Crinetics Announces First Patient Randomized in Pivotal Phase 3 CAREFNDR Trial Evaluating Paltusotine in Carcinoid Syndrome

Rhea-AI Summary

Crinetics (Nasdaq: CRNX) announced the first patient randomized in the pivotal Phase 3 CAREFNDR trial of once-daily oral paltusotine for adults with carcinoid syndrome due to well-differentiated neuroendocrine tumors on Nov 20, 2025.

The randomized, double-blind, placebo-controlled study will enroll 141 adults randomized 2:1 to paltusotine 80 mg or placebo; the primary endpoint is change in flushing episodes/day from baseline to Week 12 and a key secondary is change in bowel movements/day. The trial includes a 16-week randomized period followed by a 104-week open-label extension that will evaluate long-term efficacy, safety and monitor progression-free survival. Global enrollment is expected through 2025–2026.

Positive

• Phase 3 initiation with first patient randomized on Nov 20, 2025
• Planned enrollment of 141 adults randomized 2:1 (paltusotine 80 mg vs placebo)
• 104-week open-label extension to assess long-term efficacy, safety and progression-free survival
• Builds on Phase 2 data showing rapid, sustained symptom reductions in flushing and bowel movements
• CRN09682 received IND clearance earlier in 2025, expanding NETs development strategy

Negative

• Global enrollment window extends through 2025–2026, delaying potential near-term readouts
• Primary endpoint focuses on symptom change to Week 12, not on hard clinical outcomes for approval

Insights

Clinical development analyst

Phase 3 randomization advances paltusotine toward registration for carcinoid syndrome; primary endpoint at Week 12.

Crinetics advances its oral somatostatin receptor agonist paltusotine into a pivotal, randomized, double‑blind, placebo‑controlled Phase 3 study enrolling 141 adults with carcinoid syndrome. The trial tests daily PALSONIFY™ (paltusotine) 80 mg versus placebo with a primary endpoint of change in flushing episodes from baseline to Week 12, and a key secondary of bowel‑movement change; a 16-week randomized period precedes a 104-week open‑label extension that will also track progression‑free survival.

The program’s strength rests on prior Phase 2 signals of rapid, sustained symptom reductions and the trial’s randomized, controlled design; however, regulatory and clinical readouts depend strictly on the blinded primary endpoint at Week 12 and long‑term safety/tumor control in the OLE. Watch enrollment pace across 2025 and 2026, topline efficacy at the Week 12 analysis, and any safety signals during the 104-week extension as the key near‑ to mid‑term milestones.

CAREFNDR underscores the potential clinical value of paltusotine beyond acromegaly, and demonstrates progress in Crinetics’ commitment to addressing unmet needs in the neuroendocrine tumor community

 SAN DIEGO, Nov. 20, 2025 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today announced the first patient has been randomized in the pivotal Phase 3 CAREFNDR trial, a multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of once-daily, oral paltusotine in adults with carcinoid syndrome due to well-differentiated neuroendocrine tumors. The Phase 3 study builds on positive Phase 2 data in which paltusotine demonstrated rapid and sustained reductions in the frequency and severity of carcinoid syndrome symptoms, including flushing episodes and bowel movements.

“Patients with carcinoid syndrome need a treatment option that can consistently manage symptoms without the burden of painful monthly injections,” said Dana Pizzuti, M.D., Chief Medical and Development Officer of Crinetics. “Based on our encouraging Phase 2 results and data from our open-label extension, we believe paltusotine has the potential to transform the treatment landscape with a once-daily, oral therapy that may offer meaningful benefits for patients managing the challenging day-to-day impacts of carcinoid syndrome. The initiation of our Phase 3 CAREFNDR trial represents a significant milestone in our commitment to address this critical unmet need.”

The Phase 3 study is designed to enroll 141 adults, both naïve and previously treated patients, with carcinoid syndrome. Participants will be randomized in a 2:1 ratio to receive either once-daily paltusotine 80 mg or matching placebo. The primary endpoint will measure the change in flushing episodes per day from baseline to Week 12, with change in bowel movements per day as a key secondary endpoint. Following the 16-week randomized controlled period, the trial includes a 104-week open-label extension (OLE) to evaluate long-term efficacy, safety and additional clinical outcomes. The OLE will also monitor long-term tumor control (progression free survival).

