Rezatapopt

Updated clinical results from Phase 2 pivotal portion of the PYNNACLE study evaluating rezatapopt featured in late-breaking oral presentation at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics34% overall response rate (ORR) observed among 103 evaluable patients across all cohorts with a median duration of response of 7.6 months46% ORR observed among 48 evaluable patients in ovarian cancer cohort with a median duration of response of 8.0 monthsRezatapopt New Drug Application submission for platinum resistant/refractory ovarian cancer planned in first quarter of 2027Cash, cash equivalents, and marketable securities of $129.3 million as of September 30, 2025, providing expected cash runway to end of first quarter of 2027 PRINCETON, N.J., Nov. 12, 2025 (GLOBE NEWSWIRE) -- PMV Pharmaceuticals, Inc. (“PMV Pharma” or the “Company”; Nasdaq: PMVP), a precision oncology company pioneering the discovery and development of small molecule therapies targeting p53, today reported financial results for the third quarter ended September 30, 2025, and provided a corporate update. “I am incredibly proud of our team and their commitment to rapidly and efficiently advancing the PYNNACLE study,” said David Mack, Ph.D., President and Chief Executive Officer of PMV Pharma. “We are excited by the data emerging from this study and look forward to submitting an NDA in the first quarter of 2027 for platinum-resistant/refractory ovarian cancer.” Corporate Highlights Updated clinical results from the Phase 2 pivotal portion of the PYNNACLE study evaluating rezatapopt were featured in late-breaking oral and poster presentations at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics on October 24, 2025. Confirmed responses were observed in patients whose tumors were TP53 Y220C mutated and KRAS wild-type in eight tumor types including ovarian, lung, breast, endometrial, head and neck, colorectal, gallbladder cancers, and ampullary carcinoma.Overall response rate (ORR) of 34% (35/103 patients) per investigator assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, including confirmed and unconfirmed responses. The cohort-specific ORRs were as follows: Ovarian cancer: 46% ORR (22/48 patients, including one confirmed complete response, 18 confirmed partial responses, and three unconfirmed partial responses [uPR])Breast cancer: 17% ORR (2/12 patients)Endometrial cancer: 60% ORR (3/5 patients, including one uPR)Lung cancer: 21% ORR (4/19 patients, including one uPR)Other solid tumors: 21% ORR (4/19 patients) Across all cohorts, the median time to response was 1.3 months and the median duration of response was 7.6 months. In the ovarian cancer cohort, the median time to response was 1.3 months and median duration of response was 8.0 months.Post the September 4, 2025 data cutoff date, four uPRs were confirmed and one uPR (ovarian cancer) remains on treatment. A poster entitled, “Natural history and prognostic value of TP53 Y220C mutation in advanced solid tumors: A real-world study,” was also presented at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, which concluded that patients with TP53 Y220C-mutated solid tumors had poor prognoses and reduced overall survival compared to patients without a