (628) 241-0071 View original content:https://www.prnewswire.com/news-releases/compugen-announces-first-patient-dosed-in-phase-1-clinical-trial-to-evaluate-com503-as-monotherapy-and-in-combination-with-zimberelimab-in-advanced-solid-tumors-302345677.html SOURCE Compugen Ltd.