Yale Spin Out, Pfizer Pen Up-to-$830M Drug Development Deal
New Haven, Connecticut-based Yale Spin Out, Arvinas, has now inked an $830 million deal with Pharma major Pfizer aimed at discovering and developing small molecule drugs that degrade disease-causing cellular proteins.
Pfizer will use Arvinas’ proprietary PROTAC (PROteolysis TArgeting Chimeras) Platform to create small molecule therapeutics aimed at degrading disease-causing cellular proteins. John Ludwig, head of medicinal sciences at Pfizer, said the company has “considerable interest” in protein degradation. He did say the global pharma company would determine the applicability of Arvinas’ PROTAC Platform across multiple therapeutic areas, but did not name them.
Arvinas says its PROTAC Platform offers the potential for improved performance over traditional small-molecule inhibitors by using the cell’s natural and selective ubiquitin-proteasome system, which routinely degrades disease-causing proteins. PROTAC degraders recruit an E3 ligase to tag the target protein for ubiquitination and degradation through the proteasome, a large complex that degrades the ubiquitinated protein into small peptides.
By removing target proteins directly rather than simply inhibiting them, Arvinas reasons, PROTACs can provide multiple advantages over small-molecule inhibitors, which can require high systemic exposure to achieve sufficient inhibition, often resulting in toxic side effects and eventual drug resistance.
PROTAC has
demonstrated that a transient binding event at a range of binding sites and affinities can translate into very potent degradation of the target protein in multiple protein targets, according to Arvinas.The Pfizer collaboration spans multiple therapeutic areas, reflecting the wide array of problems that can arise when proteins – particularly damaged or misfolded proteins – aren’t regularly broken down and cleared. Toxic protein build-up is believed to play a role in many neurodegenerative diseases, cancers, autoimmune diseases and more.
Per the latest deal, Pfizer has put $830 million on the table, it will be responsible for the clinical development and commercialization of any eventual drugs. Arvinas declined to specify how the deal is split between the upfront payments, milestones, and royalties — though some money is apparently being delivered upfront. According to the spokesman, those funds will go towards the startup’s own drug development efforts.
“As a global industry leader, Pfizer is uniquely positioned to partner with us as we exploit the potential of PROTACs in multiple disease areas,” said John Houston, Ph.D., president and CEO of Arvinas. “This marks another key milestone as we continue to expand the use of our targeted protein degradation platform and advance Arvinas’ first candidates into the clinic.”
“Protein degradation is an area of considerable interest for us, and we look forward to working with Arvinas to determine the potential applicability of this approach across multiple therapeutic areas,” added John Ludwig, Ph.D., head of medicinal sciences at Pfizer.
