Revolution Medicines, Inc.

REDWOOD CITY, CA & MIAMI, FL, USA I June 30, 2025 I Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers and Summit Therapeutics Inc. (Nasdaq: SMMT), a biopharmaceutical oncology company focused on patient-friendly medicinal therapies intended to improve quality of life, increase potential duration of life, and resolve serious unmet medical needs, today announced the companies have entered into a clinical collaboration in multiple solid tumor settings to evaluate the safety and efficacy of each of Revolution Medicines’ clinical-stage RAS(ON) inhibitors, including the multi-selective inhibitor daraxonrasib (RMC-6236), G12D-selective inhibitor zoldonrasib (RMC-9805) and G12C-selective inhibitor elironrasib (RMC-6291), in combination with Summit Therapeutics’ ivonescimab, a PD-1 / VEGF bispecific antibody. “We’ve disclosed promising initial evidence that each of daraxonrasib and elironrasib can deliver additive antitumor activity safely when combined with a PD-1 antibody in first-line treatment of patients with RAS mutant non-small cell lung cancer,” said Mark A. Goldsmith, M.D., Ph.D., Chairman and Chief Executive Officer of Revolution Medicines. “Combinations with novel PD-1 bispecific inhibitors could unlock further therapeutic potential. We are eager to evaluate combinations of investigational drugs from our RAS(ON) inhibitor portfolio with ivonescimab, an advanced PD-1 / VEGF bispecific inhibitor with a differentiated profile, in a range of common RAS mutant cancers.” The clinical collaboration aims to evaluate these combinations across three priority tumor types including RAS mutant non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC). Under the terms of the agreement, Summit Therapeutics will supply ivonescimab for clinical research and Revolution Medicines will be the study sponsor. Each company will retain commercial rights to their respective compounds, and the agreement is mutually non-exclusive. “We’re thrilled to partner with Revolution Medicines to evaluate in a clinical setting how our highly promising ivonescimab combined with their compelling RAS(ON) inhibitors could potentially improve outcomes for patients with lung and gastrointestinal cancers,” said Robert W. Duggan, Chairman and Co-Chief Executive Officer and Dr. Maky Zanganeh, President and Co-Chief Executive Officer of Summit Therapeutics. “As we continue to rapidly advance the clinical development of ivonescimab across non-small cell lung cancer and other solid tumors, we believe that it is critically important to combine ivonescimab with some of the most promising medicines and drug candidates as we seek to provide innovative therapy options to patients facing high unmet needs.” About Revolution Medicines, Inc. Revolution Medicines is a late-stage clinical oncology company developing novel targeted therapies for patients with RAS-addicted cancers. The company’s R&D pipeline comprises RAS(ON) inhibitors designed to suppress diverse oncogenic variants of RAS proteins. The company’s RAS(ON) inhibitors daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor; elironrasib (RMC-6291), a RAS(ON) G12C-selective inhibitor; and zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor, are currently in clinical development. The company anticipates that RMC-5127, a RAS(ON) G12V-selective inhibitor, will be its next RAS(ON) inhibitor to enter clinical development. Additional development opportunities in the company’s pipeline focus on RAS(ON) mutant-selective inhibitors, including RMC-0708 (Q61H) and RMC-8839 (G13C). For more information, please visit www.revmed.com and follow us on LinkedIn . About Summit Therapeutics Inc. Summit Therapeutics Inc. is a biopharmaceutical oncology company focused on the discovery, development, and commercialization of patient-, physician-, caregiver- and societal-friendly medicinal therapies intended to improve quality of life, increase potential duration of life, and resolve serious unmet medical needs. Summit was founded in 2003 and its shares are listed on the Nasdaq Global Market (symbol “SMMT”). It is headquartered in Miami, Florida, and has additional offices in Menlo Park, California, and Oxford, UK. For more information, please visit https://www.smmttx.com and follow us on X @SMMT_TX . About Ivonescimab Ivonescimab, known as SMT112 in Summit’s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity to PD-1 when in the presence of VEGF. This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al, SITC, 2023). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al, SITC, 2023), is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets. Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 2,300 patients have been treated with ivonescimab in clinical studies globally. Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multiregional Phase III clinical trials, HARMONi and HARMONi-3, and the Company has begun to enroll patients in the United States for HARMONi-7. HARMONi is a Phase III clinical trial which is evaluating ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a 3rd generation EGFR TKI (e.g., osimertinib). Top-line results were announced in May 2025, which included a statistically significant and clinically meaningful benefit in progression-free survival and a positive trend in overall survival, the trial’s two primary endpoints. Consistent results were noted between the single region HARMONi-A study and the multiregional HARMONi study. HARMONi-3 is a Phase III clinical trial which is intended to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic, squamous and non-squamous NSCLC. HARMONi-7 is a Phase III clinical trial which is intended to evaluate ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression. In addition, Akeso has recently had positive read-outs in three single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC: HARMONi-A, HARMONi-2, and HARMONi-6. HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI. Approximately 85% of patients received a 3 rd generation EGFR-TKI prior to randomization in the study. HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression. HARMONi-6 is a Phase III clinical trial evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous NSCLC, irrespective of PD-L1 expression. Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was initially approved for marketing authorization in China in May 2024, and its label was expanded in China in April 2025. Ivonescimab was granted Fast Track designation by the US Food & Drug Administration (“FDA”) for the HARMONi clinical trial setting. SOURCE: Summit Therapeutics

REDWOOD CITY, Calif. and MIAMI, June 30, 2025 (GLOBE NEWSWIRE) -- Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers and Summit Therapeutics, Inc. (Nasdaq: SMMT), a biopharmaceutical oncology company focused on patient-friendly medicinal therapies intended to improve quality of life, increase potential duration of life, and resolve serious unmet medical needs, today announced the companies have entered into a clinical collaboration in multiple solid tumor settings to evaluate the safety and efficacy of each of Revolution Medicines’ clinical-stage RAS(ON) inhibitors, including the multi-selective inhibitor daraxonrasib (RMC-6236), G12D-selective inhibitor zoldonrasib (RMC-9805) and G12C-selective inhibitor elironrasib (RMC-6291), in combination with Summit Therapeutics’ ivonescimab, a PD-1 / VEGF bispecific antibody. “We’ve disclosed promising initial evidence that each of daraxonrasib and elironrasib can deliver additive antitumor activity safely when combined with a PD-1 antibody in first-line treatment of patients with RAS mutant non-small cell lung cancer,” said Mark A. Goldsmith, M.D., Ph.D., chairman and chief executive officer of Revolution Medicines. “Combinations with novel PD-1 bispecific inhibitors could unlock further therapeutic potential. We are eager to evaluate combinations of investigational drugs from