BOSTON--(BUSINESS WIRE)--Verastem Oncology (Nasdaq: VSTM) (the “Company”), a biopharmaceutical company committed to advancing new medicines for patients with cancer, today announced a potential best-in-class KRAS G12D oral inhibitor as the lead program of its discovery and development collaboration with GenFleet Therapeutics (“GenFleet”)..

波士顿--（商业新闻短讯）--Verastem Oncology（Nasdaq:VSTM）（以下简称“公司”）是一家致力于为癌症患者开发新药的生物制药公司，今天宣布了一种潜在的同类最佳KRAS G12D口服抑制剂，作为其与GenFleet Therapeutics（“GenFleet”）发现和开发合作的主要项目。。

“We are pleased to announce this oral KRAS G12D inhibitor with a potential best-in-class profile as the lead program from our collaboration with GenFleet supporting our mission to bring needed therapies to patients with RAS pathway-driven cancers,” said Dan Paterson, President and Chief Executive Officer of Verastem Oncology.

Verastem Oncology总裁兼首席执行官丹·帕特森（DanPaterson）表示：“我们很高兴宣布，这种口服KRAS G12D抑制剂具有潜在的同类最佳概况，是我们与GenFleet合作的牵头项目，支持我们为RAS途径驱动的癌症患者带来所需治疗的使命。”。

“Although there has been significant progress in therapeutics targeting KRAS mutations, there are currently no available therapies approved by the U.S. Food and Drug Administration targeting KRAS G12D, the most prevalent KRAS mutation across human cancers. The GLP toxicology studies are complete and we look forward to GenFleet’s anticipated filing of the IND for this KRAS G12D inhibitor in the first half of 2024.”.

“尽管针对KRAS突变的治疗方法取得了重大进展，但目前还没有美国食品和药物管理局批准的针对KRAS G12D的治疗方法，KRAS G12D是人类癌症中最普遍的KRAS突变。GLP毒理学研究已经完成，我们期待着GenFleet预期将这种KRAS G12D抑制剂的IND提交给e 2024年上半年。”。

GFH375/VS-7375 is an orally bioavailable, potent and selective small molecule KRAS G12D (ON/OFF) inhibitor. Preclinical models demonstrate strong tumor regression as a single agent and support approaches in combination with Verastem Oncology’s RAF/MEK clamp avutometinib as well as other rational combinations across KRAS G12D-driven cancers.

GFH375/VS-7375是一种口服生物可利用，有效和选择性的小分子KRAS G12D（开/关）抑制剂。临床前模型显示，作为单一药物，肿瘤消退强烈，并支持与Verastem Oncology的RAF/MEK钳夹avutometinib以及KRAS G12D驱动的癌症的其他合理组合相结合的方法。

KRAS G12D represents 26% of all KRAS mutations, making it the most prevalent KRAS mutation in human cancer. KRAS G12D mutation occurs most commonly in pancreatic (37%), colorectal (12.5%), endometrial (8%) and non-small cell lung (5%) cancers..

KRAS G12D占所有KRAS突变的26%，使其成为人类癌症中最普遍的KRAS突变。KRAS G12D突变最常见于胰腺癌（37%），结直肠癌（12.5%），子宫内膜癌（8%）和非小细胞肺癌（5%）。。

As previously announced, the discovery and development collaboration between Verastem Oncology and GenFleet aims to advance three oncology discovery programs related to RAS pathway-driven cancers. The collaboration builds on the strengths of both companies in oncology small molecule drug development, enabling Verastem Oncology to partner its clinical development and regulatory expertise with GenFleet’s accomplished discovery capabilities.

如前所述，Verastem Oncology和GenFleet之间的发现和开发合作旨在推进与RAS途径驱动的癌症相关的三个肿瘤学发现项目。该合作建立在两家公司在肿瘤学小分子药物开发方面的优势之上，使Verastem oncology能够将其临床开发和监管专业知识与GenFleet的成熟发现能力相结合。

This synergistic collaboration includes Verastem Oncology’s experience and established network of collaborators, including scientific and clinical experts in RAS biology and RAS pathway-driven cancers and GenFleet’s accomplishments with its KRAS G12C inhibitor program. The IND filing and initial Phase 1 studies will be led and funded by GenFleet in China.

