Vebreltinib

Vebreltinib is efficacious in both treatment naïve and previously treated patients with NSCLC with METex14 skipping, and regardless of co-occurring MET amplificationFOSTER CITY, Calif., Sept. 16, 2024 (GLOBE NEWSWIRE) -- Apollomics Inc. (Nasdaq: APLM) (“Apollomics” or the “Company”), a late-stage clinical biopharmaceutical company developing multiple oncology drug candidates to address difficult-to-treat and treatment-resistant cancers, announced today a poster presentation at the 2024 European Society for Medical Oncology (ESMO) Congress, taking place September 13-17, 2024 in Barcelona, Spain. “We are pleased to share the efficacy and safety data of vebreltinib showing it is efficacious in both treatment naïve and previously treated patients with non-small cell lung cancer (NSCLS) and confirmed METex14 mutation, with longer treatment follow-ups,” said Guo-Liang Yu, Ph.D., Chairman and Chief Executive Officer of Apollomics. “Interestingly, the analysis of efficacy by MET gene copy number (GCN) demonstrated that not only the majority of the patient population in the vebreltinib program does not have co-occurring MET amplification and therefore resembles the real-world patient population reported in registries, but also that vebreltinib is efficacious regardless of co-occurring METamp, achieving as high as 67% overall response rate in patients with MET GCN<4, and outperforming other MET inhibitors. The data further supports verbreltinib’s high potency and its best-in-class potential.” The poster presentation titled “Vebreltinib Efficacy and Safety in NSCLC Patients with METex14 Skipping Mutations” highlighted data from the ongoing global Phase 2 SPARTA-II trial and the Company’s partner, Avistone, Phase 2/3 KUNPENG trial in China. The analysis of the data included 108 patients without prior exposure to MET inhibitors (72 treatment-naive and 36 previously treated NSCLC patients) that received vebreltinib, 200 mg BID in 28-day cycle, with 12 months of follow up data. With centrally confirmed METex14 skipping, overall response rate (ORR) to vebreltinib in treatment-naïve patients was 66.7% (95% CI: 54.6, 77.3) with median duration of response (DOR) of 17.3 months and median progression free survival (PFS) of 13.8 months. In the previously treated patients, ORR was 61.1% (95% CI: 43.5, 76.9) with median DOR of 16.7 months and median PFS of 7.4 months. Among the 91 vebreltinib-treated NSCLC patients with METex14 for whom GCN data was available, GCN distribution was similar to those reported in AACR project GENIE and cBioportal. The ORRs by GCN continue to support vebreltinib’s efficacy, including in the GCN<4 cohort (ORR 67.8%; n=86) - a subgroup that was reported in other MET inhibitor trials to be less responsive: 18% ORR with capmatinib in patients with METex14 NSCLC and GCN<4, and 38.6% with savolitinib in METex14 NSCLC without METamp. Similarly, ORR was 69.2% in GCN<6 (n=91) and 100% (5/5) in GCN>4 cohorts. Treatment-related adverse events (TRAE) of grade 3 or higher were reported in 48.1% of patients, with the most common being edema (16.7%). No death was reported due to TEAEs. The poster presentation will be available on the Apollomics website under the Presentations page under the News and Events section. About vebreltinib (APL-101) Vebreltinib is a potent, small molecule, orally bioavailable and highly selective c-MET inhibitor. It works by inhibiting the aberrant activation of the HGF/c-MET axis, a key pathway involved in tumor growth, proliferation, and the development of resistance to certain targeted therapies such as osimertinib. By targeting c-MET dysregulation, vebreltinib has demonstrated strong tumor inhibitory effect in a variety of preclinical c-MET