atumelnant (CRN04894) / Vertex - LARVOL DELTA

Drug-Drug Interaction Study of Atumelnant in Healthy Participants (clinicaltrials.gov) - P1 | N=46 | Completed | Sponsor: Crinetics Pharmaceuticals Inc. | Active, not recruiting ➔ Completed | Trial completion date: Dec 2026 ➔ Jul 2026 | Trial primary completion date: Dec 2026 ➔ Jun 2026

Trial completion • Trial completion date • Trial primary completion date

A Study to Evaluate the Safety and PK of CRN04894 for the Treatment of Cushing's Syndrome (clinicaltrials.gov) - P1/2 | N=19 | Active, not recruiting | Sponsor: Crinetics Pharmaceuticals Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Cushing’s Disease • Endocrine Disorders

Palsonify (paltusotine); atumelnant / Vertex Pharmaceuticals; Crinetics Pharmaceuticals Vertex Pharmaceuticals…agreed to acquire Crinetics Pharmaceuticals for approximately $10 billion in cash (MSN News) - "The acquisition adds Palsonify, the first and only once-daily oral therapy for acromegaly, and late-stage candidate atumelnant for congenital adrenal hyperplasia (CAH)...The transaction is expected to close in the third quarter of 2026, subject to regulatory and shareholder approvals."

M&A • Acromegaly • Congenital Adrenal Hyperplasia

Drug-Drug Interaction Study of Atumelnant in Healthy Participants (clinicaltrials.gov) - P1 | N=46 | Active, not recruiting | Sponsor: Crinetics Pharmaceuticals Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed

CRN04894-09: An Extension Study to Evaluate Safety and Efficacy of Atumelnant in Participants With Congenital Adrenal Hyperplasia (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Crinetics Pharmaceuticals Inc. | N=150 ➔ 200 | Trial completion date: Nov 2027 ➔ Aug 2029 | Trial primary completion date: Nov 2027 ➔ Jul 2029

Enrollment change • Trial completion date • Trial primary completion date • Congenital Adrenal Hyperplasia • Endocrine Disorders

Model-Informed Atumelnant Dose Selection for a Phase 3 Study in Adult Patients with Classic Congenital Adrenal Hyperplasia (ENDO 2026) - P2 | "Atumelnant (CRN04894) is a first-in-class, once-daily, oral, selective melanocortin type 2 receptor antagonist in development for the treatment of diseases of ACTH excess, including CAH...Most (=95%) patients are predicted to achieve robust 17-OHP reductions at 80- or 120 mg once daily; however, the probability of achieving robust A4 reductions doubled from 35% of patients at 80 mg once daily to 70% of patients at 120 mg once daily, suggesting some patients would see further benefit from a 120 mg once daily dose. Thus, the atumelnant dose regimens of 80 and 120 mg once daily were selected for further investigation in the Phase 3 study in adult patients with CAH, with the goal of reducing daily GC dosage while maintaining androgen control."

Clinical • P3 data • Congenital Adrenal Hyperplasia • Endocrine Disorders

Model-Informed Atumelnant Dose Selection for a Phase 3 Study in Adult Patients with Classic Congenital Adrenal Hyperplasia (ENDO 2026) - P2 | "Atumelnant (CRN04894) is a first-in-class, once-daily, oral, selective melanocortin type 2 receptor antagonist in development for the treatment of diseases of ACTH excess, including CAH...Most (=95%) patients are predicted to achieve robust 17-OHP reductions at 80- or 120 mg once daily; however, the probability of achieving robust A4 reductions doubled from 35% of patients at 80 mg once daily to 70% of patients at 120 mg once daily, suggesting some patients would see further benefit from a 120 mg once daily dose. Thus, the atumelnant dose regimens of 80 and 120 mg once daily were selected for further investigation in the Phase 3 study in adult patients with CAH, with the goal of reducing daily GC dosage while maintaining androgen control."

