Iberdomide

- TIGIT program clinical data readouts anticipated in 2024, including two Phase 2 trials assessing belrestotug + dostarlimab in 1L NSCLC and 1L HNSCC - Adenosine portfolio clinical data readouts anticipated in second half of 2024, including inupadenant’s Phase 2 A2A-005 and EOS-984’s Phase 1 trial - EOS-984 preclinical data demonstrating novel mechanism of action in the adenosine pathway anticipated in second quarter of 2024 - Cash balance and investment balance of $644.9 million as of September 30, 2023 expected to provide runway through 2026 WATERTOWN, Mass. and GOSSELIES, Belgium, Jan. 08, 2024 (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 2024. “Over the past twelve months, the TIGIT competitive landscape has substantially evolved, further positioning iTeos and GSK as a potential leader with our high-quality TIGIT:PD-1 doublet, belrestotug + dostarlimab. We remain very encouraged by our progress ahead of a defining year for the company where we anticipate multiple data readouts across our IO portfolio throughout 2024, including three Phase 2 trials, one Phase 1 trial, and the unveiling of preclinical data and the novel mechanism of action for EOS-984,” said Michel Detheux, Ph.D., president and chief executive officer of iTeos. “We believe 2024 will be an exciting year where we anticipate furthering our ambition to bring best- and first-in-class science to patients and validate our vision of building a pipeline of highly differentiated IO therapies.” Program Highlights Belrestotug (EOS-448/GSK4428859A): IgG1 anti-TIGIT monoclonal antibody targeting first-line non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) in collaboration with GSK Preparation underway for Phase 3 registrational studies that will evaluate the belrestotug + dostarlimab doubletGALAXIES Lung-201: topline data from Phase 2 platform trial assessing belrestotug + dostarlimab doublet in first-line advanced/metastatic non-small cell lung cancer anticipated in 2024GALAXIES H&N-202: enrollment ongoing in Phase 2 platform study assessing belrestotug + dostarlimab doublet and a triplet with GSK’s investigational anti-CD96 antibody (GSK’608) in first-line patients with PD-L1 positive recurrent / metastatic HNSCCTIG-006 HNSCC: topline data from Phase 2 expansion trial assessing belrestotug + dostarlimab doublet in first-line PD-L1 positive advanced or metastatic HNSCC anticipated in 2024TIG-006 mNSCLC: enrollment ongoing in Phase 2 expansion trial assessing belrestotug, dostarlimab, and chemotherapy triplet in first-line advanced or metastatic NSCLCTIG-007: the Company has deprioritized the Phase 1/2 TIG-007 trial assessing belrestotug and in combination with Bristol Myers Squibb’s iberdomide due to the evolving treatment landscape in relapsed/refractory multiple myeloma (r/r MM)Continued advancement of Phase 1b trials exploring two novel triplets in advanced solid tumors: belrestotug + dostarlimab and GSK’s investigational anti-CD96 antibody (GSK’608), and belrestotug + dostarlimab and GSK’s investigational anti-PVRIG antibody (GSK’562) Adenosine Pathway Inupadenant (EOS-850): insurmountable small molecule antagonist targeting adenosine A2A receptor in second-line NSCLC A2A-005: topline data from the dose escalation portion of the Phase 2 trial with inupadenant and platinum-doublet chemotherapy in post-IO metastatic non-squamous NSCLC anticipated in late 2024IO-001: completed enrollment of the Phase 2 IO-001 monotherapy high biomarker trial in advanced solid tumors. The Company plans to integrate IO-001 biomarker knowledge into the development strategy of future inupadenant clinical trials. EOS-984: first-in-class small molecule targeting equilibrative nucleoside transporter 1 (ENT1), a dominant transporter of adenosine on lymphocytes involved in T cell metabolism, expansion, effector function, and survival Preclinical mechanism of action data anticipated in the second quarter of 2024Topline data from the Phase 1 dose escalation trial in advanced malignancies anticipated in the second half of 2024 Financial Updates Cash Position: The Company’s cash and cash equivalent position was $644.9 million as of September 30, 2023. The Company continues to expect its cash balance to provide runway through 2026, which includes the initiation of multiple Phase 3 registrational trials assessing the 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 immuno-oncology 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 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 Inupadenant (EOS-850) Inupadenant is a next-generation small molecule antagonist targeting adenosine A2A receptor (A2AR), the primary receptor on immune cells whose activation by adenosine suppresses innate and adaptive immune cell responses leading to inhibition of antitumor responses. Optimized for potency, high selectivity of A2AR, and activity at high adenosine concentrations in solid tumors, inupadenant is uniquely designed with its insurmountable profile to inhibit the ATP-adenosine pathway and has the potential for enhanced antitumor activity as compared to other A2AR antagonists in clinical development. The therapeutic candidate is in Phase 2 development. About EOS-984 EOS-984 is a 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. Internet Posting of Information iTeos Therapeutics 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 Therapeutics. 