Gotistobart

Designation granted for gotistobart (BNT316/ONC392) for the treatment of patients with squamous non-small cell lung cancer (sqNSCLC), an aggressive subtype of lung cancer Breakthrough Therapy designation will allow for an expedited development and regulatory review of gotistobart in China Global pivotal PRESERVE-003 Phase 3 clinical trial in squamous non-small cell lung cancer Is Ongoing ROCKVILLE, Md., Oct. 27, 2025 /PRNewswire/ -- OncoC4 announced today that China's National Medical Product Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for gotistobart (BNT316/ONC392) for the treatment of patients with squamous non-small cell lung cancer (sqNSCLC) who have progressed on prior standard immuno-oncology therapies (IO). Gotistobart is a next-generation anti-CTLA-4 antibody candidate which is being jointly developed by BioNTech and OncoC4. Continue Reading Squamous non-small cell lung cancer (sqNSCLC) is an aggressive subtype of lung cancer accounting for approximately 25-30% of all NSCLC cases, the most common type of lung cancer1. The 5-year relative survival rate for patients with sqNSCLC is 15%2. While novel first line treatments combining immune-checkpoint inhibition and chemotherapy have improved outcomes of patients with NSCLC, the medical need remains high for novel treatments options, especially for patients with lung cancer that have progressed on first-line therapy and have limited treatment options3. Breakthrough Therapy Designation for Anti-CTLA-4 Antibody Candidate Gotistobart (BNT316/ONC-392) Post this "For the past 5 years, limited advances in treatment outcomes have been reported for EGFR wild-type NSCLC patients who progressed on the first-line IO and chemotherapies. We believe gotistobart has the potential to broaden the reach of CTLA-4-targeting immunotherapy and to improve outcomes for patients living with sqNSCLC." said Pan Zheng, MD, PhD, Co-founder and Chief Medical Officer of OncoC4. "Gotistobart is a next-gen acid pH-sensitive anti-CTLA4 mAb that conferred an improved therapeutic index compared with approved anti-CTLA-4 antibodies by preserving CTLA-4 on regulatory T cells as demonstrated in preclinical models. The emerging data support clinical proof of concept for this new approach", added Yang Liu, PhD, Co-Founder, Chief Executive Officer, and Chief Scientific Officer of OncoC4. Gotistobart is currently being evaluated in a registrational two-stage randomized Phase 3 trial, PRESERVE-003 (NCT05671510). The clinical trial assesses the efficacy and safety of gotistobart as monotherapy compared to the standard-of-care chemotherapy (docetaxel) in patients with metastatic sqNSCLC that progressed under previous PD-(L)1-inhibitor treatment. The initiation of the Phase 3 trial was based on positive safety and efficacy data from an ongoing Phase 1/2 trial (NCT04140526) with gotistobart alone and in combination with pembrolizumab in patients with advanced solid tumors. The program received Fast Track Designation from the U.S. Food and Drug Administration (FDA) in 2022 and represents an innovative approach which aims to leverage the full potential of CTLA-4-targeting therapies. Breakthrough Therapy Designation is an NMPA program designed to expedite the development and regulatory review of investigational therapies that are designed to address serious or life-threatening conditions. To receive the designation, the candidate needs to demonstrate preliminary clinical evidence that indicates that it may offer substantial improvement over existing therapies on one or more clinically significant endpoints. The NMPA's BTD designation is based on the Stage 1 safety and efficacy data of the PRESERVE-003 trial. The detailed data will be reported in an upcoming medical conference in December 2025. With the Breakthrough Therapy designation, the development of gotistobart may benefit from more frequent engagement with the NMPA, which will support the collection of appropriate data needed to accelerate development and may also allow for priority review if the relevant criteria are met. About PRESERVE-003 The two-stage, open-label, randomized Phase 3 trial, PRESERVE-003 (NCT05671510), will assess the efficacy and safety of gotistobart (BNT316/ONC-392) as monotherapy compared to the standard-of-care chemotherapy (docetaxel) in patients with metastatic NSCLC that progressed under previous PD-(L)1-inhibitor treatment. Stage 1, the non-pivotal dose-confirmation stage, assessed the efficacy and safety of two gotistobart dosing regimens in comparison to docetaxel in patients with squamous and non-squamous non-small cell lung cancer (NSCLC). Stage 2 is the pivotal stage of the trial and will assess the safety and efficacy of gotistobart in squamous cell NSCLC. The primary endpoint measure is overall survival. Secondary endpoints include overall response rate, progression-free survival and adverse event profile. Approximately 600 patients are planned to be enrolled at clinical sites in 12 countries and regions globally, including China, Germany, Italy, South Korea, Türkiye, the United Kingdom, and the United States. About gotistobart (BNT316/ONC392) Gotistobart is licensed to BioNTech for commercialization and jointly developed