Oxaliplatin

劲方医药（2595.HK）宣布口服KRAS G12D（ON/OFF）抑制剂GFH375已获得国家药品监督管理局颁发的第三项突破性疗法认定（BTD），联合西妥昔单抗（EGFR单抗）用于治疗既往化疗（奥沙利铂、氟尿嘧啶类和伊立替康为基础）失败的KRAS G12D突变型转移性结直肠癌（CRC）患者。此前GFH375已成为国内首个纳入经治非小细胞肺癌（NSCLC）、胰腺癌BTD名单的口服KRAS G12D抑制剂，并已开展单药治疗经治胰腺癌、非小细胞肺癌两项注册性III期研究。GFH375联合西妥昔单抗治疗实体瘤的初步研究数据，将于10月在线上投资者交流沟通会发布。 依据国际癌症研究机构（IARC）及弗若斯特沙利文数据，2024年全球新发CRC病例超200万例，KRAS突变率约40%、KRAS G12D突变率超过10%。目前，一线及二线CRC治疗均以化疗为主，化疗耐药后缺乏后续靶向疗法；而全球在研KRAS G12D抑制剂临床试验中，单药治疗CRC效果均低于胰腺癌和NSCLC人群。EGFR通路代偿性激活是KRAS抑制剂耐药机制之一，KRAS G12C抑制剂sotorasib联合帕尼单抗（EGFR单抗）后线治疗CRC已在美国获批上市，展现显著超越sotorasib单药的客观缓解率（30.2% vs 9.7%），为KRAS突变CRC治疗提供联用方案验证。 根据今年AACR壁报，GFH375（switch II pocket/SIIP抑制剂）与西妥昔单抗联用后，在多种KRAS G12D实体瘤的动物模型中展现优于单药的抗肿瘤活性，在CRC模型中抑瘤活性最为显著。此外，依据两项氟泽雷塞的联合疗法数据，同为SIIP抑制剂的氟泽雷塞联合西妥昔单抗β治疗二线CRC（2026 CSCO发布IIT数据）、联合西妥昔单抗治疗一线NSCLC（2026 Lancet Oncology刊发劲方KROCUS研究数据），均展现了显著超越单药的疗效和安全性，为劲方后续开展SIIP抑制剂与EGFR单抗联用的临床开发提供借鉴。 劲方医药首席医学官汪裕博士  “GFH375在多个瘤种的单药临床试验中展现了优秀的疗效和成药性，支持该产品获得多项BTD、并进入多种适应症的中后期临床试验。KRAS G12D突变的CRC患者群体庞大，但KRAS G12D抑制剂单药治疗在CRC患者临床试验中遇到较大挑战。我们希望借鉴业界KRAS抑制剂的联用经验，并基于劲方主导的KROCUS研究经验，开展无化疗联合疗法解决未满足的临床需求，为亟待靶向药突破的CRC患者带来创新疗法选择。”  参考文献： 1. Global cancer statistics 2024: GLOBOCAN estimates of incidence and mortality worldwide for 34 cancers in 186 countries, GLOBOCAN 2. Fulzerasib plus cetuximab in first-line KRAS G12C mutated non-small-cell lung cancer (KROCUS): a single-arm, multicentre, phase lb/2 trial, 2026 Lancet Oncology 3. 氟泽雷塞联合西妥昔单抗β±FOLFIRI方案在KRAS G12C突变型mCRC一线及二线治疗中的疗效与安全性（CRUCIAL研究），2026 CSCO 4. VS-7375: An oral, selective KRAS G12D dual ON/OFF inhibitor with potent anti-tumor activity as a single agent and in combination with other agents, 2026 AACR 5. Overall Survival Analysis of the Phase III CodeBreaK 300 Study of Sotorasib Plus Panitumumab Versus Investigator's Choice in Chemorefractory KRAS G12C Colorectal Cancer, 2025 ASCO 6. Sotorasib for previously treated colorectal cancers with KRAS G12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial, 2022 Lancet Oncology 关于GFH375/VS-7375 GFH375为口服高活性、高选择性小分子KRAS G12D（ON/OFF）抑制剂，通过非共价形式结合KRAS G12D蛋白，抑制其与下游效应蛋白结合，从而在细胞中破坏KRAS G12D对下游通路的持续活化，最终高效抑制肿瘤细胞增殖。临床前研究已显示GFH375单药对肿瘤生长的抑制效应随用药剂量和周期增长而提升，且在激酶选择性和安全性靶点测试中显示低脱靶风险。 2023年8月，劲方医药与纳斯达克上市公司Verastem Oncology（纳斯达克股票代码：VSTM）对劲方开发的三款产品达成授权及早期合作开发协议。2025年1月，Verastem宣布对GFH375/VS-7375行使选择权，获得GFH375在大中华区之外的开发和商业化权利。劲方合作伙伴Verastem Oncology在海外已经开启一项注册导向性II期NSCLC临床研究（TARGET-D 202）。 劲方医药于2026年获得中国CDE授予的GFH375突破性疗法认定，治疗经治KRAS G12D突变的转移性胰腺癌。Verastem于2025年获得美国FDA授予的VS-7375快速通道资格认定，治疗各线KRAS G12D突变胰腺导管腺癌。 关于劲方医药 劲方医药（2595.HK）是一家全球布局的创新药物开发企业，聚焦肿瘤、免疫类疾病领域高度未满足的临床需求，以疾病生物学机理和临床转化医学为核心，构建并发挥自主化、一体化研发体系优势，主攻尚无临床验证的创新靶点与适应症，并拥有全球自主知识产权。自2017年成立以来，劲方医药已建立包含多个自主研发的“全球新”大、小分子项目，多个产品在中国、欧洲、美国进入全球多中心临床试验，包括多项后期或关键性临床研究。 达伯特®（氟泽雷塞）为劲方管线中首个国内上市获批产品，也是国内首个、全球第三个上市的KRAS G12C抑制剂；目前公司已形成RAS靶向疗法的一体化深耕矩阵，包括多靶点、多种分子类型的选择性及泛RAS抑制剂，多个产品开发进度在国内外同靶点赛道处于领先，且研究数据多次登陆国际学术会议突破性研究摘要及口头报告。同时，公司积极拓展其他“全球新”靶向药开发，采用协同机制打造全球首创的多类型双靶点疗法；并结合临床需求与治疗理念的创新，以产品矩阵进军胰腺癌、非小细胞肺癌、恶病质等大适应症市场。 劲方已获得国家级专精特新“小巨人”、国家级高新技术企业称号，并获得上海市专精特新中小企业、上海市跨国公司研发中心、上海市企业技术中心认定。公司近年来不断深化商业合作网络，已与多个境内外上市公司达成战略授权协议、或开展“全球新”临床合作并已取得积极进展。 联系我们 电话：021-68821388 邮箱：pr@genfleet.com; bd@genfleet.com 官网：www.genfleet.com        地址：上海市浦东新区张江路1206号A座  邮编：201203 前瞻性声明 本新闻稿包含的特定信息可能包含或可能构成非历史事实的前瞻性陈述。前瞻性陈述可通过使用如下具有前瞻性的词汇辨识，例如“预计”、“相信”、“计划”、“预估”、“期望”、“将”、“可能”、“应”和其他具有类似含义的词汇。 前瞻性陈述表达了公司对未来的信念、计划、预估以及期望，是基于公司管理层目前对于公司的经营情况和市场变化情况（该等变化情况不受其控制）所持的信念、计划、预估以及期望而作出。受市场、政策、研发等不确定性因素影响，实际结果可能与该等前瞻性陈述有较大差异。 在前述不确定性的前提下，公司不保证前瞻性陈述的准确性、完整性或可实现性，并提请您注意不应单独依赖于该等前瞻性陈述，公司及其任何董事、管理人员、雇员、股东、代理人、关联方、顾问或代表均不因使用相关文稿而对您或其他人士承担任何责任。请您审慎评估，并参考公司正式披露文件作出决策。