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 belrestotug, inupadenant, and EOS-984; iTeos and GSK being a potential leader with our high-quality TIGIT:PD-1 doublet, belrestotug + dostarlimab; our anticipation to further our ambition to bring best- and first-in-class science to patients and validate our vision of building a pipeline of highly differentiated IO therapies; our expectation to initiate Phase 3 registrational studies that will evaluate the belrestotug + dostarlimab doublet; our plans and expected milestones, including having topline data from GALAXIES Lung-201 and TIG-006 HNSCC in 2024, having topline data from the dose escalation portion of A2A-005 in late 2024, presenting preclinical mechanism of action data from EOS-984 in the second quarter of 2024, and having topline data from the Phase 1 dose escalation trial in advanced malignancies in the second half of 2024; our plan to integrate IO-001 biomarker knowledge into the development strategy of future inupadenant clinical trials; and our expectation that our cash balance will provide runway through 2026, which includes the initiation of multiple Phase 3 registrational trials assessing the belrestotug + dostarlimab doublet. 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; 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; 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; 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’ Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 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 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 considerable 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

Updated results highlight the range of differentiated research platforms across BMS’ multiple myeloma pipeline, including cell therapy and protein degradation Data will be presented for first-in-class GPRC5D CAR T BMS-986393, novel CELMoD™ agent mezigdomide, and unique 2+1 bispecific T cell engager alnuctamab PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced updated results from three key programs within its broad multiple myeloma research pipeline, highlighting its diverse targets and molecular approaches to address unique patient needs within the disease. These data were presented at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, California. “The data from our multiple myeloma pipeline at ASH this year continue to demonstrate the progress we are making to deliver the best possible outcomes for patients, leveraging an array of targets matched to the right therapeutic modality based on insights from causal human biology,” said Michael Pourdehnad, M.D., senior vice president, Head of Early Clinical Development, Hematology Oncology and Cell Therapy Development, Bristol Myers Squibb. “These programs also represent the strength of our promising pipeline with a growing wave of registrational assets. As we continue to advance these programs, these data provide further evidence of the transformational potential of our cell therapy, protein degradation, and cell engager platforms.” Results being presented at ASH provide updated evidence for programs including chimeric antigen receptor (CAR) T cell therapies, novel CELMoD™ agents from our leading protein degradation research platform, and bispecific T cell engagers (TCE): Updated data from the Phase 1 study of CAR T BMS-986393, a potential first-in-class cell therapy targeting GPRC5D, show deepening responses, a tolerable safety profile, and activity across both B-cell maturation antigen (BCMA)-naïve and -exposed patients (Oral Presentation #219) New results from the Phase 1 CC-92480-MM-002 study of oral CELMoD agent mezigdomide, including first results for cohorts evaluating mezigdomide and dexamethasone with monoclonal antibodies (anti-CD38 mAbs) daratumumab and elotuzumab (Oral Presentation #1013) Updated results of the Phase 1 study of alnuctamab, a 2+1 BCMA x CD3 bispecific TCE, show deepening and durable responses, including minimal residual disease (MRD) negativity, along with manageable safety (Poster Presentation #2011) “Despite continuing advances in care for multiple myeloma, critical unmet needs remain as patients reflect a diverse spectrum of characteristics. Moreover, the disease remains marked by eventual relapse, making the long-term management of the disease paramount,” said Joseph Mikhael, M.D., Professor in the Applied Cancer Research and Drug Discovery Division at the Translational Genomics Research Institute and Chief Medical