our RAS(ON) inhibitor portfolio with ivonescimab, an advanced PD-1 / VEGF bispecific inhibitor with a differentiated profile, in a range of common RAS mutant cancers.” The clinical collaboration aims to evaluate these combinations across three priority tumor types including RAS mutant non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC). Under the terms of the agreement, Summit Therapeutics will supply ivonescimab for clinical research and Revolution Medicines will be the study sponsor. Each company will retain commercial rights to their respective compounds, and the agreement is mutually non-exclusive. “We’re thrilled to partner with Revolution Medicines to evaluate in a clinical setting how our highly promising ivonescimab combined with their compelling RAS(ON) inhibitors could potentially improve outcomes for patients with lung and gastrointestinal cancers,” said Robert W. Duggan, Chairman and Co-Chief Executive Officer and Dr. Maky Zanganeh, President and Co-Chief Executive Officer of Summit Therapeutics. “As we continue to rapidly advance the development of ivonescimab across non-small cell lung cancer and other solid tumors, we believe that it is critically important to combine ivonescimab with some of the most promising medicines and drug candidates as we seek to provide innovative therapy options to patients facing high unmet needs.” About Revolution Medicines, Inc. Revolution Medicines is a late-stage clinical oncology company developing novel targeted therapies for patients with RAS-addicted cancers. The company’s R&D pipeline comprises RAS(ON) inhibitors designed to suppress diverse oncogenic variants of RAS proteins. The company’s RAS(ON) inhibitors daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor; elironrasib (RMC-6291), a RAS(ON) G12C-selective inhibitor; and zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor, are currently in clinical development. The company anticipates that RMC-5127, a RAS(ON) G12V-selective inhibitor, will be its next RAS(ON) inhibitor to enter clinical development. Additional development opportunities in the company’s pipeline focus on RAS(ON) mutant-selective inhibitors, including RMC-0708 (Q61H) and RMC-8839 (G13C). For more information, please visit www.revmed.com and follow us on LinkedIn. About Summit Therapeutics, Inc.Summit Therapeutics Inc. is a biopharmaceutical oncology company focused on the discovery, development, and commercialization of patient-, physician-, caregiver- and societal-friendly medicinal therapies intended to improve quality of life, increase potential duration of life, and resolve serious unmet medical needs. Summit was founded in 2003 and its shares are listed on the Nasdaq Global Market (symbol “SMMT”). It is headquartered in Miami, Florida, and has additional offices in Menlo Park, California, and Oxford, UK. For more information, please visit https://www.smmttx.com and follow us on X @SMMT_TX. Revolution Medicines Forward Looking Statements This press release contains forward-looking statements regarding Revolution Medicines within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Any statements in this press release that are not historical facts may be considered "forward-looking statements," including without limitation statements regarding progression of clinical studies and findings from these studies, including the safety, tolerability and antitumor activity of the company’s candidates being studied and the durability of these results; the ability of the company’s RAS(ON) inhibitors to deliver additive antitumor activity in combination with a PD-1 antibody or a PD-1 / VEGF bi-specific inhibitor and related therapeutic options; and the aims and plans of the clinical collaboration with Summit Therapeutics. Forward-looking statements are typically, but not always, identified by the use of words such as "may," "will," "would," "believe," "intend," "plan," "anticipate," "estimate," "expect," and other similar terminology