Nivolumab

Eight participants achieved HBsAg loss at any time. Two participants met criteria for functional cure. Two participants who discontinued NUC therapy seroconverted to HBsAb positivity. Nov. 15, 2024 -- Barinthus Biotherapeutics plc (NASDAQ: BRNS), today announced the most significant data so far from the ongoing Phase 2b HBV003 clinical trial. The data will be presented by Dr. Chun-Jen Liu as an oral presentation on November 18, 2024, at 17:30 PT at the American Association for the Study of Liver Diseases (AASLD) – The Liver Meeting® 2024. Barinthus Bio is a clinical-stage biopharmaceutical company developing novel immunotherapeutic candidates that guide T cells to control disease. The HBV003 study (NCT05343481) is fully recruited with a total of 121 participants, including 69 participants who had entered the trial with HBsAg levels below 200 IU/mL. The study is evaluating different dosing regimens of VTP-300 in combination with low-dose nivolumab, an anti-PD-1 monoclonal antibody. The new data showed that as of data cut off, eight participants were reported with complete HBsAg loss (defined as HBsAg levels below the lower limit of quantitation [ Uniquely, two of the eight participants with HBsAg loss, became positive for anti-hepatitis B antibodies (HBsAb) that they did not have before, including one of those who met functional cure criteria. The data from this ongoing study indicate that stronger responses may happen in participants treated with the combination of VTP-300 and a low dose of the anti-PD1 antibody nivolumab (Groups 1 and 2). “Sustained HBsAg loss has proven to be the largest hurdle in getting chronic hepatitis B patients to functional cure,” said Dr. Chun-Jen Liu, investigator on HBV003 and Director of the Hepatitis Research Center and Clinical Trial Center, National Taiwan University Hospital, Taiwan. “The data we are seeing with VTP-300 is unique because they indicate a durable loss of HBsAg in participants, including two who met the criteria for functional cure. Although the study is still ongoing, these early data may bring us a step closer to potentially allowing some patients with chronic hepatitis B to come off antiviral treatment without their chronic hepatitis B progressing.” 40 participants, with HBsAg below 200 IU/mL at screening, who had reached Day 169 were assessed for nucleos(t)ide analogue (NUC) discontinuation. The data showed the following: 24 were eligible for NUC discontinuation. Eight achieved HBsAg loss at any time, two of whom achieved it after Day 169. Nine participants chose to discontinue NUCs. 66% (n=6/9) remained off NUC therapy, five for more than six months. Two of these six have met the criteria for functional cure. Two of these six seroconverted to HBsAb positivity. Follow up is continuing with the remaining participants to assess if they will meet functional cure criteria. Durable HBsAg declines were observed in all treatment groups, consistent with data previously presented at the European Association for the Study of the Liver (EASL) Congress, in June 2024. Preliminary