TP53 Y220C mutation. Third Quarter 2025 Financial Results PMV Pharma ended the third quarter with $129.3 million in cash, cash equivalents, and marketable securities, compared to $148.3 million as of June 30, 2025. Net cash used in operations was $56.4 million for the nine months ended September 30, 2025, compared to $34.6 million for the nine months ended September 30, 2024. Net loss for the quarter ended September 30, 2025, was $21.1 million compared to $19.2 million for the quarter ended September 30, 2024. The net loss increase was primarily due to increased research and development (R&D) costs.R&D expenses were $18.2 million for the quarter ended September 30, 2025, compared to $16.9 million for the quarter ended September 30, 2024. The increase in R&D expenses was primarily due to increased contractual research organization costs for the advancement of the rezatapopt program.General and administrative (G&A) expenses were $4.3 million for the quarter ended September 30, 2025, compared to $4.9 million for the quarter ended September 30, 2024. The decrease in G&A expenses was primarily due to reduced spend for stock-based compensation and facility and operational expenses. About Rezatapopt Rezatapopt (PC14586) is a first-in-class, small molecule, p53 reactivator designed to selectively bind to the pocket in the p53 Y220C mutant protein, restoring the wild-type tumor-suppressor function. The U.S. Food and Drug Administration granted Fast Track designation to rezatapopt for the treatment of patients with locally advanced or metastatic solid tumors with a p53 Y220C mutation. About the PYNNACLE Clinical Trial The ongoing Phase 1/2 PYNNACLE clinical trial is evaluating rezatapopt in patients with advanced solid tumors harboring a TP53 Y220C mutation. The primary objective of the Phase 1 portion of the clinical trial was to determine the maximum tolerated dose and recommended Phase 2 dose (RP2D) of rezatapopt when administered orally to patients. Safety, tolerability, pharmacokinetics and effects on biomarkers were also assessed. The Phase 2 portion is a registrational, single arm, expansion basket clinical trial comprising five cohorts (ovarian, lung, breast, and endometrial cancers, and other solid tumors) with the primary objective of evaluating the efficacy of rezatapopt at the RP2D in patients with TP53 Y220C and KRAS wild-type advanced solid tumors. For more information about the Phase 1/2 PYNNACLE clinical trial, refer to www.clinicaltrials.gov (NCT trial identifier NCT04585750). About PMV Pharma PMV Pharma is a precision oncology company pioneering the discovery and development of small molecule therapies targeting p53. TP53 mutations are found in approximately half of all cancers. Our co-founder, Dr. Arnold Levine, established the field of p53 biology when he discovered the p53 protein in 1979. Bringing together leaders in the field to utilize over four decades of p53 biology, PMV Pharma combines unique biological understanding with a pharmaceutical development focus. PMV Pharma is headquartered in Princeton, New Jersey. For more information, please visit www.pmvpharma.com. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding the Company’s future plans or expectations for rezatapopt, including our ability to obtain approval as a treatment option as a monotherapy, expectations regarding timing, number of patients and treatment durations for our interim data readouts, expectations regarding timing and success of the Phase 2 portion of the current clinical trial for rezatapopt and filing of an NDA for platinum-resistant/refractory ovarian cancer, and the timing and expectations with respect to our projected cash runway. Any forward-looking statements in this statement are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost, and timing of the Company’s product candidate development activities, including the successful filing of NDAs, and planned clinical trials, the Company’s ability to execute on its strategy and operate as a clinical stage company, the potential for clinical trials of rezatapopt or any future clinical trials of other product candidates to differ from preclinical, preliminary or expected results, the Company’s ability to fund operations, and the impact that a global pandemic, other public health emergencies or geopolitical tensions or conflicts may have on the Company’s clinical trials, supply chain, and operations, as well as those risks and uncertainties set forth in the section entitled “Risk Factors” in the Company’s Annual Report on Form 10-K, filed with the Securities and Exchange Commission (the “SEC”) on March 3, 2025, the Company’s Quarterly Report on Form 10-Q for the three months ended March 31, 2025, filed with the SEC on May 9, 2025, and the Company’s Quarterly Report on Form 10-Q for the three months ended June 30, 2025, filed with the SEC on August 7, 2025, and its other filings filed with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Investors Contact:Tim SmithSenior Vice President, Head of Corporate Development and Investor Relationsinvestors@pmvpharma.com Media Contact:Kathy VincentGreig Communicationskathy@greigcommunications.com PMV Pharmaceuticals, Inc.Condensed Consolidated Balance Sheets(unaudited)(in thousands, except share and per share amounts) September 30,2025 December 31,2024Assets Current assets: Cash and cash equivalents$36,337 $40,876 Marketable securities, current 92,913 128,578 Prepaid expenses and other current assets 3,199 6,204 Total current assets 132,449 175,658 Property and equipment, net 255 409 Marketable securities, noncurrent — 13,843 Right-of-use assets 891 1,143 Other assets 249 235 Total assets$133,844 $191,288 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable$3,399 $6,579 Accrued expenses 8,515 7,439 Operating lease liabilities, current 390 352 Total current liabilities 12,304 14,370 Operating lease liabilities, noncurrent 541 838 Total liabilities 12,845 15,208 Stockholders’ equity: Additional paid-in capital 549,325 544,653 Accumulated deficit (428,417) (368,712)Accumulated other comprehensive income 91 139 Total stockholders’ equity 120,999 176,080 Total liabilities and stockholders’ equity$133,844 $191,288 PMV Pharmaceuticals, Inc.Condensed Consolidated Statements of Operations and Comprehensive Loss(unaudited)(in thousands, except share and per share amounts) Three Months EndedSeptember 30, Nine Months EndedSeptember 30, 2025 2024 2025 2024 Operating expenses: Research and