Welcome to Crinetics Pharmaceuticals' Fourth Quarter and F ull Year 2025 Financial Results Conference Call. At this time, all participants are in listen only mode. Following management's prepared remarks, we will hold a question and answer session. In order to ask a question, please press star then one on your telephone. I'd now like to turn the call over to Gayathri Diwakar, Head of Investor Relations. Please go ahead. Thank you, operator. Good afternoon, everyone, thank you for joining us to discuss the fourth quarter and full year 2025 results. Today on the call, we have Dr. Scott Struthers, Founder and Chief Executive Officer, Dr. Alan Krasner, Chief Endocrinologist, and Toby Schilke, Chief Financial Officer. Also joining for the Q&A portion will be Isabel Kalofonos, Chief Commercial Officer. Please note there's a slide deck for today's presentation, which is in the Events and Presentation section of the Investors page on the Crinetics website. In addition, a press release was issued earlier today and is also available on the corporate website. As a reminder, we'll be making forward-looking statements, and I invite you to learn more about the risks and uncertainties associated with these statements as disclosed in our SEC filings. Such forward-looking statements are not a guarantee of performance, and the company's actual results could differ materially from those stated or implied in such statements due to risks and uncertainties associated with the company's business. In particular, today we'll be reviewing launch progress to date, our commercialization plan, as well as estimates relating to market size, future performance, and other data about the acromegaly market, which are all necessarily subject to a high degree of uncertainty and risk. These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's news release, the company's other news releases and Crinetics SEC filings, including its annual report on Form 10-K and quarterly report on Form 10-Q. I would also like to specify that the content of this conference call contains time-sensitive information that's accurate only as of this live broadcast. Crinetics takes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. With that, I'll hand the call over to Scott. Thank you, Gayathri, and thank you all for joining us today. 2025 was a breakout year for Crinetics. We're transitioning from building a pipeline to building a business. In 2025, we successfully launched our first commercial product with a label that reflects its ability to become the preferred medical treatment for acromegaly. PALSONIFY uptake continues to grow. We presented compelling phase II data on our second late-stage candidate that illustrates its potential to be the preferred medical treatment for congenital adrenal hyperplasia, or CAH, and Cushing's disease. Atumelnant phase III studies in both adult and pediatric participants with CAH are underway. Today, we will tell you about its phase II/III study in Cushing's disease. The first candidate from our new nonpeptide drug conjugate program, CRN09682, has begun the dose escalation phase of a phase I/II study in a broad basket of people with SST2-expressing tumors. With this growing pipeline and the support of our strong balance sheet, we are now focusing on building a successful commercial business that will grow into the leading endocrinology company. Turning to Slide five, before I turn the call over to Alan to talk about the Atumelnant development program in Cushing's disease, let me take a few minutes to review results from the PALSONIFY launch. As we previously shared, in Q4, we received more than 200 enrollment forms. As a reminder, this included all 22 U.S. participants in the open label extension studies of the clinical program. We're effectively getting the word out about PALSONIFY. More than 125 unique prescribers in both community and pituitary treatment center practices have entrusted the treatment of their patients to PALSONIFY. Finally, we're making significant progress with payers. As we announced in January, we are seeing early and encouraging formulary momentum. Payers recognize the transformative value we're bringing to the acromegaly community. We are already securing wins with some of the top plans in the country, adding PALSONIFY to their formulary with straightforward prior authorization written directly to our label and no step edits. In the interim, we expect to continue seeing reimbursement through the medical exceptions process for patients from all payer types, including all government payers. Turning to Slide six, with the launch of PALSONIFY in the U.S., we have built a fully integrated and highly capable commercial enterprise. Our sales professionals are in physician practices educating about PALSONIFY and the services Crinetics provides to patients and offices, including help from our nurse educators and field reimbursement specialists. Our efficacy-first messaging, shown on our HCP side on the left side of this slide, is resonating with healthcare providers, and they understand the importance of symptom control as well as biochemical control. Our medical affairs team is there to help with deeper scientific and medical support for providers. We're presenting data on PALSONIFY and the rest of our pipeline at regional and international endocrinology conferences every month. CrinetiCARE is online and staffed by nurses to help patients navigate their acromegaly healthcare. Our first patient ambassadors, two of whom are shown on the right side of this slide, have been deployed to provide patient-to-patient conversations and testimonials. Our market access team is ensuring that all patients can get access to PALSONIFY. I'm very proud of the great team we've built and their