Clinical • P3 data • Congenital Adrenal Hyperplasia • Endocrine Disorders

Once Daily Atumelnant (CRN04894) Enables Lowering of Glucocorticoid Doses with Sustained Androgen Reduction in Adults with Congenital Adrenal Hyperplasia (ENDO 2026) - P2 | "Cohorts 1-3 (40, 80, or 120 mg at bedtime) maintained stable GC dosing (=15 mg hydrocortisone equivalent) for =6 months prior to screening and throughout the study. In conclusion, GC dose reduction did not diminish the atumelnant-induced decline in A4 in adults with classic CAH. These results highlight the potential for adrenocorticotropic hormone receptor antagonism as a means by which to achieve correction of hyperandrogenism in CAH while allowing for GC use at doses that do not exceed those needed for physiologic replacement."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders

ORF35-04 - BLOCK AND REPLACE' ATUMELNANT (CRN04894) AND PHYSIOLOGIC HYDROCORTISONE REPLACEMENT RAPIDLY CONTROLS HYPERCORTISOLISM IN ACTH-DEPENDENT CUSHING SYNDROME (ENDO 2026) - P1/2 | "ATU 40 mg QD rapidly lowered EMC and normalized UFC in 4/6 Pts. UFC remained =ULN in 3 Pts on D10 despite PHRT. Symptoms of AI improved with initiation of PHRT."

Anorexia • CNS Disorders • Congenital Adrenal Hyperplasia • Cushing’s Disease • Depression • Endocrine Disorders • Insomnia • Mood Disorders • Nephrology • Renal Disease • Sleep Disorder

Drug-Drug Interaction Study of Atumelnant in Healthy Participants (clinicaltrials.gov) - P1 | N=46 | Recruiting | Sponsor: Crinetics Pharmaceuticals Inc.

New P1 trial

A Study in Pediatric Participants With Congenital Adrenal Hyperplasia (Balance-CAH) (clinicaltrials.gov) - P2/3 | N=153 | Recruiting | Sponsor: Crinetics Pharmaceuticals Inc.

Trial initiation date • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics • CYP1A2 • CYP21A2

A Study in Pediatric Participants With Congenital Adrenal Hyperplasia (Balance-CAH) (clinicaltrials.gov) - P2/3 | N=153 | Recruiting | Sponsor: Crinetics Pharmaceuticals Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics • CYP1A2 • CYP21A2

A Study to Evaluate Atumelnant in Adults With Congenital Adrenal Hyperplasia (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Crinetics Pharmaceuticals Inc.

Trial initiation date • Congenital Adrenal Hyperplasia • Endocrine Disorders

A Study to Assess Pharmacokinetics, Safety, and Tolerability of Atumelnant in Healthy Japanese and Caucasian Participants (clinicaltrials.gov) - P1 | N=21 | Completed | Sponsor: Crinetics Pharmaceuticals Inc. | Recruiting ➔ Completed

Trial completion

A Study in Pediatric Participants With Congenital Adrenal Hyperplasia (Balance-CAH) (clinicaltrials.gov) - P2/3 | N=153 | Recruiting | Sponsor: Crinetics Pharmaceuticals Inc.

Trial initiation date • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics • CYP1A2 • CYP21A2

A Study to Evaluate Atumelnant in Adults With Congenital Adrenal Hyperplasia (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Crinetics Pharmaceuticals Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Congenital Adrenal Hyperplasia • Endocrine Disorders

A Study to Evaluate Atumelnant in Adults With Congenital Adrenal Hyperplasia (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Crinetics Pharmaceuticals Inc. | Not yet recruiting ➔ Recruiting | Initiation date: Sep 2025 ➔ Dec 2025

Enrollment open • Trial initiation date • Congenital Adrenal Hyperplasia • Endocrine Disorders

Crinetics Announces First Patient Dosed in Pivotal Adult Trial of Atumelnant in Congenital Adrenal Hyperplasia (CAH) (Crinetics Press Release) - "The CALM-CAH Phase 3 study is a randomized, placebo-controlled trial evaluating atumelnant in adults with classic CAH, designed to assess reductions in excess androgens, improvements in glucocorticoid use, and other clinical outcomes that reflect disease control."

