Crinetics Announces First Patient Dosed in Pivotal Adult Trial of Atumelnant in Congenital Adrenal Hyperplasia (CAH)

Rhea-AI Summary

Crinetics (Nasdaq: CRNX) announced dosing of the first patient in the CALM-CAH Phase 3 trial of atumelnant on December 11, 2025. The randomized, placebo-controlled adult study will evaluate atumelnant’s ability to reduce excess adrenal androgens and lower glucocorticoid use while assessing other clinical outcomes that reflect disease control.

Atumelnant is described as the first-and-only small-molecule ACTH receptor antagonist in late-stage clinical development for classic congenital adrenal hyperplasia (CAH). Phase 2 data showed rapid, sustained reductions in biomarkers including androstenedione and 17-hydroxyprogesterone, plus clinical measures such as adrenal size and resumption of menses. Atumelnant has also received FDA Orphan Drug designation for classic CAH.

Positive

• First patient dosed in CALM-CAH Phase 3 (December 11, 2025)
• Phase 2: reductions in androstenedione and 17-hydroxyprogesterone
• FDA Orphan Drug designation for atumelnant in classic CAH
• First-and-only small-molecule ACTH receptor antagonist in late-stage development

Negative

• Phase 3 limited to adults, excluding pediatric patients in this trial

Key Figures

Phase 3 trial Phase 3 CALM-CAH Pivotal adult trial of atumelnant in classic CAH

Prior phase Phase 2 Positive Phase 2 results in adults with classic CAH

Dosing frequency Once-daily Oral ACTH receptor antagonist regimen for atumelnant

Orphan status Orphan Drug Designation U.S. FDA designation for atumelnant in classic CAH

ClinicalTrials.gov ID NCT07159841 Registry identifier for CALM-CAH Phase 3 study

Market Reality Check

$48.06 Last Close

Volume Volume 564,564 is below the 20-day average (about 0.45x recent activity). low

Technical Shares at $48.06 are trading above the 200-day MA of $34.80 and about one-fifth below the $60.34 52-week high.

Peers on Argus

CRNX gained 0.33% with below-average volume while peers were mixed: IMVT +3.97%, PTGX +3.18%, APLS +3.48%, VKTX +1.02%, and KYMR -3.42%. This pattern points to stock-specific rather than broad sector momentum.

Common Catalyst Several peers had financing and clinical development headlines, but no single sector-wide catalyst is evident.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Dec 03	Clinical trial start	Positive	+4.4%	First patient dosed in Phase 1/2 BRAVESST2 trial for CRN09682.
Nov 20	Clinical trial start	Positive	+2.1%	First patient randomized in pivotal Phase 3 CAREFNDR trial for paltusotine.
Nov 10	Equity compensation	Neutral	+3.6%	Inducement grants of options and RSUs to new employees under 2021 plan.
Nov 06	Earnings & update	Neutral	+2.3%	Q3 2025 results and business update following PALSONIFY approval and launch.
Oct 23	Conference data	Positive	-0.9%	NANETS 2025 abstracts including 74% one-year PFS for paltusotine.

Pattern Detected

Recent clinical and corporate updates have typically coincided with modestly positive next-day returns, with one small divergence on conference data.

Recent Company History

Over the past few months, Crinetics reported multiple clinical and corporate milestones. On Oct 23, 2025, it highlighted neuroendocrine tumor data and a 74% one-year PFS rate, followed by Q3 2025 financials and the PALSONIFY launch on Nov 6. Subsequent news included inducement equity grants, a pivotal Phase 3 carcinoid syndrome trial start on Nov 20, and a Phase 1/2 trial initiation for CRN09682 on Dec 3. These events mostly saw positive 24-hour reactions, providing a constructive backdrop to today’s Phase 3 atumelnant update.

Market Pulse Summary

This announcement marked an important step as Crinetics dosed the first patient in the pivotal Phase 3 CALM-CAH trial of atumelnant for classic CAH, following positive Phase 2 data and FDA Orphan Drug Designation. It adds to a series of recent milestones, including new trials for CRN09682 and paltusotine. Investors may watch recruitment progress, biomarker and androgen readouts, and regulatory interactions from this study identified as NCT07159841 for future updates.