GenFleet Therapeutics (2595.HK) announced that GFH375, an oral KRAS G12D (ON/OFF) inhibitor, has received its third Breakthrough Therapy Designation (BTD) from China’s National Medical Products Administration (NMPA), in combination with cetuximab (an anti-EGFR antibody) among patients with KRAS G12D-mutant metastatic colorectal cancer (CRC) who had failed prior chemotherapy regimens (oxaliplatin, fluoropyrimidine and irinotecan-based). GFH375 was the first oral KRAS G12D inhibitor in China to have been granted BTDs for pretreated non-small cell lung cancer (NSCLC) and pancreatic cancer, and has entered two registrational phase III studies evaluating monotherapy in pretreated pancreatic cancer and NSCLC. Preliminary data from the study of GFH375 in combination with cetuximab in solid tumors will be released via an online investor call in October. According to data from the International Agency for Research on Cancer (IARC) and Frost & Sullivan, over 2 million new CRC cases were diagnosed worldwide in 2024, with KRAS mutations occurring in approximately 40% of CRC cases and KRAS G12D mutations in over 10%. Currently, both first-line and second-line CRC regimens rely primarily on chemotherapy with limited options of subsequent targeted therapies upon chemotherapy resistance. Meanwhile, monotherapy trials of KRAS G12D inhibitors in global landscape have demonstrated lower efficacy in CRC than in pancreatic cancer and NSCLC populations. Compensatory activation of the EGFR pathway is identified as one of the resistance mechanisms for KRAS inhibitors. Sotorasib, a marketed KRAS G12C inhibitor, in combination with panitumumab (an anti-EGFR antibody) has been approved in the United States for later-line CRC treatment, demonstrating an objective response rate (ORR) substantially superior to sotorasib monotherapy (30.2% vs 9.7%) and providing clinical validation for combination strategies in KRAS-mutant CRC. According to a poster presentation at this year’s AACR annual meeting, GFH375 (switch II pocket/SIIP inhibitor) in combination with cetuximab demonstrated superior anti-tumor activity over monotherapy across animal models with multiple KRAS G12D-mutant solid tumors, and the most notable tumor inhibition was observed in CRC models. In addition, data from two fulzerasib (a KRAS G12C inhibitor) combination regimens – fulzerasib, also a SIIP inhibitor, plus cetuximabβ in second-line CRC (investigator-initiated trial data released at 2026 CSCO) and fulzerasib plus cetuximab in first-line NSCLC (GenFleet's KROCUS data published in Lancet Oncology in 2026) – both demonstrated efficacy and safety profiles markedly superior to monotherapy, providing insights for GenFleet’s subsequent clinical development of SIIP inhibitors in combination with anti-EGFR antibodies.   