SERVIER PHARMA LLC

- Multiple clinical milestones across portfolio anticipated in 2024, including two Phase 2 trials assessing belrestotug + dostarlimab in 1L NSCLC and 1L HNSCC- Completed enrollment of third dose cohort in Phase 1 trial of EOS-984- Preclinical presentations on role of ENT1 at SITC Spring Scientific and profile of EOS-984 at AACR annual meeting- Cash and investment balance of $632.7 million as of December 31, 2023 expected to provide runway through 2026 across a number of impactful portfolio milestones- Oncology veterans Jill DeSimone and David K. Lee to join Board of Directors WATERTOWN, Mass. and GOSSELIES, Belgium, March 06, 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 reported financial results for the fourth quarter and full year ended December 31, 2023 and provided a business update. “As we anticipate four clinical readouts across the portfolio, 2024 is poised to be a transformative year for iTeos,” said Michel Detheux, Ph.D., president and chief executive officer of iTeos. “With the recent developments in the TIGIT field, we believe belrestotug is in an advantageous position and are excited for its future prospects. We look forward to sharing updates from our Phase 2 trials focused on 1L NSCLC and 1L HNSCC in 2024. Additionally, our strong comprehension of the adenosine pathway has enabled us to develop two innovative and optimized assets – inupadenant, an A2AR antagonist in a class of its own, and EOS-984, a potential first-in-class inhibitor targeting the novel mechanism of ENT1. With our strategic cash position and robust pipeline, we are focused on the execution of these clinical trials to deliver on our highly anticipated milestones this year.” Corporate Developments On March 6, 2024, iTeos announced the appointment of Jill DeSimone to the Company’s Board of Directors. With over 40 years of global business expertise in life sciences, Ms. DeSimone is recognized for her role as President of U.S. Oncology at Merck & Co., Inc., where she established the company’s oncology division, growing it from less than $500 million in annual revenue to $9 billion in eight years. On December 7, 2023, iTeos announced the appointment of David K. Lee to the Company’s Board of Directors. A seasoned pharmaceutical veteran with a proven track record of building successful businesses focused on oncology and rare diseases, Mr. Lee currently serves as the Chief Executive Officer of Servier Pharmaceuticals (U.S.), where he established and grew Servier Pharmaceuticals to a fully innovative oncology company with four commercialized products and a robust pipeline. 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 doublet GALAXIES Lung-201: topline data from Phase 2 platform trial assessing belrestotug + dostarlimab doublet in first-line advanced/metastatic NSCLC anticipated in 2024 GALAXIES 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 HNSCC TIG-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 2024 TIG-006 mNSCLC: enrollment ongoing in Phase 1b expansion trial assessing belrestotug, dostarlimab, and chemotherapy triplet in first-line advanced or metastatic NSCLC 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: 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 2024. EOS-984: first-in-class small molecule inhibiting equilibrative nucleoside transporter 1 (ENT1), a dominant transporter of adenosine on lymphocytes involved in T cell metabolism, expansion, effector function, and survival Completed enrollment of the third dose cohort and continued advancement in the dose escalation of the Phase 1 trial in advanced malignancies Abstract acceptance by The American Association for Cancer Research (AACR) for EOS-984, which highlights preclinical data on the novel mechanism of action, monotherapy activity, and combination activity with anti-PD-1 therapy Oral presentation by Matthew Vander Heiden, M.D., Ph.D., from the Koch Institute for Integrative Cancer Research in collaboration with iTeos Therapeutics on the role of ENT1 on the metabolism and the immune system in cancer at The SITC Spring Scientific, Metabolism at the Hub of Cancer and Immunity in Miami, FL Session: Influence of Nutrient Environment on Immune ResponseDate and Time: Sunday, March 10, 2024, 9:10 AM – 10:10AM Topline data from the Phase 1 trial anticipated in the second half of 2024 Fourth Quarter and Full Year 2023 Financial Results Cash and Investment Position: The Company’s cash, cash equivalents, and investments position was $632.7 million as of December 31, 2023, as compared to $731.4 million as of December 31, 2022. The Company continues to expect its cash balance to provide runway through 2026. Research and Development (R&D) Expenses: R&D expenses were $27.9 million for the fourth quarter and $113.3 million for the year ended December 31, 2023, as compared to $25.4 million for the fourth quarter and $97.4 million for the year ended December 31, 2022. The increases in each comparative period were primarily due to increases in activities related to the belrestotug, inupadenant, and EOS-984 programs, and included the addition of new R&D employees hired to help advance these programs. General and Administrative (G&A) Expenses: G&A expenses were $12.4 million for the fourth quarter and $50.4 million for the year ended December 