Trial status • Congenital Adrenal Hyperplasia

A Study in Pediatric Participants With Congenital Adrenal Hyperplasia (Balance-CAH) (clinicaltrials.gov) - P2/3 | N=153 | Recruiting | Sponsor: Crinetics Pharmaceuticals Inc. | Not yet recruiting ➔ Recruiting | Initiation date: Sep 2025 ➔ Nov 2025

Enrollment open • Trial initiation date • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics

A Study to Assess Pharmacokinetics, Safety, and Tolerability of Atumelnant in Healthy Japanese and Caucasian Participants (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Crinetics Pharmaceuticals Inc.

New P1 trial

Evaluate the Safety, Efficacy, and Pharmacokinetics of CRN04894 in Participants With Congenital Adrenal Hyperplasia (TouCAHn) (clinicaltrials.gov) - P2 | N=38 | Completed | Sponsor: Crinetics Pharmaceuticals Inc. | Active, not recruiting ➔ Completed

Trial completion • Congenital Adrenal Hyperplasia • Endocrine Disorders

A Study in Pediatric Participants With Congenital Adrenal Hyperplasia (Balance-CAH) (clinicaltrials.gov) - P2/3 | N=153 | Not yet recruiting | Sponsor: Crinetics Pharmaceuticals Inc.

New P2/3 trial • Congenital Adrenal Hyperplasia • Endocrine Disorders • Pediatrics

A Study to Evaluate Atumelnant in Adults With Congenital Adrenal Hyperplasia (clinicaltrials.gov) - P3 | N=150 | Not yet recruiting | Sponsor: Crinetics Pharmaceuticals Inc.

New P3 trial • Congenital Adrenal Hyperplasia • Endocrine Disorders

Reductions in Adrenal Volume in Patients With Congenital Adrenal Hyperplasia Receiving Once-Daily Oral Atumelnant (CRN04894): Interim Results From a 12-Week, Phase 2, Open-Label Study (ENDO 2025) - P2 | "In conclusion, through potent blockade of the adrenal MC2R and reduction or normalization of adrenal androgens, consistent reduction in adrenal size was demonstrated with 12 weeks of once-daily atumelnant. Furthermore, these results demonstrate the plasticity of hyperplastic adrenal tissue in adults with long-standing CAH and that ongoing adrenal hyperplasia is dependent on continued exposure to excess ACTH."

Clinical • P2 data • Congenital Adrenal Hyperplasia • Endocrine Disorders

Once-Daily Oral Atumelnant (CRN04894) Induces Rapid, Substantial, and Sustained Reductions of Androstenedione and 17‑Hydroxyprogesterone in Adults With Classical Congenital Adrenal Hyperplasia: Interim Results From a 12-Week, Phase 2, Open-Label Study (ENDO 2025) - P2 | "Adults with classic CAH (21-hydroxylase deficiency) on a stable dose of glucocorticoid (GC) replacement (≥15 mg hydrocortisone equivalent) for ≥6 months and androstenedione (A4) level ≥1.5 times the upper limit of normal (ULN) were enrolled in 3 dose cohorts (40 mg, 80 mg, or 120 mg) and received oral atumelnant once daily for 12 weeks. The most common treatment-emergent AEs were headache (n=7) and fatigue (n=5). Overall, rapid, substantial, and sustained reductions in A4 and 17-OHP were demonstrated with administration of atumelnant in adult patients with classical CAH."

Clinical • P2 data • Congenital Adrenal Hyperplasia • Endocrine Disorders • Fatigue • Nephrology • Pain • Renal Disease