passionate dedication to serving our patients. Every day, they're working hard, spreading the word and helping people with acromegaly get access to PALSONIFY. Our goal for PALSONIFY is to become the new standard of care for people with acromegaly, and we are well on our way. This is about more than just the launch of PALSONIFY. This is about building, testing, refining, and honing an enterprise to launch many new innovative pharmaceuticals to come from our pipeline. This is the core of the team that will launch paltusotine for the treatment of carcinoid syndrome, Atumelnant for CAH and Cushing's, and our other pipeline candidates pending their own approvals. As I said, we're now in the stage of building a sustainable business to create, develop, and deliver novel therapeutics using the tools of endocrinology. With that, I'll hand it over to our Chief Endocrinologist, Alan Krasner, to talk about the pipeline and the upcoming Cushing study in particular. Alan? Thank you, Scott. As seen on Slide eight, our late-stage pipeline is guided by compelling science and the ability to develop innovative candidates in-house. My very talented colleagues at Crinetics design novel molecules which are rationally aimed at the key targets of endocrine disease. These drug candidates have consistently demonstrated the intended pharmacology in healthy human volunteers and in patients. Paltusotine is already approved in the U.S. for the treatment of acromegaly. We are in phase III evaluating paltusotine for the control of carcinoid syndrome. We are also actively enrolling patients in both the later-stage studies of Atumelnant in adult and pediatric patients with congenital adrenal hyperplasia, or CAH, and in the phase I study of our novel nonpeptide drug conjugate, CRN09682, in patients with SST2-expressing tumors. Today, I want to focus on Atumelnant and why we believe ACTH antagonism is a very promising approach for both CAH and ACTH-dependent Cushing's syndrome, or ADCS. ADCS is a rare but devastating disease that endocrinologists will tell you is among the most difficult diseases to treat medically. The multitude of symptoms and disfiguring physical changes that occur in the body can be overwhelming. If untreated, ADCS results in significant morbidity and premature mortality. We hear from patients with ADCS that they feel a profound loss of control, which may reflect the unstable nature of this disease characterized by unpredictable exacerbation patterns. There are also often difficult years leading to a clear diagnosis, followed by cycling through many different treatment options, not to mention unrelenting financial, psychological, physical, and emotional burdens. Many patients with ADCS are very sick, and the risk-benefit profiles of existing medical therapies are not ideal for the long-term control of this disease. Although the first-line treatment for ADCS is attempted surgical removal of the causative tumor, many patients are not cured by surgery. Uncured patients typically undergo attempts at medical therapy, but predictable prevention of disease exacerbation cycles at tolerable doses can be difficult to achieve. Often, patients need to undergo repeat pituitary surgeries, radiotherapy, or in the most severe cases, bilateral adrenalectomy. There remains a significant unmet need for a simple and reliable medical treatment for this life-threatening condition. This is why we are eager to proceed with the research necessary to evaluate whether Atumelnant might represent a significant step forward for the many patients who have been waiting for a new, dependable approach. Moving on to Slide 10. Here we see a more detailed view of the cause of ADCS and Atumelnant's mechanism of action. Cortisol is an essential glucocorticoid hormone produced in the adrenal glands. Its main purpose is to make it possible for our bodies to cope with any kind of stress, including illness or injury. Although we can't live without it, if we are exposed to too much cortisol, we can get very sick. Exposure to too much cortisol or cortisol-like medication is called Cushing's syndrome. Cushing's syndrome is most commonly caused by taking too much exogenous glucocorticoid prescribed for a variety of conditions. However, Cushing's syndrome can also arise from endogenous or spontaneously occurring causes. Most endogenous Cushing's syndrome is caused by overproduction of ACTH by pituitary gland tumors. The normal function of ACTH is to stimulate the adrenal glands to produce more cortisol, and it stimulates growth of the glands. Sometimes, tumors that secrete too much ACTH arise outside the pituitary gland. When this happens, it is called ectopic ACTH syndrome. The key driver in both pituitary disease and ectopic ACTH syndrome is ACTH, and together these conditions are called ACTH-dependent Cushing's syndrome. These tumors secrete ACTH autonomously, which means they do not depend on CRF secretion to drive disease, and therefore ADCS would not respond to CRF receptor blockers. For nearly a century since the discovery of ACTH, blocking the ACTH effect at the adrenals has been a long-sought fundamental treatment target for ACTH-dependent Cushing's syndrome. Atumelnant is a once-daily oral tablet and is the first ACTH receptor antagonist tested in humans for the treatment of ACTH-mediated disease. As you know, we have already reported promising phase II results from the studies evaluating Atumelnant for the treatment of another ACTH-mediated disease, congenital adrenal hyperplasia. Now let's focus on ADCS. Turning to Slide 11. In June 2024, we reported initial results from an ongoing collaboration with colleagues at the NIH. In this single center phase I-B/II-A study, participants with active ADCS were initially treated with 