CLDN18.2 Positive Advanced Malignant Solid Neoplasm

SHANGHAI, Aug. 19, 2024 /PRNewswire/ -- CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, announces that the completion of enrollment in the pivotal Phase II clinical trial of satricabtagene autoleucel ("satri-cel", R&D code: CT041, an autologous CAR-T product candidate against Claudin18.2) in accordance with the clinical protocol, for advanced gastric/gastroesophageal junction cancers (GC/GEJ) in China. This study is an open-label, multicenter, randomized clinical trial in China evaluating the efficacy and safety of satri-cel in subjects with Claudin18.2-positive advanced GC/GEJ patients who have failed at least two prior lines of therapy. Treatment for the control group is physician's choice (paclitaxel, docetaxel, irinotecan, apatinib, or nivolumab). Gastric cancer is one of the most common malignant tumors in China, with an incidence of approximately 359,000 incident cases and a mortality of approximately 260,000 deaths in 2022[1]. Patients with advanced gastric cancer often face limited treatment options and poor prognosis. There is a strong need for more innovative and efficacious therapies. Satri-cel is an autologous CAR T-cell product candidate against Claudin18.2 that has the potential to be first-in-class globally. It primarily targets GC/GEJ and pancreatic cancer (PC). The published clinical data on satri-cel have shown promising safety and efficacy. The final results of the investigator-initiated Phase I clinical trial CT041-CG4006 (NCT03874897) were published in Nature Medicine and orally presented at the 2024 ASCO annual meeting. There were no dose-limiting toxicities (DLTs), no Grade 3 or higher cytokine release syndrome (CRS), or immune effector cell-associated neurotoxicity syndrome (ICANS) observed. In 51 patients with GC/GEJ with target lesions at baseline who received satri-cel monotherapy, the overall response rate (ORR) was 54.9% (28/51), the disease control rate (DCR) was 96.1% (49/51), and the median duration of response (mDOR) was 6.4 months.[2][3] The phase Ib results from CT041-ST-01 (NCT04581473) clinical trial presented at the 2022 ASCO annual meeting, further showed the manageable safety and promising efficacy of satri-cel. Among 14 GC/GEJ patients who had received at least 2 prior lines of treatment and received satri-cel monotherapy, there were no DLTs or AEs leading to death. No ICANS or gastrointestinal mucosal injury were reported. The ORR and DCR were 57.1% and 78.6% respectively.[4] Dr. Zonghai Li, Founder, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics, said, "We are very pleased to announce the successful completion of patient enrollment in the pivotal Phase II clinical trial of satri-cel in China. This significant milestone marks another solid step forward in our development of CAR T-cell therapies for solid tumors. We extend our gratitude to all the investigators, the patients and their families for their trust and support. We look forward to the submission of New Drug Application and the approval in China, to benefit patients with gastric cancer. As one of the leading companies in the field of CAR T-cell therapies, we remain committed to addressing the major challenges faced by existing CAR T-cell therapies and will develop more innovative CAR-T products for cancer patients." About Satri-cel Satri-cel is an autologous CAR T-cell product candidate against the protein Claudin18.2 that has the potential to be first-in-class