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Ambagon Therapeutics (based in hub Catalyst) raises $85 million

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Ambagon Therapeutics, a biotechnology company (spinn off from TU/e) based in hub Catalyst on the TU/e campus since last year, yesterday raised a Series A worth $85 million to expand its modular drug research platform. Congratulations to team Ambagon!

The financing was led by Nextech Invest. Ambagon was previously set up by RA Capital Management, Droia Ventures, Inkef Capital, AbbVie Ventures, MRL Ventures Fund and Mission BioCapital. Investors from the seed round joined the A round, along with new investor Surveyor Capital (a Citadel company).

Many disease-relevant proteins have regions of intrinsic disorder that cannot be targeted by conventional small-molecule drugs. Several thousand proteins with such intrinsically disordered regions have been identified that interact with the hub protein 14-3-3. By binding to a disordered protein region, 14-3-3 induces order, leading to suitability for drug treatment.

By stabilizing naturally occurring 14-3-3:client interactions, Ambagon aims to rapidly develop new therapeutic candidates for proteins that are difficult to treat with drugs. The pipeline is currently focused on oncology, where many opportunities exist to address targets not currently suitable for drug treatment.

Ambagon was founded by world leaders in 14-3-3 biology and drug-based protein-protein interactions:

  • Michelle Arkin, professor and chair of Pharmaceutical Chemistry and co-Director of the Small Molecule Discovery Center at UCSF;
  • Luc Brunsveld, professor of chemical biology at Eindhoven University of Technology (TU/e);
  • Christian Ottmann, Senior Lecturer in Molecular Cell and Structural Biology, TU/e and Chief Technology Officer of Ambagon.

Ambagon's experienced leadership team includes Chief Executive Officer Scott Clarke, formerly CEO of Tizona Therapeutics and Trishula Therapeutics, and Chief Scientific Officer Nancy Pryer, formerly CSO at Day One Biopharmaceuticals and Chief Development Officer at Nurix Therapeutics.

"Our deep understanding of 14-3-3 biology has broad applications for drug discovery because it opens up disordered protein regions as therapeutic targets," stated Scott Clarke. "Combined with our proprietary structural insights, compound chemical library and custom drug discovery tools, our experienced drug development team is well positioned to bring forward new drugs that target targets previously unsuitable for drug treatment."

"Ambagon's modular approach to leveraging 14-3-3 biology to enable drug discovery is not only unique, but uniquely deliberate," noted Melissa McCracken, partner of Nextech Invest. "We are excited to see such an exciting platform translate into a very rich pipeline."

"We are proud of our continued support of Ambagon in creating first-in-class and best-in-class drugs through targeted stabilization of protein complexes," stated Adam Rosenberg, Ambagon president and RA Capital Venture Partner. "Since our seed investment, the team has developed an impressive proprietary dataset and systemic understanding of 14-3-3 interactions. Ambagon truly has the potential to change the narrative for disordered targets."

About Ambagon Therapeutics
Ambagon Therapeutics is a biotechnology company that uses breakthrough methods to unlock intrinsically disordered protein targets using small molecules. Ambagon applies deep knowledge of 14-3-3 proteins and a proprietary suite of drug discovery tools to create molecular glues that stabilize 14-3-3:target complexes. These molecular glue stabilizers enhance the original biology to restore or inhibit target function, enhance target activity, or promote or block target degradation. Ambagon's initial focus is on oncology, with five programs in discovery. It has facilities in San Carlos, California and Eindhoven, the Netherlands.

About 14-3-3 biology
Ambagon's platform leverages the biology of the regulatory hub protein 14-3-3, which reads the phosphorylation of serine/threonine. With more than 3,000 reported client proteins, 14-3-3 has a huge interactome, allowing the manipulation of a wide range of biology across indications.

By binding its clients, 14-3-3 imposes order on disordered client protein sequences, imparting drug-like properties to otherwise non-medicated proteins and protein regions.

About Ambagon's modular drug discovery platform
By selectively stabilizing the interaction between 14-3-3 and a 14-3-3 client protein, Ambagon can create first-in-class drugs that target high-value targets not accessible by other means, particularly those with high levels of disorder, including transcription factors, adapter/scaffolding proteins and RNA-binding proteins.

Because of the way 14-3-3 interacts with its clients, Ambagon can also manipulate the biology of targets that could otherwise be medicalized in orthogonal ways, enabling the development of the best molecules.

Ambagon's projects begin with an X-ray crystal structure of a binary 14-3-3:target complex to inform chemical starting points from Ambagon's own chemical library, giving the platform a high degree of modularity. Drug discovery efforts are then driven by both high-throughput X-ray crystallography that characterizes ternary 14-3-3:target:compound complexes and proprietary functional readouts that elucidate the biological consequences of stabilization.