Calithera Biosciences, Inc.

Mantle cell lymphoma is a rare and aggressive type of non-Hodgkin lymphoma originating from B-cells in the "mantle zone" of the lymph nodes. The development of novel targeted therapies and immunotherapies, such as Bruton's tyrosine kinase (BTK) inhibitors, is improving treatment outcomes and driving market growth for Mantle cell lymphoma. LAS VEGAS, Sept. 19, 2024 /PRNewswire/ -- DelveInsight's ' Mantle Cell Lymphoma Pipeline Insight 2024 ' report provides comprehensive global coverage of pipeline mantle cell lymphoma therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the mantle cell lymphoma pipeline domain. Key Takeaways from the Mantle Cell Lymphoma Pipeline Report DelveInsight's mantle cell lymphoma pipeline report depicts a robust space with 20+ active players working to develop 22+ pipeline therapies for mantle cell lymphoma treatment. Key mantle cell lymphoma companies such as AbbVie, Adicet Bio, InnoCare Pharma Inc., Guangzhou Lupeng Pharmaceutical Company LTD., BeiGene, Nurix, LegoChem Biosciences, Xynomic Pharmaceuticals, Merck & Co, Incyte Corporation, TG Therapeutics, Janssen/Pharmacyclics, Eternity Bioscience, Traws Pharm, Advenchen Laboratories, and others are evaluating new mantle cell lymphoma drugs to improve the treatment landscape. Promising mantle cell lymphoma pipeline therapies such as Venetoclax, ADI-001, Orelabrutinib, LP-168, BGB-11417, NX 2127, LCB 71, NX 5948, Abexinostat, Pembrolizumab, Parsaclisib, Umbralisib, Ibrutinib, Edralbrutinib, Narazaciclib, Lucitanib, and others are under different phases of mantle cell lymphoma clinical trials. In May 2024, AstraZeneca had announced positive interim results from the Phase III ECHO clinical trial, which evaluated Bruton's tyrosine kinase (BTK) inhibitor Calquence (acalabrutinib) in combination with standard chemoimmunotherapy for treating mantle cell lymphoma (MCL). In March 2024, BeiGene, Ltd. announced the presentation of emerging oncology pipeline data at the American Association for Cancer Research (AACR) Annual Meeting. Additional highlights include preclinical characterization data for an investigational BTK degrader, BGB-16673, currently in clinical development for B-cell malignancies, including mantle cell lymphoma In October 2023, Ascentage Pharma announced that it has entered into a clinical collaboration with AstraZeneca Investment. The two companies will jointly conduct a registrational Phase III study of the Bcl-2 inhibitor, APG-2575 (lisaftoclax), in combination with AstraZeneca's Bruton's tyrosine kinase (BTK) inhibitor, CALQUENCE® (acalabrutinib), in treatment-naive patients with first-line chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). In January 2023, the FDA granted an orphan drug designation to LP-284, a novel small-molecule, next-generation acylfulvene, for the treatment of mantle cell lymphoma (MCL), a rare and aggressive form of B-cell non-Hodgkin lymphoma (NHL), according to an announcement from Lantern Pharma. Request a sample and discover the recent advances in mantle cell lymphoma treatment drugs @ Mantle Cell Lymphoma Pipeline Report The mantle cell lymphoma pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage mantle cell lymphoma drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the mantle cell lymphoma clinical trial landscape. Mantle Cell Lymphoma Overview Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin lymphomas (NHLs) characterized by the (11,14) translocation, leading to overexpression of the cyclin D1 (CCND1) gene. Its various morphological variants can make diagnosis challenging, though some cases are straightforward. Many individuals with MCL are asymptomatic in the early stages, but may later seek medical attention due to persistent, typically painless swelling of lymph nodes, especially in the neck and throat region (e.g., Waldeyer's ring). MCL is marked by a reciprocal chromosomal translocation t(11;14)(q13;q32), which places the cyclin D1 gene next to the immunoglobulin heavy chain gene, causing continuous cyclin D1 expression. This overexpression contributes to tumor cell proliferation through cell cycle dysregulation, chromosomal instability, and epigenetic changes. Rarely, MCL cases without this translocation may involve CCND2 or CCND3 translocations. Hypothetical molecular subtypes, based on the cell of origin, correlate with clinical phenotypes: classical or aggressive MCL arises from naive B cells lacking or having limited iGVH mutations and expressing SOX11, a neural transcription factor inhibiting terminal B cell differentiation. The indolent variant originates from antigen-experienced B cells with IGVH somatic hypermutations, typically SOX11-negative and genetically stable. Diagnosis of MCL involves detailed patient history, thorough clinical evaluation, and specialized tests, including biopsy of an affected lymph node or bone marrow. These tests confirm the NHL type and subtype, assess disease extent, and determine appropriate treatments. Treatment for MCL is multifaceted and tailored to each patient, often including chemotherapy, immunotherapy drugs like rituximab, targeted therapies such as ibrutinib, and stem cell transplants, particularly for aggressive disease or younger patients. Radiation therapy may target specific lymphoma areas. Participation in clinical trials can offer new treatment options. Treatment plans are developed collaboratively by healthcare professionals and patients, considering disease stage, overall health, and personal preferences. Regular monitoring and follow-up care are essential to track treatment response and manage side effects effectively. Find out more about mantle cell lymphoma treatment drugs @ Drugs for Mantle Cell Lymphoma Treatment A snapshot of the Mantle Cell Lymphoma Pipeline Drugs mentioned in the report: Learn more about the emerging mantle cell lymphoma pipeline therapies @ Mantle Cell Lymphoma Clinical Trials Mantle Cell Lymphoma Therapeutics Assessment The mantle cell lymphoma pipeline report proffers an integral view of the mantle cell lymphoma emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Mantle Cell Lymphoma Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Oral, Parenteral, Intravenous, Subcutaneous, Topical Therapeutics Assessment By Molecule Type: Recombinant fusion proteins, Small molecule, Monoclonal antibody, Peptide, Polymer, Gene therapy Therapeutics Assessment By Mechanism of Action: Apoptosis stimulants, Proto-oncogene protein c-bcl-2 inhibitors, Proteasome inhibitors, Immunologic cytotoxicity, T lymphocyte replacements, Agammaglobulinemia tyrosine kinase inhibitors Key Mantle Cell Lymphoma Companies: AbbVie, Adicet Bio, InnoCare Pharma Inc., Guangzhou Lupeng Pharmaceutical Company LTD., BeiGene, Nurix, LegoChem Biosciences, Xynomic Pharmaceuticals, Merck & Co, Incyte Corporation, TG Therapeutics, Janssen/Pharmacyclics, Eternity Bioscience, Traws Pharm, Advenchen