globally. Satri-cel targets Claudin18.2 positive solid tumors with a primary focus on gastric cancer/gastroesophageal junction cancer (GC/GEJ) and pancreatic cancer (PC). Ongoing trials include investigator-initiated trials (CT041-CG4006, NCT03874897), a confirmatory Phase II clinical trial for advanced GC/GEJ in China (CT041-ST-01, NCT04581473), a Phase I clinical trial for PC adjuvant therapy in China (CT041-ST-05, NCT05911217), and a Phase 1b/2 clinical trial for advanced gastric or pancreatic adenocarcinoma in North America (CT041-ST-02, NCT04404595). Satri-cel was granted Regenerative Medicine Advanced Therapy (RMAT) designation by the U.S. FDA for the treatment of Claudin18.2-positive advanced GC/GEJ cancers in January 2022 and PRIME eligibility by the EMA for the treatment of advanced gastric cancer in November 2021. Satri-cel received an Orphan Drug designation from the U.S. FDA in 2020 for the treatment of GC/GEJ and an Orphan Medicinal Product designation from the EMA in 2021 for the treatment of advanced gastric cancer. About CARsgen Therapeutics Holdings Limited CARsgen is a biopharmaceutical company with operations in China and the U.S., focusing on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors. CARsgen has established a comprehensive CAR T-cell research and development platform that covers target discovery, innovative CAR T-cell development, clinical trials, and commercial-scale production. Internally, CARsgen has developed novel technologies and a product pipeline with global rights to address significant challenges faced by existing CAR T-cell therapies. Efforts include improving safety profile, enhancing the efficacy in treating solid tumors, and reducing treatment costs. CARsgen's mission is to become a global biopharmaceutical leader that provides innovative and differentiated cell therapies for cancer patients worldwide and makes cancer curable. Forward-looking Statements All statements in this press release that are not historical fact or that do not relate to present facts or current conditions are forward-looking statements. Such forward-looking statements express the Group's current views, projections, beliefs and expectations with respect to future events as of the date of this press release. Such forward-looking statements are based on a number of assumptions and factors beyond the Group's control. As a result, they are subject to significant risks and uncertainties, and actual events or results may differ materially from these forward-looking statements and the forward-looking events discussed in this press release might not occur. Such risks and uncertainties include, but are not limited to, those detailed under the heading "Principal Risks and Uncertainties" in our most recent annual report and interim report and other announcements and reports made available on our corporate website, . No representation or warranty is given as to the achievement or reasonableness of, and no reliance should be placed on, any projections, targets, estimates or forecasts contained in this press release. References [1] Han B, et al. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024 Feb 2;4(1):47-53. doi: 10.1016/j.jncc.2024.01.006 [2] Qi C, et al. Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial final results. Nat Med. 2024 Jun 3. doi: 10.1038/s41591-024-03037-z [3] Qi C, et al. 2024 ASCO Abstract #2501 [4] Qi C, et al. 2022 ASCO Abstract #4017 SOURCE CARsgen Therapeutics

