Crinetics Announces Positive Initial Findings at ENDO 2024 for Atumelnant in Two Ongoing, Open-Label Studies for the Treatment of Congenital Adrenal Hyperplasia (CAH) and ACTH-Dependent Cushing’s Syndrome (ADCS)

100% of Participants (n=6) With CAH Maintained Androstenedione (A4) Below the Upper Limit of Normal at all Time Points on Atumelnant (80 mg)

CAH Participants Achieved More Than a 90% Reduction of A4 and 97% Reduction of 17-OHP on Atumelnant (80 mg), Beginning at Two Weeks and Sustained Through 12 Weeks

In the ADCS Trial, Atumelnant (80 mg) Normalized 24-hr Urinary Free Cortisol Levels for 100% of Participants (n=5) During Treatment

Management to Host Investor Conference Call Today at 4:30 PM ET and Onsite KOL Event at ENDO for Investors and Analysts at 6:00 PM ET

SAN DIEGO, June 03, 2024 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today announced initial findings from the development program of its second clinical product candidate, atumelnant* (CRN04894), a novel, once-daily oral adrenocorticotropic hormone (ACTH) receptor antagonist. The results, presented at the Endocrine Society’s annual meeting (ENDO2024), include initial data from the Phase 1b/2a, open-label study in participants with ACTH-dependent Cushing’s syndrome (ADCS) conducted in collaboration with the National Institutes of Health, and the Phase 2 open-label TouCAHn study in participants with congenital adrenal hyperplasia (CAH).

“Despite knowing about ACTH’s pivotal role in the endocrine stress response for nearly a century, no other ACTH antagonist drug candidates have been developed and studied in humans. Achieving physiologically normal hormone levels is critical for people living with CAH and ADCS, and today’s data show an impressive ability of atumelnant to reduce key disease drivers like A4 or cortisol to healthy levels,” said Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. “These data also reinforce the strength of our in-house discovery engine and our ability to purposefully design medicines with groundbreaking mechanisms of action like atumelnant, the second novel drug candidate in our pipeline to have demonstrated remarkable results in clinical studies.”

*Proposed international nonproprietary name under review

Once Daily Oral Atumelnant (CRN04894) Induces Rapid and Profound Reductions of Androstenedione and 17-hydroxyprogesterone in Participants with Classical Congenital Adrenal Hyperplasia: Initial Results from A 12-week, Phase 2, Open-label Study (Abstract #MON-677):In this initial analysis of this Phase 2 trial (TouCAHn), people with classic CAH were treated with once-daily, oral atumelnant and assessed for safety and efficacy. The trial continues to enroll three treatment cohorts: 80 mg once daily (n=9), 40 mg once daily (n=9) and 120 mg once daily (n=6).

Data presented at ENDO (n=10) reflect a cutoff date of May 21, 2024. Available data for 80 mg includes: n=4 at 12 weeks of treatment, with two additional participant’s data up to six weeks of treatment. For 40 mg, available data was with n=4 for two weeks of treatment. The TouCAHn study is ongoing, with topline results from the complete study expected in the second half of 2024.

Baseline biomarker levels for subjects in Cohort 1 were:

• Androstenedione (A4) mean: 838 ng/dL
• 17-hydroxyprogesterone (17-OHP) mean: 9,880 ng/dL

Initial results from Cohort 1:

• Atumelnant resulted in profound, rapid and sustained reductions in key adrenal steroids that are hallmarks of CAH.
• 100% of participants had A4 levels below the upper limit of normal (ULN) at two weeks with atumelnant, which was sustained through 12 weeks.
• A4 reductions, a potential endpoint in registrational trials, from the baseline mean were:
  • 91% at two weeks (n=6)
  • 93% at six weeks (n=6)
  • 96% at 12 weeks (n=4)
• 17-OHP changes in serum levels from the baseline mean were:
  • 97% at two weeks (n=6)
  • 95% at six weeks (n=6)
  • 94% at 12 weeks (n=4)

Two-week data from the first four patients in Cohort 2 (40 mg atumelnant once daily) are also presented at ENDO2024.

No severe or serious treatment emergent adverse events have been observed to date, and no participants have discontinued from the trial. All AEs to-date have been mild to moderate and transient. There were no significant changes in safety labs or electrocardiograms. The most common treatment-emergent adverse events included: fatigue (3), headache (2) and upper respiratory tract infection (2).

“In CAH, androgen production can go into overdrive and have a profound effect on people living with this difficult-to-manage disease,” said Dr. Umasuthan Srirangalingam, consultant physician in endocrinology and diabetes at University College London Hospitals NHS Foundation Trust and TouCAHn investigator. “Atumelnant’s unique ability to inhibit ACTH directly at its receptor sets it apart from how we’ve historically pursued controlling androgen production through supra-physiological doses of glucocorticoids. It’s compelling to see initial Phase 2 results showing atumelnant dramatically reduced A4 and 17-OHP.”

Atumelnant (CRN04894) Induces Rapid and Sustained Reductions in Serum and Urine Cortisol in Patients with ACTH-dependent Cushing Syndrome During a Phase 1b/2a, Single Center, 10-day, Inpatient, Open-label Study (Abstract #MON-680):Initial data from five ACTH-dependent Cushing’s syndrome trial participants who completed 10 days of once- daily oral atumelnant treatment (80 mg) in this dose-finding study shows rapid and profound impact on cortisol:

• In all participants, 24h urine free cortisol was below the upper limit of normal during the treatment period even while receiving oral hydrocortisone replacement. UFC normalization has been recommended by the U.S. Food and Drug Administration as a primary endpoint for drugs that decrease cortisol levels in Cushing’s syndrome.
• All five participants (100%) experienced serum cortisol