Key Terms

phase 3 medical

"the CALM-CAH Phase 3 trial evaluating investigational candidate atumelnant"

Phase 3 is the late-stage clinical testing step for a new drug or medical treatment, where the product is given to large groups of patients to confirm effectiveness, monitor side effects, and compare it to standard care. Successful Phase 3 results are often the final scientific hurdle before regulators decide on approval and market launch—like passing a final exam before graduation—and can sharply change a company's valuation and future revenue prospects.

orphan drug designation regulatory

"Crinetics recently received Orphan Drug Designation from the U.S. Food & Drug Administration"

Orphan drug designation is a special status given to medicines developed to treat rare diseases affecting only a small number of people. This status often provides benefits like faster approval processes and financial incentives, making it more attractive for companies to develop these drugs. For investors, it signals potential for exclusive market rights and reduced competition, which can impact the drug’s profitability.

acth receptor antagonist medical

"oral adrenocorticotropic hormone (ACTH) receptor antagonist candidate for the proposed treatment"

An ACTH receptor antagonist is a drug that blocks the body’s receptor for adrenocorticotropic hormone (ACTH), which stops the hormone from telling the adrenal glands to make stress hormones like cortisol. For investors this matters because such drugs can treat conditions driven by excess cortisol (for example certain endocrine disorders), so successful development or approval can create new revenue streams; think of it as cutting the signal to an overactive factory to slow production.

congenital adrenal hyperplasia medical

"for the proposed treatment of classic congenital adrenal hyperplasia (CAH)"

Congenital adrenal hyperplasia is a group of inherited disorders in which the adrenal glands lack an enzyme needed to make certain hormones, causing a chronic imbalance of cortisol, aldosterone and/or sex hormones. Think of it as a factory assembly line missing a key part, so the body overproduces some products and underproduces others, requiring lifelong monitoring or hormone treatment. For investors, it matters because diagnosis, ongoing therapy, newborn screening and potential new drugs or gene therapies can drive medical spending, regulatory approvals and market opportunity in endocrinology and rare disease care.

biomarkers medical

"reductions in key disease biomarkers and clinical measures of CAH"

Biomarkers are measurable indicators found in the body, such as substances in blood or tissues, that reveal information about health or disease. For investors, they can signal how well a medical treatment is working or whether a disease is developing, helping to assess the potential success or risks of healthcare companies or innovations. Think of biomarkers as biological signals that provide clues about a person’s health status.

glucocorticoid medical

"reducing glucocorticoid levels to the physiologically normal range"

A glucocorticoid is a type of steroid hormone—produced naturally by the body and also made as a medicine—that quiets inflammation and helps control how the body uses energy and responds to stress. Investors watch glucocorticoids because they are widely used drugs whose effectiveness, side effects and regulatory approval or supply issues can drive sales, affect healthcare costs and change demand for related treatments, much like a widely used tool that can both fix a problem and create new ones.

AI-generated analysis. Not financial advice.

Phase 3 study builds on positive phase 2 results showing rapid and sustained reductions in key disease biomarkers and clinical measures of CAH

SAN DIEGO, Dec. 11, 2025 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today announced that the first patient has been dosed in the CALM-CAH Phase 3 trial evaluating investigational candidate atumelnant, a novel, once-daily, oral adrenocorticotropic hormone (ACTH) receptor antagonist candidate for the proposed treatment of classic congenital adrenal hyperplasia (CAH).

“Dosing the first patient in this Phase 3 study underscores our commitment to addressing the unmet needs of people living with CAH and our excitement about the potential of atumelnant,” said Dana Pizzuti, M.D., Chief Medical and Development Officer of Crinetics. “Through the CALM-CAH study, we will evaluate atumelnant’s ability to normalize adrenal androgen levels while simultaneously reducing glucocorticoid levels to the physiologically normal range. With a unique endpoint measuring both of these objectives, CALM-CAH sets a new standard in terms of assessing overall disease control.”

