CD96

- Clinically meaningful objective response rate (ORR) of 63.3-76.7% observed with belrestotug + dostarlimab combinations, with confirmed ORR (cORR) at ~60% for every dose- >30% cORR difference between belrestotug + dostarlimab vs dostarlimab monotherapy- Belrestotug + dostarlimab safety profile broadly consistent with known safety profile of checkpoint inhibitor combinations- GALAXIES Lung-301, global Phase 3 registration study, enrolling in same indication and setting- iTeos to host a conference call on Monday, September 16, 2024 at 8:00am ET WATERTOWN, Mass. and GOSSELIES, Belgium, Sept. 14, 2024 (GLOBE NEWSWIRE) -- iTeos Therapeutics, Inc. (Nasdaq: ITOS) (“iTeos”), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients, today announced follow-up interim data from GALAXIES Lung-201, the Phase 2 platform study sponsored by iTeos’ development partner GSK, assessing the belrestotug + dostarlimab doublet in previously untreated, unresectable, locally advanced or metastatic PD-L1 high non-small cell lung cancer (NSCLC). “We are encouraged by this interim cut of GALAXIES Lung-201 data in which a clinically meaningful, investigator-assessed Objective Response Rate was observed with belrestotug in combination with dostarlimab in first-line, PD-L1 high non-small cell lung cancer patients. Further, with roughly 60 percent confirmed ORR at three distinct doses and a meaningful difference of 30 percent compared to dostarlimab alone, we believe this underscores the potential differentiation of our TIGIT:PD-1 doublet,” said Michel Detheux, Ph.D., president and chief executive officer of iTeos. “The improvement in depth of response in tumor measurement in patients treated with the doublet compared to those treated with PD-1 alone holds promising therapeutic potential for a patient population with limited options. We believe these encouraging data further support the recent initiation of GALAXIES Lung-301, the registrational Phase 3 trial assessing the TIGIT:PD-1 doublet in the same indication and setting. Based on these results, we are committed to leveraging our science to impact the lives of people living with cancer and are excited to see longer-term follow-up data in 2025.” “While checkpoint inhibitor therapies have played a significant role in how we treat non-small cell lung cancer, the medical community continues to look for new patient-centered treatment options to meaningfully improve this life-threatening condition,” said Brian Henick, M.D., interim director of experimental therapeutics and director of translational research in upper-aerodigestive malignancies in medical oncology of Columbia University Irving Medical Center. “The follow-up interim analysis from the GALAXIES Lung-201 study represent promising progress and the deep responses observed in the belrestotug + dostarlimab doublet provide a strong, consistent signal. We eagerly anticipate gaining further insights from this trial over the next year as the dataset matures.” Highlights of Interim GALAXIES Lung-201 DataAs of the June 7, 2024 data cutoff, the late-breaking interim data presented at the ESMO Congress were based on 124 patients eligible for safety and efficacy evaluation (modified intention-to-treat ≥5.6 months follow-up). Patients received dostarlimab or belrestotug + dostarlimab at the following dose levels: dostarlimab 500mg, belrestotug 100mg + dostarlimab 500mg (Dose A), belrestotug 400mg + dostarlimab 500mg (Dose B), and belrestotug 1000mg + dostarlimab 500mg (Dose C). Clinically meaningful improvement in the primary endpoint of ORR was observed consistently across each belrestotug + dostarlimab cohort (63.3% Dose A, 65.6% Dose B and 76.7% Dose C compared to 37.5% with dostarlimab alone). cORR, defined as complete or partial response confirmed by repeat imaging ≥4 weeks after response criteria first met, was roughly 60.0% for each dose compared to 28.1% cORR for dostarlimab alone.Of the patients with evaluable paired ctDNA samples (baseline and week 7), median ctDNA reduction was 65% for dostarlimab monotherapy compared to 55% for Dose A, 94% for Dose B, and 97% for Dose C.Belrestotug + dostarlimab led to an increase in immune-related adverse events compared to dostarlimab monotherapy, which were generally manageable. The safety profile of belrestotug in combination with dostarlimab has been broadly consistent with the known safety profile of combination therapy with checkpoint inhibitors. The