On July 28 Vicinitas Therapeutics, a biotechnology company advancing a proprietary targeted protein stabilization platform to develop novel therapeutics in cancer and genetic disorders, reported that launched with $65 million in Series A financing (Press release, Vicinitas Therapeutics, JUL 28, 2022, View Source [SID1234617106]). The financing was co-led by a16z and Deerfield Management, 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.
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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, Dr. Nomura, the Nomura Lab and Novartis colleagues 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.
"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," said Daniel K. Nomura, Ph.D., founder of Vicinitas Therapeutics and Professor of Chemical Biology in the Departments of Chemistry, Molecular and Cell Biology, and Nutritional Sciences and Toxicology at UC Berkeley.
"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."
Leadership Team and Formation of Scientific Advisory Board
The Vicinitas Therapeutics team is comprised of scientific leaders from academia and industry who have demonstrated years of commitment and success in the field, and who remain dedicated to advancing science and technology and delivering highly impactful drugs.
Vicinitas Therapeutics’ leadership team includes:
Daniel K. Nomura, Ph.D., Founder and Professor of Chemical Biology in the Departments of Chemistry, Molecular and Cell Biology and the Molecular Therapeutics Division, and Nutritional Sciences and Toxicology, UC Berkeley; Investigator at the Innovative Genomics Institute
Daniel Marquess, D.Phil, Chief Scientific Officer
Joe Budman, Ph.D., Vice President of Biology
Vicinitas Therapeutics’ board of directors includes:
Jorge Conde, General Partner, a16z
Cameron Wheeler, Ph.D., Partner, Deerfield Management
George Golumbeski, Ph.D., Partner, Droia Ventures
Daniel K. Nomura, Ph.D., Founder and Professor of Chemical Biology in the Departments of Chemistry, Molecular and Cell Biology and the Molecular Therapeutics Division, and Nutritional Sciences and Toxicology, UC Berkeley; Investigator at the Innovative Genomics Institute
Vicinitas has also established a scientific advisory board, including:
Daniel K. Nomura, Ph.D., Founder and Professor of Chemical Biology in the Departments of Chemistry, Molecular and Cell Biology and the Molecular Therapeutics Division, and Nutritional Sciences and Toxicology, UC Berkeley; Investigator at the Innovative Genomics Institute
Michael Rape, Ph.D., Professor, Department of Molecular and Cell Biology, UC Berkeley; Investigator of the Howard Hughes Medical Institute
Thomas Maimone, Ph.D., Associate Professor in the Department of Chemistry, UC Berkeley
James Olzmann, Ph.D., Associate Professor, Departments of Molecular and Cell Biology and Nutritional Sciences and Toxicology, UC Berkeley; Investigator of the Chan Zuckerberg Biohub
Kevan Shokat, Ph.D., Professor, Department of Cellular and Molecular Pharmacology, UCSF; Investigator of the Howard Hughes Medical Institute
F. Dean Toste, Ph.D., Gerald E. K. Branch Distinguished Professor of Chemistry, UC Berkeley
Angela Koehler, Ph.D., Associate Professor, Biological Engineering, MIT, Associate Director, Koch Institute for Integrative Cancer Research at MIT
"Vicinitas Therapeutics has emerged as a pioneer of targeted protein stabilization, and we’re excited to be a part of the Series A funding," said Cameron Wheeler, Ph.D., Partner at Deerfield Management. "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."