Arvinas is a biotechnology company developing treatments for serious illnesses. They address diseases caused by specific proteins within the body. Their goal is to create medicines for patients with limited or ineffective treatment options.
Targeted Protein Degradation Technology
Arvinas utilizes targeted protein degradation, an approach involving PROTACs (PROteolysis TArgeting Chimeras). PROTACs harness the cell’s natural protein disposal system to remove disease-causing proteins. Each PROTAC is a heterobifunctional molecule, with two distinct ends connected by a linker.
One end of the PROTAC molecule binds specifically to the target protein, while the other recruits an E3 ubiquitin ligase, part of the cell’s natural waste disposal machinery. This proximity causes the E3 ligase to attach a ubiquitin tag to the target protein.
Once tagged with ubiquitin, the protein is recognized by the proteasome, the cell’s “garbage disposal” unit. The proteasome then breaks down the tagged protein into smaller, harmless fragments. PROTACs are catalytic; they are not consumed and can degrade multiple copies of the target protein. This allows PROTACs to address proteins that traditional small-molecule inhibitors cannot, expanding the range of treatable conditions.
Oncology Drug Candidates
Arvinas has advanced several drug candidates in oncology, focusing on cancers driven by hormone receptors. One of their most advanced programs is Vepdegestrant (ARV-471), developed for ER+/HER2- metastatic breast cancer. This drug works by degrading the estrogen receptor (ER), a protein fueling this cancer’s growth.
Vepdegestrant is in multiple clinical trials, including the Phase 3 VERITAC-2 trial as a monotherapy for second-line treatment, and the Phase 3 VERITAC-3 trial in combination with palbociclib for first-line treatment. It is also being explored in combination with other therapies, aiming to position it as a foundational endocrine therapy across various stages of breast cancer.
Another oncology candidate is Bavdegalutamide (ARV-110), which targets metastatic castration-resistant prostate cancer (mCRPC). It targets the androgen receptor (AR), a protein central to prostate cancer progression. While Bavdegalutamide showed promising results, Arvinas has prioritized a next-generation AR degrader, ARV-766, for a Phase 3 trial in mCRPC.
Neuroscience Program
Beyond oncology, Arvinas has broadened its therapeutic pipeline to include programs for neurodegenerative diseases, showcasing the versatility of their targeted protein degradation platform. The company is exploring preclinical candidates aimed at proteins implicated in serious neurological conditions.
One focus is the degradation of tau protein, which accumulates in Alzheimer’s disease. Another target is alpha-synuclein, a protein associated with Parkinson’s disease. These preclinical neuroscience programs highlight PROTAC technology’s potential to address a wider spectrum of diseases by selectively removing problematic proteins.
Strategic Partnerships and Collaborations
Arvinas has forged strategic partnerships with major pharmaceutical companies, validating their technology and supporting pipeline progression. A collaboration with Pfizer involves co-development and co-commercialization of Vepdegestrant for breast cancer. This partnership involves equally sharing worldwide development costs, commercialization expenses, and profits.
Collaborations with Bayer and Genentech have also been established. These agreements often involve licensing their targeted protein degradation technology for new drug candidates across various therapeutic areas. These collaborations provide financial backing and leverage expertise, accelerating the advancement of Arvinas’s investigational therapies.