Ociperlimab

“People went for Fc-competent [TIGITs] because it worked best in mice,” said Leerink Partners analyst Daina Graybosch, Ph.D. “They couldn\'t help themselves.\"\n Once hailed as the future of immuno-oncology, it’s been a tough few months for any remaining fans of anti-TIGIT antibodies.In April, BeOne Medicines, formerly known as BeiGene, announced it was scrapping ociperlimab over a disappointing phase 3 outlook two years after Novartis handed back the asset. Specifically, the study’s independent data monitoring committee deemed the trial unlikely to show that a combination of ociperlimab and BeOne’s own PD-1 inhibitor Tevimbra would beat Keytruda in patients with PD-L1-high non-small cell lung cancer (NSCLC).The following month brought more tough times for TIGITs, as GSK halted development of its own candidate belrestotug after deciding the iTeos Therapeutics-partnered drug in combination with anti-PD-1 inhibitor Jemperli wouldn’t score a phase 2 win in a similar NSCLC population.Even executives at Roche, whose tiragolumab appeared to buck the trend with a caveated phase 3 win in esophageal cancer in 2024, reaffirmed to Fierce Biotech earlier this year that “we stopped all of the tiragolumab trials that we could stop, and those that couldn\'t be stopped are just running out.”With Big Pharma having pumped $6 billion into this modality, what went so wrong for TIGITs?Daina Graybosch, Ph.D., a senior research analyst at Leerink Partners who covers immuno-oncology, traces the problems back to the exuberant reaction to Roche’s impressive phase 2 tiragolumab data that read out across 2020 and 2021. The Cityscape trial demonstrated that the TIGIT drug in combination with Roche’s own PD-L1 blocker Tecentriq shrank tumors in 31% of patients with metastatic lung cancer—twice as many patients as Tecentriq alone.“That\'s probably the biggest point where the field went wrong, in that they looked at this massive benefit in the small phase 2, and everybody ran after it in a parallel and broad way,” Graybosch told Fierce in an interview.“We had randomized phase 2 data from Roche, from Arcus-Gilead, from iTeos-GSK, and they all consistently showed benefit in response rate and in [progression-free survival],” she added.“I think the challenge ultimately was: How much benefit is there really? Is it enough benefit to be clinically meaningful? And are we developing the drugs in the right way, in the right format, to optimize and bring that benefit to patients?”The industry’s “overenthusiasm” for the potential of TIGITs led to a “simplistic approach” to how other companies planned to develop their own candidates, according to Graybosch.If pharmas had anticipated a “more realistic demonstration of benefit,” as seen in the failed Skyscraper-01 phase 3 study in NSCLC, “I think everybody would have developed [TIGITs] differently,” she suggested.Companies swimming in the TIGIT space have broadly fallen into two camps. Roche’s tiragolumab, along with Merck & Co.’s vibostolimab, GSK and iTeos’ EOS-448, and BeOne’s ociperlimab, are all Fc-enabled. These antibodies retain a fully functional Fc region, meaning they can bind to Fc receptors found on the cell surface and contribute