Deerfield-Backed Vicinitas Launches to Target Key Protein Stabilization

Cancer Research

South San Francisco-based Vicinitas Therapeutics launched with a Series A round worth $65 million. The company is a spin-out between Novartis Institutes for BioMedical Research and researchers at the University of California, Berkeley, who were focusing on a Deubiquitinase targeting Chimera (DUBTAC) platform.

The funding was co-led by a16z and Deerfield Management, with participants including Droia Ventures, GV, The Mark Foundation for Cancer Research and the Berkeley Catalyst Fund.

Ubiquitin chains are tags on proteins that alert the cell that these proteins need to be degraded and eliminated via the cells protein disposal system, a kind of garbage can or recycling system. A number of diseases are caused by proteins that are degraded abnormally, which includes cancer and some single-gene diseases. 

In cancer, the proteins that are accidentally destroyed are protective tumor suppressors. In monogenic diseases, mutations in specific genes cause the protein to become unstable and be degraded, leading to abnormally low protein levels, which lead to the disease.

Several companies have been founded in the last decade to focus on ubiquitin research. These include Arvinas, Monte Rose Therapeutics, Mission Therapeutics, Stablix Therapeutics, Nurix, C4 Therapeutics and others.

In March, Mission received approval to initiate a Phase I trial of its mitochondrial-associated DUB inhibitor, MTX652. When mitochondria are damaged, they become labeled with ubiquitin, which tags them for degradation, which affects cell health. Its drug, MTX652, inhibits USP30, a mitochondrial-associated deubiquitylating enzyme (DUB). Mitochondrial dysfunction is implicated in kidney injury and chronic kidney disease.

In May, C4 Therapeutics dosed the first patient in its Phase I/II trial of CFT8634, an orally bioavailable BiDAC degrader that targets BRD9 for the treatment of SMARCB1-perturbed cancers, including synovial sarcoma and SMARCB1-null tumors.

The DUBTAC platform was developed by Novartis and Berkeley researchers to target the degraded proteins by removing ubiquitin chains. DUBTACs are bifunctional small molecules made up of a ligand that targets proteins attached by way of a molecular linker to a deubiquitinase (DUB) recruiter. Vicinitas notes, “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.”

Jorge Conde, General Partner at a16z, said, “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. 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.”

Vicinitas has exclusively licensed the DUBTAC platform from UC Berkeley and Novartis. It plans to initially focus on cancer and monogenic diseases.

“We are excited about the potential of the DUBTAC platform to develop novel therapies against therapeutic targets that were previously deemed undruggable and will respond to protein stabilization,” Daniel K. Nomura, Ph.D., founder of Vicinitas and professor of Chemical Biology in the Departments of Chemistry, Molecular and Cell Biology, and Nutritional Sciences and Toxicology at UC Berkeley, said.

The company’s leadership team includes Nomura; Daniel Marquess, D.Phil, chief scientific officer; and Joe Budman, Ph.D., vice president of biology.

The company’s board of directors includes Conde; Cameron Wheeler, Ph.D., partner, Deerfield Management; George Golumbeski, Ph.D., partner, Droia Ventures; and Nomura.

In a press release, Wheeler said, “Vicinitas Therapeutics has emerged as a pioneer of targeted protein stabilization, and we’re excited to be a part of the Series A funding. As a therapeutic modality, stabilization has the power to elicit substantial changes to disease biology with relatively minor alterations to target proteins, and we are optimistic about the potential of the DUBTAC platform across oncology, rare and chronic diseases.”

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