为打造全球ADC/RDC未来产业高地，成都医学城拟于2024年4月18日-19日举办首届未来XDC新药大会！大会以“共创偶联药物产业未来”为主题，由同写意策划，安排一场主论坛和九场主题论坛，邀请“政、产、学、研、金、媒”各领域专家，通过“成果发布、主题演讲、热点对话、表彰颁奖、展览展示”五位一体的多元化的组织形式，迸发更多XDC产业新科技、新业态、新模式，构建XDC产业全新生态，触摸医药产业未来脉动。年初，安斯泰来的Claudin18.2单抗zolbetuximab收到了FDA发出的完整回复函（CRL），被暂时拒绝批准上市，根本原因是安斯泰来合作方第三方生产工厂存在未解决的缺陷，而zolbetuximab的临床数据并未受到质疑。既往有数据表明，CRL会将产品进入市场的时间平均推迟14个月。意味着，zolbetuximab的先发时间窗口将被大大减弱，这也给在CLDN18.2靶点上，通过各个技术路线来围猎Z药的国内药企，带来了更多的机会。ADC是国内药企的主攻方向之一。目前，全球共有13款CLDN18.2 ADC处于临床活跃阶段，12款由国内药企研发。其中，美股Elevation oncology，凭借引进自石药集团的EO-3021（SYSA1801），年初至今股价已经大涨近770%（截至最近交易日收盘），其他多款CLDN18.2 ADC也在近半年取得不菲的突破。1股价大涨770%CLDN18.2 ADC引进自石药在正常组织中，CLDN埋藏在胃粘膜里，表达受限，而在肿瘤中，紧密连接蛋白会遭到破坏，使肿瘤细胞表面的CLDN表位暴露出来，两者的表达差异使得CLDN18.2成为理想的抗肿瘤靶点。因此，近年来国内企业对该靶点的布局急速跃升，尤其是在ADC路线上，诸多药企进行了布局。石药集团是较早布局CLDN18.2 ADC的药企，旗下CLDN18.2 ADC药物SYSA1801分别在2020年及2021年获得了FDA用于治疗胃癌（包括食道胃结合部癌症）及胰脏癌的孤儿药资格认定。在药物设计上，SYSA1801在多个方面进行了差异化的设计，抗体方面对CLDN18.2具有高度选择性，不结合CLDN18.1，Fc端保持完整的CDC/ADCC功能，同时采用MMAE作为payload，酶裂解工艺，Q295的定点偶联，DAR值为2。SYSA1801结构在研发上，SYSA1801最早于2021年9月在国内首次获批进入临床，用于治疗CLDN18.2阳性晚期恶性实体瘤和胃食管交界处癌。因此，基于SYSA1801优异的早期数据，以及CLDN18.2靶点和ADC越来越热之际，SYSA1801也是较早完成了出海。在2022年7月，石药集团与Elevation Oncology达成合作协议，后者取得SYSA1801大中华区以外的权益，并支付2700万美元预付款、11.5亿美元里程碑金额以及一定比例的销售分成。在引进SYSA1801前，Elevation Oncology由于管线受挫，股价徘徊在1美元附近，市值长期低于5000万美元。而引进SYSA1801后，Elevation Oncology似乎开始了大刀阔斧地转型。2023年初，Elevation Oncology宣布裁员30%，公司CEO Shawn M.Leland也同时离职，在研发上将专注于SYSA1801的开发，并寻求合作伙伴共同开发HER3抗体Seribantumab。目前，Elevation Oncology官网显示的在研管线仅有SYSA1801和一款HER3-ADC。与此同时，在引进SYSA1801后，Elevation Oncology的股价也得到了一定的修复，尤其是在2023年5月6日，Elevation Oncology公布SYSA1801在中国的临床1期试验取得了积极结果后，股价大涨66%，当日市值达到1.2216亿美元。而在今年年初，安斯泰来的CLDN18.2单抗zolbetuximab被FDA拒绝上市，缩短了其他在研CLDN18.2疗法的时间差距。同时伴随着美股XBI指数持续上涨，SYSA1801临床试验的扩大，以及开展联合疗法的预期等消息影响，年初至今，Elevation Oncology的股价大幅飙升，整体已经上涨约830%（需要修改）。3竞争加速信达闯入三期，恒瑞实现出海SOTIO Biotech暂停研发…2023年9月28日，小编对CLDN18.2靶点在研的CAR-T、双抗、ADC疗法进行了详细盘点（详见：）。在短短五个月时间内，多款国产CLDN 18.2 ADC取得了新的研发进展，恒瑞的SHR-A1904出海德国默克，成为第6款出海的CLDN18.2 ADC，SOTIO Biotech则是暂停了旗下SOT-102的研发…CLDN18.2 ADC最新在研格局，根据智慧芽数据库整理01恒瑞医药SHR-A1904SHR-A1904是恒瑞医药第四款申请临床试验的ADC候选药物，同时也是恒瑞医药首个ADC交易。2023年10月，恒瑞医药将两款创新药以14.15亿欧元的总价出海给了德国默克，其中一款便是SHR-A1904。02信达生物IBI343IBI343是重组人源抗CLDN18.2 ADC，抗体为HB37A6，Payload为Exatecan，Linker使用的是Synaffix的技术，DAR值为4。IBI343在2022年12月23日获批进入临床，也是信达生物管线中第一个进入临床阶段的ADC药物。日前，ClinicaltriaIs官网显示信达生物注册了IBI343治疗CLDN18.2阳性、HER2阴性胃癌的临床三期试验，成为全球首款进入临床三期阶段的CLDN18.2 ADC。该临床试验以紫杉醇和伊立替康对照，计划入组450例胃癌患者，预计将于2026年5月初步完成试验。03科伦博泰SKB-315SKB-315是科伦博泰受默沙东青睐的临床资产之一，后者以3500万美元首付款，累计不超过9.01亿美元里程碑付款及销售提成的价格获得其全球权益。SKB315结构ClinicaltriaIs官网显示，默沙东在近期注册了评估SKB315（MK-1200）治疗晚期实体瘤安全性和有效性的临床2期试验，在CLDN18.2靶点成药性已经确认之际，默沙东继续推进SKB315也是顺理成章。默沙东将SKB315推进临床2期，科伦博泰也有望获得部分里程碑付款。目前SKB315的临床阶段仅落后于信达的SKB315，与多款国产CLDN18.2 ADC同处临床2期。更多优质内容，欢迎关注↓↓↓

SHANGHAI, Jan. 19, 2024 /PRNewswire/ -- CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, announces that at the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium ("ASCO GI"), the Company presented a poster with study results for satricabtagene autoleucel ("satri-cel", R&D code: CT041, an autologous CAR-T product candidate against Claudin18.2), which include the dose escalation results of the Phase 1b ELIMYN18.2 study (Cohort A) in gastric/gastroesophageal (GC/GEJ) or pancreatic cancer (PC) in the US. "The treatment options for advanced GC/GEJ or PC patients are limited. The data we presented at the 2024 ASCO GI of the Phase 1b ELIMYN18.2 study demonstrated encouraging safety and efficacy profile of satri-cel (CT041), a first-in-class CAR T-cell against Claudin18.2. We will continue to drive the global