Genentech Dumps Another $650M in New Haven Biotech Arvinas

New Haven, Conn.-based Arvinas expanded an ongoing licensing deal with Genentech. The agreement is to develop new drugs using Arvinas’ PROTAC technology. The original deal was inked in October 2015.

Under the new terms, Arvinas may receive development and commercialization milestones totaling more than $650 million. It is also eligible for tiered royalties on sales of any products that come out of the collaboration. The original deal had $300 million in possible milestones.

PROTAC directly removes target proteins instead of inhibiting them. This is believed to have several advantages over the more traditional small molecule inhibitors. PROTACs stands for PROteolysis TArgeting Chimeras, which degrade disease-causing cellular proteins by way of proteolysis. The platform was developed in the Yale University laboratory of Craig Crews, who is the company’s founder and chief scientific advisor.

"Genentech’s decision to expand our original agreement to include additional disease targets shows the promise seen in our first two years together and further supports our targeted protein degradation platform as a novel drug modality to treat a broad array of diseases," said John Houston, Arvinas’ president and chief executive officer, in a statement. "This expansion also supports our initial decision to work with Genentech in 2015 and we look forward to this growing collaboration."

Genentech didn’t disclose its disease targets in 2015, and it didn’t reveal them now. Houston told Endpoints News’ Brittany Meiling that, in theory, the platform could apply to several targets. "We’re not limited by disease area, as almost any disease with a cell you want to degrade could be targeted."

However, the company’s two main programs are for prostate and breast cancer, with a focus on androgen and estrogen receptor degradation. Arvinas hopes to get into the clinic for both programs next year, although the breast cancer program is a little more advanced. Houston also indicated that after those two target programs are underway, it may look at lung cancer and melanoma, and possibly in the future, look at neurodegeneration.

Meiling writes, "The concept behind protein degradation is simple enough. Where protein inhibition has led to some advanced medicines, degrading proteins could prove a much more durable solution. In short, Arvinas plans to tag certain disease-causing proteins for destruction by recruiting an E3 ligase to the target, thereby sending the protein to the cell’s natural ‘garbage disposal’ called the ubiquitin-proteasome system."

Other companies working in this area include C4 Therapeutics, Kymera, Celgene, Takeda,GlaxoSmithKline and Novartis.

On Nov. 2, the company announced it had selected its first candidate for its prostate cancer program, ARV-110. The compound is an orally bioavailable small molecule PROTAC that targets and induces the degradation of the androgen receptor (AR) protein. Essentially the drug takes over the cancer cell’s process for controlling protein levels.

Houston said in a statement, "We believe that our first clinical candidate from our protein degradation platform will offer a novel therapeutic modality to patients with mCRPC (metastatic castration-resistant prostate cancer). ARV-110 is an oral, potent androgen receptor degrader that demonstrated efficacy in preclinical models in settings where standard of care therapies are ineffective, specifically, when the androgen receptor is overexpressed, mutated, or in high androgen ligand concentration environments. Having met customary criteria for preclinical efficacy and safety, we are on track to initiate a clinical study of the AR PROTAC in mCRPC patients in the second half of 2018."