Cobolimab

GSK made some pipeline cuts and raised expectations for profit growth this year as it reported its final set of earnings under outgoing CEO Emma Walmsley. The UK drugmaker axed several programs that were originally developed by other companies, starting with an anti-TIM-3 antibody called cobolimab. The drug flunked a Phase 3 trial in non-small cell lung cancer in June. GSK obtained cobolimab as part of its $5.1 billion acquisition of Tesaro in 2018. The company also dropped a Phase 2 candidate for pulmonary fibrosis called GSK3915393 that it got from its 2019 buyout of Sitari Pharmaceuticals for an undisclosed amount. The candidate was originally developed for the treatment of celiac disease, but GSK ended that work in 2023. It also nixed an anti-PVRIG antibody that was in Phase 2 development for cancer, known as GSK4381562, which it licensed from Surface Oncology in 2020. GSK declined to comment on the specific reasons for each termination. The drugmaker also got rid of four programs that it developed in-house. There’s a Phase 1 DNMT1 inhibitor for sickle cell disease, two Phase 2 vaccine candidates for cytomegalovirus and meningococcal disease, and an anti-CD96 antibody for cancer called nelistotug, which was partnered with iTeos and 23andMe. Elsewhere, GSK reported robust Q3 sales, which rose about 8% to £8.5 billion. The strong performance was supported by “sustained double-digit growth” in specialty medicines across respiratory, immunology and inflammation, oncology and HIV, Walmsley said on its media call Wednesday. Based on the strong performance, the company bumped expected turnover growth this year to 6% to 7%, from a previous range of 3% to 5%. It also expects core operating profit to increase between 9% and 11%, up from the higher end of 6% to 8%. Meanwhile, earnings per share are set to grow between 10% to 12%, compared with a prior range of 6% to 8%. GSK’s stock is up 1.5% on the London exchange. One area of weakness was the company’s influenza franchise, which saw sales dip about 22% to £216 million due in part to competition in the US. “We remain very cautious about the [vaccine] environment in the US,” Walmsley said. Last week, Sanofi’s CFO François Roger also highlighted how “negative buzz” around vaccines had impacted its sales.

葛兰素史克（GSK）的cobolimab成为最新一款在关键肿瘤学试验中失败的抗TIM-3抗体。与此同时，这家英国制药公司还因抗TIGIT药物研发失败承受了超过6亿美元的损失。GSK一直在评估cobolimab——该药物是其2018年以51亿美元收购Tesaro时获得的，与其肿瘤药物Jemperli及化疗药物多西他赛的多种联合方案，用于一项针对750名非小细胞肺癌（NSCLC）患者的三期临床试验。该公司在7月30日发布的第二季度财报中透露，这项研究未能达到其主要终点，即在患者接受过前期免疫肿瘤治疗后，延长晚期非小细胞肺癌患者的总生存期。GSK在最新财报中表示：“所有治疗方案的耐受性良好，毒性与多西他赛和免疫检查点抑制剂已知的安全特征一致。这仍是一个具有挑战性的治疗领域，目前新型联合疗法尚未能改善大多数患者的预后。”尽管这一晚期试验失败，GSK对cobolimab的希望并未彻底破灭。该公司仍在一项针对多种儿童癌症的1/2期试验，以及一项针对晚期肝癌的中期试验中对该药物进行评估。01 罗氏、BMS、礼来、诺华、GSK接连折戟TIM-3抗体TIM-3在免疫效应细胞上表达，发挥免疫检查点的作用；同时也在白血病干细胞上表达。这使得多家大型制药公司将这一受体视为既能激活免疫系统、又能抑制癌细胞增殖的潜在靶点。然而，GSK的cobolimab未能在三期试验中取得成功或许并不意外。2024年初，当诺华的抗TIM-3候选药物在骨髓增生异常综合征或白血病患者的晚期试验中失败后，cobolimab便成为当时进展最快的抗TIM-3抗体。诺华的研究聚焦于血液肿瘤，而GSK及其他拥有TIM-3候选药物的巨头则主要关注实体瘤。在此之前，罗氏早在2022年已将一款PD-1×TIM-3双特异性抗体从研发管线中移除；百时美施贵宝也在2022年终止了其TIM-3候选药物BMS-986299的一期试验，理由是“业务目标”已发生变化；礼来和因赛特也已终止了各自的TIM-3药物研发。目前，阿斯利康似乎仍在抗TIM-3领域有所布局，其一款PD-1×TIM-3双特异性抗体的1/2期试验预计将于今年完成。02 GSK停止多项研发管线GSK公布2025上半年业绩，总营收155.02亿英镑（约201.57亿美元），同比增长5%。TIM-3并非GSK本季度在高风险癌症靶点领域唯一遭遇挫折的项目。该公司在同一份财报中透露，其决定终止抗TIGIT抗体belrestotug的研发，这导致了4.71亿英镑（约合6.29亿美元）的减值损失。四年前，GSK向iTeos公司支付了6.25亿美元的预付款，获得了belrestotug的相关权利。在belrestotug的二期试验失败后，iTeos公司最初计划停止运营，随后在本月初接受了Concentra Biosciences的收购要约。财报还显示，GSK已终止了一款处于二期阶段的疟疾佐剂重组蛋白疫苗（GSK3437949）的研发。该公司发言人称，此举是基于其最近宣布的向第二代多阶段疟疾疫苗领域推进的战略。此外，发言人表示，抗生素sanfetrinem的口服前药sanfetrinem cilexetil也已从公司的二期研发管线中移除，原因是“在早期研究中，其表现不如现有治疗方案以及GSK正在研发的其他结核病特异性候选药物”。基于目前的管线布局，GSK仍对2031年销售额超过400亿英镑充满信心。识别微信二维码，可添加药时空小编请注明：姓名+研究方向！