dysregulated human gastric, hepatic, pancreatic and lung cancer xenograft animal models and patient-derived xenograft models (PDX). Details on the Phase 1/2 SPARTA global clinical trial can be found on clinicaltrials.gov: NCT03175224. Apollomics is developing vebreltinib as single-agent cancer therapy in a variety of tumor types and actively assessing the potential of vebreltinib in combination with novel therapies. Vebreltinib recently received conditional approval from the National Medical Products Administration (NMPA) of China and is currently under clinical investigation and not approved for any use in any other regions in the world. About Apollomics Inc. Apollomics Inc. is an innovative clinical-stage biopharmaceutical company focused on the discovery and development of oncology therapies with the potential to be combined with other treatment options to harness the immune system and target specific molecular pathways to inhibit cancer. Apollomics’ lead programs include its core product, vebreltinib (APL-101), a potent, selective c-Met inhibitor for the treatment of non-small cell lung cancer and other advanced tumors with c-Met alterations, which is currently in a Phase 2 multicohort clinical trial in the United States, and uproleselan (APL-106), a specific E-Selectin antagonist that has the potential to be used adjunctively with standard chemotherapy to treat acute myeloid leukemia and other hematologic cancers, which is currently in Phase 1 and Phase 3 clinical trials in China. For more information, please visit www.apollomicsinc.com. Cautionary Statement Regarding Forward-Looking Statements This press release includes statements that constitute “forward-looking statements” within the meaning of the federal securities laws, including Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). All statements, other than statements of present or historical fact included in this press release, regarding the Company’s strategy, prospects, plans and objectives are forward-looking statements, including statements about the preliminary data from the Phase 2 SPARTA trial of vebreltinib in patients with non-CNS MET fusion solid tumors. When used in this press release, the words “could,” “should,” “will,” “may,” “believe,” “anticipate,” “intend,” “estimate,” “expect,” “project,” the negative of such terms and other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain such identifying words. These forward-looking statements are based on management’s current expectations and assumptions about future events and are based on currently available information as to the outcome and timing of future events. Apollomics cautions you that these forward-looking statements are subject to numerous risks and uncertainties, most of which are difficult to predict and many of which are beyond the control of Apollomics. In addition, Apollomics cautions you that the forward-looking statements contained in this press release are subject to unknown risks, uncertainties and other factors, including: (i) the impact of any current or new government regulations in the United States and China affecting Apollomics’ operations and the continued listing of Apollomics’ securities; (ii) the inability to achieve successful clinical results or to obtain licensing of third-party intellectual property rights for future discovery and development of Apollomics’ oncology projects; (iii) the failure to commercialize product candidates and achieve market acceptance of such product candidates; (iv) the failure to protect Apollomics’ intellectual property; (v) breaches in data security; (vi) the risk that Apollomics may not be able to develop and maintain effective internal controls; (vii) unfavorable changes to the