clinically by OncoC4 and BioNTech for oncology indications. There are several ongoing clinical trials in different tumor types, investigating gotistobart either as monotherapy or in combination with other therapeutic agents. About OncoC4 Based in Rockville, Maryland, OncoC4 is a privately held, late-stage biopharmaceutical company that is actively engaged in the discovery and development of novel biologicals for the treatment of cancer and immunological diseases. OncoC4's pipeline features assets with first-in-class and best-in-class potential targeting both novel and well validated targets across oncology and immunological diseases. Among them, AI-081 is a fully owned and potentially best-in-class bispecific antibody candidate targeting PD-1 and VEGF. AI-081 is currently enrolling patients in a Phase 2 trial that could enable two or more pivotal studies. ONC-841 is a first-in-class anti-SIGLEC10 antibody currently in a Phase 2 trial for oncology indications and being explored for neurodegenerative diseases. OncoC4 has a strategic collaboration with BioNTech to co-develop gotistobart (BNT316/ONC-392), a next-generation anti-CTLA-4 antibody candidate, in multiple solid tumor indications, including an ongoing pivotal clinical trial in squamous non-small cell lung cancer. More information: . Investor Contact: Ryan Cui, Executive Director of Investor Relations [email protected] 1 Houston KA, Henley SJ, Li J, White MC and Richards TB, Lung Cancer, 86:22-28, 2014. 2 Hu S, Zhang W, Guo Q, Ye J, Zhang D, Zhang Y, Zeng W, Yu D, Peng J, Wei Y, Xu J, International Journal of General Medicine, 14:9567-9588. 3 Lau SCM, Pan Y, Velcheti V and Wong K, Cancer Cell, 40:1279-1293, 2022. SOURCE OncoC4 WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

导语 2025年诺贝尔生理学或医学奖的桂冠，授予了“调节性T细胞”的发现者——玛丽·布伦科、弗雷德·拉姆斯德尔与坂口志文。但诺奖的意义远不止于褒奖过去的发现，更在于照亮未来的方向。当科学家们解码了免疫“刹车”系统后，新问题随之诞生：我能否“调控”它开辟疾病治疗新路径？本文将带您一同探寻：哪些正在研发的药物，正巧妙地作用于这一诺奖靶点？我们距离驾驭体内的“免疫警察”，还有多远？ 精准调控：修复与清除，Treg靶向药物的双轨战略 从自身免疫攻击到慢性炎症失控，再到肿瘤的免疫耐受等等，诸多疾病路径的交汇点，都指向了调节性T细胞（Treg）。它如同一个核心支点，其功能的微小改变便能撬动一张庞大的疾病网络。 疾病类别 具体疾病举例 Treg的作用 治疗潜力 自身免疫性疾病 1型糖尿病、类风湿性关节炎、多发性硬化症、系统性红斑狼疮 数量减少或功能缺陷，导致无法有效抑制对自身组织的免疫攻击 恢复/增强Treg功能 癌症 多种实体瘤（如肺癌、卵巢癌）和血液肿瘤 在肿瘤微环境中数量增多、功能过度活跃，抑制抗肿瘤免疫（细胞毒性T细胞等），促进肿瘤免疫逃逸和进展 抑制/清除Treg功能 器官移植与移植物抗宿主病（GVHD） 同种异体移植排斥、造血干细胞移植后的GVHD 功能正常时，可诱导移植耐受，防止排斥。但在移植后，其数量或功能可能不足以抑制强烈的同种免疫反应。 诱导/扩增Treg 过敏性疾病 哮喘、特应性皮炎、过敏性鼻炎 数量或功能可能相对不足，导致对无害环境抗原（过敏原）的免疫抑制失灵，引发Th2驱动的过度炎症 恢复气道/皮肤局部Treg功能 慢性感染 艾滋病（HIV）、乙型肝炎、丙型肝炎、寄生虫感染在慢性感染环境中被病原体利用或过度激活，抑制有效的抗病 在慢性感染环境中被病原体利用或过度激活，抑制有效的抗病原体免疫反应，导致病毒/细菌持续存在和疾病慢性化 适度调控Treg功能 组织修复与代谢疾病 心肌梗死后的组织修复、动脉粥样硬化、2型糖尿病（胰岛素抵抗） 具有促进组织修复和维持代谢稳态的功能。