共价

2022年12月15日

Enlaza Therapeutics是第一家共价生物平台公司，今天正式成立，获得了6100万美元的种子基金。这笔资金将用于推进Enlaza独特的共价生物平台War-Lock，并建立一个安全性和有效性更高的癌症治疗管道。Enlaza首席执行官Sergio Duron博士告诉GEN Edge:“(共价生物制剂)是以前没有人做过的事情。”“这是药物研发的‘空白地带’，我们认为这是提高(药物)安全性和有效性的巨大机会。我们希望共价成为生物制剂和蛋白质药物研发领域的标准工具箱。”在成立的第一年，Enlaza已发展到约30名员工，并组建了一个领导团队，其中还包括总裁兼首席商务官桑福德·马迪根(Sanford Madigan)博士;Analeah Heidt博士，首席科学官;王磊博士，加州大学旧金山分校(UCSF)科学顾问和教授。enlaza的融资来自西班牙语enlazar，意思是连接或连接，描述了一种以共价结合蛋白质的War-Lock技术，由Avalon Ventures牵头，并得到光速风险投资公司、弗雷泽生命科学公司和Samsara BioCapital的协助。大多数药物都是通过弱的、可逆的化学键起作用的。 A few attempts have been made over the past decade to develop small-molecule drugs that work through covalent binding (examples include Avila and Principia—eventually bought out by Celgene and Sanofi, respectively, for their work on developing BTK targeted covalent inhibitors in a race for FDA approval and commercialization—as well as Terremotto, which launched in 2022). But these small molecules are typically inhibitors and carry an electrophile that reacts non-selectively. Duron says that there’s been significant progress in the covalent and biologic spaces, and he believes that coupling covalency with biologics, such as antibody-drug conjugates (ADCs) and radioligand therapies (RLTs), opens up a brand new field. Enlaza’s technology uses “unnatural” amino acids that are essentially non-reactive until the biologic binds the molecular target and forces proximity between the unnatural amino acid and a nucleophile on the target, resulting in cross-linking. The War-Lock technology can be applied to any protein drug that can incorporate unnatural amino acid with the aim to improve safety and efficacy. Duron says that the nature of the War-Lock platform can enable a variety of biological or drug discovery strategies with a very diverse set of potential partners. “We can mediate toxicity by leveraging high clearance but also have long-term pharmacodynamics and efficacy without exposure to the drug,” said Duron. “We can improve efficacy for targets that have low copy number or receptor density. This is something that is challenging in today’s drug discovery. If you have a target that has a low copy number or receptor density, covalency can impact the fidelity of the payload we’re trying to attach.” Culling cancer with covalency Where biologics have failed as cancer treatments because of issues with safety and efficacy, Duron thinks covalent biologics could make improvements. Enlaza intends to expand the covalent biologic platform to multiple oncology treatment strategies using antibody-drug ADCs and RLTs. The Enlaza CEO also envisions small-format protein biologics that can have very good penetration and high clearance of solid tumors without having to use half-life extension strategies. According to Duron, Enlaza has produced preclinical data for its oncology drug candidates that demonstrate rapid tumor penetration along with high systemic clearance, high tumor retention, and low off-target toxicity. The seed funding will help advance several of these programs and support IND enablement, including CMC (chemistry, manufacturing, and controls) activities. It will also enable Enlaza to continue the proof-of-concept work and industrialization of the War-Lock technology, which is built on technologies that have been exclusively licensed from UCSF and The Scripps Research Institute. Share