Afimkibart

Roche Pharma CEO Teresa Graham spoke to Fierce Biotech on the sidelines of the company\'s first-half earnings event.\n The uncertainty around the future of Elevidys hasn’t destroyed Roche’s belief in the potential of gene therapies, the Swiss company’s head of pharma has told Fierce Biotech, as the pharma continues to expand its research reach outside of its traditional oncology focus.Roche and its partner Sarepta Therapeutics both paused trials of Elevidys back in April following the death of a 16-year-old patient in the U.S. Since then, Roche—which markets the drug outside of the U.S.—has stopped all ex-U.S. distribution of the drug in the commercial setting for non-ambulatory patients, while the FDA requested that Sarepta halt Elevidys shipments in the U.S. Earlier this week, Roche paused shipments in all patients in countries where Elevidys’ approvals referenced the FDA.But Roche Pharma CEO Teresa Graham denied Fierce’s suggestion that the issues around Elevidys have altered how the company views gene therapy as a modality.“It doesn’t, actually,” Graham told Fierce in an interview at Roche’s headquarters in Basel, Switzerland on Thursday.“The reality is that gene therapy will be an important modality in the treatment of human health,” Graham continued. “There is a lot of promise in gene therapy. I think what the entire industry is learning is that, scientifically, it\'s just a little harder than we might have thought.” Even before the latest difficulties with Elevidys, Roche had announced a “fundamental reorganization” of Spark Therapeutics, the gene therapy unit the Swiss pharma bought for $4.3 billion in 2019. That overhaul closely followed Roche’s decision to end work on a hemophilia A gene therapy candidate, which was a focus of the Spark acquisition.Roche’s move came against a backdrop of wider industry retreat from gene therapy, with Pfizer pulling its FDA-approved hemophilia B treatment Beqvez. Bluebird bio, a gene therapy pioneer once valued at $10 billion at its peak, was sold for just $49 million upfront to private equity firms.But Roche still sees potential in the modality, according to Graham.“I am firmly convicted that over time we will crack gene therapy and we will be able to deliver really meaningful treatments to patients,” she said.Graham spoke to Fierce on the sidelines of the company’s first-half earnings event, where Roche CEO Thomas Schinecker reminded journalists that 760 boys have successfully received Elevidys in the ambulatory setting.“I\'m really hopeful that we can find a path forward for this medicine,” Graham said in the interview on Thursday. “We clearly need to talk to regulators; we clearly need to have some good conversations about the safety—but we do firmly believe in the risk-benefit of this product.”Not all regulators sound ready to be convinced, with the European Medicines Agency (EMA) announcing Friday morning that it won\'t recommend Elevidys for approval in the ambulatory setting. Roche said in a statement that it “plans to continue to work with the EMA to explore a potential path forward.” Mixed results from emerging pipeline Another drug that Roche is keeping faith in is the Parkinson’s disease prospect prasinezumab. The future of the Prothena Biosciences–partnered asset looked in doubt after the anti-alpha-synuclein antibody failed a phase 2 study in December 2024.But Roche is giving prasinezumab a second chance, with plans to launch a phase 3 trial by the end of the year off the back of an analysis of data from the failed study. Specifically, the pharma pointed to longer-term follow-up data from an open-label portion of the study suggesting a clinical benefit on top of symptomatic treatment in early-stage Parkinson’s.“Given the dramatic unmet need in Parkinson\'s, it does feel like it would be a miss not to explore this,” Graham explained.“There\'s only really been minor improvements in treatments for these patients over the last 50 years, and, in every conversation I\'ve had with [key opinion leaders], they have really encouraged us to take this forward,” she said.“There\'s a little bit of a finger feel that there\'s something there, and we\'re only really ever going to be able to pull the signal out in a phase 3,” Graham added. Roche had less faith in CT-173, an early-stage obesity drug picked up as part of its $2.7 billion acquisition of Carmot Therapeutics in 2023. The Swiss pharma had previously touted the long-acting PYY analog’s potential to drive weight loss past the GLP-1 plateau, but Graham announced at the earnings event that Roche would no longer take CT-173 into human trials after assessing its “developability and competitiveness.”Despite this early-stage setback, Graham still feels that combinations offer Roche a path to carving out its own corner of the increasingly crowded obesity space.“Obesity is inherent in something like 200 other diseases,” she said. “So the ability to actually look at where we believe our portfolio in combination with other drugs can really help address some of these comorbidities is one of the more exciting pieces.”“This is an incredibly big market,” Graham added. “It is very diverse. There are a lot of scientific pathways to explore here.”One of those pathways is amylin, a hormone involved in the regulation of food intake. In March, Roche paid Zealand Pharma $1.6 billion for the long-acting amylin analog petrelintide. Graham sees the drug’s potential growing as the obesity market segments among patients “looking for maybe different depths of weight loss or different tolerability profiles.”Meanwhile, Roche has yet to make a final call on whether to take the GLP-1/GIP receptor agonist CT-388—another Carmot asset—into a phase 3 obesity trial, but Graham said the company is “right on the cusp” of taking that program forward.“We plan to make those decisions later this year, and, once we get rolling here, I think you\'re really going to see us flesh out our [obesity] strategy,” she said. When it comes to bringing new drugs into Roche’s pipeline, Graham was tight-lipped on which of the company’s five core focus areas—neurology, oncology/hematology, immunology, ophthalmology and CVRM (cardiovascular renal metabolic)—the company is prioritizing for M&A.“Clearly, within our five therapeutic areas, there are definitely places where we would like to bring in additional assets,” she told Fierce. “As Thomas [Schinecker] said, we look at an unbelievably large number of deals every year, and are constantly on the hunt, not only for things that will fit that strategy but things that are truly transformational.”With such a multifaceted pipeline, what are the readouts Graham is most excited about?“It\'s like trying to choose your favorite child,” she said, before name-checking the recent “super exciting” phase 2 results for the BTK inhibitor fenebrutinib in relapsing multiple sclerosis (MS). “It could be a really huge step forward for MS patients,” she explained.There’s also the “high-risk, high-reward bet” on the Parkinson’s drug prasinezumab, said Graham, who ended by referencing the IgG1 monoclonal antibody afimkibart.Along with CT-388 and the Alzheimer’s disease prospect trontinemab, afimkibart was one of the assets Roche fast-tracked as part of its reallocation of R&D resources.“I\'m an immunology girl at heart—it’s where I started my career,” Graham explained. “There\'s so much opportunity in the immunological space and so many diseases that we could potentially tackle with afimki.”

