Crinetics' Single Ascending Dose Data Shows Proof Of ACTH Antagonism In Healthy Volunteers

Crinetics Pharmaceuticals Inc CRNX announced preliminary findings from the single ascending dose (SAD) portion of Phase 1 study evaluating CRN04894 for conditions of ACTH excess, including Cushing's disease and congenital adrenal hyperplasia.
The data demonstrated pharmacologic proof-of-concept for this nonpeptide adrenocorticotropic hormone (ACTH) antagonist.
The 39 healthy volunteers were administered oral doses of CRN04894 (10 mg to 80 mg, or placebo) two hours before a challenge with synthetic ACTH.
Analyses of basal cortisol levels (before the ACTH challenge) showed that CRN04894 produced a rapid and dose-dependent reduction of cortisol by 25-56%.
After the challenge with a supra-pathophysiologic dose of ACTH (250 mcg), CRN04894 suppressed cortisol up to 41%.
After the challenge with a disease-relevant dose of ACTH (1 mcg), CRN04894 showed a clinically meaningful reduction in cortisol AUC of 48%.
CRN04894 was well tolerated in the healthy volunteers who enrolled in these SAD cohorts, and all adverse events were considered mild.
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