Officer of the International Myeloma Foundation. “Because of this heterogenous profile, having a broad array of options across the treatment path is extremely valuable. Seeing the range of new and updated data being presented at this meeting is encouraging as we look toward the future of myeloma therapy.” GPRC5D CAR T (BMS-986393) Phase 1 Study Results BMS-986393 is a first-in-class GPRC5D-directed autologous CAR T cell therapy that has the potential to be a best-in-class option for this emerging target. This Phase 1, first-in-human, multicenter, open-label study is evaluating BMS-986393 in patients with relapsed/refractory multiple myeloma (RRMM) who had received three or more prior lines of therapy. Prior BCMA-targeted treatment, including CAR T cell therapy, was allowed. Primary objectives of the study were to determine safety and tolerability of BMS-986393 and inform the recommended dose for future development. At the data cutoff of September 11, 2023 (median follow-up of 8.8 months), BMS-986393 continued to demonstrate an efficacy benefit with deep and durable responses in these heavily pretreated patients, including those with prior exposure to BCMA-targeted treatment. The overall response rate (ORR) was 91% (48% complete response rate) among patients treated with the recommended Phase 2 dose (RP2D, n=23), including an ORR of 100% (n=8) in patients with previous exposure to anti-BCMA targeting therapy. Minimal residual disease-negativity was observed in 86% (n=14) of evaluable patients. BMS-986393 demonstrated a well-tolerated safety profile, and the RP2D was declared as 150 x 106 CAR T cells without reaching the maximum tolerated dose. The benefit-risk pro consistent with earlier, previously presented data cuts. Overall, most patients regardless of treatment dose experienced a treatment emergent adverse event (n=84; any Grade: 91.7%, Grade 3/4: 82.1%). Cytokine release syndrome (CRS) was common with the majority of events being manageable and low grade (any Grade: 76.2%, Grade 3/4: 3.6%) including in patients treated at RP2D where all CRS events were Grade 1 (88.5%). ICANS-type neurotoxicity events were not common across all dose levels (any Grade: 9.5%, Grade 3: 2.4%) and were reversible with or without intervention; among patients treated at RP2D all ICANS events were low grade (any Grade: 3.8%, Grade 3/4: 0%). The incidence of non-ICANS neurotoxicity was similar for patients treated at RP2D as compared with all patients (15.4% vs. 10.7%, respectively). On-target/off-tumor skin, nail, and oral adverse events (AEs) were all low-grade, transient, and the majority (86%) did not require treatment. These early clinical data suggest a single infusion of BMS-986393 is tolerable and efficacious in RRMM, including in those with prior exposure to BCMA-targeted therapy​, and a single-arm Phase 2 trial of BMS-986393 in patients with RRMM exposed to four or more classes of therapy (quadruple-class exposed) is planned to open in the first half of 2024. Novel oral CELMoD™ agent mezigdomide Phase 1/2 Study Results Cereblon E3 ligase modulators (CELMoDs), representing one of three modalities from the company’s leading protein degradation platform, are a class of oral therapeutics that are optimized to both stimulate the immune system and directly kill cancer cells by inducing the degradation of tumor-promoting proteins. The CELMoD agents, mezigdomide and iberdomide, are adaptable combination and sequencing partners being investigated in multiple myeloma. The mezigdomide CC-92480-MM-002 trial is an ongoing open-label, international Phase 1/2 study evaluating the safety and efficacy of mezigdomide with different treatment combinations in patients with RRMM. At ASH, first results were presented for combinations of mezigdomide and dexamethasone plus monoclonal antibodies (anti-CD38 mAbs) elotuzumab (MeziEd, Cohort H=21/28 days) or one of three dosing schedules of daratumumab (MeziDd, Cohort B1= 21/28 days, Cohort B2=14/21 days, Cohort B3=7/14 days x2). Patients had a median of 3 (range 2-5) prior therapies including stem cell transplantation, proteasome inhibitors, anti-CD38 agents or IMiD agents. The primary objectives of the study were to determine the RP2D, safety, and preliminary overall response rate (ORR). Results at ASH showed mezigdomide combined with anti-CD38 mAbs showed encouraging efficacy in previously treated patients. Patients treated with MeziDd achieved a response regardless of dose and schedule, with ORR observed in 82.6% of patients in Cohort B1 (n=23), 62.1% of patients in Cohort B2 (n=18) and 88.9% of patients in Cohort B3 (n=18). MeziEd was active in patients who were refractory to prior anti-CD38 mAb therapy, with an ORR of 45% in Cohort H (n=20). MeziDd and MeziEd were pharmacodynamically active at all schedules and dose levels tested. Further investigation is underway to determine the optimal dose and schedule for MeziDd based on Cohort B3. The safety pro