safety data indicate that VTP-300 in combination with low-dose nivolumab was generally well tolerated with no treatment-related SAEs observed or reported as of data cut off. "These Phase 2 data are incredibly encouraging and highlight the ability of VTP-300 to stimulate the immune response and induce sustained reductions in HBsAg to the point of meeting functional cure criteria,” said Dr. Nadege Pelletier, Chief Scientific Officer of Barinthus Bio. "Moreover, the finding that one of the participants meeting functional cure criteria had antibodies against hepatitis B is promising as HBsAb positivity is associated with long-term control of the infection by the immune system.” Functional cure is defined by AASLD as sustained HBsAg loss and hepatitis B virus DNA About the HBV003 Trial The HBV003 trial is designed to obtain critical information on treatment dosing regimen with participants receiving VTP-300 and low-dose (LD) nivolumab. All Groups received ChAdOx at Day 1; Groups 1 & 2 received MVA with nivolumab at Day 29; Group 2 was dosed again with MVA and nivolumab at Day 85; Group 3 received only MVA at Day 29, nivolumab at Day 36, and a conditional second MVA dose at Day 85 to evaluate anti-PD-1 inhibition timing. The conditional MVA dose was administered if participants had HBsAg ≥10 IU/mL. In 2023, the study inclusion criteria was amended from people with CHB with HBsAg ≥10 and About VTP-300 VTP-300 is an immunotherapeutic candidate consisting of an initial dose using the ChAdOx vector and a secondary dose(s) using the MVA vector, both encoding multiple HBsAg, including full-length surface, modified polymerase, and core antigens. VTP-300 is the first antigen-specific immunotherapy that has been shown to induce sustained reductions in HBsAg. Barinthus Bio is studying VTP-300 in combination with other agents, including siRNA and low-dose anti-PD-1 antibodies in the ongoing IM-PROVE II trial, to control the infection, and counterbalance the immune suppression and T cell exhaustion in the liver caused by chronic HBV infection. Barinthus Bio is a clinical-stage biopharmaceutical company developing novel immunotherapeutic candidates designed to guide the immune system to overcome chronic infectious diseases and autoimmunity. Helping people living with serious diseases and their families is the guiding principle at the heart of Barinthus Bio. With a focused pipeline built around our proprietary platform technologies, Barinthus Bio is advancing immunotherapeutic product candidates in infectious diseases and autoimmunity, including: VTP-300, utilizing our ChAdOx/MVA platform designed as a potential component of a functional cure for chronic HBV infection and VTP-1000, utilizing our SNAP-Tolerance Immunotherapy (SNAP-TI) platform and designed to treat people with celiac disease. Barinthus Bio is also conducting a Phase 1 clinical trial for VTP-850, a second-generation immunotherapeutic candidate designed to treat recurrent prostate cancer. Barinthus Bio’s differentiated technology platforms and therapeutic approach, coupled with deep scientific expertise and focus on clinical development, uniquely positions the company to navigate towards delivering treatments that improve the lives of people with chronic infectious diseases and autoimmunity. For more information, visit www.barinthusbio.com. The content above comes from the network. if any infringement, please contact us to modify.