31, 2023, as compared to $11.1 million for the fourth quarter and $43.9 million for the year ended December 31, 2022. The increases were primarily due to increases in headcount and related costs and an increase in stock-based compensation compared to the prior year. The increases were partially offset by a decrease in recruiting costs. Net Income/Loss: Net loss attributable to common shareholders was $30.6 million, or net loss of $0.85 per basic and diluted share for the quarter ended December 31, 2023, as compared to a net income of $20.5 million, or a net income of $0.57 per basic share and $0.54 per diluted share for the quarter ended December 31, 2022. Net loss was $112.6 million, or net loss of $3.15 per basic and diluted share, for the year ended December 31, 2023, as compared to a net income of $96.7 million, or net income of $2.72 per basic share and $2.56 per diluted share, for the year ended December 31, 2022. 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-984EOS-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 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, inupadenant, and EOS-984; 2024 being poised to be a transformative year for iTeos; the future prospects of belrestotug; our plans and expected milestones, including initiating Phase 3 registrational studies that will evaluate the belrestotug + dostarlimab doublet, having topline data from GALAXIES Lung-201 and TIG-006 HNSCC in 2024, having topline data from A2A-005 in late 2024, having topline data from the Phase 1 trial in EOS-984 in the second half of 2024; and our expectation that our cash balance will provide runway through 2026 across a number of impactful portfolio milestones. 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: market conditions; 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’ Annual Report on Form 10-K for the year ended December 31, 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 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 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

[21-February-2024] If approved, vorasidenib would be the first targeted therapy in IDH-mutant diffuse glioma, a malignant and incurable brain tumor In clinical studies, vorasidenib has demonstrated strong blood-brain barrier penetrance alongside clinically meaningful and statistically significant improvements in progression-free survival and time-to-next intervention Approval of vorasidenib would mark Servier's sixth approval for a first-in-class treatment option in IDH-mutant cancers BOSTON and SURESNES, France, Feb. 21, 2024 /PRNewswire/ -- Servier, a global leader in oncology focused on delivering meaningful therapeutic progress for the patients it serves, today announced the FDA filing acceptance and priority review for a New Drug Application (NDA) for vorasidenib, as well as the EMA granting accelerated assessment for the vorasidenib Marketing Authorization Application (MAA). This innovative targeted therapy is an oral, selective, highly brain-penetrant dual inhibitor of mutant isocitrate dehydrogenase 1 and 2 (IDH1/2) enzymes for the treatment of IDH-mutant diffuse glioma. If approved, vorasidenib would become a first-in-class targeted therapy for patients with IDH-mutant gliomas and would mark Servier's sixth approval across IDH-mutant cancers. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of August 20, 2024, while the European Commission approval is anticipated in the second half of 2024. "In the realm of glioma treatment, innovation has been stagnant for nearly a quarter-century, posing challenges for patients who, post-surgery, may opt to defer treatment due to concerns around potential toxic side effects. As a drug specifically designed to be highly blood-brain barrier penetrant, vorasidenib has demonstrated clinically meaningful efficacy in patients with IDH1/2 mutant gliomas alongside a consistently manageable safety profile," said Susan Pandya, M.D., Head of Cancer Metabolism Global Development Oncology & Immuno-Oncology, Servier. "This promising outcome brings hope to patients grappling with IDH-mutant diffuse gliomas, offering a potential breakthrough for those eagerly awaiting a new therapeutic option." Adult-type diffuse gliomas represent approximately 81% of primary malignant brain tumors. Of those, approximately 20% harbor an IDH mutation, including 100% of grade 2 and grade 3 adult-type diffuse gliomas, as well as a much smaller portion of the grade 4 tumors.1,2 Testing for IDH mutations is essential for the accurate diagnosis of adult-type diffuse gliomas and can offer more information on the pathogenesis and prognosis of the disease.3 The 2021 WHO Classification includes disease defining histologic and molecular features, including IDH mutation status, to diagnose adult-type diffuse gliomas.4 Additionally, the National Clinical Practice Guidelines in Oncology (NCCN Guidelines) recommend IDH mutation testing in all patients with glioma, noting IDH mutation status impacts diagnosis, prognosis and treatment recommendations.5 "As a dedicated pioneer in the field of mutant IDH inhibition, Servier has consistently spearheaded the development of cutting-edge treatment options for various cancer types characterized by IDH mutations. The compelling efficacy results observed with vorasidenib in