'Tip of the iceberg': Novartis-partnered UC Berkeley lab churns out a startup to tackle protein stabilization
For the past decade, Daniel Nomura’s lab at UC Berkeley has been working to find chemical approaches to drug the so-called “undruggable,” and with the help of Novartis’ research arm for the past five years, he has built out the foundation for a new biotech in the protein stabilization field.
Vicinitas Therapeutics joins a small field of upstarts looking to flip the switch and focus on stabilizing certain proteins, rather than degrading them. Cystic fibrosis is a good example of a disease that could benefit from small molecules aimed at stabilizing the CFTR protein, which is what Nomura’s lab did in a recent Nature Chemical Biology paper, serving as the basis for Vicinitas.
The biotech emerged Thursday morning with $65 million in Series A financing, nearly the same sized round that its main competitor in the stabilization field, the aptly named Stablix Therapeutics, launched with last June. A coastal challenge could be brewing as the South San Francisco biotech thinks it can move into the driver’s seat in a race against its Columbia University peer. Vicinitas has named its platform the Deubiquitinase Targeting Chimera, or DUBTAC, whereas Stablix is calling its drugs RESTORACs.
“We are certainly the first ones to publish on a fully synthetic small molecule-based DUBTAC platform for targeted protein stabilization, and I believe that really puts us in a strong position to become the leading company in the space,” Nomura told Endpoints News.
The professor serves as founder, scientific advisor to and board member of Vicinitas, which is currently searching for a CEO after having landed CSO Daniel Marquess, who previously served in the same position at Unity Biotechnology.
In the paper, Nomura’s lab was able to link its “deubiquitinase recruiter on to the Vertex drug lumacaftor that helps to act as a chemical chaperone for CFTR to subsequently deubiquitinate and stabilize the levels of the CFTR protein, and also improve chloride channel function in cystic fibrosis cells,” the professor said. The two lead co-authors on the paper are scientists at the biotech, he added.
Compared to the degradation field’s PROTACs, Nomura characterized Vicinitas’ DUBTACs as “essentially the opposite.” In a nod to the biotech’s name, he said the company’s small molecules “induce the proximity, or vicinity, of two proteins that usually don’t interact in this case to stabilize the levels of aberrantly degraded proteins.”
While cystic fibrosis was one of the focuses of the lab’s paper, the lung and digestive disease is not the only area Vicinitas will pursue. CF will serve as a “testbed” for broadening the platform’s reach, which could go into cancer, monogenic diseases and haploinsufficiency diseases, Nomura said. The latter involves having “only one good copy of a gene, resulting in half the level of the protein and,” the professor explained, “by slowing down the natural turnover rate of that protein, you can potentially increase the level of that protein and subsequently confer therapeutic benefit.”
Deerfield Management and a16z led the Series A, with additional backing from Droia Ventures, GV, The Mark Foundation for Cancer Research and the Berkeley Catalyst Fund. The biotech holds the exclusive license to the work from Nomura’s lab in conjunction with Novartis. Deerfield is also a backer of another Nomura-founded biotech, Frontier Medicines, a protein degradation startup allied with AbbVie.
Aside from Vicinitas, Nomura will continue working with the Novartis Institutes for BioMedical Research in a second research collaboration, also unveiled Thursday. He will be part of a team that includes fellow UC Berkeley professors Dean Toste, Thomas Maimone, Ziyang Zhang, and James Olzmann. The aim of the new Novartis-Berkeley Translational Chemical Biology Institute is to find small molecule compounds that could lay the groundwork for new proximity-based therapeutics.
“This whole space of induced proximity, we’re really just at the tip of the iceberg of the full potential of that general approach, beyond degradation and stabilization,” Nomura said.
