Pfizer is the latest company to get in on the swell of interest in small molecules that send problematic proteins to the cellular trash bin. The big pharma firm and Arvinas have established a multi-year protein degradation drug discovery pact worth up to $830 million.
Arvinas launched in 2013 based on technology developed in the labs of Yale University chemist Craig Crews. While conventional small molecules are typically designed to turn off or attenuate the activity of a protein, Crews came up with compounds that cause an unwanted protein to be disposed of altogether.
His bifunctional compounds, called protein-targeting chimeric molecules (Protacs), feature a protein-binding domain and a ubiquitin ligase domain. The idea is to bring a ubiquitin ligase close enough to the protein for it to be tagged for the proteasome, the cell’s trash compactor. The Protac then moves on to the next protein.
Pfizer will use Arvinas’ technology to work on proteins relevant in multiple diseases. Under the pact, the biotech firm will design molecules and Pfizer will handle their clinical development.
Pfizer joins a cluster of big firms that in the past two years have invested in protein degradation technology. Arvinas also has deals with Merck & Co. and Genentech. Another firm developing protein degraders, C4 Therapeutics, has lucrative pacts with Roche and Calico, Alphabet’s life sciences arm.
Novartis, meanwhile, is working on degraders through a collaboration with the University of California, Berkeley, and Boehringer Ingelheim has a protein degradation pact with the University of Dundee.
Since 2016, venture capital firms have put significant resources behind degraders. Arvinas has raised nearly $60 million since its launch, and C4 brought in a whopping $75 million in its first round of funding. The most recent company to emerge, Kymera Therapeutics, launched in October with $30 million in its first funding round.