Crinetics Pharmaceuticals (NASDAQ:CRNX) executives highlighted early commercial momentum for PALSONIFY, outlined a global phase II/III study plan for atumelnant in ACTH-dependent Cushing’s syndrome (ADCS), and reviewed fourth-quarter and full-year 2025 financial results during the company’s earnings call.
PALSONIFY launch: early prescriber adoption and payer progress
Chief Executive Officer Scott Struthers said 2025 marked a transition “from building a pipeline to building a business,” pointing to the U.S. launch of PALSONIFY as the company’s first commercial product. In the fourth quarter, Crinetics received “more than 200 enrollment forms,” which management noted included all 22 U.S. participants from the open-label extension studies in its clinical program.
On execution, the company described building an integrated commercial organization supported by sales, medical affairs, nurse educators, field reimbursement specialists, and its CrinetiCARE nurse-staffed support program. Chief Commercial Officer Isabel Kalofonos said feedback is centering on efficacy and symptom control, and she noted physicians and patients are responding to the drug’s observed “patterns of action and the symptom controls,” including that it “works in two to four weeks.”
Management was cautious about giving quantitative updates beyond the fourth quarter. Struthers declined to provide “quantitative comments on trends,” calling it “still early days.” CFO Toby Schilke also said it was “premature” to extrapolate the fourth-quarter enrollment form volume, citing mixed launch dynamics such as open-label extension patients transitioning to commercial supply.
On patient starts and coverage, Schilke said that at the company’s “initial point of kind of measurement,” about half of patients are reimbursed through commercial or government coverage, while the other half enter the company’s Quick Start program. He described the first bottle as a 30-day supply with check-ins every 15 days thereafter, while noting the company has not provided guidance on how long patients typically remain on Quick Start before transitioning to reimbursed therapy. Kalofonos added that over time Quick Start should become “less prominent” as formulary access expands, and she anticipated the program could remain in place “perhaps for the next like 18 months” before transitioning predominantly to paid treatment.
Atumelnant in ADCS: mechanism and a “seamless” phase II/III plan
Chief Endocrinologist Alan Krasner focused his remarks on atumelnant, which Crinetics is also studying in adult and pediatric congenital adrenal hyperplasia (CAH). Krasner described ADCS as a rare and difficult-to-treat condition in which medical therapies can have challenging risk-benefit profiles, and he emphasized the need for more reliable long-term disease control.
Krasner explained that ADCS is driven by excessive ACTH stimulating adrenal cortisol production and said atumelnant is “the first ACTH receptor antagonist tested in humans for the treatment of ACTH-mediated disease.” He characterized atumelnant as a once-daily oral tablet.
Discussing results from an NIH collaboration previously reported in June 2024, Krasner said participants with active ADCS received 80 mg once daily for 10 consecutive days, with 24-hour urinary free cortisol (UFC) among the measured biomarkers. He said UFC responses occurred within days and described the speed and magnitude of effect as “unprecedented,” while emphasizing the need for confirmation in longer-term trials. He also said atumelnant was “generally well tolerated” in the NIH study.
Krasner noted all patients experienced declines in serum cortisol below 5 micrograms per deciliter and, per protocol, were started promptly on low-dose physiologic oral cortisol (hydrocortisone) replacement. He said patients did well without “worrisome episodes of acute adrenal insufficiency,” and that most ended treatment with normal UFC levels even while taking small amounts of exogenous cortisol. He contrasted this with currently available cortisol-lowering therapies that can lead to glucocorticoid deficiency and unpredictable acute adrenal insufficiency, and he said the company is considering how best to use a “proactive block and replace approach” for glucocorticoid replacement with atumelnant.
Crinetics plans to initiate a global “operationally seamless” phase II/III study, EQUILIBRIUM ADCS, in the first half of the year. Krasner said the three-month phase II segment will evaluate safety and efficacy across a 20 mg to 80 mg daily dose range to identify the dose and glucocorticoid replacement paradigm for the confirmatory phase III portion. The 20 mg dose will be studied in an open-label arm with reactive glucocorticoid replacement if low serum cortisol occurs, while 40 mg and 80 mg will be evaluated in a randomized placebo-controlled phase II segment with a proactive replacement strategy initiated alongside atumelnant.
