Selective Estrogen Receptor Degrader Program
Aragon is developing Selective Estrogen Receptor Degraders (SERDs) that not only bind the estrogen receptor and function as antagonists but also induce a conformational change that results in degradation of the receptor.
Each year in the US, there are approximately 191,000 new breast cancer diagnoses and 41,000 deaths related to breast cancer. Because 70% of breast cancers are dependent on estrogen for growth and survival, women with estrogen receptor positive breast cancer are treated with antihormonal therapies such as tamoxifen or aromatase inhibitors. These antihormonal therapies are initially effective in hormone-sensitive cancers, but many patients experience disease progression due to acquired resistance to these treatments.
Aragon Pharmaceuticals’ orally active selective estrogen receptor degraders represent a new treatment for progressive metastatic breast cancer that may circumvent the problem of resistance to antihormonal therapies. SERDs bind to the estrogen receptor, and induce a conformational change that results in the degradation of the receptor.
Aragon has identified multiple SERDs that have pharmacokinetic profiles sufficient to drive a robust therapeutic response and result in degradation of the receptor and anti-tumor activity. The novel profile of these potent, orally bioavailable, nonsteroidal agents may result in greater efficacy and response rates in patients with hormone-refractory breast cancer compared to other drugs in development. Aragon’s most advanced leads induce tumor regressions in both tamoxfen sensitive and tamoxifen resistant tumor models in vivo. Based on these results and others, the company is currently advancing multiple, distinct lead SERD chemical scaffolds toward clinical development.
Aragon’s SERDs are initially being developed for the treatment of women with late-stage, progressive metastatic disease, but these SERDs also have tremendous potential in treating patients with early-stage disease.