the INDIGO study underscore its full potential to emerge as the benchmark treatment for patients grappling with IDH-mutant diffuse glioma harboring IDH1/2 mutations," stated Claude Bertrand, Executive Vice-President of Research & Development and Chief Scientific Officer at Servier. "The submission of global regulatory filings for vorasidenib serve as validation of Servier's global oncology commitment while marking a possibly significant milestone for patients who have endured more than two decades without access to new therapeutic solutions." The submissions are based on results from the pivotal Phase 3 INDIGO clinical trial, which met its primary endpoint of progression-free survival (PFS) per blinded independent review committee (BIRC) and key secondary endpoint of time to next intervention (TTNI) at the prespecified second interim analysis. The primary endpoint, PFS per BIRC, was statistically significant and clinically meaningful in favor of the vorasidenib arm (Hazard Ratio [HR], 0.39; 95% Confidence Interval [CI], 0.27 to 0.56; 1-sided P=0.000000067), median PFS for vorasidenib and placebo was 27.7 and 11.1 months, respectively. TTNI was also statistically significant (HR, 0.26; 95% CI, 0.15 to 0.43; 1-sided P=0.000000019). Median TTNI was not reached for vorasidenib and was 17.8 months for placebo. Vorasidenib was also shown to reduce the tumor volume by a mean of 2.5% (TGR of –2.5%; 95% CI: -4.7% to -0.2%) every 6 months, while tumor volume increased by a mean of 13.9% (TGR of 13.9%; 95% CI: 11.1% to 16.8%) every 6 months for patients randomized to the placebo arm, as measured by a blinded independent radiology committee. The INDIGO study showed that vorasidenib was well-tolerated, and its safety pro consistent with results from the Phase 1 studies. The results of INDIGO were presented at the 2023 Annual Meeting of the American Society of Clinical Oncology (ASCO) and simultaneously published in The New England Journal of Medicine. The results of additional secondary endpoints, including vorasidenib's impact on tumor growth rate (TGR) of IDH-mutant gliomas, were presented at the 2023 Annual Meeting of the Society for Neuro-Oncology (SNO) among other presentations including results on health-related quality of life, seizure control, neurocognition, and preliminary molecular translational analyses. Priority Review is granted to FDA applications for medicines that, if approved, would provide significant improvements in the effectiveness or safety of the treatment, diagnosis or prevention of serious conditions.6 Vorasidenib was granted Fast Track Designation by the FDA in February 2023 and Breakthrough Therapy Designation by the FDA in August 2023. The EMA's accelerated assessment is granted if the Committee for Medicinal Products for Human Use decides the new medicine is expected to be of major public health interest, particularly from the viewpoint of therapeutic innovation.7 Servier has also submitted an application for project Orbis member countries, including Brazil, Canada, Australia, Israel and Switzerland. In addition, Servier plans to submit a Marketing Application in the United Kingdom if a positive CHMP opinion is received. More information about Project Orbis can be found on the FDA website. In its ongoing commitment to addressing patient's needs, Servier recognizes that patients and their physicians may believe that a patient with a serious or immediately life-threatening disease could benefit from Servier's investigational drugs. An Expanded Access Program, also known as "compassionate use," is a potential pathway for a patient with an immediately life-threatening condition or serious disease or condition to gain access to an investigational medical product for treatment outside of clinical trials. More information about Servier's expanded access program can be found at clinicaltrials.gov. About the INDIGO Phase 3 Trial (NCT04164901) INDIGO was a registration-enabling Phase 3 global, randomized, double-blind placebo-controlled study of vorasidenib in patients with residual or recurrent grade 2 glioma with an isocitrate dehydrogenase 1/2 (IDH1/2) mutation who have undergone surgery as their only treatment. Results were published in The New England Journal of Medicine. About Glioma8 Adult-type diffuse gliomas represent approximately 81% of primary malignant brain tumors. Of those, approximately 20% harbor an IDH mutation, including 100% of grade 2 and grade 3 adult-type diffuse gliomas, as well as a much smaller portion of the grade 4 tumors.1,2 Establishing the IDH mutation status of these tumors is essential to both diagnosis and prognosis, per the 2021 WHO classification of CNS tumors and the NCCN treatment guidelines, respectively. As of 2021, adult-type diffuse gliomas are sub-divided into only three categories: Astrocytoma, IDH-mutant (CNS WHO grades 2-4) Oligodendroglioma, IDH-mutant and 1p19q-codeleted (CNS WHO grades 2-3) Glioblastoma, IDH-wildtype (CNS WHO grade 4) About Servier in Oncology Servier is a global leader in oncology focused on delivering meaningful therapeutic progress for the patients it serves. Governed by a non-profit foundation, Servier approaches innovation with a long-term vision, free of influence from investors and outside pressure to chase short-term monetary targets. As a