to the protective antitumor functions of the immune system.The theory behind Fc-enabled anti-TIGIT antibodies is that they have enhanced tumor-killing effects. However, the risk is that they could possibly also eliminate certain regulatory T cells and therefore lead to unwanted immune responses.In fact, side effects did cast a shadow over some of the Fc-enabled TIGIT trials, with Merck halting a phase 3 trial of vibostolimab due to a higher than expected rate of discontinuations blamed on “immune-mediated adverse experiences.”“Toxicity that may lead patients to discontinue I think ended up being a contributing factor across the Fc-enabled TIGITs that are all now dead,” Graybosch said.The last TIGITs still standing—Arcus Biosciences and Gilead’s domvanalimab, as well as AstraZeneca’s TIGIT/PD-1 bispecific antibody rilvegostomig—have mutated out the Fc function. This should mean they are less toxic for patients.“People went for Fc-competent because it worked best in mice,” Graybosch explained. “They couldn\'t help themselves, even though they knew there was some risk of depleting T effector cells that are actually what you need to fight your tumor.” Focusing on \'modest benefit\'So, what would a more measured approach to the TIGIT gold rush have meant in practice?“I think you ultimately do what Astra is doing,” said Graybosch, referring to AstraZeneca’s ongoing phase 3 trials of its bispecific rilvegostomig in a range of phase 3 studies for NSCLC or stomach cancer, including in combination with its Daiichi Sankyo-partnered antibody-drug conjugates Enhertu or Datroway.“Astra is recognizing the modest benefit,” she explained. “Their bispecific is very safe because it\'s Fc silent. And in some ways, Astra can\'t lose because [rilvegostomig] doesn\'t need to work that much for a lot of their trials to be successful.”AstraZeneca’s Puja Sapra, Ph.D., senior vice president for biologics engineering and oncology target discovery, was also upbeat about rilvegostomig’s prospects when she spoke to Fierce back in April. She pointed to the fact that engineering the bispecific to reduce Fc effector functionality should reduce unwanted side effects, while blocking both PD-1 and TIGIT at the same time “should hopefully help us increase the response rate and durability.”“At least in preclinical studies, we see that a bispecific molecule has better responses than a combination of both agents alone,” Sapra said at the time. “The molecule is doing very well in the clinic so far, so we continue to believe in this molecule.”Gilead is also staying loyal to its TIGIT candidate, which is being evaluated in phase 3 trials for first-line NSCLC as well as for locally advanced unresectable or metastatic gastric, gastroesophageal junction and esophageal adenocarcinoma.The pharma’s chief medical officer Dietmar Berger, M.D., Ph.D., told Fierce earlier this month that the Arcus-partnered domvanalimab still has a chance, pointing to its Fc-silent character.“We believe there is differentiation but, of course, we need to see how those studies read out,” Berger said. “Any additional activities around that will be based on what we see in those studies.”With AstraZeneca and Gilead still holding a candle for their Fc-silent candidates, Leerink’s Graybosch doesn’t think “it\'s fair to completely write off TIGIT.”“But if you ask 99% of average investors, generalists or specialists and [key opinion leaders], I think they’ll tell you it\'s dead,” she added.Angus Liu contributed to this reporting.