clinical development of satri-cel and look forward to sharing more data updates on satri-cel in the future." Raffaele Baffa, MD, PhD, Chief Medical Officer of CARsgen Therapeutics, remarked. Poster #356: CLDN18.2 Chimeric Antigen Receptor T Cell Therapy for Patients with Advanced Gastric and Pancreatic Adenocarcinoma: Results of ELIMYN18.2 Phase 1b Clinical Trial The single-arm, open-label, Phase 1b/2 study (NCT04404595) evaluated the safety and efficacy of satri-cel in patients with Claudin18.2-positive histologically confirmed advanced GC/GEJ or PC who had progressed or were intolerant of at least 2 prior lines (GC/GEJ) or 1 prior line (PC) of systemic therapy. The Phase 1b study consisted of a modified 3+3 dose escalation/de-escalation with 5 dose levels (DLs) to be tested. Patients received a preconditioning regimen of fludarabine, cyclophosphamide, and nab-paclitaxel, followed by 1-3 cycles of satri-cel. Herein, the Company presented the updated results of safety and determination of the Recommended Phase 2 Dose (RP2D). DL3 (600×106 cells) was selected as RP2D and enrollment in Phase 2 is currently ongoing. Adverse Events (AEs) were graded per CTCAE Version 5.0 and CRS and ICANS were graded by ASTCT 2019 consensus criteria. Objective Response Rate (ORR) and Clinical Benefit Rate (CBR) were assessed per RECIST 1.1, and tumor response (CR or PR) was confirmed by an imaging scan after the initial response assessment. CBR is defined as the incidence of a best overall response of CR, PR, or SD≥180 days. As of September 15, 2023, the median follow-up duration was 8.9 months (range:1.5-18.7 months). 19 patients were treated (7 GC/GEJ, 12 PC) across 3 DLs ranging from 250-600×106 cells: DL1: 250-300×106 (n=6), DL2: 375-400×106 (n=6), DL3: 600×106 (n=7). All patients received prior systemic therapy, among which 6 GC/GEJ (85.7%) and 7 PC (58.3%) patients received ≥ 3 lines of prior systemic treatment. Median number of prior systemic treatment lines of patients with GC/GEJ or PC were 4 (2,10) and 3 (1,5) respectively. Median number of metastatic organs of all patients was 2.0. All patients received at least one infusion and median number of infusions for all patients was 2.0 (1,3). Safety Overall, the safety profile of satri-cel was encouraging. No hemophagocytic lymphohistiocytosis (HLH), dose-limiting toxicities (DLTs), or treatment-related deaths were reported. The vast majority of CRS was Grade 1 with three Grade 2 events and two Grade 3 events. Apart from 1 patient who experienced Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS), no other ICANS events of any grade were observed. All events resolved. Efficacy As of September 15, 2023, the median follow-up duration was 8.9 months (range:1.5 to 18.7 months). 1 patient with GC/GEJ in DL3 achieved a CR. The confirmed ORR in patients with GC/GEJ in all DLs was 42.9% (3/7). CBR in patients with GC/GEJ or PC in DL3 was 71.4% (5/7) and in patients with GC/GEJ in all DLs was 57.1% (4/7). The median progression-free survival (mPFS) and median duration of response (mDOR) was 5.7 months and 6.9 months respectively in patients with GC/GEJ in all DLs. In DL3, median overall survival (mOS) in patients with GC/GEJ or PC was 12.9 months. The mOS in patients with GC/GEJ or PC in all DLs was 8.9 months. Conclusion The safety profile of satri-cel, the first autologous Claudin18.2 CAR T cell therapy, was encouraging. Initial efficacy was promising in heavily pre-treated Claudin18.2-positive advanced