Crinetics Announces Positive Topline Results From Phase 2 Trial of Atumelnant in Congenital Adrenal Hyperplasia (CAH)

Clinical Trial Results - Substantial, rapid, and sustained statistically significant reductions in key biomarkers, including up to 80% mean reduction of androstenedione (A4), were achieved across doses [1] - Meaningful improvements demonstrated in multiple clinical signs and symptoms of congenital adrenal hyperplasia (CAH) affecting patient health [1] - Safety and efficacy data support the initiation of a Phase 3 clinical trial [1] Phase 2 TouCAHn Trial Highlights - The TouCAHn trial is an open-label, global, Phase 2 study evaluating the efficacy, safety, and pharmacokinetics of atumelnant in 28 patients with CAH caused by 21-hydroxylase deficiency [3] - Primary endpoints included change from baseline in morning serum androstenedione (A4) levels and incidence of treatment-emergent adverse events [4] - Secondary endpoint evaluated change from baseline in morning serum 17-hydroxyprogesterone (17-OHP) [4] Atumelnant Efficacy Data - Rapid, substantial, and sustained statistically significant reductions in A4 levels were observed across all doses: 40 mg (-619 ng/dL, p=0.0003), 80 mg (-774 ng/dL, p<0.0001), and 120 mg (-954 ng/dL, p<0.0001) [7] - Significant reductions in 17-OHP, a confirmatory secondary biomarker, were also achieved across doses [7] - Substantial reduction and normalization of testosterone in the majority of female participants (8/13), with 6 of the 11 impacted participants resuming menses [14] - Consistent reduction in total adrenal volume observed across dose cohorts [14] - Resolution of androgen-mediated polycythemia in 5 of the 6 impacted participants [14] Safety Profile - Atumelnant has been generally well tolerated with no treatment-related severe or serious adverse events to date [8] - No participants required dose reduction or discontinued from the trial [8] - All adverse events to-date have been mild to moderate and generally transient [8] - The most common treatment-emergent adverse events included headache (7/28) and fatigue (5/28) [8] Company Strategy and Pipeline - Crinetics Pharmaceuticals is advancing atumelnant into a global Phase 3 pivotal trial for adults with CAH and preparing to start a Phase 2b/3 trial in pediatric patients this year [2] - The company's internally discovered pipeline now has two drug candidates with positive later-stage data [2] - Crinetics plans to submit INDs for four additional candidates currently in first-in-human enabling studies [2] - The company aims to build the premier global endocrine company [2] About Atumelnant - Atumelnant is the first once-daily, oral adrenocorticotropic hormone (ACTH) receptor antagonist that acts selectively at the melanocortin type 2 receptor (MC2R) on the adrenal gland [10] - It is currently in development for congenital adrenal hyperplasia and ACTH-dependent Cushing's syndrome [10] - Atumelnant has exhibited strong binding affinity for MC2R in preclinical models and demonstrated suppression of adrenally derived glucocorticoids and androgens [10] About Crinetics Pharmaceuticals - Crinetics Pharmaceuticals is a clinical-stage pharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors [12] - The company's lead development candidate, paltusotine, is in clinical development for acromegaly and carcinoid syndrome associated with neuroendocrine tumors [12] - All of the company's drug candidates are orally delivered, small molecule, new chemical entities resulting from in-house drug discovery efforts [12]