leader in oncology, Servier has significantly accelerated its investment in difficult and hard-to-treat cancers, with more than 50% of its research and development dedicated to delivering significant advances in areas of high unmet need throughout oncology with the potential to change the lives of the patients it serves. Within these areas, Servier is the leader in mutant IDH inhibition, with the first ever mutant IDH1 inhibitor approved in the U.S. and the European Union, and the company continues to drive the science behind targeted mutant IDH inhibition. Servier's commitment to therapeutic progress guides its collaboration strategy. While many companies across the industry are scaling back investments, Servier is actively building alliances, completing acquisitions, conducting licensing deals and entering new partnerships that can help to accelerate access to therapies for patients in need. With the company's commercial expertise, global reach, scientific expertise and commitment to clinical excellence, Servier is dedicated to bringing the promise of tomorrow to the patients it serves. Press Contacts Servier Group (Global) marion.breyer@servier.com Servier Pharmaceuticals (U.S.) Nathan Mellor nathan.mellor@servier.com Disclosures This release contains general information about the Servier Group and its entities (hereinafter "Servier and its Affiliates") and is intended for informational purposes only. The information is thought to be reliable; however, Servier and its Affiliates make no representation as to the accuracy or completeness of the information contained herein or otherwise provided and accept no responsibility or liability, in contract, in tort, in negligence, or otherwise, should the information be found to be inaccurate or incomplete in any respect. Servier and its Affiliates are not acting as an advisor to the recipient of this information, and the ultimate decision to proceed with any transaction rests solely with the recipient of this information. Therefore, prior to entering into any proposed transaction, the recipient of this information should determine, without reliance upon Servier or its Affiliates, the economic risks and merits, as well as the legal, tax, and accounting characterizations and consequences, of the transaction and that it is able to assume these risks. This statement also contains forward-looking statements that are subject to varying levels of uncertainty and risk. Investigational new drugs and indications are subject to further scientific and medical review and regulatory approval. They are not approved for use by the FDA. Any reliance placed on this document is done entirely at the risk of the person placing such reliance. The information contained in this document is neither an offer to sell nor the solicitation of an offer to enter into a transaction. The content of this document is a summary only, is not complete, and does not include all material information about Servier and its Affiliates, including potential conflicts of interest. To the maximum extent permitted by applicable laws and regulations, Servier and its Affiliates disclaim all representations, warranties, conditions and guarantees, whether express, implied, statutory or of other kind, nor does it accept any duty to any person, in connection with this document. Without prejudice to the generality of the foregoing, Servier and its Affiliates do not warrant or represent that the information or opinions contained in this document is accurate or complete. To the maximum extent permitted by applicable laws and regulations, Servier and its Affiliates shall not be liable for any loss, damage or expense whatsoever, whether direct or indirect, howsoever arising, whether in contract, tort (including negligence), strict liability or otherwise, for direct, indirect, incidental, consequential, punitive or special damages arising out of or in connection with this document, including (without limitation) any course of action taken on the basis of the same. The estimates, strategies, and views expressed in this document are based upon past or current data and information and are subject to change without notice. 1 Louis, D. et. al (2021). The 2021 WHO Classification of Tumors of the Central Nervous System: a summary, Neuro-Oncology, 23(8): 1231–1251. . Accessed February 2024. 2 Ostrom, Q. T., Price, M., Neff, C., Cioffi, G., Waite, K. A., Kruchko, C., & Barnholtz-Sloan, J. S. (2022). CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015-2019. Neuro-oncology, 24(Suppl 5), v1–v95. . Accessed February 2024. 3 Isocitrate Dehydrogenase. Science Direct. . Accessed February 2024. 4 Antonelli M, Poliani PL. Adult type diffuse gliomas in the new 2021 WHO Classification. Pathologica. 2022 Dec;114(6):397-409. doi: 10.32074/1591-951X-823. PMID: 36534419; PMCID: PMC9763975. 5 NCCN. Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Brain Cancer Gliomas 2021. © National Comprehensive Cancer Network, Inc. 2023. Accessed February 2024. 6 U.S. Food and Drug Administration (FDA). Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review. . Accessed February 2024. 7 European Medicines Agency (EMA). Accelerated assessment. . Accessed February 2024. 8 Neuro Oncology. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. . Accessed February 2024.