regulatory environment; and (viii) those risks and uncertainties discussed in the Annual Report on Form 20-F for the year ended December 31, 2023, filed by Apollomics Inc. with the U.S. Securities and Exchange Commission (“SEC”) under the heading “Risk Factors” and the other documents filed, or to be filed, by the Company with the SEC. Additional information concerning these and other factors that may impact the operations and projections discussed herein can be found in the reports that Apollomics has filed and will file from time to time with the SEC. These SEC filings are available publicly on the SEC’s website at www.sec.gov. Forward-looking statements speak only as of the date made by the Company. Apollomics undertakes no obligation to update publicly any of its forward-looking statements to reflect actual results, new information or future events, changes in assumptions or changes in other factors affecting forward-looking statements, except to the extent required by applicable law. Investor Contact: Eric RibnerLifeSci Advisors, LLC(646) 751-4363eric@lifesciadvisors.com

欢迎关注凯莱英药闻 近日，鞍石生物（“Avistone”）在2024 年世界肺癌大会上公布了两种小分子 c-MET 和 EGFR 抑制剂在非小细胞肺癌（NSCLC）患者中联合使用的最新研究数据。 关于最新研究数据 公司口头报告了旗下伯瑞替尼（vebreltinib）联合安达替尼（PLB1004）治疗EGFR 突变、EGFR-TKI 后出现 MET 扩增或 MET 过表达的NSCLC患者中的最新进展；其中，44 名患者分别接受了 Vebreltinib 100mg 联合 PLB1004 160mg（n=15）、Vebreltinib 150mg 联合 PLB1004 160mg（n=13）、Vebreltinib 200mg 联合 PLB1004 80mg（n=3）、Vebreltinib 150mg 联合 PLB1004 80mg（n=13）治疗。 结果显示： 在接受评估的 44 名患者中，36.4%的患者有脑转移，86.4% 的患者之前曾接受过第三代EGFR-TKI 治疗。 所有测试的 Vebreltinib 和PLB1004 剂量水平均出现了客观反应，在 19/32 (59.4%) 可评估反应的患者中观察到部分反应 (PR)。 在脑转移患者中，ORR 为 75.0% (9/12)。 在接受过第三代 EGFR-TKI 治疗的患者中，ORR 为 58.6% (17/29)。 最常见的 TRAE 是皮疹和甲沟炎。没有患者因 TRAE 而停止治疗。 关于伯瑞替尼 伯瑞替尼（Bozitinib）是一种细胞-间质上皮转化因子(c-MET)受体酪氨酸激酶抑制剂，可抑制 c-MET高表达肿瘤细胞的增殖。该药物可以透过血脑屏障，非临床药效实验表明，伯瑞替尼对在多种临床前MET异常的人类胃癌、肝癌、胰腺癌和肺癌细胞移植动物模型和人源肿瘤移植小鼠模型中显示出强大的抑制肿瘤作用。I期研究结果初步证明，伯瑞替尼对METex14跳跃突变、MET扩增和过表达等MET异常的NSCLC均有良好的抗肿瘤作用。 该药物曾于2023年11月获NMPA附条件批准上市，用于治疗具有间质-上皮转化因子（MET）外显子14跳变的局部晚期或转移性非小细胞肺癌（NSCLC）患者。截至2021年12月31日，接受伯瑞替尼（200mgBID）治疗的52例METex14晚期NSCLC患者，经判定临床研究达到预设主要终点，由IRC判定的确认的客观缓解率（cORR）高达75%，缓解持续时间（DoR）达到16.7个月，无进展生存期（PFS）达到12个月。 2024年4月，该药物用于治疗经放疗和替莫唑胺（TMZ）治疗后复发或不可耐受的，具有PTPRZ1-MET（ZM）融合基因的异柠檬酸脱氢酶（IDH）突变型WHO 4级星形细胞瘤或既往有较低级别病史的胶质母细胞瘤（GBM）成人患者的新适应症再次获NMPA批准上市。 关于安达替尼 安达替尼是一款新型的EGFR单苯胺基嘧啶小分子不可逆抑制剂，具有高选择性，可以透过血脑屏障。非临床药效实验表明该化合物对EGFR 20号外显子插入（ex20 ins）突变、HER2 20号外显子插入（ex20 ins）突变、EGFR敏感突变、EGFR耐药突变和EGFR罕见突变均有效。在EGFR NSCLC 患者中展示出同类最佳的潜力。 根据2023 AACR披露的数据，一项在NSCLC患者开展的多中心、开放、剂量递增与剂量扩展I期试验表明，截至2022年7月31日： 经研究者评估达到客观缓解的15例，ORR为57.7%（15/26）；42.3%（11/26）的受试者达到疾病稳定（SD），疾病控制率（DCR）为100%。 在15例PR受试者中，3例受试者的持续缓解时间（DOR）已超过240天（其中2例受试者的DOR已超过300天，且仍在持续获益）。 此外，亚组分析显示，在≥160mg QD剂量水平且至少完成一次肿瘤评估的26例携带EGFR ex20ins受试者中，8例受试者基线时伴有脑转移，其中3例疗效评估达到PR，ORR达到37.5%。 剂量递增阶段的每个剂量组均无DLT发生，试验中未观察到MTD。试验中不良事件大部分为1~2级。 关于c-MET / EGFR药物的最新进展 EGFR是NSCLC最主要的驱动基因，在东亚人群中突变率高达40%-50%，而西方人群中突变率为10%-20%。在EGFRmt NSCLC患者中，25%至39%的患者由于疾病进展和缺乏治疗选择而从未接受过二线治疗。所有接受目前标准疗法TKI单药治疗的晚期EGFRmt NSCLC患者的5年生存率不到20%。EGFR TKI治疗后出现获得性耐药的肿瘤中有5%-22%出现c-MET扩增。 据悉，全球唯一获批的EGFR/c-Met药物为强生的埃万妥单抗能同时与EGFR和c-MET高亲和力结合，并将这两种蛋白封闭在异源二聚体中，防止同源二聚化和下游信号传导。这样的设计意味着它既能延缓TKI不耐受肿瘤的耐药性，又能对抗TKI耐药肿瘤的耐药性。埃万妥单抗具有诱导抗肿瘤效应的多种机制：1、可诱导多种细胞系产生自然杀伤细胞介导的ADCC；2、介导了肿瘤细胞与巨噬细胞和单核细胞的相互作用，使EGFR和c-MET 受体从肿瘤细胞表面转移到免疫细胞表面（胞啃作用，trogocytosis），导致肿瘤细胞表面抗原密度降低，从而下调下游信号转导。 目前，有多家公司的EGFR/c-Met双抗进入临床，其中，国内普米斯/翰森制药的进度处于全球第二。EGFR/c-Met ADC竞争格局良好，仅有阿斯利康的AZD9592以及百奥赛图/多玛医药的DM005进入临床，在早研竞争格局上，全部处于临床前的EGFR/c-Met ADC均来自国内生物制药企业，布局数量遥遥领先。小分子药物相较于抗体药物的优势主要包括成本低、安全性高、细胞通透性好、以及可能具有更好的药代动力学特性；期待未来鞍石公布更多关于两种小分子抑制剂联用的数据。 目前在研的c-MET / EGFR药物 关于鞍石生物 鞍石生物致力于健康服务产业，研发主要涉及肿瘤治疗领域，旨在克服现有疗法局限性的创新药物（“Best in class”及“First in class”），通过优化靶标选择性和药物过脑性，让患者持久获益。 参考资料 1、公司官网 2、华创证券 感谢关注、转发，转载授权、加行业交流群，请加管理员微信号“hxsjjf1618”。 “在看”点一下