Yu Wang, M.D., Ph.D.  Chief Medical Officer of GenFleet “GFH375 monotherapy has demonstrated encouraging efficacy in various tumor types, underpinning multiple BTDs granted to this asset and its advancement into late-stage clinical trials across indications. KRAS G12D-mutant CRC represents a substantial patient population, but KRAS G12D inhibitor monotherapy has shown limited success in CRC trials. Leveraging industry experience with KRAS inhibitor combination trials and from our own KROCUS study, we aim to address unmet needs through chemo-free combination and bring innovative options to patients awaiting breakthroughs in CRC targeted therapy.” References: 1. Global cancer statistics 2024: GLOBOCAN estimates of incidence and mortality worldwide for 34 cancers in 186 countries, GLOBOCAN 2. Fulzerasib plus cetuximab in first-line KRAS G12C mutated non-small-cell lung cancer (KROCUS): a single-arm, multicentre, phase Ib/2 trial, 2026 Lancet Oncology 3. Efficacy and safety of fulzerasib plus cetuximabβ with or without FOLFIRI in first- and second-line treatment of KRAS G12C-mutant mCRC (CRUCIAL study), 2026 CSCO 4. VS-7375: An oral, selective KRAS G12D dual ON/OFF inhibitor with potent anti-tumor activity as a single agent and in combination with other agents, 2026 AACR 5. Overall Survival Analysis of the Phase III CodeBreaK 300 Study of Sotorasib Plus Panitumumab Versus Investigator’s Choice in Chemorefractory KRAS G12C Colorectal Cancer, 2025 ASCO 6. Sotorasib for previously treated colorectal cancers with KRAS G12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial, 2022 Lancet Oncology About GFH375/VS-7375 GFH375 is an orally active, potent, highly selective small-molecule KRAS G12D (ON/OFF) inhibitor designed to target the GTP/GDP exchange, thereby disrupting the activation of downstream pathways and effectively inhibiting tumor cell proliferation. Preclinical studies demonstrated dose-dependent inhibition in models bearing KRAS G12D mutation; GFH375 also demonstrated low off-target risk in kinase selectivity and safety target assays. GenFleet entered into a discovery and development collaboration with Verastem Oncology (Nasdaq: VSTM) to advance three novel oncology discovery programs related to RAS/MAPK pathway-driven cancers. The collaboration provides Verastem with an exclusive option to obtain a license for each of the three compounds in the collaboration after the successful completion of pre-determined milestones in a Phase I trial. Verastem selected GFH375/VS-7375, an oral KRAS G12D (ON/OFF) inhibitor, as its lead program from the collaboration, in December 2023 and the license for GFH375 that was exercised in January 2025 is the first one from this collaboration. The licenses would give Verastem development and commercialization rights outside of China while GenFleet would retain rights inside of China. Outside of China, GenFleet’s partner Verastem Oncology is evaluating VS-7375 in TARGET-D 202, a registration-directed phase 2 study in NSCLC.GenFleet received the Breakthrough Therapy Designations granted by China’s CDE in 2026 for GFH375 in pretreated KRAS