For many diseases, the challenge is not just to identify the disease-causing protein, but to make the drug stick to it. One solution is molecular glue, a small molecule that sticks together proteins that don’t normally interact.Biotechnology startup Ambagon Therapeutics is applying its molecular glue to some of the most difficult-to-target proteins, and preclinical biotechnology has Raised $85 million Advance research that initially focused on cancer.
The Series A financing announced on Thursday was led by Nextech Invest.
Small molecule drugs work by binding to the target. For proteins with obvious binding sites, this is not a problem, but not all proteins have such a goal. Molecular glue may be widely known for its role in an emerging treatment called targeted protein degradation. This type of treatment involves the use of small molecules to get disease-causing proteins into the built-in processing system of the cell.
For proteins that do not have pockets to which small-molecule drugs can attach, molecular glue can help. These glues combine the problematic protein with the molecular tag and mark it as pending.Located in Boston Monte Rosa Therapeutics is developing a protein degradation therapy based on its molecular glue technology. Kymera Therapeutics of Cambridge, Massachusetts, has a series of protein degrading drugs and recently started Molecular glue discovery and Protein-protein interaction startup A-Alpha Bio.
Ambagon’s method can be used to degrade target proteins, but the biotech company is conducting more extensive research on the potential of its molecular glues. Some proteins are known for their inherent disorder, and their lack of structure makes it difficult to design drugs that can bind to them. Ambagon’s research focuses on the 14-3-3 protein family, which plays a key role in many disease-related pathways. According to the company, more than 3,000 proteins interact with 14-3-3 proteins. When these proteins are combined with 14-3-3, their internal disorder becomes orderly, making them medicinal. Ambagon operates in San Carlos, California and Eindhoven, the Netherlands, and aims to stabilize naturally occurring 14-3-3 protein interactions. The company said that by doing so, the target protein can be enhanced, inhibited, or degraded. These proteins can also move to desired locations or away from disease-driven activities.
Cancer-related proteins that interact with 14-3-3 include Raf kinase, FOXO transcription factor, and tumor suppressor protein p53. In neurological diseases, proteins such as tau, alpha-synuclein and LRRK2 kinase interact with 14-3-3.Anbakon pipeline To date, it consists of five early detection projects aimed at addressing undrugged targets related to various cancer-driven processes. The company stated on its website that its goal is to identify at least one drug development candidate by the second half of 2023.
Ambagon was founded by scientific experts in 14-3-3 biology and protein-protein interaction drugs: Michelle Arkin, Professor and Chair of Medicinal Chemistry, University of California, San Francisco; Professor of Chemical Biology, Eindhoven University of Technology (TU/e) Luc Brunsveld; and Christian Ottmann, Associate Professor of Molecular Cellular and Structural Biology at TU/e and CTO of Ambagon. The startup is led by Scott Clarke, the former CEO of Tizona Therapeutics and Trishula Therapeutics. Nancy Pryer, Chief Scientific Officer of Ambagon, is the CSO of Day One Biopharmaceuticals for anti-cancer drug biotechnology and Chief Development Officer of Nurik Therapeutics of protein degradation biotechnology.
“Our in-depth understanding of 14-3-3 biology has a wide range of applications in drug discovery because it opens up areas of disordered proteins as therapeutic targets,” Clark said in the company’s financing announcement. “Combined with our proprietary structural insights, selected chemical libraries, and customized drug discovery tools, our experienced drug development team is fully capable of launching new drugs for targets that were previously impossible to cure.”
Ambagon was previously founded by RA Capital Management, Droia Ventures, Inkef Capital, AbbVie Ventures, MRL Ventures Fund and Mission BioCapital. These seed investors also joined the A round of financing, as well as a new investor, Surveyor Capital.
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