Yale biotech company Arvinas recently announced deals worth hundreds of millions of dollars with pharmaceutical companies Genentech and Pfizer. The moves have fueled Arvinas’ expansion in New Haven’s Science Park, further establishing the New Haven startup as a force in the field of protein degradation therapeutics.

As the first company to use protein degradation technology, Arvinas makes use of the PROTAC Platform, invented by the company’s founder, Yale molecular, cellular and developmental biology professor Craig Crews. PROTACs — or PROteolysis Targeting Chimeras — break down proteins of interest using the cell’s natural protein degradation machinery rather than merely inhibiting the function of the proteins, as traditional drugs do.

“We hope to continue to be in the lead in this degrader space — progressing our compounds in the clinic from our pipeline internally in oncology and neuroscience and delivering high-quality degrader programs through our partnership companies,” Arvinas President and CEO John Houston said.

Arvinas announced its $850 million collaboration with Pfizer on Jan. 4 and its $650 million partnership with Genentech last November. With the funding came specified targets for the biotech startup to focus on and, for the pharmaceutical companies, access to Arvinas’ innovative technology.

Moving from a purely “discovery-platform” company to a clinical company will be a very important transition point for Arvinas, Houston added.

“Pfizer sees this collaboration as an opportunity to develop some new first-class drugs against tough-to-treat diseases,” said Jon Soderstrom, the managing director of the Yale Office of Cooperative Research. “Arvinas is going to try to develop drugs against those targets that Pfizer can then take through clinical trials and introduce into therapies.”

Arvinas’ partnerships with the two companies, in addition to its own growth in the fields of oncology and neuroscience, have led to its expansion in Science Park, a development that houses technology and biotech startups. Previously located on the second and third floors of 5 Science Park, Arvinas will now occupy the first through third floors of one wing of the building, which sits a few blocks away from Science Hill. The expansion will also increase the number of employees from 40 to 75, according to Crews.

“This exciting juxtaposition of new alliances, expansion of work and growth in our own internal pipeline has led us to expand both in our physical space and in the number of new staff that we have to hire,” Houston said.

Arvinas’ proximity to Crews’ lab at Yale has been a crucial element of its success, allowing for close collaboration between the company and the lab, according to the researchers interviewed.

Soderstrom noted that the current startup climate in New Haven is the most robust he has seen in his more than 20 years at Yale.

“New Haven offers exciting potential: The faculty [at Yale] wants to have an impact by translating their basic science discoveries into drugs that can help society,” Crews said. “That’s best done by starting local biotech companies whereby faculty can continue to help guide the company as they take the science from the faculty’s lab into commercialization.”

Crews, the chief scientific advisor of Arvinas, founded the company in 2013 to further develop his protein degradation technology, which has become the company’s patented PROTAC Platform.

PROTAC works by “hijacking” the cell’s natural quality control machinery — which gets rid of old or dysfunctional proteins — and instead eliminating proteins that are causing disease, Crews explained. Specifically, one end of the PROTAC attaches to the protein that’s causing the disease, and their other end to part of the quality control machinery, he explained.

Although Arvinas’ major focus is currently oncology, the PROTAC platform is disease-agnostic, Houston said, meaning that it can theoretically be used to target any disease area.

The technology also offers other advantages over protein inhibition, as PROTAC drugs do not bind to active sites on the protein. Since traditional approaches that make use of active site binding must be constantly replenished, PROTAC has a more durable effect than these approaches, Houston said.

“The nature of the technology in that it’s not based on occupancy-driven interactions, but rather on protein-protein interactions, will help us overcome resistance and overcome overproduction of a ligand that competes with an inhibitor,” Houston said.

Outside of the collaborations, Arvinas has been working on developing compounds to target breast cancer and prostate cancer and aims to go into clinical trials for these compounds this year, according to Houston. Recently, he added, the company has also delved into neuroscience and developed PROTACs that can penetrate the brain.

One brain disease they could target, Crews suggested, is dementia. PROTACs could be designed to eliminate proteins accumulating in the brains of dementia patients, he explained.

Science Park was established in 1981 as a collaboration between the city of New Haven, Yale and the Olin Corporation.

Amy Xiong | amy.xiong@yale.edu