Arvinas is pioneering the development of novel PROTAC® (proteolysis-targeted chimera) protein degraders. We have been successful in degrading over 90% of proteins tested and are engineering new PROTAC® protein degraders against new targets in the areas of oncology and neurodegenerative disease. We believe that our PROTAC® technology platform may enable the targeting of proteins that are considered “undruggable” by traditional small molecule inhibitors. These PROTAC® protein degraders will become Arvinas’ pipeline of the future.
Arvinas believes PROTAC® protein degraders have significant potential for the treatment of neurodegenerative diseases. There is a high unmet need in many neurodegenerative diseases where no disease-modifying therapies have been approved, including Alzheimer’s and Parkinson’s diseases (US prevalence of ~6M and ~1M, respectively).
Preclinically, we have demonstrated that a direct injection of tau-directed PROTACTM protein degrader to the hippocampus reduced tau levels by 50% (below). We have also shown in in vivo models that tau- and α-synuclein-targeted PROTAC® protein degraders are able to penetrate the blood-brain barrier, and plan to further investigate them for tau degradation in vivo.
The 80% of proteins not addressable by small-molecule inhibitors may be degradable using our PROTAC® technology platform, due to our ability to degrade proteins via sites other than enzymatic active sites, and their potential to degrade proteins using weak binders.
Other Oncology Targets
In oncology, we are exploring both established and “undruggable” targets to make progress for patients in new therapeutic areas, including colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). Our team has deep experience in target advancement and drug optimization and we plan to leverage that as we progress our early stage pipeline.