Therapeutic Programs

therapeutic programs

Estrogen Receptor

Developing Oral PROTAC for ER+ Metastatic Breast Cancer

Arvinas is developing a novel ER (estrogen receptor) PROTACTM for the targeted degradation of ER alpha with the goal of reducing its levels in cancer cells and providing greater clinical benefit to patients. It is estimated that approximately 80% of all newly diagnosed cases of breast cancer are ER alpha-positive. While currently approved treatments have produced some success in this patient population, many estrogen receptor positive (ER+) breast cancers become resistant to these therapies and continue to signal through the estrogen receptor.

Today, fulvestrant—a selective estrogen receptor degrader (SERD)—is the standard of care for ER+ metastatic breast cancer post anti-estrogen therapy. Unlike fulvestrant, which is administered via two monthly intramuscular injections, Arvinas’ ER PROTAC is being developed as an oral therapy, a more convenient route of administration.

ER PROTAC degrades ER in ER-dependent T47D cells in culture

ER PROTAC degrades ER in ER-dependent T47D cells in culture.

 

 

 

 

 

 

 

 

 

 

 

In early studies, our estrogen receptor program has demonstrated superior degradation relative to SERDs such as GDC-810, GDC-927, AZD9496 and RAD1901. We are currently optimizing the ER PROTAC to improve both oral bioavailability and degradation activity with the long-term goal of replacing fulvestrant as a monotherapy and in combination with CDK4/6 inhibitors.

ER PROTAC significantly inhibits growth of ER dependent MCF-7 tumors in mice (daily, subcutaneous dosing)

ER PROTAC significantly inhibits growth of ER dependent MCF-7 tumors in mice (daily, subcutaneous dosing).