TST-005

精彩内容近日，武汉友芝友生物以新药1类申报的Y101D获得临床试验默示许可，预计为新适应症获批临床，拟用于晚期或转移性胰腺癌。这是一款靶向PD-L1/TGF-β的双特异性抗体，国内暂无同靶点双抗获批。双抗药物是石药集团重点布局的研发方向之一，目前公司已有6款1类新药在国内开展临床。来源：CDE官网Y101D是一款针对PD-L1和TGF-β的双靶点抗体。研究发现，肿瘤微环境中PD-(L)1和TGF-β通常会同时高表达，TGF-β是免疫抑制的重要驱动因素，进而介导抗PD-(L)1单抗的原发性耐药，同时阻断PD-(L)1和TGF-β两个免疫抑制信号可产生协同作用。国内暂无PD-L1/TGF-β双抗获批，多款产品已步入临床阶段，包括恒瑞的SHR-1701、石药的Y-101D（重组抗PD-L1和TGF-β双特异性抗体注射液）、泽璟制药/开拓药业的GS-19（GT90008）、创胜集团的TST-005（TST005注射液）等。国内部分在开展临床的PD-L1/TGF-β双抗来源：米内网新版数据库作为国内领先的综合型制药企业，石药集团近年来积极布局创新药研发与开拓海外市场。季报数据显示，2022前三季度公司研发费用29.2亿元，同比增加16.4%，约占成药业务收入的15.7%。在大分子药物研发方面，石药集团重点开发多功能化的蛋白及抗体药物，如双抗、三抗、ADC等。在双抗赛道上，目前公司已有6款1类新药在国内开展临床，其中重组人源化抗HER2双特异性抗体注射液（KN026）进展最快，HER2阳性胃癌（包括胃-食管结合部腺癌）适应症已步入II/III期临床。石药集团在国内开展临床的双抗来源：米内网全球新药研发数据库近年来，石药集团业绩增长稳健，神经系统产品及抗肿瘤产品成为公司业绩的两大支柱。2022前三季度，上述两大类产品分别实现60.12亿元、59.09亿元的销售收入。资料来源：米内网数据库、CDE官网等注：数据统计截至12月6日，如有疏漏，欢迎指正！本文为原创稿件，转载请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092【分享、点赞、在看】点一点不失联哦

SUZHOU, China, Nov. 10, 2022 /PRNewswire/ -- Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, announces that it has presented two scientific posters at the 37th Society for Immunotherapy of Cancer's (SITC) Annual Meeting in Boston, MA, November 8-12, 2022. One related to TST001 (Osemitamab), a high affinity humanized anti-Claudin18.2 monoclonal antibody with enhanced ADCC, regarding the prevalence of Claudin18.2 and PD-L1 Expression in Chinese patients with gastric/gastroesophageal junction adenocarcinoma using Transcenta's proprietary Claudin18.2 specific IHC antibody and a commercial kit for PD-L1 detection. The other is a Trial in Progress (TiP) abstract on TST005, a bi-functional anti-PD-L1 and TGF-β trap fusion protein: a phase 1, first in human, open-label, dose escalation and dose expansion study in patients with locally advanced or metastatic solid tumors. Details are as follows: Abstract#105: Prevalence of Claudin18.2 and PD-L1 Expression in Chinese Gastric/Gastroesophageal Junction Adenocarcinoma Claudin18.2, expressed at a significant level in multiple tumor types including gastric cancer, is a promising target for gastric cancer treatment. Immunotherapy targeting PD-1 combined with chemotherapy has been approved as the first line treatment of gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Understanding the expression profiles of Claudin18.2 and PD-L1 could offer guidance for the development of combination therapies that maximize the benefits of both agents. This study investigated the prevalence of Claudin18.2 expression from surgical resections of G/GEJ adenocarcinoma at diagnosis and its correlation with PD-L1 expression in a cohort of Chinese patients. A total of 300 G/GEJ resected adenocarcinoma tissue samples were assessed using Transcenta's proprietary Claudin18.2 specific antibody 14G11 and commercial kit PD-L1 IHC 28-8 pharmDx. Claudin18.2 staining in ≥ 10% of the tumor cells at 1+ or above intensity was present in 216 (72%) tissue samples tested. For PD-L1 expression, 51 (17%) had PD-L1 CPS ≥ 5. About 19% (n=41/216) of the Claudin18.2 positive samples also showed PD-L1 CPS ≥ 5. No correlation between the two markers expression was observed. Abstract#771: A phase 1, first in human, open-label, dose escalation and dose expansion study of TST005 in patients with locally advanced or metastatic solid tumors TST005 is a novel bi-functional fusion protein combining a high affinity PD-L1 monoclonal antibody (mAb) in a fragment crystallizable (Fc) silenced immunoglobulin G1 (IgG1) backbone and a differentiated transforming growth factor beta (TGF‑β) trap with improved stability. This study investigated the safety, tolerability and preliminary anti-tumor activity of TST005 in solid tumors. In a preclinical EMT6/hPD-L1 breast tumor model with high TGF-β expression, TST005 treatment showed better tumor inhibition compared to M7824 analog, a PD-L1/TGFβ bi-functional fusion protein. This study is ongoing at 4 sites in the US and China. As of Aug 24, 2022, the first three dose cohorts have been completed and no DLT was observed. The full text of posters is available on Transcenta's