Crinetics Pharmaceuticals, Inc. Q4 FY2025 earnings call

• Initiating operationally seamless global Phase 2-3 study in first half of 2026 for ADCS, testing dose range of 20 - 80 mg per day of etumelanin. - Fourth quarter 2025 financial results show continued disciplined execution and strategic investment in pipeline and commercialization of Pelsonify. - 2026 operating expense expectations reflect investment in clinical trials and commercialization of Pelsonify. - Received positive CHMP opinion for Pelsonify in treatment of acromegaly. - Advancing clinical trials of paltucetine, etimelnet, and CRN9682 across multiple indications. - Rapidly advancing early stage assets in discovery.

Fourth quarter 2025 net revenue was $6.2 million, with $5.4 million from U.S. commercial launch of Pelsonify and $0.8 million from licensing agreement with Japanese partner SKK. Full year 2025 revenue was $7.7 million. Cost of product revenue in fourth quarter was $1.1 million. R&D expenses in fourth quarter were $85.1 million, SG&A expenses were $53.7 million. For 2026, expected GAAP operating expenses between $600 - $650 million, non-GAAP operating expenses (excluding cost of revenue, stock-based compensation, depreciation and amortization) between $480 - $520 million.

• For 2026, expect GAAP operating expenses between $600 and $650 million. - Expect non-GAAP operating expenses (excluding cost of revenue, stock-based compensation, depreciation and amortization) between $480 and $520 million. - Believes existing cash and investments will be sufficient to fund operations into 2030. - Immediately after January 2026 public offering, cash, cash equivalents, and investments totaled approximately $1.4 billion.

Q: Now that you've outlined the Phase 2-3 design today, were there any key learnings from the Lancet GRACE data or the FDA's relic-correlant PRL that informed how you're thinking about clinically meaningful endpoints or just overall study structure?

A: The basic structure of a Cushing's disease study is well-precedented. Relacoralent and other glucocorticoid receptor antagonists prevent using cortisol as a marker of activity, so have to use downstream surrogates like improvement in glycemia.

Q: Just wanted to ask a question on Pelfontify. I would love to maybe get color around how maybe starting script shaped up into January and February. And if you saw any trends, just trends going from December to the beginning of the year.

A: Super pleased with launch of Pelsonify, hearing good stories from prescribers and patients. Don't want to get into quantitative comments on trends for the quarter as it's early days.

Q: Could you comment as to whether you think sort of this 200 enrollment form that you recorded in 4Q is a reasonable run rate moving forward? Is that bolus or are you seeing consistency with what you saw in 4Q? And if you're not able to sort of answer that, can you talk about the sort of time from enrollment form to commercial therapy?

A: Premature to comment on extrapolating 200 enrollment form. At initial point of measurement, about 50% of patients are reimbursed for commercial or Medicare, Medicaid, and 50% go on Quick Start program.

Q: What do you expect a cadence to look like for Pelsonify launch over the course of the year? Is it going to be lumpy because it's kind of an orphan launch? Or is it going to be more linear or exponential as we exit the year? And second, since you mentioned the zero cost inventory, can you tell us what level of sales that inventory equates to roughly?

A: Suspect it'll be lumpy. Cost of product revenue in fourth quarter was $1 million, broken down into manufacturing readiness, packaging distribution fulfillment, and less than $100,000 related to zero cost inventory.

Q: How pair dynamics are looking so far, and specifically if you're noticing any significant pushback on the pair side or new cadence in terms of step edits to get on Pelsonify?

A: Very pleased with market access progress, most coverage already based on labels, prior authorizations proceeding well.

Q: On the ADCS study, there's a mention that the phase three endpoints may change based on phase two data. I suppose is that something that's agreed on in advance with FDA? And can you help us understand what would trigger this change?

A: Main purpose of Phase 2 is to find right dose for Phase 3. Primary endpoint is percentage of patients who achieve a normal urine-free cortisol at end of treatment, unlikely to change for phase three.

Q: Can you give us any insight into how you're selecting patients for the BRAVIS trial? Are you, do you have a working hypothesis for particular biology that are more likely to respond to it based on the turnover of their disease or their SST receptor density? Have you detected any signals in preclinical data? And how do you hope to put it relative to current options?

A: Patient selection for BRAVIS trial is simple, basket study with all kinds of different patients with somatostatin-2 receptor-expressing tumors. Core criteria are higher density in tumors compared to liver on somatostatin PET scan and progressive disease. Preclinical data showed fabulous results with small cell lung carcinomas.

Q: Wondering how you're thinking about disclosure data from the phase two before the phase three, if the same patients are going to be able to roll over, and if you discussed it all with FDA, a randomized withdrawal design, and any advantages and disadvantages to what you landed on here.

A: Phase two part of ADCF study is three-month treatment experience, patients eligible to roll into open-label extension. Randomized withdrawal has methodologic problems, prospective parallel group trial placebo-controlled is cleaner.

Q: Maybe another one from us on the BRAVUS study. Just a couple of questions. I guess if you could comment on what we can expect from an initial data readout here in terms of, you know, metrics and cohorts we can expect to see. And then maybe on the bar for safety, what are your internal benchmarks that you're striving for? And I guess how does that relate to whether or not you pursue a PRRT-naive versus experienced patient populations going forward?

A: In dose escalation phase, traditionally in oncology study primary endpoint is safety and toleration. PRRT not a prerequisite for 9682.

Q: What's the big picture strategy here for NDC? And I'm curious if you plan to be a major player in oncology, like If you see good activity in HR-positive breast cancer or small cell, is that an area你 would move aggressively into, or is your priority to remain mainly in endocrinology and in endocrine-related tumors? And then number two, for the phase one, I'm assuming you'll get a lot of nets. So how does SST2 expression change in the second and third line, and there's any difference in patients who have had experience with Lutathera versus those who didn't? And if you can comment on the ORR for chemo in this late line setting that we should be thinking about once you go into dose expansion, that'd be helpful.

A: Big picture strategy is to use small molecule targeting for variety of payloads. Expect to move outside core neuroendocrine tumors. Patients have to have known SST2 expressing a tumor at time of enrollment into study.

Q: Thinking about CAH, you know, now that prescribers have had about a year of experience with chronicity, are you hearing anything from them about reimbursement or price point? Do you anticipate having similar pricing power when it comes to your launch in CAH? And similarly, do you anticipate having different price points for pediatrics and adults? Just wondering what we can learn from their launch so far.

A: Premature to think about pricing. Palsonify has highly differentiated profile, capabilities built for CAH patient population are transferable.

Q: I'm just curious if you have Any insight or perspective on how we should think about how the Quick Start program might evolve over the next year or a couple of years? You know, would你 anticipate we sort of stay at that level or should it trend down?

A: Over time, Quick Start program will be less prominent as access improves, expecting to transition to paid treatment within 18 months.

Q: Just curious if you can comment on your competition's growth, recent revenue trajectory in CAH. What do you think is happening here? Do you feel like you have a greater opportunity, or do you think you have a lesser opportunity given the recent trajectory? Do you think it's slowing down? And if you have any commentary on whether you think certain patient segments are tougher to capture, that'd be great.

A: Don't have field force talking to docs about CAH, capabilities built for acromegaly prescribers are transferable to CAH patient population.