If approved, vorasidenib would be the first targeted therapy in IDH-mutant diffuse glioma, a malignant and incurable brain tumor In clinical studies, vorasidenib has demonstrated strong blood-brain barrier penetrance alongside clinically meaningful and statistically significant improvements in progression-free survival and time-to-next intervention Approval of vorasidenib would mark Servier's sixth approval for a first-in-class treatment option in IDH-mutant cancers BOSTON and SURESNES, France, Feb. 20, 2024 /PRNewswire/ -- Servier, a global leader in oncology focused on delivering meaningful therapeutic progress for the patients it serves, today announced the FDA filing acceptance and priority review for a New Drug Application (NDA) for vorasidenib, as well as the EMA granting accelerated assessment for the vorasidenib Marketing Authorization Application (MAA). This innovative targeted therapy is an oral, selective, highly brain-penetrant dual inhibitor of mutant isocitrate dehydrogenase 1 and 2 (IDH1/2) enzymes for the treatment of IDH-mutant diffuse glioma. If approved, vorasidenib would become a first-in-class targeted therapy for patients with IDH-mutant gliomas and would mark Servier's sixth approval across IDH-mutant cancers. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of August 20, 2024, and the the European Commission approval is anticipated in the second half of 2024. "In the realm of glioma treatment, innovation has been stagnant for nearly a quarter-century, posing challenges for patients who, post-surgery, may opt to defer treatment due to concerns around potential toxic side effects. As a drug specifically designed to be highly blood-brain barrier penetrant, vorasidenib has demonstrated clinically meaningful efficacy in patients with IDH1/2 mutant gliomas alongside a consistently manageable safety profile, " said Susan Pandya, M.D., Head of Cancer Metabolism Global Development Oncology & Immuno-Oncology, Servier. "This promising outcome brings hope to patients grappling with IDH-mutant diffuse gliomas, offering a potential breakthrough for those eagerly awaiting a new therapeutic option." Adult-type diffuse gliomas represent approximately 81% of primary malignant brain tumors. Of those, approximately 20% harbor an IDH mutation, including 100% of grade 2 and grade 3 adult-type diffuse gliomas, as well as a much smaller portion of the grade 4 tumors.1,2 Testing for IDH mutations is essential for the accurate diagnosis of adult-type diffuse gliomas and can offer more information on the pathogenesis and prognosis of the disease.3 The 2021 WHO Classification includes disease defining histologic and molecular features, including IDH mutation status, to diagnose adult-type diffuse gliomas.4 Additionally, the National Clinical Practice Guidelines in Oncology (NCCN Guidelines) recommend IDH mutation testing in all patients with glioma, noting IDH mutation status impacts diagnosis, prognosis and treatment recommendations.5 "As the pioneer in the field of mutant IDH inhibition, Servier has consistently spearheaded the development of cutting-edge treatment options for various cancer types characterized by IDH mutations. The compelling efficacy results observed with vorasidenib in the INDIGO study underscore its full potential to emerge as the benchmark treatment for patients grappling with IDH-mutant diffuse glioma harboring IDH1/2 mutations," stated Claude Bertrand, Executive Vice-President of Research & Development and Chief Scientific Officer at Servier. "The submission of global regulatory filings for vorasidenib serve as validation of Servier's global oncology commitment while marking a possibly significant milestone for patients who have endured more than two decades without access to new therapeutic solutions." The submissions are based on results from the pivotal Phase 3 INDIGO clinical trial, which met its primary endpoint of progression-free survival (PFS) per blinded independent review committee (BIRC) and key secondary endpoint of time to next intervention (TTNI) at the prespecified second interim analysis. The primary endpoint, PFS per BIRC, was statistically significant and clinically meaningful in favor of the vorasidenib arm (Hazard Ratio [HR], 0.39; 95% Confidence Interval [CI], 0.27 to 0.56; 1-sided P=0.000000067), median PFS for vorasidenib and placebo was 27.7 and 11.1 months, respectively. TTNI was also statistically significant (HR, 0.26; 95% CI, 0.15 to 0.43; 1-sided P=0.000000019). Median TTNI was not reached for vorasidenib and was 17.8 months for placebo. Vorasidenib was also shown to reduce the tumor volume by a mean of 