这种协同合作包括Verastem肿瘤学的经验和建立的合作者网络，包括RAS生物学和RAS途径驱动癌症的科学和临床专家，以及GenFleet在其KRAS G12C抑制剂计划中取得的成就。IND申报和第一阶段初步研究将由GenFleet在中国领导和资助。

The collaboration provides Verastem Oncology with an exclusive option to obtain a license to each of the three compounds in the collaboration after successful completion of pre-determined milestones in a Phase 1 trial. The licenses would give Verastem Oncology development and commercialization rights outside of China while GenFleet would retain development and commercialization rights inside of China..

该合作为Verastem Oncology提供了一个独家选项，在成功完成第一阶段试验中预定的里程碑后，可以获得合作中三种化合物的许可证。这些许可证将授予Verastem肿瘤学在中国境外的开发和商业化权利，而GenFleet将保留在中国境内的开发和商业化权利。。

About Avutometinib

关于Avutometinib

Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS pathway inhibition. Avutometinib is currently in late-stage development.

Avutometinib是一种RAF/MEK钳，可诱导MEK与ARAF，BRAF和CRAF的无活性复合物，从而通过最大程度的RAS途径抑制产生更完整和持久的抗肿瘤反应。Avutometinib目前处于后期开发阶段。

In contrast to currently available MEK inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors.

与目前可用的MEK抑制剂相反，avutometinib阻断MEK激酶活性和RAF磷酸化MEK的能力。这种独特的机制允许avutometinib阻断MEK信号传导，而不需要MEK的补偿性激活，这似乎限制了其他抑制剂的功效。

The U.S. Food and Drug Administration granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK clamp avutometinib, with defactinib, its FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy..

美国食品和药物管理局授予了突破性治疗指定，将Verastem Oncology的研究性RAF/MEK钳夹avutometinib与其FAK抑制剂defactinib联合用于治疗所有复发性低度浆液性卵巢癌（LGSOC）患者，无论其在一种或多种治疗方案后的KRAS状态如何，包括铂类化疗。。

Verastem Oncology is currently conducting clinical trials with its RAF/MEK clamp avutometinib in RAS pathway-driven tumors as part of its RAMP (Raf And Mek Program) trials. RAMP 201 is a Phase 2 registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC and has completed enrollment in the dose optimization and expansion phases and is enrolling for low-dose evaluation.

作为RAMP（RAF和MEK计划）试验的一部分，Verastem Oncology目前正在RAS途径驱动的肿瘤中使用其RAF/MEK钳avutometinib进行临床试验。RAMP 201是avutometinib联合defactinib治疗复发性LGSOC患者的2期登记指导试验，已完成剂量优化和扩大阶段的登记，并正在进行低剂量评估。

Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS™ (sotorasib) and KRAZATI™ (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 and RAMP 204 trials, respectively. Supported by the “Therapeutic Accelerator Award” Verastem Oncology received from PanCAN, the Company is conducting RAMP 205, a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer..

Verastem肿瘤学与Amgen和Mirati建立了临床合作，以评估LUMAKRAS™（sotorasib）和KRAZATI™（adagrasib）与avutometinib联合用于KRAS G12C突变NSCLC，分别作为RAMP 203和RAMP 204试验的一部分。在PanCAN获得的“治疗加速器奖”Verastem Oncology的支持下，该公司正在进行RAMP 205，这是一项1b/2期临床试验，评估阿维托替尼和defactinib与吉西他滨/纳布-紫杉醇联合治疗一线转移性胰腺癌患者。。

About Verastem Oncology

关于真性肿瘤学

Verastem Oncology (Nasdaq: VSTM) is a development-stage biopharmaceutical company committed to the development and commercialization of new medicines to improve the lives of patients diagnosed with cancer. Our pipeline is focused on novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition and focal adhesion kinase (FAK) inhibition.

Verastem Oncology（纳斯达克股票代码：VSTM）是一家处于发展阶段的生物制药公司，致力于新药的开发和商业化，以改善被诊断患有癌症的患者的生活。我们的管道专注于抑制癌症中促进癌细胞存活和肿瘤生长的关键信号传导途径的新型小分子药物，包括RAF/MEK抑制和粘着斑激酶（FAK）抑制。

For more information, please visit www.verastem.com..

欲了解更多信息，请访问www.verastem.com。。

Forward-Looking Statements Notice

前瞻性声明通知

This press release includes forward-looking statements about Verastem Oncology’s strategy, future plans and prospects, including statements related to the expected outcome and benefits of the collaboration with Genfleet, the potential clinical value of various of its clinical trials, the timing of commencing and completing trials, including topline data reports, interactions with regulators and potential for additional development programs involving Verastem Oncology’s lead compound.

