Arvinas degraders get another vote of confidence

With Pfizer already a partner for the Protac SERD vepdegestrant, Arvinas now has a second endorsement for its degradation approach: Novartis today paid $150m up front, mainly for rights to the androgen receptor (AR) degrader ARV-766. Anti-androgen drugs like Zytiga and Xtandi are an established treatment standard for prostate cancer, but the idea behind ARV-766 is that it might be active in patients in whom the AR has become mutated, especially via a resistance pathway called L702H. Last year a phase 1/2 trial in post-Xtandi/Zytiga metastatic castration-resistant prostate cancer showed the potential: three of five patients with the L702H mutation reported PSA50 responses. Arvinas is also running a phase 1/2 study combining ARV-766 with Zytiga. This is all fine in theory, but the specific target population for late-stage trials will have to be considered carefully. The cautionary tale is Tokai, a now defunct biotech that had tried to develop galeterone, a molecule that specifically hit the AR’s AR-V7 splice variant. This was sunk by trial design problems and lack of clarity about the difference between de-novo and acquired AR-V7 mutations. Intriguingly, the Novartis deal also includes rights to an unnamed preclinical Arvinas project targeting AR-V7 degradation.

AR-V7 degraders

Source: OncologyPipeline.