The Phase 3 CAREFNDR trial represents the latest step in Crinetics' goal of expanding the value of PALSONIFY™ (paltusotine) beyond its lead indication for the treatment of acromegaly. Crinetics is also investigating meeting the unmet needs of NETs patients through CRN09682, the first candidate from its nonpeptide drug conjugate platform. CRN09682, an investigational anti-tumor candidate targeting SST2-expressing neuroendocrine and other solid tumors, received Investigational New Drug clearance earlier this year. This broader development strategy reflects Crinetics' dedication to developing transformative therapies that address serious endocrine disorders and endocrine-related cancers.

For more information about the CAREFNDR trial, visit https://carefndr.com/. Global enrollment in CAREFNDR is expected throughout 2025 and 2026.

About Paltusotine
Paltusotine, a selectively-targeted somatostatin receptor type 2 (SST2) nonpeptide, is in Phase 3 clinical development for carcinoid syndrome associated with neuroendocrine tumors (CAREFNDR). Results from a Phase 2 study in carcinoid syndrome demonstrated rapid and sustained reductions in flushing episodes and bowel movement frequency, which are the most common symptoms of carcinoid syndrome. PALSONIFY™ (paltusotine) is currently approved in the U.S. for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option.

About Carcinoid Syndrome
Carcinoid syndrome is found in approximately 20% of patients with neuroendocrine tumors (NETs). NETs are a rare, slow-growing type of cancer that arise most often in the digestive tract. When these tumors metastasize to the liver, carcinoid syndrome can occur and is most commonly characterized by diarrhea and flushing. While injectable depot somatostatin receptor ligand therapies are mainstay treatments for carcinoid syndrome, these injections are associated with considerable treatment burden and offer inadequate relief of carcinoid syndrome symptoms for many patients.

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 investigational candidate atumelnant, which is currently in late-stage development for congenital adrenal hyperplasia and ACTH-dependent Cushing’s syndrome. 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 approval of additional product candidates in our pipeline; the plans and timelines for the clinical development of paltusotine for the treatment of carcinoid syndrome, including the therapeutic potential and clinical benefits or safety profiles thereof and the timeline for global enrollment for CAREFNDR; or the therapeutic potential, clinical benefits or safety profiles for atumelnant or our development candidates, including their potential 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, data that we report may change following completion or a more comprehensive review of the data related to the clinical studies, and the FDA and other regulatory authorities may not agree with our interpretation of such results; 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, 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; the success of Crinetics’ clinical studies and nonclinical studies; regulatory developments or political changes, including 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 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, 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 Nov 20, 2025 about the CAREFNDR trial?

Crinetics announced the first patient randomized in the pivotal Phase 3 CAREFNDR trial of once-daily oral paltusotine for carcinoid syndrome.

How many patients will be enrolled in the CRNX CAREFNDR Phase 3 trial and what is the randomization?

The trial is designed to enroll 141 adults randomized in a 2:1 ratio to paltusotine 80 mg or matching placebo.

What are the primary and key secondary endpoints in Crinetics' CAREFNDR (CRNX) trial?

The primary endpoint is change in flushing episodes per day from baseline to Week 12; a key secondary endpoint is change in bowel movements per day.

Does the CRNX Phase 3 CAREFNDR trial include long-term follow-up?

Yes; after a 16-week randomized period the trial includes a 104-week open-label extension to evaluate long-term efficacy, safety and progression-free survival.

What dose of paltusotine is being tested in the CRNX CAREFNDR Phase 3 trial?

Participants randomized to active therapy will receive once-daily oral paltusotine 80 mg.

Where can investors find more information about Crinetics' CAREFNDR trial enrollment timeline?

Global enrollment for CAREFNDR is expected to continue throughout 2025 and 2026, and trial details are available at the CAREFNDR trial website.