GC/GEJ and PC population and consistent with earlier reports. About Satri-cel Satri-cel (CT041) is an autologous CAR T-cell product candidate against the protein Claudin18.2 that has the potential to be the first-in-class globally. Satri-cel targets the treatment of Claudin18.2 positive solid tumors with a primary focus on gastric cancer/gastroesophageal junction cancer (GC/GEJ) and pancreatic cancer (PC). Trials in CARsgen include investigator-initiated trials (NCT03874897), a Phase Ib clinical trial for advanced GC/GEJ and PC and a confirmatory Phase II clinical trial for advanced GC/GEJ in China (CT041-ST-01, NCT04581473), a Phase I clinical trial for PC adjuvant therapy in China (CT041-ST-05, NCT05911217), and a Phase 1b/2 clinical trial for advanced gastric or pancreatic adenocarcinoma in North America (CT041-ST-02, NCT04404595). Satri-cel was granted Regenerative Medicine Advanced Therapy (RMAT) Designation by U.S. FDA for the treatment of advanced GC/GEJ with Claudin18.2-positive tumors in January 2022 and was granted PRIME eligibility by the EMA for the treatment of advanced gastric cancer in November 2021. Satri-cel received Orphan Drug designation from the U.S. FDA in 2020 for the treatment of GC/GEJ and Orphan Medicinal Product designation from the EMA in 2021 for the treatment of advanced gastric cancer. About CARsgen Therapeutics Holdings Limited CARsgen is a biopharmaceutical company with operations in China and the U.S. and is focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors. CARsgen has established a comprehensive CAR T-cell research and development platform, encompassing target discovery, innovative CAR T-cell development, clinical trials, and commercial-scale production. CARsgen has internally developed novel technologies and a product pipeline with global rights to address major challenges of CAR T-cell therapies, such as improving the safety profile, enhancing the efficacy in treating solid tumors, and reducing treatment costs. CARsgen's vision is to become a global biopharmaceutical leader that brings innovative and differentiated cell therapies to cancer patients worldwide and makes cancer curable. Forward-looking Statements All statements in this press release that are not historical fact or that do not relate to present facts or current conditions are forward-looking statements. Such forward-looking statements express the Group's current views, projections, beliefs and expectations with respect to future events as of the date of this press release. Such forward-looking statements are based on a number of assumptions and factors beyond the Group's control. As a result, they are subject to significant risks and uncertainties, and actual events or results may differ materially from these forward-looking statements and the forward-looking events discussed in this press release might not occur. Such risks and uncertainties include, but are not limited to, those detailed under the heading "Principal Risks and Uncertainties" in our most recent annual report and interim report and other announcements and reports made available on our corporate website, . No representation or warranty is given as to the achievement or reasonableness of, and no reliance should be placed on, any projections, targets, estimates or forecasts contained in this press release. Contact CARsgen For more information, please visit Public Relations: [email protected] Investor Relations: [email protected] SOURCE CARsgen Therapeutics