Phase III is designed to show a statistically significant difference between active drug and placebo in 24-hour UFC output, with an open-label extension included. In Q&A, Krasner said the primary endpoint for phase III is established by regulators and centers on the percentage of patients who achieve normal UFC at the end of treatment, while phase II is intended primarily to determine the appropriate dose for phase III.
Pipeline updates: paltusotine beyond acromegaly and CRN09682 in oncology
In addition to PALSONIFY, management reiterated that paltusotine is in phase III for carcinoid syndrome. The company also discussed CRN09682, the first candidate from its nonpeptide drug conjugate program, which has entered dose escalation in a phase I/II basket study in patients with SST2-expressing tumors.
Struthers said patient selection in the CRN09682 study is based on somatostatin PET scan criteria showing higher tumor uptake than liver, and participants must have progressive disease. He said the study is intended to capture signals across a broad range of SST2-positive tumors, including neuroendocrine tumors across grades, meningiomas, and other tumor types the company expects to explore as the program advances.
Financial results: Q4 revenue, expense levels, and cash runway
Schilke reported fourth-quarter 2025 total net revenue of $6.2 million, consisting of $5.4 million in U.S. net product revenue from PALSONIFY and $0.8 million from a licensing agreement with Japanese partner SKK. Full-year 2025 total revenue was $7.7 million.
Cost of product revenue in the fourth quarter was $1.1 million. Schilke said that prior to PALSONIFY’s September approval, manufacturing costs were expensed through R&D as “zero cost inventory,” and the company has distributed only zero cost inventory to date and expects to continue doing so for the next several quarters. He said fourth-quarter cost of product revenue reflected expansion of commercial manufacturing capacity along with distribution and fulfillment costs. Later in Q&A, he referenced the company’s Form 10-K, describing approximately $826,000 tied to manufacturing readiness and supplier qualification, about $250,000 for packaging/distribution/fulfillment, and less than $100,000 related to the zero cost inventory.
Fourth-quarter R&D expense was $85.1 million, down from $90.5 million in the third quarter due to clinical study startup costs recognized in Q3. SG&A expense was $53.7 million, roughly in line with $52.3 million in Q3, as the field force and commercial infrastructure were already in place before approval.
Crinetics used $326.2 million of total net cash in full-year 2025, which Schilke said was favorable to the company’s guidance range of $340 million to $370 million, driven by working capital timing and increased cash flows from employee option proceeds in the fourth quarter.
The company ended 2025 with over $1 billion in cash, cash equivalents, and investments, excluding $380 million in net proceeds from a January 2026 public offering. Schilke said that immediately after the offering, cash, cash equivalents, and investments totaled approximately $1.4 billion. As of Feb. 13, 2026, Crinetics had about 104.7 million shares of common stock outstanding, and 121 million shares on a fully diluted basis.
For 2026, Crinetics expects GAAP operating expenses of $600 million to $650 million and non-GAAP operating expenses of $480 million to $520 million, excluding cost of revenue, stock-based compensation, and depreciation and amortization. Management said the increase reflects recently initiated clinical trials and a full year of commercialization activity for PALSONIFY. Based on current operating plans and cash position, the company said it believes it can fund operations into 2030.
Regulatory update: positive CHMP opinion in Europe
In closing remarks, Struthers said Crinetics received a positive CHMP opinion for PALSONIFY in acromegaly, calling it a milestone supporting the company’s global regulatory plans. He added that Crinetics expects to advance clinical trials across paltusotine, atumelnant, and CRN09682, while continuing discovery efforts for earlier-stage assets.
About Crinetics Pharmaceuticals (NASDAQ:CRNX)
Crinetics Pharmaceuticals, Inc is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for rare endocrine diseases. The company’s proprietary platform leverages insights into hormone receptor signaling to design small-molecule candidates that address conditions driven by dysregulated hormone activity. Crinetics’ research efforts center on targeting somatostatin, vasopressin and other GPCR-mediated pathways with orally bioavailable molecules intended to improve patient convenience and adherence.
The company’s lead product candidate, paltusotine (formerly CRN04777), is a selective, non-peptide somatostatin receptor type 2 agonist being evaluated for the treatment of acromegaly and carcinoid syndrome diarrhea.