2.5% (TGR of –2.5%; 95% CI: -4.7% to -0.2%) every 6 months, while tumor volume increased by a mean of 13.9% (TGR of 13.9%; 95% CI: 11.1% to 16.8%) every 6 months for patients randomized to the placebo arm, as measured by a blinded independent radiology committee. The INDIGO study showed that vorasidenib was well-tolerated, and its safety profile was consistent with results from the Phase 1 studies. The results of INDIGO were presented at the 2023 Annual Meeting of the American Society of Clinical Oncology (ASCO) and simultaneously published in The New England Journal of Medicine. The results of additional secondary endpoints, including vorasidenib's impact on tumor growth rate (TGR) of IDH-mutant gliomas, were presented at the 2023 Annual Meeting of the Society for Neuro-Oncology (SNO) among other presentations including results on health-related quality of life, seizure control, neurocognition, and preliminary molecular translational analyses. Priority Review is granted to FDA applications for medicines that, if approved, would provide significant improvements in the effectiveness or safety of the treatment, diagnosis or prevention of serious conditions.6 Vorasidenib was granted Fast Track Designation by the FDA in February 2023 and Breakthrough Therapy Designation by the FDA in August 2023. The EMA's accelerated assessment is granted if the Committee for Medicinal Products for Human Use (CHMP) decides the new medicine is expected to be of major public health interest, particularly from the viewpoint of therapeutic innovation.7 Servier has also submitted an application for project Orbis member countries, including Brazil, Canada, Australia, Israel and Switzerland. In addition, Servier plans to submit a Marketing Application in the United Kingdom if a positive CHMP opinion is received. More information about Project Orbis can be found on the FDA website. In its ongoing commitment to addressing patient's needs, Servier recognizes that patients and their physicians may believe that a patient with a serious or immediately life-threatening disease could benefit from Servier's investigational drugs. An Expanded Access Program, also known as "compassionate use," is a potential pathway for a patient with an immediately life-threatening condition or serious disease or condition to gain access to an investigational medical product for treatment outside of clinical trials. More information about Servier's expanded access program can be found at clinicaltrials.gov. About the INDIGO Phase 3 Trial ( NCT04164901 ) INDIGO was a registration-enabling Phase 3 global, randomized, double-blind placebo-controlled study of vorasidenib in patients with residual or recurrent grade 2 glioma with an isocitrate dehydrogenase 1/2 (IDH1/2) mutation who have undergone surgery as their only treatment. Results were published in The New England Journal of Medicine. About Glioma 8 Adult-type diffuse gliomas represent approximately 81% of primary malignant brain tumors. Of those, approximately 20% harbor an IDH mutation, including 100% of grade 2 and grade 3 adult-type diffuse gliomas, as well as a much smaller portion of the grade 4 tumors.1,2 Establishing the IDH mutation status of these tumors is essential to both diagnosis and prognosis, per the 2021 WHO classification of CNS tumors and the NCCN treatment guidelines, respectively. As of 2021, adult-type diffuse gliomas are sub-divided into only three categories: Astrocytoma, IDH-mutant (CNS WHO grades 2-4) Oligodendroglioma, IDH-mutant and 1p19q-codeleted (CNS WHO grades 2-3) Glioblastoma, IDH-wildtype (CNS WHO grade 4) About Servier in Oncology Servier is a global leader in oncology focused on delivering meaningful therapeutic progress for the patients it serves. Governed by a non-profit foundation, Servier approaches innovation with a long-term vision, free of influence from investors and outside pressure to chase short-term monetary targets. As a leader in oncology, Servier has significantly accelerated its investment in difficult and hard-to-treat cancers, with more than 50% of its research and development dedicated to delivering significant advances in areas of high unmet need throughout oncology with the potential to change the lives of the patients it serves. Within these areas, Servier is the leader in mutant IDH inhibition, with the first ever mutant IDH1 inhibitor approved in the U.S. and the European Union, and the company continues to drive the science behind targeted mutant IDH inhibition. Servier's commitment to therapeutic progress guides its collaboration strategy. While many companies across the industry are scaling back