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Vicinitas Launches with $65 Million to Advance Protein Stabilization Platform to Treat Cancer and Genetic Disorders

July 28, 2022

Vicinitas Therapeutics, a biotechnology company advancing a proprietary targeted protein stabilization platform to develop novel therapeutics in cancer and genetic disorders, launched with $65 million in series A financing.

Photo: Jorge Conde, general partner at a16z

a16z and Deerfield Management led the financing, with participation from Droia Ventures, GV, The Mark Foundation for Cancer Research, and the Berkeley Catalyst Fund.

Vicinitas Therapeutics is a spin-out company that resulted from the Deubiquitinase Targeting Chimera (DUBTAC) platform, which was developed through an academic-industry research collaboration between the Novartis Institutes for BioMedical Research and researchers at the University of California, Berkeley.

Many diseases, including cancer and monogenic diseases, are often caused by specific proteins that are abnormally degraded and lost from the cell. In cancer, protective tumor suppressors are aberrantly destroyed, allowing cancer cells to circumvent cell death, thus promoting unobstructed cell proliferation. In monogenic disorders, mutations in certain genes cause the resulting protein to become unstable and degraded, which leads to abnormally low levels of the particular protein and the disease pathology. To date, many aberrantly degraded proteins have been considered “undruggable” or intractable to drug discovery efforts, and patients with these diseases would greatly benefit from a therapeutic that stabilizes and restores the levels of these proteins, allowing normal function to be restored.

The DUBTAC platform was developed to therapeutically target these degraded proteins by removing ubiquitin chains (tags on proteins that signal the cell to degrade and eliminate the protein using the cell’s protein disposal system) from specific proteins to stop their degradation and stabilize their levels for therapeutic benefit. DUBTACs, developed through an academic-industry research collaboration between Professor Daniel Nomura, his research group at UC Berkeley, and scientists at the Novartis Institutes for BioMedical Research, are bifunctional small molecules consisting of a protein-targeting ligand connected via a linker to a deubiquitinase (DUB) recruiter. In a unique application of induced-proximity biology, DUBTACs bring a DUB into the vicinity of a ubiquitin-tagged protein to remove the ubiquitin chain and subsequently prevent degradation of the target protein.

In a hallmark study published in Nature Chemical Biology, Nomura, the Nomura Lab, and colleagues at Novartis discovered covalent allosteric recruiters against OTUB1, a known DUB. They showed that this covalent OTUB1 recruiter could be linked to various protein-targeting ligands to stabilize the levels of aberrantly degraded proteins, including the mutated chloride channel CFTR that causes cystic fibrosis and the tumor suppressor WEE1 kinase in cancer cells.

Vicinitas Therapeutics has exclusively licensed the DUBTAC platform from both UC Berkeley and Novartis and aims to become the leading company in targeted protein stabilization by developing next-generation disease therapies against an entire class of previously inaccessible aberrantly degraded proteins. The company is initially focused on developing therapies in cancer and monogenic diseases.

“The concept of chemically induced proximity – using multispecific molecules to bring two targets physically together – has yielded notable successes in the field of protein degradation,” said Jorge Conde, general partner at a16z. “Vicinitas is leveraging its proprietary DUBTAC platform to pioneer the emerging space of targeted protein stabilization. This approach has the potential to access highly valued yet currently undruggable proteins and create differentiated therapies that will impact patient lives.”

Author: Rare Daily Staff

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