indicating future results. Such forward-looking statements are subject to substantial risks and uncertainties that could cause the company’s development programs, future results, performance or achievements to differ materially from those anticipated in the forward-looking statements. Such risks and uncertainties include without limitation risks and uncertainties inherent in the drug development process, including the company’s programs’ current stage of development, the process of designing and conducting preclinical and clinical trials, risks that the results of prior clinical trials may not be predictive of future clinical trials, clinical efficacy, or other future results, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, the company’s ability to successfully establish, protect and defend its intellectual property, other matters that could affect the sufficiency of the company’s capital resources to fund operations, reliance on third parties for manufacturing and development efforts, changes in the competitive landscape, and the effects on the company’s business of the global events, such as international conflicts or global pandemics. For a further description of the risks and uncertainties that could cause actual results to differ from those anticipated in these forward-looking statements, as well as risks relating to the business of Revolution Medicines in general, see Revolution Medicines’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on May 7, 2025, and its future periodic reports to be filed with the SEC. Except as required by law, Revolution Medicines undertakes no obligation to update any forward-looking statements to reflect new information, events or circumstances, or to reflect the occurrence of unanticipated events. Summit Forward-looking Statements Any statements in this press release about the Summit Therapeutics’ future expectations, plans and prospects, including but not limited to, statements about the clinical and preclinical development of the Summit Therapeutics’ product candidates, entry into and actions related to the Summit Therapeutics’ partnership with Akeso Inc., the Summit Therapeutics' anticipated spending and cash runway, the therapeutic potential of the Summit Therapeutics’ product candidates, the potential commercialization of the Summit Therapeutics’ product candidates, the timing of initiation, completion and availability of data from clinical trials, the potential submission of applications for marketing approvals, potential acquisitions, statements about the previously disclosed At-The-Market equity offering program (“ATM Program”), the expected proceeds and uses thereof, and other statements containing the words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "would," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the Summit Therapeutics’ ability to sell shares of our common stock under the ATM Program, the conditions affecting the capital markets, general economic, industry, or political conditions, the results of our evaluation of the underlying data in connection with the development and commercialization activities for ivonescimab, the outcome of discussions with regulatory authorities, including the Food and Drug Administration, the uncertainties inherent in the initiation of future clinical trials, availability and timing of data from ongoing and future clinical trials, the results of such trials, and their success, global public health crises, that may affect timing and status of our clinical trials and operations, whether preliminary results from a clinical trial will be predictive of the final results of that trial or whether results of early clinical trials or preclinical studies will be indicative of the results of later clinical trials, whether business development opportunities to expand the Summit Therapeutics’ pipeline of drug candidates, including without limitation, through potential acquisitions of, and/or collaborations with, other