本新闻稿包括关于Verastem Oncology战略、未来计划和前景的前瞻性声明，包括与Genfleet合作的预期结果和益处、其各种临床试验的潜在临床价值、开始和完成试验的时间，包括topline数据报告，与监管机构的互动以及涉及Verastem Oncology先导化合物的其他发展计划的潜力。

The words 'anticipate,' 'believe,' 'estimate,' 'expect,' 'intend,' 'may,' 'plan,' 'predict,' 'project,' 'target,' 'potential,' 'will,' 'would,' 'could,' 'should,' 'continue,' “can,” “promising” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.

“预期”，“相信”，“估计”，“期望”，“打算”，“可能”，“计划”，“预测”，“项目”，“目标”，“潜力”，“意志”，“会”，“可能”，“应该”，“继续”，“可以”，“有希望”和类似的表达旨在识别前瞻性陈述，尽管并非所有前瞻性陈述都包含这些识别词。

Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement..

每个前瞻性声明都有可能导致实际结果与该声明中明示或暗示的结果产生重大差异的风险和不确定性。。

Applicable risks and uncertainties include the risks and uncertainties, among other things, regarding: the success in the development and potential commercialization of our product candidates, including avutometinib in combination with other compounds, including defactinib, LUMAKRASTM and others; the uncertainties inherent in research and development, such as negative or unexpected results of clinical trials, the occurrence or timing of applications for our product candidates that may be filed with regulatory authorities in any jurisdictions; whether and when regulatory authorities in any jurisdictions may approve any such applications that may be filed for our product candidates, and, if approved, whether our product candidates will be commercially successful in such jurisdictions; our ability to obtain, maintain and enforce patent and other intellectual property protection for our product candidates; the scope, timing, and outcome of any legal proceedings; decisions by regulatory authorities regarding trial design, labeling and other matters that could affect the timing, availability or commercial potential of our product candidates; whether preclinical testing of our product candidates and preliminary or interim data from clinical trials will be predictive of the results or success of ongoing or later clinical trials; that the timing, scope and rate of reimbursement for our product candidates is uncertain; that third-party payors (including government agencies) may not reimburse; that there may be competitive developments affecting our product candidates; that data may not be available when expected; that enrollment of clinical trials may take longer than expected; that our product candidates will cause adverse safety events and/or unexpected concerns may arise from .

适用的风险和不确定性包括以下方面的风险和不确定性：我们的候选产品（包括avutometinib与其他化合物（包括defactinib，LUMAKRASTM等）的开发成功和潜在商业化；研究和开发中固有的不确定性，例如临床试验的负面或意外结果，可能向任何司法管辖区的监管机构提交的候选产品申请的发生或时间；任何司法管辖区的监管机构是否以及何时可以批准可能为我们的候选产品提交的任何此类申请，如果获得批准，我们的候选产品是否会在这些司法管辖区取得商业成功；我们为候选产品获得、维护和实施专利和其他知识产权保护的能力；任何法律诉讼的范围、时间和结果；监管机构关于试验设计、标签和其他可能影响我们候选产品的时间、可用性或商业潜力的事项的决定；我们的候选产品的临床前测试以及临床试验的初步或中期数据是否可以预测正在进行或以后的临床试验的结果或成功；我们候选产品的报销时间、范围和费率不确定；第三方付款人（包括政府机构）可能无法报销；可能有竞争发展影响我们的候选产品；该数据可能在预期时不可用；临床试验的注册可能需要比预期更长的时间；我们的候选产品可能会导致不良安全事件和/或意外问题。

Other risks and uncertainties include those identified under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2022 as filed with the Securities and Exchange Commission (SEC) on March 14, 2023 and in any subsequent filings with the SEC. The forward-looking statements contained in this press release reflect Verastem Oncology’s views as of the date hereof, and the Company does not assume and specifically disclaims any obligation to update any forward-looking statements whether as a result of new information, future events or otherwise, except as required by law..

其他风险和不确定性包括2023年3月14日提交给美国证券交易委员会（SEC）的截至2022年12月31日的公司年度报告表格10-K中“风险因素”标题下确定的风险和不确定性，以及随后提交给SEC的任何文件中确定的风险和不确定性。本新闻稿中包含的前瞻性声明反映了Verastem Oncology截至本新闻稿发布之日的观点，除法律要求外，公司不承担并明确否认因新信息、未来事件或其他原因而更新任何前瞻性声明的义务。。