ALK5

▎药明康德内容团队编辑 聚焦下一代CAR-T疗法，Lyell Immunopharma收购ImmPACT Bio Lyell Immunopharma今日宣布已签订最终协议，将收购ImmPACT Bio。ImmPACT的主打在研疗法IMPT-314是一款靶向CD19/CD20的嵌合抗原受体（CAR）T细胞疗法，Lyell将继续推进该产品在血液恶性肿瘤（包括大B细胞淋巴瘤）中的开发。IMPT-314采用双靶向设计，旨在超越已获批的CD19靶向CAR-T细胞疗法的疗效，并通过在生产过程中富集初始和中心记忆T细胞来增强CAR-T细胞疗法的持久性。收购ImmPACT预计将显著增强Lyell的临床阶段新一代CAR-T细胞疗法管线，并补充其专有技术组合，以生成更持久的功能性T细胞，为实体瘤和血液恶性肿瘤患者提供更持久的疗效。 在今年早些时候发布的临床试验数据显示，在13名接受IMPT-314治疗的复发/难治性（R/R）侵袭性非霍奇金淋巴瘤患者中，12名达到了完全或部分缓解（92%的客观缓解率），其中10名患者达到了确认的完全缓解（CR），完全缓解率为77%。中位随访时间为32个月时，中位无进展生存期为50.1个月，中位总生存期尚未达到。 BridgeBio Pharma基因疗法显著改善患者指标 日前，BridgeBio Pharma公司公布了在研基因疗法BBP-812在治疗卡纳万病（Canavan disease）患者的1/2期临床试验CANaspire中的最新数据。试验结果显示，BBP-812显著改善患者的生物标志物指标。与自然病史数据相比，接受治疗患者的运动功能也获得渐进、持久的改善。新闻稿指出，如果获得批准，BBP-812可能成为卡纳万病患者的首个获批疗法。 CANaspire是一项1/2期开放标签研究，旨在评估BBP-812在患有卡纳万病的儿童患者中的安全性、耐受性和药效学活性。试验结果显示，在BBP-812给药后，参与者的尿液和脑中的N-乙酰天冬氨酸（NAA）水平迅速且持续降低。低剂量治疗后12个月NAA平均下降64%，高剂量治疗后3个月NAA平均下降73%。最早接受治疗的参与者在接近三年内维持了较低的尿液NAA水平。脑脊液（CSF）中的NAA在接受低剂量治疗后12个月平均减少70%。在T2加权核磁共振成像（MRI）中，观察到大多数接受BBP-812治疗的参与者的髓鞘形成获得改善。与自然病史相比，接受BBP-812治疗的患者运动功能逐渐改善（通过GMFM-88量表评估），并且达到运动功能里程碑（通过HINE-2量表评估）。 卡纳万病是一种由编码天冬氨酸酶的ASPA基因突变引起的超罕见、可致残或致命的疾病。大多数儿童无法爬行、行走、坐着或说话，在婴幼儿时期就会面临死亡的威胁。天冬氨酸酶活性的缺乏会导致NAA的积累，并最终导致对髓鞘的毒性。目前，该病尚无获批的疗法。BBP-812利用腺相关病毒9载体将ASPA基因的功能拷贝递送到全身并进入大脑，从而可能根治疾病。它已获得美国FDA授予再生医学先进疗法（RMAT）认定、孤儿药资格、罕见儿科疾病资格和快速通道资格。 治疗纤维化疾病，新锐完成8900万美元融资 Agomab Therapeutics今日宣布完成8900万美元的D轮融资，获得资金将用于进一步推进其核心候选药物AGMB-129的临床开发。 AGMB-129是一种针对纤维狭窄型克罗恩病（FSCD）患者的口服、肠道限制性ALK5小分子抑制剂。其2a期临床试验STENOVA的中期数据预计将于2025年第一季度发布。此外，这些资金还将用于推进AGMB-447的临床开发，这是一种针对肺部、吸入式的ALK5小分子抑制剂，目前正在1期临床试验中接受检验，用于治疗特发性肺纤维化（IPF）。该公司的研发管线中还有一款MET激动性抗体AGMB-101，目前处于支持IND申请的临床前研究的最后阶段，计划用于治疗肝硬化。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料： [1] Agomab Announces $89 Million Series D Financing to Support Broad Fibrosis-Focused Pipeline. Retrieved October 25, 2024, from https://www.businesswire.com/news/home/20241024624593/en [2] Lyell Immunopharma to Acquire ImmPACT Bio and Prioritizes its Pipeline to Focus on Next-Generation CAR T-cell Therapies. Retrieved October 25, 2024, from https://www.globenewswire.com/news-release/2024/10/24/2969054/0/en/Lyell-Immunopharma-to-Acquire-ImmPACT-Bio-and-Prioritizes-its-Pipeline-to-Focus-on-Next-Generation-CAR-T-cell-Therapies.html [3] BridgeBio Shares Positive Data from High Dose Cohort of Phase 1/2 CANaspire Study of Gene Therapy BBP-812 for Canavan Disease at ESGCT 2024. Retrieved October 25, 2024, from https://investor.bridgebio.com/news-releases/news-release-details/bridgebio-shares-positive-data-high-dose-cohort-phase-12 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新

Agomab’s lead candidate is being investigated as a treatment for patients with fibrostenosing Crohn’s disease (FSCD). Credit: Hananeko_Studio via Shutterstock. Agomab Therapeutics has secured $89m in Series D funding to support clinical trials of its fibrotic disease treatments, with some help from Sanofi . Belgium-based Agomab announced that Sanofi and Invus have joined as new investors in its latest funding round, following on from a $100m Series C round in October 2023, and a $114m Series B where Pfizer led an extension round. The funds will be used to advance the development of Agomab’s lead candidate AGMB-129, a treatment for patients with fibrostenosing Crohn’s disease (FSCD). The oral small molecule inhibitor of ALK5 (TGFβ1R) is currently being investigated in the Phase IIa STENOVA trial (NCT05843578). The company expects to share interim results from the 90-patient trial in early 2025. Positive data from the Phase I trial (NCT04933565) of AGMB-129 was reported in February 2023, where the candidate demonstrated high local exposure in the ileum, with no drug-related safety signals or dose-limiting toxicities. Patients with FSCD have strictures in the intestines caused by inflammation and scarring, for which there is no cure. The company also has an inhaled treatment for idiopathic pulmonary fibrosis (IPF), named AGMB-447, and a liver cirrhosis candidate AGMB-101. AGMB-447 is being investigated in a Phase I trial (NCT06181370) and Agomab plans to start clinical development of AGMB-101, which is “in the final stages of IND-enabling studies”. See Also: Dyno and Roche collaborate on neurological gene therapies Takeda and BMC partner to decarbonise US healthcare sector Sanofi continues to assert itself in the immunology space, signing deals with parties such as Recludix, Teva Pharmaceutical and IGM Biosciences . The company expanded its immunology pipeline further in June 2024, entering a $700m strategic partnership with Belharra Therapeutics to spur the development of small molecule therapies for immunological diseases. Sanofi and Regeneron’s immune-targeting biologic Dupixent (dupilumab) has been picking up label expansions since its 2017 US Food and Drug Administration (FDA) approval for atopic dermatitis. The drug earned $11.6bn last year, as per Regeneron’s financials, and is set to generate $23.6bn in 2030, according to GlobalData consensus forecasts. GlobalData is the parent company of Pharmaceutical Technology. In the announcement accompanying the funding, Agomab’s CEO Tim Knotnerus said: “We are thrilled to have Sanofi and Invus joining our investor syndicate. Their investment as well as the continued support from our existing shareholders is another validation of the trailblazing work our team is conducting in the fields of fibrostenosing Crohn’s disease and idiopathic pulmonary fibrosis.”

Agomab Therapeutics is benefiting from Sanofi’s push to become an immunology powerhouse. The Antwerp-based biotech said Friday that the French drug giant and Invus are new investors in its $89 million Series D that arrived one year after its $100 million Series C . Pfizer and Boehringer Ingelheim have also backed Agomab. The company wasn’t seeking additional money. “The $100 million is still in the bank,” Agomab CEO Tim Knotnerus said in an interview. But after receiving inbound interest from Sanofi, the biotech’s execs discussed it with the board and then did a “very selective reach-out” to other investors. It took only a month to close the round, the CEO said. The new financing will fund an ongoing Phase 2a of Agomab’s lead therapy — an oral small molecule for a subset of Crohn’s disease patients — and another oral drug candidate already in Phase 1 for idiopathic pulmonary fibrosis. It also plans to take a MET agonistic antibody into human studies in the first half of next year for liver cirrhosis. Agomab anticipates interim data for the first 40 of 90 patients from the Phase 2a of AGMB-129 in early 2025. Investigators are testing the gut-restricted ALK5 inhibitor in patients with fibrostenosing Crohn’s disease, which impacts about half the people with the inflammatory bowel disease. It has the FDA fast track tag. “Can we indeed avoid the known cardio toxicity that is associated with ALK5?” Knotnerus said. “We believe we can because of the way our compound has been designed, so that we have high local exposure of our ALK5 asset in the gastrointestinal tract and very low systemic exposure.” In the first half of next year, the biotech also expects to have the first batch of healthy volunteer data from the Phase 1 trial in IPF for its ALK5 inhibitor that is lung-restricted, according to Knotnerus. IPF leads to difficulties with breathing and impairs multiple other functions, eventually leading to death for many patients within about five years. Boehringer and Roche each market medicines for IPF, and both were approved by the FDA 10 years ago. Many drug developers are following up with next-generation medicines. Amid a broader restructuring of its business, Sanofi has continued to bet on oncology and I&I. In recent months, it invested in several companies developing IPF medicines like Vicore Pharma and Graviton Bioscience . The company also earmarked up to $1.5 billion for the anti-TL1A race in a partnership with Teva . Agomab broke cover in 2019 with a $23 million Series A. It snagged a $74 million Series B in 2021 and bought Spanish startup Origo Biopharma later that year. The 60-employee startup also now has an office in Cambridge, MA. It added former Seagen leader David Epstein to its board this summer, and Pierre Kemula — who headed finance at CureVac when it went public — is set to start as CFO on Nov. 1.