Laboratories, and others Key Mantle Cell Lymphoma Pipeline Therapies: Venetoclax, ADI-001, Orelabrutinib, LP-168, BGB-11417, NX 2127, LCB 71, NX 5948, Abexinostat, Pembrolizumab, Parsaclisib, Umbralisib, Ibrutinib, Edralbrutinib, Narazaciclib, Lucitanib, and others Dive deep into rich insights for new drugs for mantle cell lymphoma treatment, visit @ Mantle Cell Lymphoma Drugs Table of Contents For further information on the mantle cell lymphoma pipeline therapeutics, reach out @ Mantle Cell Lymphoma Treatment Drugs Related Reports B-Cell Lymphoma Epidemiology B-Cell Lymphoma Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology as well as the B-cell lymphoma epidemiology trends. B-Cell Lymphoma Market B-Cell Lymphoma Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key B-cell lymphoma companies, including Vincerx Pharma, Ubix Therapeutics, Biomea Fusion Inc, Shanghai Hengrui Pharmaceutical, BeiGene, Hanmi Pharmaceutical, among others. Diffuse Large B-Cell Lymphoma Pipeline Diffuse Large B-Cell Lymphoma Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key DLBCL companies, including Genmab, Roche, Acerta Pharma, Autolus, Xynomic Pharmaceuticals, Genentech, Celgene, AbbVie, Mabion, among others. Diffuse Large B-Cell Lymphoma Market Diffuse Large B-Cell Lymphoma Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key B-cell lymphoma companies, including AbbVie, Genmab, Merck, Roche, Xencor and Janssen, Denovo Biopharma, Calithera Biosciences, IMV, Biogen, Autolus Therapeutics, Allogene Therapeutics, Novartis, Miltenyi Biomedicine, Regeneron Pharmaceuticals, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

欢迎关注凯莱英药闻 近日，德琪医药公布了2024年上半年业绩：截至2024年6月30日止六个月，公司收入6077.9万元(人民币)；其中，商业化产品希维奥（塞利尼索片）已在亚太市场的8个国家和地区获批上市，并被纳入其中4个市场的医保。截至2024年6月30日，公司持有现金10.24亿元人民币。 公司在产品研发和商业化方面均取得了诸多里程碑式进展；值得注意的是，旗下靶向Claudin18.2抗体偶联药物（ADC）ATG-022在正在进行二期临床研究，初步结果显示它对胃癌患者具有显著疗效；特别对于那些低表达及极低表达的患者，ATG-022可能提供新的治疗希望，甚至有潜力成为全球市场中的领先药物。 一 公司简介 德琪医药是一家以研发为驱动，并已进入商业化阶段的生物制药领先企业，专注于血液及实体肿瘤领域的同类首款和同类最优疗法的早期研发、临床研究、药物生产及商业化，致力于通过提供突破性疗法，改善全球患者生活质量。 自2017年以来，德琪医药现已建立起一条拥有9款从临床延展至商业化阶段的肿瘤药物资产研发管线，其中，6款产品具有全球权益，3款产品具有亚太权益。公司已在美国及多个亚太市场获得29个临床批件（IND），并递交了10个新药上市申请（NDA）。 德琪医药全球产品管线 德琪医药亚太区产品管线 二 专有平台 T细胞衔接器（TCE）已在血液系统肿瘤的治疗中显示良好疗效，且在近期开始显示出治疗实体瘤的潜力。但由于不理想的疗效和较高的CRS风险，TCE在实体瘤治疗中的应用仍非常有限。 德琪医药的新型“2+1”TCE技术平台AnTenGager™ 可以有效克服这些问题，因为它可通过诱导疾病相关抗原（DAA）依赖的T细胞结合和激活，在实现较强的活性的同时降低发生CRS的风险。其优势在于可实现与DAA（包括表达水平较低的DAA）的二价结合，同时使用了由德琪医药自主研发的可靶向作用于一个特殊构象表位的CD3抗体序列。它利用长度优化过的连接子将一个CD3单链抗体（scFv）结合至DAA抗体铰链区，这让起初被Fab抗体臂掩盖的CD3结合域仅在DAA交联条件下暴露，进而实现T细胞的条件性激活。 三 交易合作 除了授权引进具有竞争力的产品外，德琪医药在商业化产品的发展选择上十分值得借鉴。公司在塞利尼索在获批后，持续拓展适应症研发；商业化则选择联手翰森制药，将已有适应症进行推广、销售。这一举措缓解了德琪医药的销售费用，将更多精力放在创新药研发上。 德琪医药的部分交易布局 四 重点药物介绍 1、塞利尼索 塞利尼索是全球首个全新机制的口服选择性人类核输出蛋白（XPO-1）抑制剂，XPO-1是细胞中关键的核质转运蛋白，负责将蛋白质（包括肿瘤抑制蛋白）运输出细胞核，肿瘤抑制蛋白的核输出是肿瘤细胞逃避凋亡的重要机制。塞利尼索通过抑制XPO-1 功能，上调核内肿瘤抑制因子数量与转录活性，抑制肿瘤蛋白mRNA 的翻译，诱导肿瘤细胞凋亡，进而完成疾病治疗。 该药物最早由Karyopharm研发，2019 年FDA批准其治疗5 线复发难治性多发性骨髓瘤，后继续向前线推进，2020年获批治疗2 线复发难治性多发性骨髓瘤。德琪医药引进塞利尼索中国权益，并于2023 年将国内商业化权益授权给翰森制药。2023 年，塞利尼索在美国销售额1.12 亿美元。 临床数据角度，2 线复发难治性多发性骨髓瘤适应症的获批依据为与硼替佐米+地塞米松组相比，塞利尼索+硼替佐米+地塞米松的ORR 为76.4% vs 62.3%，CR 率为17% vs 10%。5 线复发难治性多发性骨髓瘤适应症的获批依据为ORR25.3%。安全性方面，关注塞利尼索消化相关不良反应如恶心、腹泻、呕吐等。 2、ATG-008 ATG-008 (Onatasertib) 是一款有潜力成为同类首款的第二代口服mTOR 抑制剂，能够同时靶向mTORC1 及mTORC2。临床前研究表明，相较于传统的mTOR复合体1 （mTORC1）抑制剂，ATG008抑制mTOR信号通路的疗效提高，具有克服传统mTORC1 抑制剂促癌反馈激活的潜力。 根据半年报披露的数据，对于晚期转移性宫颈癌患者的II期TORCH-2研究，ATG-008联合特瑞普利单抗（抗PD-1抗体）的初步疗效数据表现突出；截至2024年8月20日，30名既往未接受过CPI治疗的晚期二线及以上宫颈癌患者接受了 ATG-008 RP2D 联合特瑞普利单抗的治疗并至少有一次治疗后疗效评估；最佳总体缓解（BOR）包括6例完全缓解（CR）、10例部分缓解（PR）、11例疾病稳定（SD）及4例疾病进展（PD）；总体缓解率（ORR）为53.3%，疾病控制率（DCR）为86.7%；PD-L1表达阳性、PD-L1表达阴性和PD-L1表达状态不明（NA）患者的ORR分别为61.5%（8/13）、55.6%（5/9）和37.5%（3/8）。 截至2024年8月20日，27名既往接受过CPI治疗的晚期二线及以上宫颈癌患者接受了 ATG-008 RP2D 联合特瑞普利单抗的治疗并至少有一次治疗后疗效评估，结果显示：最佳总体缓解（BOR）包括1例完全缓解（CR）、5例部分缓解（PR）、17例疾病稳定（SD）及4例疾病进展（PD）。总体缓解率（ORR）为22.2%，疾病控制率（DCR）为92.6%。总体耐受性良好，没有出现新的安全信号。 3、ATG-022 ATG-022是一款作用于紧密连接蛋白18.2（Claudin 18.2）的ADC，CLDN18.2是一种细胞旁紧密连接结构中的膜蛋白，具有维持屏障、细胞旁运输和信号转导等作用，在正常组织中特异性地表达于胃黏膜上皮细胞，在胃癌（GC）、胰腺癌（PC）和食管癌等消化系统恶性肿瘤中常异位激活并高表达。 临床前数据显示，ATG-022对于Claudin 18.2具有低纳摩尔级别的亲和力以及强效的体外和体内抗肿瘤活性。此外，ATG-022还在药物非临床研究质量管理规范（GLP）毒理研究中显示了良好的安全性。 该药物 I期CLINCH剂量爬坡研究已于今年年初结束。目前已进入II期试验的单药剂量扩展部分，2.4 mg/kg被选定为II期推荐使用剂量（RP2D）；截至8月21日，已有21 例CLDN18.2阳性的胃癌患者接受了ATG-022治疗。在12 例至少接受了一次治疗后肿瘤评估的患者中，5 例获得了部分缓解（PR）。总体缓解率（ORR）为41.7%（包括一名CLDN18.2 表达极低的患者），疾病控制率（DCR）为100%。 3、ATG-037 ATG-037为国内第一款口服小分子CD73抑制剂，可完全阻断CD73的活性并克服在其他抗CD73抗体药物治疗中常见的“钩状效应”（Hook effect）。2021年5月，德琪医药与Calithera就ATG-037的开发和商业化达成一项全球独家授权协议：根据授权协议条款，Calithera获得一笔首付款并有资格获得基于开发、注册和销售进展的里程碑付款，以及授权产品销售收入的十几个百分点之内的分级特许权使用费。2023年1月，德琪医药与Calithera就ATG-037的全部剩余权益达成转让协议。 目前，公司已与默沙东达成一项全球临床合作，正在局部晚期或转移性实体瘤患者中对ATG-037联合抗PD-1药物KEYTRUDA®（帕博利珠单抗）进行评估。 目前，公司开展的I期剂量爬坡研究已经结束，该药物联合PD-1表现出相当好的安全性，未观察到剂量限制性毒性（DLT），所有与治疗相关的不良事件（TRAE）均为1-2级且不需要调整给药剂量；已在既往接受过检查点抑制剂治疗的受试患者中观察到4例PR，其中2例为黑色素瘤患者，另外2例为非小细胞肺癌患者。公司计划于2024年第三季度在中国和澳大利亚启动STAMINA研究的II期剂量扩展部分。 4、ATG-101 ATG-101是一款靶向PD-L1/4-1BB双特异性抗体，具有对于PD-L1的高亲和力和条件性激活4-1BB的能力，可有效降低肝脏毒性风险。 目前，公司针对ATG-101的剂量爬坡研究正在美国、中国大陆和澳大利亚进行中，已观察到良好的耐受性，且未发现明显的肝脏毒性。令人鼓舞的是，研究还在低剂量水平观察到持久的疾病稳定，且在1例微卫星稳定（MSS）的结直肠癌患者身上观察到PR。公司将按计划于2025年上半年完成I期剂量爬坡研究。 5、ATG-031 ATG-031是一款靶向CD24 单克隆抗体，通过阻断CD24与Singlec-10在巨噬细胞上的互动来强化对于肿瘤细胞吞噬和T细胞活性，同时还可激活抗体依赖性细胞介导的细胞毒性（ADCC）及补体依赖性细胞毒性（CDC）。临床前数据显示，ATG-031可以纳摩尔级别亲和力与CD24特异性结合并阻断CD24与Siglec-10的互动；此外，ATG-031可诱导皮摩尔EC50水平的高效吞噬作用，并促进巨噬细胞分泌促炎细胞因子。 目前，针对ATG-031开展的I期PERFORM研究中，19例晚期癌症患者在剂量爬坡阶段接受了早期低剂量治疗，且未出现剂量限制毒性（DLT）。该研究已在受试患者中观察到包含疾病稳定（SD）、肿瘤客观缩小和临床改善在内的初步疗效。公司计划在2025年上半年发布PERFORM研究的I期研究数据。 此外，公司将继续推进临床前资产的开发，这些资产包括可靶向作用于MTAP-null肿瘤的选择性PRMT5抑制剂ATG-042和CD19 x CD3 T细胞衔接器ATG-201。 6、ATG-042 ATG-042是一款具有同类最佳潜力的口服小分子选择性PRMT5抑制剂，PRMT5 是一种表观遗传酶，参与多种生理过程，包括转录调控、RNA 代谢、核糖体生物合成和细胞周期调控。已有证据表明，PRMT5过度表达可能在多种癌症中起着关键作用，包括B 和T 细胞淋巴瘤、转移性黑色素瘤、神经母细胞瘤、胶质母细胞瘤、生殖细胞瘤、卵巢癌、乳腺癌等。 临床前研究显示，ATG-042对于MTAP敲除的细胞存在明显的选择性抑制效应、较高的渗透性、良好的代谢稳定性、较低的药物相互作用（DDI）风险以及较高的口服生物利用度。重要的是，ATG-042显示了良好的脑部穿透。此外，在CDX模型中，ATG-042也强效和选择性地抑制了肿瘤生长，且未造成体重下降。 7、ATG-201 ATG-201是一款靶向CD19/CD3的双特异性抗体，正被开发用于治疗自身免疫性疾病；该药物可诱导体内和体外的深度 B 细胞清除，且诱发 CRS 的风险较低。 临床前研究显示，ATG-201在系统性红斑狼疮 (SLE) 和多发性硬化症 (MS) 动物模型中观察到强效疗效，具有很好的可开发性。公司计划于2025年第3季度递交ATG-201的IND申请。 参考资料 1、公司官网 2、医药笔记、格隆汇、药时代 3、招商证券、中泰证券 感谢关注、转发，转载授权、加行业交流群，请加管理员微信号“hxsjjf1618”。 “在看”点一下

CAMBRIDGE, Mass. & MONTREAL--(BUSINESS WIRE)-- Repare Therapeutics Inc. (“Repare” or the “Company”) (Nasdaq: RPTX), a leading clinical-stage precision oncology company, today provided a corporate update and highlighted key milestones anticipated in 2024. “We significantly advanced our pipeline in 2023 and presented strong data from key programs, notably for lunresertib in combination with camonsertib, and for camonsertib in combination with PARP inhibitors. In addition, we presented compelling preclinical data sets for RP-3467, which we’re developing as a potential best-in-class Polθ inhibitor, and for RP-1664, a potential first- and best-in-class PLK4 inhibitor,” said Lloyd M. Segal, President and Chief Executive Officer of Repare. “2024 will be a substantial year for Repare as we aim to expand our pipeline to four clinical-stage programs by the second half of 2024, and we expect to share data readouts from ongoing studies of lunresertib combinations.” Recent Accomplishments: Presented initial clinical data from the Phase 1/2 TRESR and ATTACC trials evaluating camonsertib (RP-3500/RG6526, now partnered globally with Roche) in combination with three poly (ADP-ribose) polymerase (PARP) inhibitors in a Clinical Trials Plenary Session at the 2023 American Association for Cancer Research (AACR) Annual Meeting. Camonsertib, a potent and selective oral small molecule inhibitor of ATR (Ataxia-Telangiectasia and Rad3-related protein kinase), showed 48% overall clinical benefit rate in patients with advanced solid tumors across tumor types regardless of choice of PARP inhibitor or platinum resistance, with a favorable safety and tolerability profile. Data from the TRESR trial were also published in Nature Medicine highlighting the clinical benefit of camonsertib in advanced solid tumors. Presented initial positive data from its ongoing Phase 1 MYTHIC trial evaluating lunresertib (RP-6306) alone and in combination with camonsertib in patients with advanced solid tumors harboring CCNE1 amplification or FBXW7 or PPP2R1A deleterious alterations at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. Initial combination data included an overall RECIST response rate of 50% in patients with heavily pre-treated gynecological tumors at the preliminary recommended Phase 2 dose. Disclosed polo-like kinase 4 (PLK4) as the target of its RP-1664 development program and reported comprehensive preclinical data for both RP-1664 and the Company’s Polθ inhibitor, RP-3467, both of which we expect to enter clinical trials in 2024. RP-1664 demonstrated potent and selective inhibition of PLK4 and synthetic lethality in TRIM37-high tumor cells in preclinical studies. RP-3467 demonstrated complete, sustained regressions preclinically in combination with PARP inhibitors, and compelling anti-tumor activity in combination with radioligand therapy (RLT) and chemotherapy. Announced a partnership with Debiopharm to explore the potential clinical synergy of Debio 0123, a highly selective clinical WEE1 inhibitor, and lunresertib in a trial expected to start in H1 and for which the companies have developed substantial pre-clinical validation. Repare will sponsor the global study as a new arm in the ongoing MYTHIC study with costs being shared equally by Debiopharm and Repare. Enrollment of patients is ongoing in the camonsertib arm of Roche’s TAPISTRY trial (NCT04589845), a Phase 2, global, open-label, multi-cohort study designed to evaluate the safety and efficacy of targeted therapies or immunotherapy in patients with unresectable, locally advanced or metastatic solid tumors determined to harbor specific oncogenic genomic alterations. With multiple patients in advanced stages of screening, dosing of the first patient with camonsertib is expected in the near term, which would result in the achievement of a $40 million milestone payment from Roche to Repare. In October 2023, Roche also dosed the first patient in a camonsertib-based arm in its Phase 1b/2 clinical trial of multiple immunotherapy-based treatment combinations in participants with metastatic non-small cell lung cancer (Morpheus Lung; NCT03337698). Announced the appointment of Susan M. Molineaux, Ph.D., to its Board of Directors. Dr. Molineaux currently serves as President and Chief Executive Officer at Para Therapeutics and previously served as Chief Executive Officer of Calithera Biosciences and of Proteolix. Additionally, Repare expanded its senior leadership team with the appointment of Daniel Bélanger as EVP of Human Resources. Anticipated Key Milestones in 2024: Initiation of a Phase 1 dose escalation study of RP-1664, a potential first-in-class, oral PLK4 inhibitor, in adult and adolescent patients with TRIM37-high solid tumors in the first half of 2024. Initiation of a Phase 1/1b study of lunresertib and Debio 0123, a WEE1 inhibitor, in the first half of 2024. Report initial data from the Phase 1 MINOTAUR study evaluating lunresertib in combination with FOLFIRI for the treatment of advanced solid tumors in the first half of 2024. Report data from the dose expansion cohorts of the Phase 1 MYTHIC study evaluating lunresertib in combination with camonsertib in selectively advanced solid tumors in the second half of 2024. Repare has closed enrollment in the Phase 1 MAGNETIC study evaluating lunresertib in combination with gemcitabine for the treatment of advanced solid tumors. The Company expects to report initial data from this study in the second half of 2024. Initiation of a Phase 1 dose finding study of RP-3467, a potential best-in-class Polθ inhibitor, in the second half of 2024. Cash Position and Financial Guidance Repare ended 2023 with approximately $223 million in cash, cash equivalents and marketable securities, which is anticipated to fund planned operations into mid-2026. About Repare Therapeutics’ SNIPRx® Platform Repare’s SNIPRx® platform is a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines to identify novel and known synthetic lethal gene pairs and the corresponding patients who are most likely to benefit from the Company’s therapies based on the genetic pro their tumors. Repare’s platform enables the development of precision therapeutics in patients whose tumors contain one or more genomic alterations identified by SNIPRx® screening, in order to selectively target those tumors in patients most likely to achieve clinical benefit from resulting product candidates. About Repare Therapeutics Inc. Repare Therapeutics is a leading clinical-stage precision oncology company enabled by its proprietary synthetic lethality approach to the discovery and development of novel therapeutics. The Company utilizes its genome-wide, CRISPR-enabled SNIPRx® platform to systematically discover and develop highly targeted cancer therapies focused on genomic instability, including DNA damage repair. The Company’s pipeline includes lunresertib (also known as RP-6306), a PKMYT1 inhibitor currently in Phase 1/2 clinical development; camonsertib (also known as RP-3500 or RG6526), a potential leading ATR inhibitor currently in Phase 1/2 clinical development and partnered with Roche; RP-1664, a preclinical PLK4 inhibitor; RP-3467, a preclinical Polθ inhibitor program; as well as additional, undisclosed preclinical programs. For more information, please visit and follow @Reparerx on X (formerly Twitter) and LinkedIn. SNIPRx® is a registered trademark of Repare Therapeutics Inc. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 and securities laws in Canada. All statements in this press release other than statements of historical facts are “forward-looking statements. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding: the design, objectives, initiation, timing, progress and results of current and future preclinical studies and clinical trials of the Company’s product candidates, including its Phase 1 MYTHIC trial evaluating lunresertib alone and in combination with camonsertib, its MINOTAUR trial evaluating lunresertib in combination with FOLFIRI, its MAGNETIC trial evaluating lunresertib in combination with gemcitabine, its Phase 1/1b trial of Debio 0123 and lunresertib in partnership with Debiopharm, its Phase 1 trial of RP-1664, and its phase 1 trial of RP-3467; the tolerability, efficacy and clinical progress of camonsertib, lunresertib, RP-1664 and RP-3467; the potential of RP-1664 as a first-in-class oral PLK4 inhibitor and RP-3467 as a best-in-class Polθ inhibitor; the potential synergy of Debio 0123 and lunresertib; the Company’s anticipated cash runway and financial guidance; the timing and benefits of potential milestone payments under the Roche collaboration agreement; and the benefits and ability to discover further targets and clinical candidates from the Company’s discovery platform. These forward-looking statements are based on the Company’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties that could cause the Company’s clinical development programs, future results or performance to differ materially from those expressed or implied by the forward-looking statements. Many factors may cause differences between current expectations and actual results, including: success in preclinical testing and earlier clinical trials does not ensure that later clinical trials will generate the same results or otherwise provide adequate data to demonstrate the efficacy and safety of a product candidate; the impacts of macroeconomic conditions, including the COVID-19 pandemic, the conflict in Ukraine and the conflict between Israel and Hamas, heightened inflation and uncertain credit and financial markets on the Company’s business, clinical trials and financial position; unexpected safety or efficacy data observed during preclinical studies or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; changes in expected or existing competition; changes in the regulatory environment; the uncertainties and timing of the regulatory approval process; and unexpected litigation or other disputes. Other factors that may cause the Company’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are identified in the section titled "Risk Factors" in the Company’s Annual Report on Form 10-K for the year ended December 31, 2022 filed with the Securities and Exchange Commission (“SEC”) and the Québec Autorité des Marchés Financiers ("AMF") on February 28, 2023, and its other documents subsequently filed with or furnished to the SEC and AMF including the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 filed with the SEC on November 9, 2023. The Company expressly disclaims any obligation to update any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise, except as otherwise required by law. For more information, please visit reparerx.com and follow Repare on Twitter at @RepareRx and on LinkedIn at . View source version on businesswire.com: Contacts Repare Contact: Robin Garner Vice President and Head of Investor Relations Repare Therapeutics Inc. investor@reparerx.com Investors: Matthew DeYoung Argot Partners repare@argotpartners.com Media: David Rosen Argot Partners david.rosen@argotpartners.com 212-600-1902 Source: Repare Therapeutics Inc. View this news release online at: