Crinetics Pharmaceuticals presented full results from its Phase 2 trial of atumelnant in congenital adrenal hyperplasia (CAH) and new data from a Phase 1b/2a trial in ACTH-dependent Cushing's syndrome during an oral presentation at the Endocrine Society's Annual Meeting, ENDO 2026. The investigational once-daily oral adrenocorticotropic hormone (ACTH) receptor antagonist demonstrated sustained androgen reductions and enabled the lowering of glucocorticoid supplementation to physiologically normal levels in adults with classic CAH. In the Cushing's syndrome trial, atumelnant rapidly lowered early morning cortisol and normalized urinary free cortisol levels even at lower doses.

Phase 2 CAH Cohort 4 Results

Findings from Cohort 4 of the Phase 2 CAH trial were presented for the first time. Participants received 80 mg of atumelnant once daily in the morning, with glucocorticoid (GC) doses reduced stepwise by 5-10 mg hydrocortisone (HC) equivalents starting at week 2. At week 12, the mean percentage change from baseline in morning serum androstenedione (A4) levels was -67%. Seven out of eight participants (88%) who completed 12 weeks of treatment achieved a physiologic daily dose of GC. Reductions in pre-GC serum 11-OHA4 and 11-KT were rapid and sustained, with mean changes from baseline of -64% and -56% at week 12, respectively. Morning dosing resulted in similar androgen reductions as seen in previous cohorts with evening administration. Atumelnant was generally well tolerated with no treatment-related severe or serious adverse events.

Previously Reported A4 Reductions for Cohorts 1-3

Initial findings from the adult Phase 2 trial in CAH, including A4 reduction levels compared to baseline for cohorts 1-3 where participants did not change previous GC doses, were presented previously. The data showed mean A4 changes from baseline of -58% for the 40 mg dose (n=11), -70% for the 80 mg dose (n=11), and -80% for the 120 mg dose (n=6).

Phase 1b/2a ADCS Trial Results

Data presented at ENDO 2026 include findings from a cohort dosed with atumelnant 40 mg once daily (n=6). Atumelnant rapidly lowered early morning serum cortisol in all participants. Urinary free cortisol (UFC) was also rapidly lowered; at the end of the 10-day dosing period, UFC remained ≤ upper limit of normal (ULN) in 3 of 6 participants. Most adverse events were mild to moderate and consistent with symptoms of adrenal insufficiency, with most improving upon initiation of GC replacement.

Trial Backgrounds

The TouCAHn trial is an open-label, global, Phase 2 study designed to evaluate the efficacy, safety, and pharmacokinetics of atumelnant administered for 12 weeks in people with classic CAH. The Phase 1b/2a study in ACTH-dependent Cushing's syndrome is a first-in-disease, open-label, multiple-ascending dose exploratory study evaluating safety, tolerability, pharmacokinetics, and pharmacodynamic biomarker responses over a 10-day inpatient treatment period. This study is being conducted in collaboration with the National Institutes of Health.