entities occur, expectations for regulatory approvals, laws and regulations affecting government contracts and funding awards, availability of funding sufficient for the Summit Therapeutics’ foreseeable and unforeseeable operating expenses and capital expenditure requirements and other factors discussed in the "Risk Factors" section of filings that the Summit Therapeutics makes with the Securities and Exchange Commission. Any change to our ongoing trials could cause delays, affect our future expenses, and add uncertainty to our commercialization efforts, as well as to affect the likelihood of the successful completion of clinical development of ivonescimab. Accordingly, readers should not place undue reliance on forward-looking statements or information. In addition, any forward-looking statements included in this press release represent the Summit Therapeutics’ views only as of the date of this release and should not be relied upon as representing the Summit Therapeutics’ views as of any subsequent date. The Summit Therapeutics specifically disclaims any obligation to update any forward-looking statements included in this press release. Revolution Medicines Media & Investor Contact:media@revmed.cominvestors@revmed.com Summit Therapeutics’ Media & Investor Contact:Dave GancarzChief Business & Strategy Officer Nathan LiaBraatenSenior Director, Investor Relations investors@smmttx.commedia@smmttx.com

近日，FDA授予daraxonrasib突破性疗法认定，用于治疗先前接受过治疗的转移性胰腺导管腺癌（PDAC）患者，这些患者携带KRAS G12突变。新闻来源于企业网站这次认定是基于daraxonrasib在I期RMC-6236-001临床试验中观察到的令人鼓舞的早期临床证据。突破性疗法认定旨在加快针对严重疾病且解决重大未满足医疗需求的潜在新药的开发和审评。该药物需要显示出令人鼓舞的初步临床证据，证明其在临床上重要的终点上较现有药物有显著改善。胰腺癌与PDAC胰腺癌是一种致命性极高的恶性肿瘤，通常在晚期才被诊断，对标准化疗有耐药性，死亡率高。最常见的胰腺癌形式是胰腺导管腺癌（PDAC）及其变体，占所有胰腺癌病例的约92%。由于缺乏早期症状和检测方法，大约80%的患者在晚期或转移性阶段被诊断出患有PDAC。超过90%的PDAC患者携带RAS突变，其中约85%携带KRAS G12X突变，PDAC的五年生存率仅为3%。治疗现状目前主要治疗方式为多药化疗，但效果有限且毒性显著。现有的靶向治疗仅能惠及少数患者。疗效有限  目前报道的二线及以上（2L+）患者中的客观缓解率（ORR）仅3–17%，中位无进展生存期（PFS）为2.0–3.5个月，中位总生存期（OS）为6.1–6.9个月。  毒性显著  例如，NAPOLI-1方案中，62%患者需中断给药，33%需减量，以及11%终止该治疗方案。Daraxonrasib/RMC-6236RMC-6236：是一种口服的小分子RAS(ON)[RAS蛋白的活性状态]多选择性抑制剂，用于治疗携带RAS突变的癌症。靶点：针对常见的RAS突变，包括G12X、G13X和Q61X，这些突变是胰腺导管腺癌（PDAC）、非小细胞肺癌（NSCLC）和结直肠癌（CRC）等主要癌症的驱动因素。作用方式：通过阻断RAS(ON)与其下游效应因子的相互作用来抑制RAS信号传导。临床前结果：在RAS G12X突变的胰腺导管腺癌（PDAC）模型中诱导持久的无进展生存期。突破性认定的初期临床试验结果RMC-6236-001 是一项 1/1b期多中心、开放标签、剂量递增和扩展研究，旨在评估 RMC-6236（即 daraxonrasib）作为单药治疗携带RAS突变或野生型RAS晚期实体瘤患者的安全性、最佳剂量和疗效。该研究主要纳入携带RAS突变（如 KRAS G12X）的晚期实体瘤患者，包括胰腺导管腺癌（PDAC）和非小细胞肺癌（NSCLC）患者。截至2024年9月30日，共有436名患者入组，其中包含132名NSCLC患者，304名PDAC及其他实体瘤患者，治疗剂量范围为每日一次10至400毫克。其中，daraxonrasib（300mg治疗剂量）在PDAC患者中展现出良好的数据：在76名携带RAS突变的PDAC患者中，每日一次300毫克剂量的RMC-6236显示出良好的耐受性，未观察到新的安全信号，安全性可控（常见皮疹、腹泻；停药率低）。其中，在37名携带RAS任意突变的PDAC患者中，RMC-6236作为二线疗法显示出显著的抗肿瘤活性：携带 KRAS G12X 突变的PDAC患者（n=22）的中位无进展生存期（PFS）为 8.8个月（95% CI：8.5个月–不可估计），携带任意RAS突变的PDAC患者（n=37）的中位无进展生存期（PFS）为 8.5个月（95% CI：5.9个月–不可估计）。携带 KRAS G12X 突变的PDAC患者和携带任意 RAS 突变的PDAC患者的中位总生存期（OS）均不可估计。携带 KRAS G12X 突变的PDAC患者的6个月生存率为 100%，携带任意 RAS 突变的PDAC患者为 97%。携带 KRAS G12X 突变的PDAC患者的客观缓解率（ORR）为 36%，携带任意 RAS 突变的PDAC患者为 27%。其他关键结果*（160-300mg治疗剂量）在该临床结果中，还观察到二线（2L）患者的中位无进展生存期（PFS）为8.1个月（KRAS G12X患者），对比化疗基准2.0–3.5个月。在二线（2L）与三线及以上（3L+）携带KRAS G12X 突变的患者中观察到的无进展生存期（PFS）分别为8.1个月和4.2个月，对比化疗基准2.0–3.5个月和1.9个月。二线及以上（2L+）携带KRAS G12X 突变的患者的客观缓解率（ORR）为20–27%（对比基准9%）。二线（2L）患者中观察到的中期总生存期（OS）：携带 KRAS G12X 突变和任意RAS突变的PDAC患者均不可估计（或存在长生存期患者导致），对比化疗基准6.1-6.9个月。III期临床试验RASolute 302:一项针对经治转移性PDAC患者的daraxonrasib的III期注册研究。该研究设计聚焦于携带RAS G12X的PDAC核心患者群体，以及一个扩展人群，包括携带RAS G12X、RAS G13X或RAS Q61X突变的肿瘤患者，或那些未发现任何可靶向突变的患者（NCT06625320），计划作为二线疗法替代化疗。该试验设计的主要终点为核心人群的无进展生存期（PFS）和总生存期（OS）。次要终点为扩展人群的PFS和OS。预计今年将完成大部分患者入组，计划在2026年获得结果。总结RMC-6236（daraxonrasib）作为一种RAS(ON)多选择性抑制剂，在晚期实体瘤（特别是PDAC和NSCLC）患者中显示出良好的耐受性和显著的抗肿瘤活性。RMC-6236-001研究的积极结果为该药物的进一步开发提供了坚实基础，而正在进行的RASolute 302 III期研究将进一步验证其在经治转移性PDAC患者中的疗效和安全性。当前PDAC治疗以化疗为主，但疗效和耐受性不足。Revolution Medicines公司计划在一线治疗和联合治疗方案中继续探索RMC-6236的潜力，以期改变这一格局，为RAS突变癌症患者提供新的治疗选择。声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！长按关注本公众号   粉丝群/投稿/授权/广告等请联系公众号助手 觉得本文好看，请点这里↓