Data show investigational atumelnant drove sustained androgen reductions while enabling lowering of glucocorticoid supplementation to physiologically normal levels in adults with classic CAH

New results from the Phase 1b/2a ACTH-dependent Cushing's syndrome trial also presented, showing atumelnant rapidly lowered early morning cortisol and normalized urinary free cortisol levels even at lower dose

SAN DIEGO, June 14, 2026 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (NASDAQ:CRNX) presented data today from the open-label, Phase 2 congenital adrenal hyperplasia (CAH) adult study of investigational atumelnant, a novel, once-daily oral adrenocorticotropic hormone (ACTH) receptor antagonist candidate being developed for the treatment of classic CAH and ACTH-dependent Cushing's syndrome. The findings were included in an oral presentation titled "Once Daily Atumelnant (CRN04894) Enables Lowering of Glucocorticoid Doses with Sustained Androgen Reduction in Adults with Congenital Adrenal Hyperplasia" at Endocrine Society's Annual Meeting, ENDO 2026.

"Atumelnant is designed to block the effect of excess ACTH, the fundamental driver of symptoms and complications of CAH and ADCS," said Dr. Alan Krasner, M.D., Chief Endocrinologist, Crinetics. "Based on promising results from phase 2 clinical trials presented today, we are advancing atumelnant into late phase clinical development. The data suggest atumelnant could represent a uniquely effective and simple to use oral therapy for many patients who need new options."

"It's exciting to see that glucocorticoid dose reduction did not impact the atumelnant-induced decline in androstenedione in adults with classic CAH who participated in this Phase 2 trial," said Dr. Umasuthan Srirangalingam, Consultant Physician in Endocrinology and Diabetes at University College London Hospitals NHS Foundation Trust and TouCAHn Investigator. "We are looking forward to learning more about the full potential of atumelnant in the treatment of CAH from adult and pediatric Phase 3 trials that are already underway."

At ENDO 2026, findings from Cohort 4 of the Phase 2 CAH trial were presented for the first time, including the percent change from baseline in morning serum A4, 11-OHA4, and 11-KT with GC reduction. Participants in Cohort 4 received dosing of 80 mg once daily in the morning. Beginning at week 2 of treatment, each participant's previous GC dose was reduced stepwise by 5-10 mg HC equivalents, independent of A4 measurement, to target <11 mg/m²/day HC equivalents.

Phase 2 CAH Cohort 4 Results

At week 12, the mean percentage change from baseline in A4 morning serum levels in Cohort 4 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 change from baseline of -64% and -56% at week 12, respectively.
Morning dosing of atumelnant 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 to date, irrespective of disease severity or dose level.

Initial findings from the adult Phase 2 trial in CAH, including A4 reduction levels compared to baseline for cohorts 1-3, in which participants did not change previous GC doses, were presented at ENDO 2025.

Topline results from Cohort 4 were announced in January 2026.

Previously Reported A4 Reductions for Cohorts 1-3 (no GC reduction)

Atumelnant, Dosed Once Daily	Mean A4 Change from Baseline
40 mg (n=11)	-58%
80 mg (n=11)	-70%
120 mg (n=6)	-80%

New 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). Findings include:

Atumelnant rapidly lowered early morning serum cortisol in all participants.
Atumelnant also rapidly lowered UFC. At the end of the 10-day dosing period, UFC remained ≤ upper limit of normal (ULN) in 3/6 participants.
Most AEs were mild to moderate and consistent with symptoms of adrenal insufficiency. Most improved with initiation of GC replacement.

Atumelnant ENDO 2026 presentations can be found at: https://crinetics.com/news-events/endo-2026/

About Atumelnant

Atumelnant, Crinetics' second investigational compound, 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. Diseases associated with excess ACTH can have significant impact on physical and mental health. Atumelnant has exhibited strong binding affinity for MC2R in preclinical models and has demonstrated suppression of adrenally derived glucocorticoids and androgens that are under the control of ACTH. Data from a 12-week Phase 2 study demonstrated compelling treatment benefits of atumelnant, evidenced by the rapid, substantial and sustained statistically significant reductions in key CAH disease related biomarkers, including androstenedione and 17-hydroxyprogesterone, in a diverse population. Atumelnant is in development for congenital adrenal hyperplasia and ACTH-dependent Cushing's syndrome, with the Phase 3 CALM-CAH trial and a Phase 1/2b trial in ADCS currently enrolling patients.