investments, Servier is actively building alliances, completing acquisitions, conducting licensing deals and entering new partnerships that can help to accelerate access to therapies for patients in need. With the company's commercial expertise, global reach, scientific expertise and commitment to clinical excellence, Servier is dedicated to bringing the promise of tomorrow to the patients it serves. Press Contacts Servier Group (Global) [email protected] Servier Pharmaceuticals (U.S.) Nathan Mellor [email protected] Disclosures This release contains general information about the Servier Group and its entities (hereinafter "Servier and its Affiliates") and is intended for informational purposes only. The information is thought to be reliable; however, Servier and its Affiliates make no representation as to the accuracy or completeness of the information contained herein or otherwise provided and accept no responsibility or liability, in contract, in tort, in negligence, or otherwise, should the information be found to be inaccurate or incomplete in any respect. Servier and its Affiliates are not acting as an advisor to the recipient of this information, and the ultimate decision to proceed with any transaction rests solely with the recipient of this information. Therefore, prior to entering into any proposed transaction, the recipient of this information should determine, without reliance upon Servier or its Affiliates, the economic risks and merits, as well as the legal, tax, and accounting characterizations and consequences, of the transaction and that it is able to assume these risks. This statement also contains forward-looking statements that are subject to varying levels of uncertainty and risk. Investigational new drugs and indications are subject to further scientific and medical review and regulatory approval. They are not approved for use by the FDA. Any reliance placed on this document is done entirely at the risk of the person placing such reliance. The information contained in this document is neither an offer to sell nor the solicitation of an offer to enter into a transaction. The content of this document is a summary only, is not complete, and does not include all material information about Servier and its Affiliates, including potential conflicts of interest. To the maximum extent permitted by applicable laws and regulations, Servier and its Affiliates disclaim all representations, warranties, conditions and guarantees, whether express, implied, statutory or of other kind, nor does it accept any duty to any person, in connection with this document. Without prejudice to the generality of the foregoing, Servier and its Affiliates do not warrant or represent that the information or opinions contained in this document is accurate or complete. To the maximum extent permitted by applicable laws and regulations, Servier and its Affiliates shall not be liable for any loss, damage or expense whatsoever, whether direct or indirect, howsoever arising, whether in contract, tort (including negligence), strict liability or otherwise, for direct, indirect, incidental, consequential, punitive or special damages arising out of or in connection with this document, including (without limitation) any course of action taken on the basis of the same. The estimates, strategies, and views expressed in this document are based upon past or current data and information and are subject to change without notice. 1 Louis, D. et. al (2021). The 2021 WHO Classification of Tumors of the Central Nervous System: a summary, Neuro-Oncology, 23(8): 1231–1251. . Accessed February 2024. 2 Ostrom, Q. T., Price, M., Neff, C., Cioffi, G., Waite, K. A., Kruchko, C., & Barnholtz-Sloan, J. S. (2022). CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015-2019. Neuro-oncology, 24(Suppl 5), v1–v95. . Accessed February 2024. 3 Isocitrate Dehydrogenase. Science Direct. . Accessed February 2024. 4 Antonelli M, Poliani PL. Adult type diffuse gliomas in the new 2021 WHO Classification. Pathologica. 2022 Dec;114(6):397-409. doi: 10.32074/1591-951X-823. PMID: 36534419; PMCID: PMC9763975. 5 NCCN. Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Brain Cancer Gliomas 2021. © National Comprehensive Cancer Network, Inc. 2023. Accessed February 2024. 6 U.S. Food and Drug Administration (FDA). Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review. . Accessed February 2024. 7 European Medicines Agency (EMA). Accelerated assessment. . Accessed February 2024. 8 Neuro Oncology. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. . Accessed February 2024. 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