共價

2022年12月15日

Enlaza Therapeutics是第一家共價生物平台公司，今天正式成立，獲得了6100萬美元的種子基金。這筆資金將用於推進Enlaza獨特的共價生物平台War-Lock，並建立一個安全性和有效性更高的癌症治療管道。Enlaza首席執行官Sergio Duron博士告訴GEN Edge:“(共價生物製劑)是以前沒有人做過的事情。”“這是藥物研發的‘空白地帶’，我們認為這是提高(藥物)安全性和有效性的巨大機會。我們希望共價成為生物製劑和蛋白質藥物研發領域的標準工具箱。”在成立的第一年，Enlaza已發展到約30名員工，並組建了一個領導團隊，其中還包括總裁兼首席商務官桑福德·馬迪根(Sanford Madigan)博士;Analeah Heidt博士，首席科學官;王磊博士，加州大學舊金山分校(UCSF)科學顧問和教授。enlaza的融資來自西班牙語enlazar，意思是連接或連接，描述了一種以共價結合蛋白質的War-Lock技術，由Avalon Ventures牽頭，並得到光速風險投資公司、弗雷澤生命科學公司和Samsara BioCapital的協助。大多數藥物都是通過弱的、可逆的化學鍵起作用的。 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