About the Phase 2 TouCAHn Trial (CAH)

The TouCAHn trial is an open-label, global, Phase 2 study designed to evaluate the efficacy, safety, and pharmacokinetics of atumelnant when administered for 12 weeks in people with classic CAH (21-hydroxylase deficiency). A total of 38 participants were enrolled, with a median A4 of 980.8 (range=116-2755) ng/dL were enrolled in four cohorts: (40 mg, n=11; 80 mg, n=11; 120 mg, n=6; 80 mg morning dosing with GC reduction, n=10).

Primary endpoints included change from baseline in morning serum androstenedione (A4) levels and incidence of treatment-emergent adverse events. Percent change-from-baseline in GC daily dose was an exploratory endpoint for Cohort 4.

About the Phase 1b/2a Study in ACTH-dependent Cushing's Syndrome

The Phase 1b/2a, is the first-in-disease, open-label, multiple-ascending dose exploratory study to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamic biomarker responses associated with atumelnant over a 10-day inpatient treatment period in participants with ACTH-dependent Cushing's syndrome.

The study is being conducted in collaboration with the National Institutes of Health and led by Dr. Lynnette Nieman. Participants received oral atumelnant once daily for 10 days, followed by monitoring during four wash-out days.

About Crinetics Pharmaceuticals

Crinetics Pharmaceuticals is a global pharmaceutical company committed to transforming the treatment of endocrine diseases and endocrine-related tumors through science rooted in patient needs. Crinetics is focused on discovering, developing, and commercializing novel therapies, with a core expertise in targeting G-protein coupled receptors (GPCRs) with small molecules that have specifically tailored pharmacology and properties.

Crinetics' first commercial product, PALSONIFY™ (paltusotine), is the first once-daily, oral treatment approved by the U.S. FDA and EMA for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. Paltusotine is also in clinical development for carcinoid syndrome associated with neuroendocrine tumors. Crinetics' deep pipeline of 10+ disclosed programs includes late-stage investigational candidate atumelnant, which is currently in development for congenital adrenal hyperplasia and ACTH-dependent Cushing's syndrome, and CRN09682, a nonpeptide drug conjugate candidate that is being developed to treat somatostatin receptor 2 (SST2) expressing neuroendocrine tumors and other SST2 expressing solid tumors. Additional discovery programs are focused on a variety of endocrine targets such as thyroid stimulating hormone (TSH), parathyroid hormone (PTH), somatostatin receptor 3 (SST3), growth hormone (GH), glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP), as well as GPCR-targeted oncology indications.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward-looking statements, including statements regarding the plans and timelines for the clinical development of atumelnant for congenital adrenal hyperplasia and ACTH-dependent Cushing's syndrome and paltusotine for the treatment of carcinoid syndrome; or the potential for our development candidates to transition to clinical development. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "anticipate," "could," "intend," "target," "project," "contemplates," "believes," "estimates," "predicts," "potential," "upcoming" or "continue" or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including, without limitation, we may not be able to obtain, maintain and enforce our patents and other intellectual property rights, and it may be prohibitively difficult or costly to protect such rights; geopolitical events may disrupt Crinetics' business and that of the third parties on which it depends, including delaying or otherwise disrupting clinical studies and preclinical studies, manufacturing and supply chain, or impairing employee productivity; unexpected adverse side effects, complications and/or drug interactions or inadequate efficacy of the Company's product candidates that may limit their development, regulatory approval and/or commercialization; the Company's dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; regulatory developments or political changes, including policies related to pricing and pharmaceutical drug reimbursement, in the United States and foreign countries; the timing and outcome of research, development and regulatory review is uncertain, and Crinetics' drug candidates may not advance in development or be approved for marketing; Crinetics may use its capital resources sooner than expected or our cash burn rate may accelerate; any future impacts to our business resulting from geopolitical developments outside our control; and the other risks and uncertainties described in the Company's periodic filings with the Securities and Exchange Commission (SEC). The events and circumstances reflected in the company's forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Additional information on risks facing Crinetics can be found under the heading "Risk Factors" in Crinetics' periodic filings with the SEC, including its annual report on Form 10-K for the year ended December 31, 2025. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Except as required by applicable law, Crinetics does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

Media:

Natalie Badillo

Head of Corporate Communications

nbadillo@crinetics.com

(858) 345-6075

Investors:

Gyathri Diwakar

Head of Investor Relations

gdiwakar@crinetics.com

(858) 345-6340

Crinetics Presents Full Results From Phase 2 Trial of Atumelnant in Congenital Adrenal Hyperplasia (CAH) in Oral Presentation at ENDO 2026