G12D-mutant NSCLC and metastatic pancreatic cancer respectively; Verastem received the Fast Track Designations granted by U.S. FDA for VS-7375 treating KRAS G12D-mutant pancreatic ductal adenocarcinoma across all lines of therapy in 2025, and treating locally advanced unresectable or metastatic KRAS G12D-mutant NSCLC in 2026. About GenFleet Therapeutics With a focus on cutting-edge therapies, GenFleet Therapeutics is dedicated to serving significant unmet medical needs globally in oncology and immunology. Leveraging its deep understanding of disease biology and translational medicine, GenFleet has established a proprietary and fully integrated R&D system that yields a robust pipeline of multiple cutting-edge products with novel mechanisms and global IP.Since its inception in 2017, GenFleet has built up industry-leading capabilities and expertise in developing novel drug candidates spanning small molecules and biologics. Its pipeline comprises numerous programs that have advanced to later-stage or pivotal clinical trials across China, the United States and Europe. The company has set up a highly differentiated RAS-targeted matrix including selective and pan-RAS inhibitors of diverse molecular types, with most assets leading their categories in clinical progress in China or globally. In addition, the company has pioneered a series of first-in-class combination therapies based on dual-target synergistic mechanisms. By integrating clinical needs and insights, GenFleet is dedicated to expanding its portfolio into major therapeutic areas including pancreatic cancer, NSCLC, and cachexia. Furthermore, it's strengthening its commercial collaborative network through strategic out-licensing agreements or clinical cooperations with prestigious listed companies across the world.  Forward-looking Statements Specific information in this press release may contain or constitute forward-looking words that are not historical facts. They can be identified by using forward-looking terminology, such as "predict", "believe", "plan", "predict", "expect", "will", "may", "should" and other words of similar meanings.Based on the management's current beliefs, plans, estimates and expectations of the company's operation and market trends subject to changes beyond control, the forward-looking terminology reflects GenFleet Therapeutics' beliefs, plans, estimates and expectations of future development. Actual outcome in the future may differ significantly from forward-looking words owing to market, policy, and R&D uncertainties, among others.Subject to the above-mentioned uncertainties, GenFleet Therapeutics makes no expressed or implied guarantee as to the accuracy, completeness or feasibility of this presentation, and you are cautioned not to solely rely on such forward-looking words.Neither the company nor any of its directors, officers, employees, shareholders, agents, related parties, consultants or representatives will be liable to you or any other person for consequences resulting from using this presentation. Investors are advised to exercise due diligence with reference to the company's official disclosures for decision-making.