Atumelnant is the first-and-only small molecule ACTH receptor antagonist in late-stage clinical development and is designed to block the pathway in the adrenal gland that leads to the production of excess androgens associated with classic CAH. In a Phase 2 study in adults with classic CAH, treatment with atumelnant was associated with reductions in key biomarkers, including androstenedione and 17-hydroxyprogesterone, as well as other clinical measures of disease activity including adrenal size and resumption of menses. Based on Phase 2 results, Crinetics has advanced the registrational CALM-CAH Phase 3 trial in adults.

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.

Crinetics recently received Orphan Drug Designation from the U.S. Food & Drug Administration (FDA) for atumelnant in the treatment of classic CAH.

For more information, visit https://clinicaltrials.gov/study/NCT07159841.

About Atumelnant
Investigational atumelnant is the first in class and only once-daily, oral adrenocorticotropic hormone (ACTH) receptor antagonist that acts selectively at the melanocortin type 2 receptor (MC2R) on the adrenal gland in late-stage clinical development. Diseases associated with excess ACTH can have a significant impact on physical and mental health. Novel 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 consistently demonstrated compelling treatment benefits of atumelnant, evidenced by the rapid, substantial and sustained statistically significant reductions in key CAH disease related biomarkers, including A4 and 17-hydroxyprogesterone, in a diverse population. Currently in Phase 3 clinical development, atumelnant holds the potential to offer transformational care for individuals living with congenital adrenal hyperplasia and ACTH-dependent Cushing’s syndrome. This breakthrough could revolutionize the management of these conditions, providing hope for unprecedented improvements in quality of life.

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’ lead product, PALSONIFY™ (paltusotine), is the first once-daily, oral treatment approved by the U.S. FDA 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 SST2 expressing neuroendocrine tumors and other SST2 expressing solid tumors. Additional discovery programs address a variety of endocrine conditions such as neuroendocrine tumors, Graves’ disease (including Graves’ hyperthyroidism and Graves’ orbitopathy, or thyroid eye disease), polycystic kidney disease, hyperparathyroidism, diabetes, obesity, and 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 Phase 3 program for atumelnant for CAH and for a Phase 2/3 program of atumelnant for ACTH-dependent Cushing’s syndrome; the plans and timelines for the clinical development of our drug candidates, including the therapeutic potential and clinical benefits or safety profile thereof or the expected timing of the advancement of those programs. 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, data that we report may change following completion or a more comprehensive review of the data related to the clinical studies; 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 its clinical studies and preclinical studies, manufacturing and supply chain, or impairing employee productivity; unexpected adverse side effects 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; the success of Crinetics’ clinical studies and nonclinical studies; regulatory developments or political changes, including the policies related to pricing and pharmaceutical drug reimbursement, in the United States and foreign countries; clinical studies and preclinical studies may not proceed at the time or in the manner expected, or at all; the timing and outcome of research, development and regulatory review is uncertain, and Crinetics’ drug candidates may not advance in development; 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, 2024. 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:
Gayathri Diwakar
Head of Investor Relations
gdiwakar@crinetics.com
(858) 345-6340

FAQ

What did Crinetics (CRNX) announce on December 11, 2025 about atumelnant?

Crinetics announced the first patient was dosed in the CALM-CAH Phase 3 trial of atumelnant for classic CAH.

What are the primary goals of the CALM-CAH Phase 3 trial (CRNX)?

The trial will assess reductions in excess adrenal androgens, improvements in glucocorticoid use, and other clinical outcomes reflecting disease control.

What Phase 2 results supported advancing atumelnant to Phase 3 for CRNX?

Phase 2 reported rapid, sustained reductions in androstenedione and 17-hydroxyprogesterone and improvements in clinical measures like adrenal size and resumption of menses.

Does atumelnant have any regulatory designations for treating CAH (CRNX)?

Yes, atumelnant received Orphan Drug designation from the U.S. Food and Drug Administration for classic CAH.

Is atumelnant unique among CAH treatments for CRNX?

Crinetics describes atumelnant as the first-and-only small-molecule ACTH receptor antagonist in late-stage clinical development.

Where can I find more information about the CALM-CAH trial (CRNX)?

Clinical trial details are available at ClinicalTrials.gov study NCT07159841.