今日，根据CDE官网公示，智翔金泰GR2303注射液的新药临床申请已经获得受理。GR2303是一款TL1A单克隆抗体，适应症为炎症性肠病（IBD）。这是今年以来申报国内临床的第二款国产TL1A抗体。TL1A是近年来逐步走向台前的新兴靶点，众多大药厂对该靶点相当看重，均有布局。TL1A靶点管线简述肿瘤坏死因子样配体1A（TL1A）是肿瘤坏死因子家族成员。TL1A的异常表达和自身免疫疾病显著相关，包括风湿性关节炎、炎症性肠病、银屑病、原发性胆汁性肝硬化、系统性红斑狼疮和强直性脊椎炎等 。TL1A与DR3信号通路在自身免疫和炎症性疾病的关键作用，表明抑制TL1A-DR3相互作用可能是改善自身免疫性疾病及靶器官局部炎症的有效治疗策略。目前开发的靶向TL1A的单克隆抗体，临床适应症包括炎症性肠病如溃疡性结肠炎（UC），克罗恩病（CD）和系统性硬化症相关间质性肺病等。其中PF-06480605/RVT-3101和PRA023在治疗炎症性肠病的临床试验中，都观察到显著的临床缓解率和内镜改善率。这也是目前进展最快的两款进入III期临床的TL1A单抗管线。1.2022年12月，辉瑞与知名“捡漏王”Roivant Sciences成立合资公司，专注于TL1A抗体药物RVT-3101（PF-06480605）的开发。后来2023年10月，罗氏以71亿美元预付款收购了合资公司Telavant并获得RVT-3101的美国和日本权益。此外罗氏还顺便获得了一款PF-07261271（p40/TL1A双抗）的权益，目前可能处于临床II期。事后Roivant高管表示这次交易是卖低了，有点后悔。2.2023年6月，默沙东以108亿美元收购Prometheus，获得其核心管线TL1A抗体PRA-023（MK-7240）其他竞争者包括赛诺菲，安进，艾伯维等大厂。2023年10月，赛诺菲与Teva达成合作，以5亿美元首付款及最高10亿美元里程碑付款共同开发TL1A单抗TEV-574（Duvakitug）。TEV-574在2b期试验（RELIEVE UCCD）中达主要终点，治疗UC和CD均展现“best-in-class”潜力另外，2个月前，赛诺菲还收购了华深智药旗下的海外公司Earendil Labs，并获得两款TL1A双抗（HXN-1002和HXN-1003）安进曾经开发过一款TL1A/TNF-α双抗AMG 966，但遗憾的是，I期临床开发就发现药物会和靶标形成大型免疫复合物，最终导致体内抗体反应，试验就此停止开发。本月早些时候，艾伯维宣布获得明济生物下一代TL1A单抗FG-M701在全球相关权益的独家许可权。首付款和近期里程碑付款1.5亿美元，交易总额超17.1亿美元。FG-M701的优势在于，通过工程化改造达到更高的疗效和更少的给药频率。国内其他竞品除了上文介绍的明济生物和华深智药，以及本次申报的智翔金泰，国内还有多家企业在该领域进行布局，如三生国健，科兴制药等等。2025年1月，三生国健的SSGJ-627申报IND，成为国内首个申报临床的国产TL1A单抗。2025年4月，该药物获准在中国和美国同步开展I期临床试验，针对UC适应症。科兴制药布局了GB20（TL1A单抗）和GB24（TL1A双抗）两条临床前管线。华润生物申请了多项TL1A相关专利 CN119552252，CN119390843等等。参考来源：https://www.3s-guojian.com/product/develop.htmlhttp://www.kexing.com/exploration/field.htmlhttps://patentscope2.wipo.int/search/zh/detail.jsf?docId=WO2025112237&_cid=JP1-MC9UJL-34716-1近期十大明智的BD交易········