在政策与资金支持、人才回流及工程师红利等多重因素推动下，中国创新药产业正处于蓬勃发展阶段。在港股市场中，创新药领域的相关个股备受关注，它们代表着生物医药行业的创新力量，对推动全球医药研发进程起着关键作用。以下将对药明生物、百济神州、信达生物、康方生物、中国生物制药、石药集团、翰森制药、三生制药、再鼎医药、联邦制药这十家公司进行分析。01药明生物：全球生物药研发生产的赋能者药明生物通过开放式、一体化生物制药能力和技术赋能平台(CRDMO),提供从靶点发现到商业化生产的多方位端到端服务。其业务涵盖从药物发现到生产过程的多个技术平台，在哺乳动物细胞培养生物制品的发现、开发和 cGMP 生产方面具备强大的能力和专业知识。公司拥有通过 EMA、ISO(CNAS)和 CMA 认证的实验室，提供高质量的第三方生物安全性检测服务，同时还具备大肠杆菌及酵母表达系统，以及一体化 CMC 开发及 cGMP生产微生物发酵平台。在全球布局上，药明生物规划在中国、爱尔兰、美国、德国和新加坡建设生物制药生产基地，预计到 2026 年后合计产能将超过 58 万升。其质量体系已被多个全球监管机构认证，成功通过全球客户GMP审计。02百济神州：跨越国界的创新药研发企业百济神州致力于打造差异化、前沿性的创新成果，为全球患者提供更具可及性的疗法。公司跨越国界和时区，联动全球人才和资源进行药物研发。在 2025 年，百济神州公布了多项重要进展，如第一季度财务业绩及业务进展、欧司珀利单抗(BGB-A1217)临床开发项目进展等。百泽安®获欧洲药品管理局人用药品委员会积极意见，支持其用于广泛期小细胞肺癌患者的一线治疗；塔拉妥单抗中国临床研究取得积极结果，拟用于小细胞肺癌三线及以上治疗。此外，公司还将在2025年ASCO年会上展示开创性研究成果，并在2025年欧洲血液学协会年会展示血液学产品组合新数据。这些成果显示了百济神州在创新药研发上的强劲实力和持续推进的决心。03信达生物：多领域创新药物的开发者信达生物是一家致力于研发、生产和销售肿瘤、自身免疫、代谢、眼科等重大疾病领域创新药物的生物制药公司。公司成立于211 年，发展迅速，已取得众多成果。目前，信达生物已有信迪利单抗注射液(达伯舒®)、贝伐珠单抗注射液(达攸同®)等 10 个产品获得批准上市，还有多个品种在 NMPA 审评中，4个新药分子进入III期或关键性临床研究，19个新药品种已进入临床研究。回顾其发展历程，2015年与美国礼来制药集团达成战略合作；2018年在香港联交所主板挂牌上市；2020 年多个产品获批上市并纳入医保目录。2024 年，玛仕度肽头个减重适应症新药上市申请获国家药品监督管理局正式受理。信达生物通过不断的研发投入和战略合作，逐步构建起丰富的产品管线，在创新药市场中占据重要地位。04康方生物：创新双抗助力发展康方生物由经验丰富的国际化团队创建，聚焦肿瘤、自身免疫、炎症、代谢疾病等重大疾病领域。公司打造了独有的端对端康方多方位新药研究开发平台(ACE Platform)，建立了以Tetrabody双特异性抗体开发技术、抗体偶联(ADC)技术、mRNA技术及细胞治疗技术为核心的研发创新体系。其自主研发的PD-1/VEGF双抗新药依沃西成为在III期单药头对头临床研究中击败 K 药(帕博利珠单抗)的药物。然而，近期依沃西单抗的OS数据引发了市场关注。在针对经 EGFR TKI 治疗后疾病进展的 EGFR突变非小细胞肺癌患者的全球III期临床试验HARMONi 研究中，依沃西单抗联合化疗在PFS上取得显著改善，但OS数据未达到统计学显著获益。尽管如此，康方生物的依沃西单抗已通过联合用药布局18个适应症，开展超过27项临床试验，覆盖多种瘤种，且已在国内获批上市并纳入医保目录。05中国生物制药：综合性医药企业的创新转型中国生物制药是一家综合性的医药集团，在创新药研发方面不断发力。公司拥有丰富的产品线，涵盖了多个治疗领域。近年来，加大了对创新药的研发投入，通过内部研发和外部合作等多种方式，推进创新药项目的进展。例如，在肿瘤、肝病等领域积极布局创新药研发管线，部分产品已进入临床试验阶段。凭借其强大的研发实力、广泛的销售网络和品牌影响力，中国生物制药在创新药转型过程中具备较强的竞争力，有望在未来创新药市场中取得更大的市场。06石药集团：创新驱动的制药企业石药集团一直以来注重创新研发，在创新药领域成果丰硕。公司建立了完善的研发体系，投入大量资源用于创新药物的研究。在肿瘤、神经系统、心血管等疾病领域有多个创新药产品。例如，其自主研发的创新药在国内获批上市后，迅速获得市场认可，销售额不断增长。石药集团通过持续的创新投入，不断优化产品结构，提升企业的核心竞争力，在港股创新药板块中占据重要地位。07翰森制药：专注创新的制药企业翰森制药专注于创新药物的研发、生产和销售。公司在精神类、抗肿瘤类等药物领域有深厚的积累，通过持续的研发投入，建立了丰富的创新药管线。其研发的多个创新药产品在临床试验中取得良好效果，部分已获批上市。翰森制药注重研发质量和效率，与国内外科研机构开展合作，提升自身的研发实力，致力于为患者提供更多有效的创新治疗方案，在港股创新药市场中逐步崭露头角。08三生制药：生物药领域的重要参与者三生制药在生物药领域有较长时间的耕耘，产品涵盖了多个治疗领域，特别是在肿瘤、自身免疫性疾病等方面。公司拥有自己的研发团队，不断推进创新药的研发进程。通过自主研发和对外合作，三生制药在创新药管线布局上不断完善，多个项目处于不同的临床试验阶段。其在生物药生产和质量控制方面具备丰富的经验，凭借产品质量和市场口碑，在创新药市场中占据一定的份额。09再鼎医药：专注引进和开发创新疗法再鼎医药专注于从全球引进创新的治疗方案，并在中国及其他亚洲市场进行开发和商业化。公司通过与生物医药公司合作，获得了多个有潜力的创新药项目的授权。在肿瘤、罕见病等领域，再鼎医药的产品管线逐步丰富，部分产品已在中国获批上市，为国内患者带来了新的治疗选择。再鼎医药以其独特的商业模式和对创新药的敏锐洞察力，在港股创新药领域具有一定的特色和优势。10联邦制药：多元化发展的制药企业联邦制药业务涵盖化学制药、生物制药等多个领域。在创新药方面，公司不断加大研发投入，在糖尿病、抗感染等治疗领域推进创新药研发项目。联邦制药拥有完善的生产设施和质量控制体系，能够保证产品的质量和供应稳定性。通过多元化的业务布局和对创新药的持续投入，联邦制药在港股创新药市场中逐步拓展自己的发展空间，有望在未来取得更多的创新成果。港股市场上的这些创新药相关个股，各自凭借独特的研发优势、产品管线和市场策略，在创新药领域不断探索和发展。它们不仅为全球患者带来了新的治疗希望，也为投资者提供了分享创新药行业发展红利的机会。随着全球对创新药需求的不断增长以及政策环境的持续优化，这些公司有望在未来取得更大的突破和发展。免责声明：在任何情况下，本文中的信息或表述的意见，均不构成对任何人的投资建议。来源：制药网点击 阅读原文了解更多