development$18,210 $16,947 $54,050 $44,760 General and administrative 4,312 4,941 12,914 15,520 Total operating expenses 22,522 21,888 66,964 60,280 Loss from operations (22,522) (21,888) (66,964) (60,280)Other income (expense): Interest income, net 1,480 2,615 5,105 8,368 Other (expense) income, net (23) 121 (44) 103 Total other income 1,457 2,736 5,061 8,471 Loss before provision (benefit) for income taxes (21,065) (19,152) (61,903) (51,809)Provision (benefit) for income taxes (6) 74 (2,198) (16,100)Net loss (21,059) (19,226) (59,705) (35,709)Unrealized gain (loss) on available for sale investments, net of tax 69 591 (55) 211 Foreign currency translation gain (loss) 1 4 7 (25)Total other comprehensive income (loss) 70 595 (48) 186 Total comprehensive loss$(20,989) $(18,631) $(59,753) $(35,523) Net loss per share -- basic and diluted$(0.40) $(0.37) $(1.14) $(0.69)Weighted-average common shares outstanding 52,993,238 51,574,027 52,322,523 51,499,818

临床试验资讯研究交流群（点击） TP53基因是一个非常著名的基因，围绕这个基因有很多的文章和故事。很多不靠谱的基因公司检测报告都会在这个基因上给大家找到个突变，推荐比如AZD1775这种目前好像已经不存在的药物推卸检测失败的责任。TP53基因是一个抑癌基因，突变频率在很多恶性肿瘤里高达50%，但是单独TP53基因突变并不足以驱动肿瘤的发生，一般会存在一个类似EGFR、ALK的原癌基因突变。今天咱们聊的是TP53基因。那就是说说这个基因的诸多突变位点，结合最新发布的一篇文献报道。Baylor医学院的研究团队发现，并非所有的TP53基因突变都是一样的：某些突变（如R273H型）会让癌细胞对免疫治疗更敏感。 本文参考文献刊例示意图 一、从“守护者”到“叛徒”：TP53的两面性 TP53基因被誉为“基因组的守护者”，这个基因的主要作用是监控细胞的DNA是否有损伤，一旦发现异常它就会让细胞停止分裂、修复，或直接启动“自毁”来防止细胞发生癌变。 然而当TP53基因本身发生突变时，整体的局面就彻底发生了反转。突变后的TP53基因不仅失去了保护的功能，还可能“反客为主”帮助癌细胞逃避死亡、加速分裂、甚至增强癌细胞的转移能力。 在所有的人类癌症中，约有一半肿瘤都存在TP53基因的突变。过去大家普遍认为这些突变只会让癌症更难治。但这次Baylor医学院的研究团队发现了一种令人意外的现象，有些TP53基因的突变位点会让免疫系统更容易识别并攻击癌细胞。 二、新发现：R273H突变能让PD-1效果更好 在上面的这个最新发布的研究里，科学家重点研究了两种常见的TP53基因突变：R273H和R175H。在实验室的细胞模型中他们发现一些结果。 TP53基因的R273H突变会导致癌细胞的DNA复制异常加快，癌细胞细胞过度增殖，肿瘤也变得更具侵袭性。但这种“过度复制”也带来了新的问题，癌细胞的细胞核中形成了大量“微核”（micronuclei），这些微核含有破碎的DNA片段会被免疫系统识别为“危险信号”。这些DNA碎片会通过一些信号通路激发人体天然的免疫防御机制，从而引发免疫细胞对肿瘤的攻击。 在小鼠的乳腺癌模型中，携带TP53基因R273H突变的肿瘤在接受免疫检查点抑制剂（PD-1抗体）治疗后出现了显著的反应，具体表现在肿瘤中CD8+ T细胞增多，也就是说明免疫系统正在积极地清除癌细胞。 相比之下，TP53基因的R175H突变虽然也会促进癌细胞生长，但不会激活免疫反应，因此这个R175H位点突变对使用免疫治疗的反应较差。上面的这个发现意味着不同类型的TP53突变，可能决定了患者是否能从免疫治疗中获益。不是所有的TP53基因突变都是一样的。 三、不是所有TP53基因都是一样的 癌度之前有文章介绍TP53基因突变会影响免疫治疗，而且大家会有认识只要是TP53基因突变就会让PD-1效果更好。但是上面的这个研究说明并不是这样简单。 TP53基因是抑癌基因，所以基因突变必须是影响其功能或让其完全失活（后面是*），如果只是无意义的点突变则没有什么意义。 TP53基因的不同位点突变对治疗影响不同，比如R273H位点突变的患者可能从PD-1或PD-L1治疗获益很多。当然这还需要进一步的人体临床试验。 也就是说不是所有的TP53基因突变都是一样的，不同的基因突变位点其意义也是不同的。另外，存在Y220C突变的TP53基因则是最近有靶向药的临床试验，一项临床1/2期临床试验公布了结果，一款名为Rezatapopt(代号PC14586)的前沿药对于携带TP53基因Y220C突变的晚期实体瘤展现出疗效。这款药是一种P53的再激活剂“，能够选择性结合P53的Y220C突变蛋白的特定口袋，从而回复P53的抑制癌细胞的功能。现有结果表明这款药在卵巢癌、肺癌、乳腺癌、子宫内膜癌、头颈癌9、结直肠癌、胆囊癌以及壶腹癌都有效果，97名可评估疗效的患者中，总缓解治疗应答率为33%，中位缓解持续时间为6.2个月，44名卵巢癌患者的治疗应答率为43%，中位缓解持续时间7.6个月。 如果您的基因检测报告出现了TP53基因的Y220C突变，欢迎随时联系癌度申请相应的临床试验。 11月份福利 癌度联手吉因加，推出“吉爱3000”惠民检项目，最低2000+可及的基因检测专属福利，详情微信扫码联系下方小助手进行免费咨询。咨询全球新药临床试验、报告解读同样可以扫描下面二维码咨询！ 参考文献： Kang Liu et al, Mutant p53 variants differentially impact replication initiation and activate cGAS-STING to affect immune checkpoint inhibition, Communications Biology (2025).  往期推荐  明星药DS-8201在HER2低表达肿瘤的真实世界疗效如何？脑转移和TROP2抗体偶联药治疗缩短生存期！ 20多年前一小群晚期乳腺癌患者通过临床试验接种了一种疫苗。如今她们全部仍然健在！ KRAS基因G12C靶向药耐药之后怎么办？新药Elironrasib或能突破耐药瓶颈，获FDA突破性疗法认定！ 肺癌也可能遗传吗？最新研究三类非小细胞肺癌患者中10%的概率存在遗传性致癌基因突变！ 另外，由于微信公众平台的机制调整，恳请各位粉丝朋友花一两秒钟帮我们点亮文章下方的【小手】和【爱心】，这对我们至关重要。谢谢大家！ 点亮小手爱心，送来温暖鼓励