most frequent treatment-related adverse events (≥15%) were skin and subcutaneous tissue disorders (50%) and endocrine disorders (26%), both commonly observed with immunotherapies. Response measure in mITTDostarlimab(N=32)Dose A:Dostarlimab +belrestotug100 mg(N=30)Dose B:Dostarlimab +belrestotug400 mg(N=32)Dose C:Dostarimab +belrestotug1000 mg(N=30)Median follow-up, months (range)7.0 (0.2–16.6)8.5 (0.3–14.3)8.5 (0.4–16.2)6.7 (2.4–9.7)ORR,1,2%n (95% CI)37.5%n=12 (21.1–56.3)63.3%n=19 (43.9–80.1)65.6%n=21 (46.8–81.4)76.7%n=23 (57.7–90.1)Complete response, n (%)0000Partial response, n (%)12 (37.5%)19 (63.3%)21 (65.6%)23 (76.7%)Stable disease, n (%)14 (43.8%)5 (16.7%)4 (12.5%)5 (16.7%)Progressive disease, n (%)2 (6.3%)4 (13.3%)3 (9.4%)2 (6.7%)Not evaluable/no assessment,3 n (%)4 (12.5%)2 (6.7%)4 (12.5%)0Confirmed ORR,2 %n (95% CI)28.1% n=9 (13.7–46.7)60.0% n=18 (40.6–77.3)59.4% n=19 (40.6–76.3)63.3%n=19 (43.9–80.1) 1. unconfirmed ORR; 2. PD-L1 high (TPS ≥50%) was determined locally or centrally by DAKO 22C3 or VENTANA SP263 assay; 3. patients who only had "not evaluable" post baseline assessments, those who had a best response of "not evaluable" per RECIST 1.1 criteria, or those where no post-baseline tumor assessment was performed; CI, confidence interval Conference Call DetailsThe follow-up interim data from GALAXIES Lung-201 will be discussed during a conference call and webcast presentation on Monday, September 16th, 2024 at 8:00AM ET. To register for the webcast presentation, please visit the Events section on the Investors page of the iTeos website at investors.iteostherapeutics.com. A webcast replay may be accessed on the Investors section of the iTeos website. Phase 2 GALAXIES Lung-201 Trial DesignThe Phase 2 GALAXIES Lung-201 study is a randomized, open-label, global platform study evaluating the efficacy, safety, pharmacokinetics, and pharmacodynamics of novel immunotherapy combinations compared with immunotherapy monotherapy in participants with PD-L1 high (TPS ≥50%), previously untreated, unresectable, locally advanced or metastatic NSCLC.​ Arms and interventions in this study include: pembrolizumab (anti-PD-1) monotherapy, dostarlimab (anti-PD-1) monotherapy, belrestotug (anti-TIGIT) + dostarlimab doublet combination, and belrestotug + dostarlimab + nelistotug (anti-CD96) triplet combination. The primary endpoint of the study is investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Secondary endpoints include safety and additional efficacy measures such as progression free survival, overall survival, and duration of response. 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, including the TIGIT/CD226 axis and the adenosine pathway. 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 innate and adaptive 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. Internet Posting of InformationiTeos routinely posts information that may be important to investors in the 'Investors' section of its website at www.iteostherapeutics.com. The Company encourages investors and potential investors to consult our website regularly for important information about iTeos. Forward-Looking StatementsThis 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 belrestotug and the potential differentiation of belrestotug + dostarlimab; belrestotug’s market opportunity; and our plans and expected milestones, including having longer-term follow-up data from GALAXIES Lung-201 in 2025. 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: 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 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 June 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. 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

BMS’ decision to drop the asset is part of a broader rethink. Bristol Myers Squibb is axing another big bet from the Caforio era, terminating a deal for Agenus’ TIGIT bispecific antibody three years after paying $200 million to buy into the program.Agenus granted BMS an exclusive license to AGEN1777, which binds TIGIT and CD96 on T cells, in 2021 in return for $200 million upfront. BMS paid $20 million when the first patient received AGEN1777 in phase 1 later that year and handed Agenus a $25 million milestone in relation to the start of a phase 2 study in January 2024. Now, BMS has decided AGEN1777 is no longer part of its plans.The Big Pharma broke the news to Agenus last week. According to Agenus, BMS is returning