Pfizer will use Arvinas’ protein degradation technology to discover and develop new drugs for undisclosed diseases, through a collaboration that the Yale University spinout said today could generate up to $830 million-plus.

The companies have signed a multiyear research collaboration and license agreement through which they have agreed to develop an unspecified number of new treatments based on Arvinas’ proprietary PROTAC® (PROteolysis TArgeting Chimeras) Platform. The novel technology is designed to create small-molecule therapeutics aimed at degrading disease-causing cellular proteins.

Arvinas has agreed to oversee discovery efforts, while Pfizer has responsibility for clinical development and commercialization of any products that may result from the collaboration. 

In return for licensing its technology to Pfizer, Arvinas is eligible for up to $830 million in up-front payments, plus payments tied to achieving specified preclinical, clinical, and commercial milestones. Arvinas said it also stands eligible to receive tiered royalties based on global product sales on any products products that may result from the collaboration.

“This marks another key milestone as we continue to expand the use of our targeted protein degradation platform and advance Arvinas's first candidates into the clinic,” Arvinas president and CEO John Houston, Ph.D., said in a statement. “As a global industry leader, Pfizer is uniquely positioned to partner with us as we exploit the potential of PROTACs in multiple disease areas.”

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.

“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., Pfizer’s head of medicinal sciences.

The collaboration is Arvinas’ third with a pharma partner. The Yale spinout, established in 2013, launched its other two pharma partnerships in 2015—an up-to-$434 million alliance with Merck & Co., and a partnership “in excess of” $300 million with Genentech, a member of the Roche Group.

Busy Week for Pfizer

The collaboration is Pfizer’s second drug development partnership launched this week, in which the pharma giant saw another collaboration come to an end.

Yesterday, Pfizer and Sangamo Therapeutics began an up-to-$162 million-plus alliance to develop a potential gene therapy to treat amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) linked to mutations of the C9ORF72 gene—the companies’ second gene therapy collaboration. 

However, Pfizer today returned to iTeos Therapeutics rights to the immune-oncology candidate EOS200271, a highly selective, clinical-stage IDO1 inhibitor that failed to achieve efficacy or reach its maximum tolerated dose according to interim data from 17 patients in a Phase I trial (NCT02764151).

The study assessed EOS200271 as a monotherapy in patients with malignant gliomas, based on brain penetration of the compound. The study was recruiting patients as of December 14, 2017, the date of the last update posted on

Pfizer and iTeos launched their collaboration in 2014 when the pharma shelled out €24 million ($29 million) upfront to license rights to iTeos' preclinical compounds targeting indoleamine 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO2). 

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