New Haven, Connecticut-based Arvinas has signed a new deal with Pfizer that could be worth up to $830 million.
Announced Thursday, it follows in the footsteps of other multiyear, multimillion-dollar deals struck with Merck and Genentech, making Pfizer the third biopharma giant to partner with the 2013 startup.
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So what’s attracting the big fish? There are no clinical programs tied up in any of the deals. Instead, they will be drawing on the fruits of Arvinas’s proprietary PROteolysis TArgeting Chimeras (PROTAC) platform. According to a company spokesman, PROTAC has an important edge.
“This technology is based on the work of Dr. Craig Crews at Yale University and one of the key breakthroughs is the technology progressing from a peptide approach to a small molecule approach,” he said via email.
More specifically, the platform is designed to identify and develop small molecule therapeutics that can break down disease-causing proteins through the ubiquitin/proteasome system (UPS). 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 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.
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“Arvinas’s two lead programs targeting the Androgen Receptor protein (for castration resistant prostate cancer) and Estrogen Receptor protein (for ER + Breast Cancer) are orally delivered compounds and both programs are expected to file INDs in 2018,” he said.
Historically, the approach has been to inhibit production of the protein, rather than help to clear it away. However, Arvinas believes the latter has many advantages. To inhibit a protein, a drug needs to be administered systemically at a high dose, leading to potential toxicities and drug-resistance. More importantly, protein inhibitors haven’t been identified for a majority of protein targets. According to the company website, the PROTAC platform can degrade 85 percent of the proteins targeted thus far. That might help explain why many pharma companies are calling.
In April 2015, Arvinas signed a $434 million partnership agreement with Merck. A $300 million deal was also inked with Genentech later that year. Just over a month ago, Genentech announced it was expanding that deal – now worth up to $650 million – and broadening the therapeutic areas covered.
There are other players in the space. A newcomer, Kymera Therapeutics, recently raised a $30 million Series A. A 2016 startup, C4 Therapeutics, raised $75 million in initial capital and then signed a deal with Roche that could be worth up to $750 million. It’s advancing a platform dubbed DEGRONIMID, which has a dual mechanism of action. It recruits the target protein and the cellular ubiquitin/proteasome system to “naturally” breakdown harmful proteins.
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