mezigdomide in combination with anti-CD38 mAbs was manageable and consistent with prior reports. Most Grade 3/4 treatment-emergent adverse events (TEAEs) following treatment with MeziDd or MeziEd were hematologic, with neutropenia being the most common and ranging from 40-70% across cohorts. The occurrence of Grade 3/4 non-hematologic TEAEs was relatively low with either combination. Mezigdomide is currently being evaluated in two randomized pivotal Phase 3 studies, including SUCCESSOR-1 (NCT05519085: mezigdomide, bortezomib and dexamethasone vs. pomalidomide, bortezomib and dexamethasone in patients with lenalidomide-exposed RRMM) and SUCCESSOR-2 (NCT05552976: mezigdomide with carfilzomib and dexamethasone vs. carfilzomib and dexamethasone in patients with anti-CD38 and lenalidomide exposed RRMM). Alnuctamab (BMS-986349/CC-93269) Phase 1 Study Results Alnuctamab is a bispecific T cell engager (TCE) that simultaneously binds myeloma cells expressing BCMA and T cells (via CD3) in a unique 2:1 fashion. This interaction aims to drive myeloma cell death by inducing T cell activation and release of proinflammatory cytokines and cytolytic enzymes. In the ongoing alnuctamab CC-93269-MM-001 open-label, Phase 1 study, 78 patients with RRMM were treated with subcutaneous (SC) alnuctamab in two step-up doses (3 mg and 6 mg) followed by escalating target doses of 10, 15, 30, and 60 mg, given every one week for three months, then every two weeks for three months, followed by every four weeks after those six months. In updated results, SC alnuctamab showed durable responses with high anti-tumor activity observed at target dose of 30 mg (n=32), the dose selected for Phase 3. In the efficacy-evaluable patients treated with SC alnuctamab (n=73), the ORR was 53% across all doses and 67% at the 30 mg target dose. Median time to response was 1.2 months (range, 0.9–4.0) and responses deepened over time. Median progression-free survival (PFS) was 10.1 months (95% CI, 2.8–17.8) across all dose levels and 11.4 months (95% CI, 1.8 to not estimable) in the 30 mg target dose. Median duration of response (DOR) had not been reached at the time of data cutoff. All patients who achieved a response at the 30 mg target dose (14/14) were MRD-negative. The safety pro manageable and no Grade 3/4 CRS was observed. The most common Grade 3 or higher hematologic TEAEs across target doses (n=78) were neutropenia (46%), anemia (26%) and thrombocytopenia (17%) with the most common non-hematologic Grade 3 or higher TEAE being infections (17%). A Phase 3 study of alnuctamab in patients with RRMM exposed to lenalidomide and an anti-CD38 monoclonal antibody is planned and will be initiated in the first half of 2024. Bristol Myers Squibb: Transforming the Multiple Myeloma Treatment Paradigm At BMS, we believe that every patient deserves a tailored treatment approach to achieve the best possible outcome for their disease, from extended survival and reduced treatment burden to the possibility of cure. Over two decades of trailblazing work in multiple myeloma, we have driven significant scientific and clinical advancements. As we look forward, we are leveraging our deep immunotherapy experience to progress an industry-leading pipeline across targets, molecular approaches and combinations (including BCMA-targeted therapies, targeted protein degradation, CAR T cell therapies and NK-cell engagers). Understanding that continued partnership with the multiple myeloma community is key to advancing scientific progress, we pride ourselves on an openness to collaborate, which is reflected in our ongoing research fueled by academic and industry partnerships. While multiple myeloma remains a relentless disease, we continue to transform the multiple myeloma treatment paradigm by dramatically improving outcomes for every patient. Bristol Myers Squibb: Creating a Better Future for People with Cancer Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future. Learn more about the science behind cell therapy and ongoing research at Bristol Myers Squibb here. About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram. Cautionary Statement Regarding Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that future study results may not be consistent with the results to date, that the product candidates described in this release may not receive regulatory approval for the indications described in this release, that any marketing approvals, if granted, may have significant limitations on their use, and, if approved, whether such product candidates for such indications will be commercially successful. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2022, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise. corporatefinancial-news View source version on businesswire.com: Contacts Bristol Myers Squibb: Media Inquiries: media@bms.com Investors: investor.relations@bms.com Source: Bristol Myers Squibb View this news release online at: