Sunitinib Malate

Phase 3 PEAK results in 2nd-line GIST patients expected in November; pivotal APEX results in AdvSM patients expected in December Breakthrough Therapy Designation granted for bezuclastinib; New Drug Application (NDA) filing for NonAdvSM remains on track for year-end 2025 Multiple bezuclastinib abstracts selected for presentation at the 67th Annual Meeting of the American Society of Hematology (ASH); SUMMIT data in NonAdvSM selected for two oral presentations Plan to showcase novel JAK2 V617F mutant-selective candidate at ASH 2025 Strong pro forma cash position of $430 million expected to fund operations through anticipated launch of bezuclastinib and into 2027 WALTHAM, Mass. and BOULDER, Colo., Nov. 03, 2025 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today reported recent business highlights and financial results for the third quarter ended September 30, 2025. “Cogent had a very productive and busy third quarter and we now find ourselves weeks away from reporting top-line results from our Phase 3 PEAK trial of bezuclastinib plus sunitinib in Gastrointestinal Stromal Tumor (GIST) patients and our registration-directed APEX trial in Advanced Systemic Mastocytosis (AdvSM) patients. In addition, we are pleased to announce we will have three bezuclastinib presentations at ASH 2025, including two oral presentations focused on the results from the SUMMIT trial in NonAdvanced Systemic Mastocytosis (NonAdvSM) patients,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “On top of this progress, we recently presented updated preclinical data from our research pipeline that demonstrated potential best-in-class attributes of our pan-KRAS inhibitor and plan to describe for the first time at ASH 2025 our highly potent, highly selective JAK2 V617F mutant-selective inhibitor. Both of these programs are on track for IND in 2026. Our continued financial discipline and business execution position us well as we head into pivotal data readouts and prepare for our first NDA filing for NonAdvSM later this year.” Recent Business Highlights Announced alignment with the U.S. Food and Drug Administration (FDA) on the SUMMIT New Drug Application (NDA) submission plan for broad NonAdvSM patient population following a productive pre-NDA meeting, as well as the receipt of Breakthrough Therapy Designation for bezuclastinib in NonAdvSM patients previously treated with avapritinib and in patients with Smoldering Systemic Mastocytosis; populations with no currently approved standard of care. Reported positive top-line results from SUMMIT evaluating bezuclastinib in patients with NonAdvSM, achieving statistical significance across all primary and key secondary endpoints. Announced multiple presentations have been accepted at the 67th Annual Meeting of the American Society of Hematology (ASH) being held December 6-9, 2025, in Orlando, FL, including two SUMMIT oral presentations and a poster presentation on Cogent’s novel JAK2 V617F mutant-selective inhibitor, the company’s newest discovery stage program. Details of the ASH presentations can be found in a separate release issued today. Recently received clearance from the FDA on Cogent’s Investigational New Drug (IND) submission for CGT4255, a novel, selective, potent, CNS-penetrant ErbB2 inhibitor. A Phase 1 dose escalation trial is on track to initiate in November. In July, successfully closed an upsized underwritten public offering of 25,555,556 shares of common stock at $9.00 per share, including the full exercise of the underwriters’ option to purchase an additional 3,333,333 shares. This offering generated net proceeds of $215.8 million. Cogent also recently raised $39 million through targeted share sales via the Company’s at-the-market facility (ATM). Anticipated Upcoming Milestones Announce top-line results from PEAK in November 2025. PEAK is a global, randomized Phase 3 clinical trial studying the combination of bezuclastinib and sunitinib versus sunitinib alone in patients with imatinib-resistant GIST. Announce top-line results from APEX in December 2025. APEX is a registration-directed, global, open-label trial in patients with AdvSM. Submit Cogent’s first NDA for bezuclastinib by the end of 2025. Third Quarter 2025 Financial Results Cash Position: As of September 30, 2025, cash, cash equivalents and marketable securities were $390.9 million, as compared to $345.5 million as of June 30, 2025. The company believes that its cash, cash equivalents and marketable securities, together with the $39.0 million gross proceeds from shares sold through the ATM since last quarterly filing, will be sufficient to fund its operating expenses and capital expenditure requirements into 2027, including through potential FDA approval of bezuclastinib for NonAdvSM and early commercial launch activities. R&D Expenses: Research and development expenses were $69.0 million for the third quarter of 2025 as compared to $63.6 million for the third quarter of 2024. The increase was primarily due to costs incurred to support our on-going SUMMIT, PEAK and APEX clinical trials and to the continued progression of our early stage, preclinical and discovery programs. R&D expenses include non-cash stock compensation expense of $5.4 million for the third quarter of 2025 compared to $4.8 million for the third quarter of 2024. G&A Expenses: General and administrative expenses were $14.4 million for the third quarter of 2025 as compared to $11.8 million for the third quarter of 2024. The increase was primarily due to the growth of the organization. G&A expenses include non-cash stock compensation expense of $5.2 million for the third quarter of 2025 compared to $5.6 million for the third quarter of 2024. Net Loss: Net loss was $80.9 million for the third quarter of 2025 as compared to a net loss of $70.6 million for the same period of 2024. Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) Cogent also announced today that on October 22, 2025, the Compensation Committee of Cogent’s Board of Directors, made up entirely of independent directors, approved the grant of “inducement” equity awards to five new employees under the company’s 2020 Inducement Plan with a grant date of November 3, 2025. The awards were approved in accordance with Listing Rule 5635(c)(4) of the corporate governance rules of the Nasdaq Stock Market. The employees received, in the aggregate, nonqualified options to purchase 89,500 shares of Cogent common stock. Each option has a 10-year term, an exercise price equal to the closing price of Cogent’s common stock on the grant date, and a four-year vesting schedule with 25% vesting on the one-year anniversary of the grant date and the remainder vesting in equal monthly installments over the subsequent 36 months, provided such employee remains employed through each such vesting date. About Cogent Biosciences, Inc. Cogent Biosciences is a biotechnology company focused on developing precision therapies for genetically defined diseases. The most advanced clinical program, bezuclastinib, is a selective tyrosine kinase inhibitor that is designed to potently inhibit the KIT D816V mutation as well as other mutations in KIT exon 17. KIT D816V is responsible for driving systemic mastocytosis, a serious disease caused by unchecked proliferation of mast cells. Exon 17 mutations are also found in patients with advanced gastrointestinal stromal tumors (GIST), a type of cancer with strong dependence on oncogenic KIT signaling. In addition to bezuclastinib, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases initially targeting mutations in FGFR2/3, ErbB2, PI3Kα, KRAS and JAK2. Cogent Biosciences is based in Waltham, MA and Boulder, CO. Visit our website for more information at www.cogentbio.com. Follow Cogent Biosciences on social media: X (formerly known as Twitter) and LinkedIn. Information that may be important to investors will be routinely posted on our website and X. Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding: plans to present top-line results from the company’s PEAK trial in November 2025; plans to present top-line results from the company’s APEX trial in December 2025; the company’s plans to file an NDA for NonAdvSM before the end of 2025; expectations that the company’s cash is sufficient to fund operations through anticipated commercial launch and into 2027; the best-in-class potential of the company’s pan-KRAS inhibitor; the company’s plans to file INDs in 2026 for both of its KRAS and JAK2 programs; the company’s expectation that bezuclastinib will be approved by the FDA for commercial use for patients with NonAdvSM; and the company’s plans to initiate a Phase 1 trial for its ErbB2 program before the end of 2025. The use of words such as, but not limited to, "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," or "would" and similar words expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results, the rate of enrollment in our clinical trials and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. We may not actually achieve the forecasts or milestones disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Cogent's most recent Quarterly Report on Form 10-Q filed with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither we, nor our affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date hereof. Contact:Christi WaarichSenior Director, Investor Relationschristi.waarich@cogentbio.com617-830-1653

*仅供医学专业人士阅读参考FRUSICA-2研究精彩亮相ESMO2025肾细胞癌（RCC）是常见的泌尿系统恶性，晚期患者预后普遍较差。近年来，靶向、免疫治疗的应用极大地改善了患者的一线治疗获益，然而一旦疾病发生进展，后续的治疗选择有限。尤其在中国，晚期RCC的二线治疗目前仍以酪氨酸激酶抑制剂（TKI）或哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂单药治疗为主，存在未满足临床需求。FRUSICA-2 Ⅲ期研究[1]旨在评估呋喹替尼联合信迪利单抗对比现有标准疗法，用于晚期RCC二线治疗的疗效与安全性。近日，FRUSICA-2 Ⅲ期研究在2025年欧洲肿瘤内科学会（ESMO）大会上以口头报告形式隆重发布（摘要号2592MO），成为本次会议的一大亮点。医学界肿瘤频道特邀中国医学科学院肿瘤医院邢念增教授就该研究的背景、设计、主要结果及其对临床实践产生的影响进行专业解读，帮助临床医生更好地理解这一治疗方案，为未来临床实践提供循证依据，进一步改善晚期RCC患者的生存预后。专家简介邢念增 教授国家中心/中国医学科学院肿瘤医院副院长泌尿外科主任医师、博士研究生及博士后导师泌尿系统肿瘤细胞和基因治疗北京市重点实验室主任全国人大代表中央保健委员会 会诊专家首届“国家杰出医师”国家“有突出贡献中青年专家”，“百千万人才工程”国家级人才， 国家卫生健康突出贡献中青年专家。享受国务院特殊津贴。国之名医。吴杨医学药学奖获得者。担任中国医师协会泌尿外科医师分会会长、北京医学会泌尿外科分会候任主任委员、Endourological Society 委员，UroPrecison杂志主编、 J of Urology 编委、 《中华医学杂志》副总编、 《中华泌尿外科杂志》副总编、 《中华腔镜泌尿外科杂志》副总编、 《临床泌尿外科杂志》副总编国家重点研发计划首席科学家。国内外发表学术论文400余篇。主编专著23部。晚期肾癌二线治疗困局：靶向耐药与肿瘤异质性下的生存挑战邢念增教授指出，肾癌已成为全球公共卫生领域的一个重大挑战。据统计，2022年全球新发病例数超过43.4万例，每年因肾癌导致的死亡人数约为15.6万[2]。在中国，肾癌每年约造成2.4万人死亡，占全国所有癌症死亡病例的0.9%[3]。RCC占据了肾脏恶性肿瘤的90%，且转移性RCC患者的预后不佳，5年生存率仅为12%[4]。在晚期RCC患者中，传统放、化疗的疗效并不理想，患者生存预后不佳。尽管靶向治疗和免疫治疗的引入显著提高了RCC一线治疗的疗效，客观缓解率（ORR）可达到42%-71.6%，无进展生存期（PFS）延长至11.6-23.9个月[5-11]，但在二线治疗中，仍以TKI、mTOR抑制剂单药治疗为主，其ORR仅为1.0%至23%，中位PFS仅为4.0至8.3个月[11-14]，疗效有限，难以满足患者的治疗需求。更为棘手的是，接受二线治疗的患者大多数已经历过一线TKI治疗的失败，这些患者的肿瘤细胞通常表现出复杂的耐药机制和显著的异质性，亟需更有效的治疗策略以改善这类患者的预后。机制协同，疗效显著：呋喹替尼联合信迪利单抗创晚期RCC二线治疗新纪录邢念增教授表示，FRUSICA-2是一项II/III期临床研究，其中本次ESMO会议公布的数据来自其III期研究，这是一个随机、开放标签、阳性对照试验，旨在评估呋喹替尼联合信迪利单抗对比现有标准疗法（阿昔替尼或依维莫司）在局部晚期或转移性RCC患者二线治疗中的疗效与安全性。研究纳入既往接受过一线VEGFR-TKI治疗失败或不耐受的晚期RCC患者（n=234），按1:1随机分配至实验组和对照组。主要研究终点为盲态独立阅片委员会（BIRC）评估的PFS，次要终点为研究者评估的PFS、ORR、DCR等。该研究在此次ESMO大会首次公布的研究数据显示呋喹替尼联合信迪利单抗用于RCC的二线治疗，疗效优异，安全性良好，引发广泛关注。经BIRC评估，联合组的中位PFS长达22.2个月，而对照组仅为6.9个月[HR=0.373(95% CI: 0.256, 0.544);p< 0.0001]，使疾病进展或死亡风险显著降低了63%。在晚期RCC治疗领域，能够在中位PFS上突破20个月的治疗方案，此前仅见于一线治疗。呋喹替尼与信迪利单抗联合方案在二线治疗中取得如此卓越的疗效，展现出接近一线标准治疗的巨大潜力，有望为晚期RCC患者的二线治疗提供更具希望的新选择。联合组的ORR高达60.5%，是对照组（24.3%）的2.5倍（OR=4.622，p<0.0001）。这一数据表明，联合治疗方案能够更有效地抑制肿瘤生长，使更多患者获得病情缓解的机会，为患者带来了更多的生存希望。联合组的中位DoR达到了23.7个月，相较于对照组单药治疗的11.3个月，延长了12.4个月。说明呋喹替尼联合信迪利单抗这一靶免治疗方案一旦起效，就能够为患者带来更为持久的临床获益。尽管采用了联合治疗方案，但其安全性整体可控，并未出现新的非预期安全性信号。这意味着患者在接受治疗的过程中，能够在有效控制病情的同时，不良反应可管可控，保障了治疗的耐受性和依从性，为长期治疗奠定了基础。邢念增教授在深入分析该研究取得成功的关键因素时指出，本研究在lb期数据表现出色，ORR达到60%，中位PFS达15.9个月。这些优异的前期数据为Ⅲ期试验的设计提供了坚实的科学依据，保障了研究的科学性和可靠性。在该研究的研究设计中，对照组选用了当前二线标准治疗（阿昔替尼或依维莫司），具有高度的临床可比性，为后续的临床决策提供了强有力的证据支持。药物机制层面，呋喹替尼通过抑制VEGFR信号通路，有效阻断肿瘤血管生成，并可改善肿瘤免疫微环境。该药物靶点精准，脱靶毒性小，疗效和安全性已在多种已获批的实体瘤适应症中得到验证。与信迪利单抗联合使用，能够协同增效，实现抗血管生成与免疫治疗的双重机制互补，显著提升抗肿瘤效果，展现出广阔的临床应用前景。这种机制上的协同效应，是联合治疗取得成功的重要基础。此外，本研究采用亚组分析，纳入了程序性死亡配体-1（PD-L1）表达水平等因素。结果显示，呋喹替尼联合信迪利单抗的疗效与PD-L1表达情况无关，即无论PD-L1表达水平如何，该联合治疗方案均显示出优于当前二线标准治疗的疗效。说明该联合方案具备广泛的适用人群，有望让更多患者从中获益。邢念增教授表示，FRUSICA-2研究的成果，将对临床实践产生深远而积极的影响。其突出的疗效数据有望促进呋喹替尼联合信迪利单抗成为晚期RCC二线治疗的标准方案。这一研究进展有望为临床医生及患者提供更科学、有效的治疗选择，进一步改善患者的预后。晚期RCC二线治疗：多因素考量，精准制定方案邢念增教授强调，晚期RCC患者在接受一线治疗发生耐药后，如何选择合适的二线治疗方案一直是临床关注的重点问题。CSCO肾癌专家委员会达成共识，在任何情况下，评估患者是否符合临床试验入组条件应作为二线治疗决策的首要步骤。若患者无法进入临床试验，则需系统回顾其一线治疗情况，包括所用方案、治疗持续时间、最佳缓解时间以及是否出现特定不良反应等，这些信息是制定二线治疗方案的重要依据。了解一线治疗的药物作用机制以及耐药机制是选择二线药物的关键，有助于筛选出作用机制不同或可逆转耐药的药物。以FRUSICA-2研究为例，在该研究开展之时，中国的晚期RCC一线治疗仍以靶向药物单药治疗为主，免疫联合治疗在一线中的应用直至2024年才获批准。而且以TKI类药物为代表的一线靶向治疗方案，因其高级别的循证医学证据支持、口服给药的便捷性以及便于长期管理等特点，目前仍是临床广泛应用的优选方案。FRUSICA-2研究通过联合应用不同机制的药物，有效克服TKI耐药，显著提高了二线治疗的疗效，延长患者的生存期。在选择二线治疗方案时，依据权威指南和高级别临床证据（如Ⅲ期随机对照试验）是重要原则。例如FRUSICA-2Ⅲ期研究的阳性结果，为呋喹替尼联合信迪利单抗在晚期RCC二线治疗中的应用提供了坚实证据，使该联合方案有望成为新的临床标准选择之一。安全性及耐受性同样是制定二线治疗方案时不可忽视的重要因素，直接影响治疗完成度和患者生活质量。应全面评估不同治疗方案常见及罕见不良反应，并结合患者的具体身体状况和耐受能力，选择更为匹配、安全性更优的方案。同时，加强不良反应的预防与全程管理，保障患者治疗顺利和生活质量。药物可及性与经济因素也是影响治疗方案选择的实际问题，医生需要考虑治疗方案是否已在国内获批相应适应症、是否纳入医保报销范围，并结合患者的经济承受能力，制定切实可行的个体化治疗策略。总之，为一线治疗耐药后的晚期RCC患者制定二线方案是一个需整合多方面因素的临床决策过程。只有充分考虑上述各个关键因素，将临床试验机会、前线治疗方案、耐药机制分析、证据指南推荐、安全耐受评估以及药物经济药物经济学因素系统结合，才能为患者提供真正精准、个性化的治疗选择，最终提升治疗效果、改善生活质量和生存预后。未来，随着研究的不断深入和新型药物的不断涌现，晚期RCC的二线治疗格局有望迎来更多突破，为患者带来新的希望。总结与展望FRUSICA-2的III期研究结果在ESMO 2025大会上重磅发布，为晚期RCC二线治疗带来了重要突破。该研究采用呋喹替尼联合信迪利单抗方案，在PFS、ORR及DoR等关键指标上显著优于标准治疗组，且安全性可控，展现出接近一线治疗的疗效潜力。这一成果不仅为临床提供了更优的治疗选择，也有望推动国内外指南更新，改变晚期RCC二线治疗格局。展望未来，随着对肿瘤异质性和耐药机制研究的不断深入，以及生物标志物指导下的精准治疗发展，晚期RCC二线将朝着更加个体化、高效化的方向迈进。同时，随着药物可及性与经济性的持续优化，更多患者将能够从创新治疗方案中获益。FRUSICA-2研究的成功，是中国创新药研发实力的彰显，也为全球肾癌治疗领域贡献了中国智慧。期待该研究进一步推动国际多中心合作，为更多患者带来希望。参考文献：[1].Dingwei Y , Zhisong H , Yuanyuan Q,et al.Fruquintinib (FRUQ) plus sintilimab (SIN) versus axitinib (AXI) or everolimus (EVE) monotherapy as 2L treatment in pts with locally advanced or metastatic renal cell carcinoma (RCC).2025 ESMO 2592MO.[2].Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2024).[3].Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.who.int/today, accessed [DD Month YYYY].[4].Zheng RS, Chen R, Han BF, et al. [Cancer incidence and mortality in China, 2022]. Zhonghua Zhong Liu Za Zhi. 2024 Mar 23;46(3):221-231. Chinese. doi: 10.3760/cma.j.cn112152-20240119-00035. PMID: 38468501.[5].Motzer RJ, Tannir NM, McDermott DF,et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277-1290.[6].Motzer RJ, Penkov K, Haanen J,et al. Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019 Mar 21;380(12):1103-1115.[7].Rini BI, Plimack ER, Stus V,et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019 Mar 21;380(12):1116-1127.[8].Choueiri TK, Powles T, Burotto M, et al. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2021 Mar 4;384(9):829-841.[9].Lee CH, Shah AY, Rasco D,et al. Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (Study 111/KEYNOTE-146): a phase 1b/2 study. Lancet Oncol. 2021 Jul;22(7):946-958.[10].Yan XQ, Ye MJ, Zou Q,et al. Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study. Ann Oncol. 2024 Feb;35(2):190-199.[11].Xinan S,et al.First-line benmelstobart plus anlotinib versus sunitinib in advanced renal cell carcinoma: Subgroup analysis from the phase 3 ETER100 trial.2024 ESMO, Abstract LBA76.[12].Motzer RJ, Escudier B, Oudard S,et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008 Aug 9;372(9637):449-56.[13].Motzer RJ, Escudier B, Tomczak P,et al. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):552-62.[14].Choueiri TK, Escudier B, Powles T,et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):917-927.本资料由和黄医药提供支持本资料旨在促进医药信息的沟通和交流，而非广告宣传。本资料内容不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议。若您想了解更多有关疾病知识的信息，请咨询医疗卫生专业人士。*此文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场。