FIRST-IN-CLASS PIPELINE

Novel Antagonists Directed to Steroidogenic Factor-1 (SF-1)

Adrenocortical cancer (ACC) and Cushing’s syndrome are orphan indications with substantial unmet need and potential worldwide revenues of $1 B/year. These conditions are often fatal and affect as many as 7,000 Americans.

In adult ACC, expression of the orphan nuclear receptor SF-1 correlates with poor patient survival. In pediatric ACC, the gene for SF-1 is consistently amplified, indicating that SF-1 is necessary for cancer growth. The single approved drug (mitotane) is toxic and has limited efficacy. For the more than 50% of ACC patients that have metastatic disease, overall 5-year survival is very poor. We predict that an SF-1 based antagonist could have a life-saving impact for both the pediatric and adult forms of the disease.

Cushing’s syndrome is largely a tumor-driven disease in which cortisol levels are pathologically elevated. Cushing’s patients have five-fold increased mortality and available medical therapies are not highly effective. SF-1 antagonists block gene expression for enzymes of the adrenal gland that make cortisol, suggesting that antagonists could treat Cushing’s syndrome with great efficacy.

Orphagen has identified the first potent and effective small molecule antagonists to SF-1 with lead-like properties.

Cushing’s syndrome