Insight 数据库国内「申报进度」模块显示，2024 年以来（截至 11 月 19 日），正大天晴今年已经有 13 款 1 类新药首次在国内获批临床。其中，肿瘤和自免领域共计有 9 款。 根据企业在研的创新药管线整局可以看出，肿瘤领域是正大天晴的主要战场，其次是自免领域。 截图来源：Insight 数据库 这 13 款创新药中，我们选择有靶点信息披露的项目进行介绍。 TQB2029：GPRC5D×CD3 双抗 10 月 28 日，正大天晴 TQB2029 首次获 CDE 批准临床，用于多发性骨髓瘤。11 月 4 日，已经在 CDE 登记一项 TQB2029 用于多发性骨髓瘤的 I 期临床。 截图来源：CDE 官网 TQB2029 是一款同时靶向 GPRC5D 和 CD3 的双抗，通过募集和激活 T 细胞来诱导 T 细胞杀伤表达 GPRC5D 的恶性浆细胞，达到抑制肿瘤形成与生长的目的。 GPRC5D 是近几年多发性骨髓瘤领域最有潜力的新靶点，它表达于浆细胞，在正常 B 细胞、T 细胞、NK 细胞、单核细胞、粒细胞和骨髓祖细胞中几乎无表达。从表达谱上看，GPRC5D 特异性高于 CD38 和 BCMA 这两个靶点。 目前，全球在研的靶向 GPRC5D 的新药类型比较多样化，包括 CAR-T、双抗、三抗等。 截图来源：Insight 数据库 虽然 CAR-T 的布局者更多，但是双抗已经领先 CAR-T 率先获批上市。2023 年 8 月 10 日，强生的 Talquetamab（塔奎妥单抗）获 FDA 批准用于末线治疗多发性骨髓瘤成人患者，这些患者此前至少接受过四种疗法，包括蛋白酶体抑制剂、免疫调节剂和 CD38 抗体。 目前，全球在研的靶向 GPRC5D 和 CD3 的双抗共有 13 款，除了已获批的 Talquetamab 外只有 2 款进展到临床阶段，分别来自罗氏的 Forimtamig 和南京维立志博的 LBL-034；其中，罗氏今年的三季报显示，已经从管线中移除了 Forimtamig 用于多发性骨髓瘤的联合疗法研究。 TQB3002：四代 EGFR-TKI 10 月 18 日，正大天晴 1 类新药 TQB3002 获 CDE 首次批准临床，用于晚期恶性肿瘤。 TQB3002 是第四代表皮生长因子受体（EGFR）抑制剂，通过与胞内酪氨酸激酶结合域的 ATP 位点竞争性结合，抑制相关酪氨酸激酶活性和细胞内磷酸化过程，进而抑制 EGFR 下游的信号传导，最终导致肿瘤细胞死亡。 虽然 EGFR-TKI 类药物已经发展到第三代，以奥希替尼为代表的三代 GFR-TKI 为患者带来了显著的生存获益，与第一代相比，中位 PFS（18.9 v 10.2 个月）和中位 OS（38.6 v 31.8 个月）均显著延长，但是耐药仍然是临床面临的巨大问题。研究表明，针对 EGFR 通路获得性耐药中，C797S 突变是奥希替尼获得性耐药首要机制，目前已有大批在研的四代 EGFR-TKI。 TQB3002 已经不是正大天晴第一款四代 EGFR-TKI 了，据 Insight 数据库显示，此前还有一款 TQB3804，2023 年 7 月已经完成 I 期临床，目前没有看到最新进展。 TQB3002 已经在中国启动 I 期临床，11 月 15 日，该药已经获得 FDA 批准临床，即将在美国启动 I 期临床试验。 截图来源：Clinicaltrials 官网 TQB2252： 靶向 LAG3、PD-1 的混合抗体 9 月 26 日，正大天晴 1 类新药 TQB2252 首次获 CDE 批准临床，用于晚期恶性肿瘤。 公开信息显示，TQB2252 注射液是靶向 LAG-3 的单抗与派安普利单抗（PD-1）组成的复方制剂，规格为每瓶（20 ml）含 TQB2223 单克隆抗体 300 mg，派安普利单抗 100 mg 。 10 月 21 日，该药已经启动 I 期临床。 截图来源：Clinicaltrials 官网 PD-1 和 LAG-3 两个靶点的组合中，目前全球在研处于活跃状态的新药主要是双抗（7 个），混合抗体有 4 个，此外还有 3 款三抗/多抗。 截图来源：Insight 数据库 其中，只有一款混合抗体已经获批上市，来自百时美施贵宝的 Opdualag（纳武利尤单抗+瑞拉利单抗），2022 年 3 月获 FDA 批准用于黑色素瘤一线疗法，2023 年全球销售额 6.27 亿美元；百时美施贵宝还在开发 Opdualag 的皮下注射版，目前正处于 III 期阶段。 第三款是默沙东的 MK-4280A（Favezelimab+帕博利珠单抗），目前用于直肠癌、经典型霍奇金淋巴瘤适应症也已进展到 III 期阶段。 正大天晴 TQB2252 是全球第三家布局 LAG3、PD-1 混合抗体的企业。 截图来源：Insight 数据库 TQH3906：TYK2 抑制剂 1 月 12 日，正大天晴 1 类新药 TQH3906 首次获 CDE 批准临床，用于中重度斑块状银屑病。 TQH3906 是正大天晴研发的一种靶向 TYK2 变构抑制剂，目前正在开展斑块状银屑病 II 期临床。 百时美施贵宝的「氘可来昔替尼」是目前全球首个、且唯一获批的 TYK2 抑制剂，其对 TYK2 具有高选择性，IC50 为 0.2 nM，体外细胞测定中与JAK1、JAK2 和 JAK3 比对 TYK2的选择性要>100 倍。2023 年 10 月18 日，氘可来昔替尼在国内获批用于适合系统治疗或光疗的成年中重度斑块状银屑病患者。 据 Insight 数据库显示，目前全球在研的仅针对 TYK2 靶点的药物共有 21 个已进展到临床阶段，其中有三款已经进展到 III 期临床阶段，分别为武田的 Zasocitinib、诺诚健华的 ICP-332、豪森的 HS-10374，诺诚健华和豪森进度走在国产第一梯队中。 正大天晴的 TQH3906、益方生物的 D-2570、诺诚建华的 ICP-488 均进展到 II期临床阶段，处于国产第二梯队。 封面来源：企业 Logo 免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。 编辑：vvy PR 稿对接：微信 insightxb 投稿：微信 insightxb；邮箱 insight@dxy.cn 多样化功能、可溯源数据…… Insight 数据库网页版等你体验 点击阅读原文，立刻解锁！