website: About TST001 (Osemitamab) TST001 (Osemitamab) is a high affinity humanized anti-Claudin18.2 monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity ("ADCC") and complement-dependent cytotoxicity ("CDC") activities and potent anti-tumor activities in tumor xenograft models. TST001 (Osemitamab) is the second most advanced Claudin18.2 targeting antibody being developed globally. TST001 (Osemitamab) is generated using Transcenta's Immune Tolerance Breaking Technology (IMTB) platform. TST001 (Osemitamab) kills Claudin18.2 expressing tumor cells by mechanisms of ADCC and CDC. Leveraging advanced bioprocessing technology, the fucose content of TST001 (Osemitamab) was significantly reduced during the production, which further enhanced NK cells mediated ADCC activity of TST001 (Osemitamab). Clinical trials for TST001 (Osemitamab) are ongoing in the U.S. and China (NCT04396821, NCT04495296/CTR20201281). TST001 (Osemitamab) was granted Orphan Drug Designation in the U.S. by FDA for the treatment of patients with gastric or gastroesophageal junction (G/GEJ) cancer. About TST005 TST005 is the second bi-functional anti-PD-L1 and TGF-β trap fusion protein entering the global clinical stage. It simultaneously targets two immuno-suppressive pathways, transforming growth factor -β (TGF-β) and programmed cell death ligand-1 (PD-L1), that are commonly used by cancer cells to evade the immune system. TST005 consists of a high affinity PD-L1 antibody fused with an engineered TGF-β Receptor Type II protein in its C-terminal. TST005 lacks FcR binding activity and thus has reduced FcR mediated killing of PD-L1 expressing effector T cells. TST005's high PD-L1 binding activity and enhanced TGF-β trap stability enables the targeted delivery of TGF-β trap into PD-L1 expressing tumors, thereby minimizing off-target toxicities of systemic inhibition of TGF-β signaling. TST005 displayed potent activity in vitro in reversing TGF-β induced T-cell suppression. In multiple syngeneic tumor models, TST005 induced significant increase of CD8+ T-cell infiltration into PD-L1 expressing tumors and displayed dose-dependent tumor growth inhibition in tumor model not sensitive to PD-(L)1 treatment due to high level TGF-β. TST005 is well tolerated in non-human primates and displayed a linear PK profile. TST005 is a potentially differentiated bi-functional immunotherapy candidate with improved therapeutic window. TST005 is being investigated in a FIH trial in the US and China (NCT04958434/CTR20221397). About Transcenta Holding Limited Transcenta (HKEX: 06628) is a clinical stage biopharmaceutical company with fully integrated capabilities in antibody-based biotherapeutics discovery, research, development and manufacturing. Transcenta has established global footprint, with Headquarters and Discovery, Clinical and Translational Research Center in Suzhou, Process and Product Development Center and Manufacturing Facility in Hangzhou, and Clinical Development Centers in Princeton, US and in Beijing, Shanghai and Guangzhou of China, and External Partnering Center in Boston and Los Angeles, US. Transcenta has also initiated the construction of the Group Headquarters and the second high-end biopharmaceutical facility with ICB as its core technology in Suzhou Industrial Park. Transcenta is developing ten therapeutic antibody molecules for oncology and selected non-oncology indications including bone and kidney disorders. For more information, please visit and . Forward-Looking Statements This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Transcenta, are intended to identify certain of such forward-looking statements. Transcenta does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Transcenta with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Transcenta's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Transcenta's competitive environment and political, economic, legal and social conditions. Transcenta, the Directors and the employees of Transcenta assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect. SOURCE Transcenta Holding Limited