Seragon is developing Selective Estrogen Receptor Degraders (SERDs) that not only bind the estrogen receptor and function as antagonists but also induce conformational changes 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-receptor positive disease, but many patients experience disease progression due to acquired resistance to these treatments.
Seragon Pharmaceuticals' orally active selective estrogen receptor degraders (SERDs) represent a new treatment for progressive metastatic breast cancer that were designed to circumvent the problem of resistance to antihormonal therapies. Importantly, the majority of these tumors continue to depend on ERα for growth and survival. The emerging evidence that in the endocrine-resistant state ERα can signal in both a hormone-dependent and hormone-independent manner, supports the development of agents that are not only competitive ERα antagonists but also reduce steady state levels of the receptor. Seragon SERDs bind to the estrogen receptor to limit hormone action, and induce conformational changes that results in the degradation of the receptor and thus limit both modes of ER signaling.
Seragon has identified multiple SERDs that have pharmacokinetic profiles sufficient to drive a robust therapeutic response in various pre-clinical models of ER driven cancer. 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 therapies. Seragon's SERDs induce tumor regressions in both tamoxifen-sensitive and tamoxifen-resistant tumor models in vivo. Based on these results and others, the company is currently advancing two, distinct SERD chemical scaffolds through both preclinical and clinical development.
Seragon's SERDs are initially being developed for the treatment of women with late-stage, progressive metastatic breast cancer, but these SERDs also have tremendous potential in treating patients with early-stage breast cancer as well as a subset of ER+ endometrial and ovarian cancer.