功能异常可能影响损伤后的修复过程，并参与代谢性炎症 探索其保护性作用 Treg靶向药物已在路上 尽管目前尚未有Treg靶向药物正式上市，但一系列旨在精准“扩增”或“激活”Tregs的突破性疗法，已悄然进入临床后期试验阶段，预示着免疫疗法即将迎来一场全新的革命。 ➩NP001——人自体多克隆调节性T细胞注射液 适应症：肌萎缩侧索硬化症（ALS，渐冻症） 作用机制：采用患者自身的Treg细胞，经体外扩增后精准回输至病变部位，通过将巨噬细胞从促炎状态重编程为非炎性状态，从而有效抑制神经炎症；同时，它还具有多重神经保护作用，能促进神经修复与突触重塑，以一种多靶点的方式减缓如肌萎缩侧索硬化（ALS）等疾病的进展 进展阶段：Ⅰ/Ⅱa期临床研究已于2025年9月启动，作为全球首款完成中美IND申报的Treg细胞疗法，若临床试验顺利推进并获得监管批准，将填补神经退行性疾病治疗领域的空白 ➩CM512——IL-13×TSLP双特异性抗体 适应症：慢性阻塞性肺疾病、慢性荨麻疹、AD、特应性皮炎、实体瘤等 研发公司：康诺亚 作用机制：通过抗体部分精准识别并结合肿瘤微环境中高表达CCR8的免疫抑制性调节性T细胞，在被该细胞内存后，释放所携带的强效细胞毒素，从而选择性清除这些关键的“免疫刹车”细胞，进而解除其对免疫系统的压制 进展阶段：用于治疗慢性自发性荨麻疹的II期临床试验已经启动 ➩Gotistobart（ONC-392）——人源化抗CTLA-4抗体 适应症：卵巢癌、肺癌等 研发公司：OncoC4 作用机制：过选择性耗竭肿瘤微环境中的调节性T细胞（Treg）来增强免疫治疗效果 进展阶段：目前第二阶段的入组进展顺利，全球已有160个临床机构参与 ➩Rezpegaldesleukin——IL-2通路激动剂 适应症：系统性红斑狼疮、特应性皮炎、斑秃等 研发公司：Nektar Therapeutics 作用机制：通过选择性扩增Treg细胞来恢复免疫平衡，抑制炎症反应 进展阶段：‌2b期临床试验成功，在中重度特应性皮炎治疗中展现出积极疗效 ➩HBM4003——全人源抗CTLA-4抗体 适应症：晚期实体瘤、黑色素瘤、肝细胞癌等 研发公司：和铂医药 作用机制：通过增强抗体依赖的细胞毒性（ADCC）作用，可有效清除肿瘤微环境中的Treg细胞，同时降低传统CTLA-4抗体引发的系统性毒副作用 进展阶段：在2025年ESMO大会公布的II期临床数据显示，HBM4003联合替雷利珠单抗治疗微卫星稳定型转移性结直肠癌（MSS mCRC）时，对瘤内Treg细胞的清除机制展现出显著疗效，且安全性良好。此外，该药物已在结肠癌、肝癌、神经内分泌瘤等多个瘤种中观察到积极疗效信号 ➩HBM1022——CCR8抗体 适应症：腺癌、结肠癌、胃癌、非小细胞肺癌等实体瘤 研发公司：和铂医药 作用机制：通过特异性识别并结合肿瘤浸润性调节性T细胞表面的CCR8受体，促进效应性T细胞的肿瘤特异性杀伤作用，同时不影响全身免疫平衡 进展阶段：已获FDA新药研究申请许可，标志着其进入了临床试验的阶段 调节性T细胞——“免疫协调官“ Treg对众多疾病的强大调控能力，源于其多重作用机制所奠定的功能基础。主要通过以下几种方式发挥作用： (1) 分泌抑制性细胞因子：如TGF-β和IL-10，直接抑制效应T细胞等免疫细胞的活化和增殖； (2) 进行细胞接触性抑制：通过其表面的CTLA-4分子与抗原呈递细胞上的CD80/CD86高亲和力结合，“窃取”共刺激信号，使效应T细胞无法被有效激活； (3) 代谢干扰：如高表达CD25（IL-2受体α链）竞争性消耗T细胞生长所必需的IL-2，导致效应T细胞因“营养”不足而凋亡； (4) 激活颗粒酶/穿孔素途径直接杀伤活化的效应T细胞。通过这些多管齐下的精密机制，调节性T细胞有效地将免疫反应控制在一个适度的范围内，确保了免疫系统在攻击病原体与保护自身组织之间实现精确的平衡。 图1. 调节性T细胞的多重作用机制 Treg细胞的发现历程 上世纪90年代，坂口志文发现调节性T细胞（Treg），证明其在维持外周耐受中的作用，突破了免疫耐受仅由胸腺主导的传统认知。 2001年，布伦科与拉姆斯德尔在研究一种多器官自身免疫疾病的小鼠模型时，锁定其病因是Foxp3基因突变。他们进一步证实，人类该基因的突变同样会导致严重的遗传性自身免疫病，其根源在于调节性T细胞功能缺陷。 两年后，坂口志文将这两项关键发现联系起来，证明Foxp3正是调节性T细胞发育与功能的主控基因。 参考资料： [1]https://baijiahao.baidu.com/sid=1845227156434041857&wfr=spider&for=pc [2]https://vamosarema.com/ [3]https://www.novabiotx.cn/article-item-32.html [4]https://www.keymedbio.com/cn/pipeline.html [5]https://oncoc4.com/ctla-4-program/ [6]https://www.nektar.com/clinical-trials/ [7]https://www.harbourbiomed.cn/therapeutics 甲贝医药（Shell BioTech）是一家线上和线下联动的新型生物药 CDMO技术服务平台，致力于为客户的蛋白抗体类药物提供从“Shell DA™（可开发性评估） 到 IND”一站式技术服务，如靶点调研、市场分析、分子设计和筛选、成药性评估、细胞株构建、生产工艺开发、IND 申请和 cGMP 生产等,同时提供美国及欧盟报批所需的全部药学资料，也为核酸类和 XDC 药物提供专业高效的研发服务和技术支持。目前，已经与100多家医药企业合作，加速生物药创新开发。我们将始终坚守让好药、让健康属于每一位患者的使命，坚持客户第一，加速生物药创新，赋能未来！ 固定电话：021-5470 6068 手机：191 2130 9459（微信同号） 邮箱：service@shellbiotech.com 网址：www.shellbiotech.com 地址：中国上海闵行区梅陇镇景联路258号6号楼 期待您的来电！