the rights to the bispecific antibody “as part of a broader strategic realignment of their development pipeline which involves other licensed products.”Agenus plans to explore further development of the candidate, including by considering combinations with its other assets and may look for a new partner for the program. Investors sent Agenus’ stock down around 4% to below $5.40 in premarket trading. The positive spin on the news is that BMS effectively paid Agenus $245 million for the chance to advance the bispecific, which was yet to enter the clinic at the time of the deal, into phase 2. Agenus emerges with an asset that, in its words, has shown “indications of clinical activity” in humans.The more bearish take is that those indications of activity failed to persuade BMS to pump more money into the program. BMS had the best view of the candidate and its unwillingness to fund further work raises questions about whether Agenus can find a new partner—and whether it should put much of its own cash into the program.Agenus created the candidate to overcome the limitations of anti-TIGIT antibodies. TIGIT and CD96, which share a ligand that is overexpressed on cancer cells, are often found together on tumor-infiltrating lymphocytes. By engaging both targets, AGEN1777 is designed to overcome TIGIT resistance. Agenus’ preclinical data supports (PDF) the idea but it is unclear whether the effects will translate into humans.BMS’ decision to drop the asset is part of a broader rethink that the company has undertaken since Chris Boerner, Ph.D., replaced Giovanni Caforio, M.D., as CEO late last year. In recent weeks, BMS has dropped a BCMA bispecific T-cell engager months after filing to run a phase 3 trial and axed an antibody-drug conjugate it picked up from Eisai. BMS paid $450 million to co-develop the Eisai asset when Caforio was CEO.

Bristol Myers Squibb is walking away from a license agreement it signed with Agenus for the development and commercialisation of the latter's anti-TIGIT bispecific antibody programme.According to a US securities filing late last week, Agenus said BMS notified it that "as part of a broader strategic realignment of their development pipeline which involves other licensed products, it is returning AGEN1777 (also known as BMS-986442) back to [us] and voluntarily terminating" the license agreement, effective January 26 of next year.The termination comes just over three years after the initial agreement was signed in 2021. At the time, BMS had committed to a deal worth up to $1.6 billion, including a $200-million upfront payment and the rest in potential milestones. The agreement also included tiered double-digit royalties on net product sales.Since the deal's inception, BMS has made milestone payments totaling $45 million, including $20 million in late 2021 for dosing the first patient in a Phase I study, and $25 million earlier this year when the drug advanced to Phase II.Agenus remains optimistic about AGEN1777's potential, stating in the filing, "When AGEN1777 was initially licensed to BMS, it had no clinical data. Since then, significant safety data has been generated in early clinical trials with indications of clinical activity. We intend to explore further development and/or relicensing of this molecule, including potential combinations with our portfolio of synergistic immuno-oncology agents."Earlier this year, at the American Association for Cancer Research (AACR) annual meeting, Agenus presented preclinical data on AGEN1777 showing superior immune activation both as a monotherapy and in combination with PD-(L)1 blockade compared to conventional TIGIT antibodies, a class marred by a number of high-profile failures. For more, see – Spotlight On: Roche's latest TIGIT implosion - three key takeaways.Agenus says AGEN1777's differentiation lies in its ability to target two critical immune checkpoint receptors in the same pathway, TIGIT and CD96, leveraging Agenus' proprietary Fc-engineering platform.The termination agreement includes provisions that should facilitate Agenus' continued development of AGEN1777. BMS has granted the company "an exclusive, royalty-free and fully paid-up, worldwide, and sublicensable license to BMS' know-how and patent rights that arose from activities performed under the…license agreement." BMS will also transfer all regulatory registrations, applications, authorisations and approvals related to AGEN1777 to Agenus.