80 mg of oral Atumelnant once per day for 10 consecutive days with frequent measurements of biomarkers. These biomarker assessments included 24-hour urine collections for free cortisol or UFC, which is the recommended primary endpoint for registrational trials in Cushing's disease. UFC responses occurred within days of starting Atumelnant. The magnitude and speed of efficacy in this disease is unprecedented and if confirmed in longer term trials, Atumelnant could represent that single and reliable medical treatment greatly needed by people suffering with ADCS. In the NIH study, Atumelnant was generally well tolerated. All patients experienced a decline in serum cortisol below five micrograms per deciliter. Although these patients were minimally symptomatic, they were promptly started by protocol on low dose physiologic oral cortisol, otherwise known as hydrocortisone replacement therapy. All patients did well with no worrisome episodes of acute adrenal insufficiency, and most patients at the end of treatment still had normal urine-free cortisol levels even though they were taking small amounts of exogenous cortisol. Currently available cortisol-lowering drugs can cause glucocorticoid deficiency and some patients develop unpredictable episodes of acute adrenal insufficiency. For this reason, many physicians who treat ADCS are becoming increasingly interested in a proactive block and replace approach in which low doses of glucocorticoid are started earlier rather than later when initiating Cushing's medications. The idea is to prevent potentially dangerous episodes of adrenal insufficiency rather than waiting for them to happen. Determining what is the best way to replace glucocorticoid with Atumelnant treatment is an important consideration for our clinical development program. As in our acromegaly program, we strive to not only assess biochemical biomarker responses, but also the overall patient experience in our studies. We saw that participants in the NIH ADCS study experienced improvement in many of the myriad symptoms of Cushing's, even within the short treatment duration of that study. Since reporting these initial data, additional doses of Atumelnant have been explored at the NIH. We look forward to sharing these newer results at an upcoming medical meeting. We will also be initiating an operationally seamless global phase II/III study in the first half of this year, the design of which I will now review. EQUILIBRIUM ADCS is a seamless phase II/III study, which allows us to capture the many operational efficiencies of continuing sites opened in the phase II part of the study into the phase III part. The purpose of the phase II is to evaluate safety and the efficacy of a range of doses of Atumelnant in patients with active ADCS over a treatment period of three months. Based on our short-term dosing data from the NIH study, it looks like a simple single dose of Atumelnant would very effectively and rapidly correct the excess cortisol output from the adrenals in most patients with ADCS. Now that we are entering phase II-B, it is important to confirm this with longer term dosing and to identify the right dose of Atumelnant to use in the confirmatory phase III part of the study. You can see that we are testing the dose range of 20 mg-80 mg per day of Atumelnant in the phase II segment. We are testing lower doses than those used initially in the proof of concept NIH study. This is a testament to the potency of this unique mechanism of action. The 20 mg dose is being studied in an open label arm in which glucocorticoid replacement can safely be used reactively only if needed based on the occurrence of a low serum cortisol result. The 40 mg and 80 mg doses will be evaluated in a randomized placebo-controlled segment of phase II. At these higher doses, we will be evaluating the utility of a proactive approach in which glucocorticoid replacement and Atumelnant will be initiated at the same time. Based on the results of the phase II part of the study, an Atumelnant dose and glucocorticoid replacement paradigm will be selected for the phase III part. The phase III part is powered to show a statistically significant difference in 24-hour urinary free cortisol output between the active treatment arm compared to the placebo arm. An open label extension or OLE long-term treatment segment is also included in the study. Overall, the EQUILIBRIUM ADCS study is designed for efficient and comprehensive assessment of the safety and efficacy of Atumelnant in the treatment of ADCS, a disease which historically has been among the most difficult to treat medically. We believe moving the century-old treatment paradigm forward is long overdue for these patients, and we are excited to get this important study started in the first half of this year. With that, I'll turn it to Toby to walk through our financial results. Thank you, Alan. Turning to Slide 14. Our financial results for the fourth quarter 2025 reflect our continued disciplined execution and strategic investment in advancing our pipeline and commercialization of PALSONIFY. In the fourth quarter, we recognized $6.2 million in total net revenue, consisting of $5.4 million in net product revenue from the U.S. commercial launch of PALSONIFY and $0.8 million from our licensing agreement with our Japanese partner, SKK. Our total revenue for full year 2025 was $7.7 million. Cost of product revenue in the fourth quarter was $1.1 million. Prior to PALSONIFY's approval in September, manufacturing costs were expensed through R&D at zero cost inventory. To date, we have only distributed zero cost inventory and expect to continue to do so for the next several quarters. The cost of product revenue from this quarter relates to the expansion of our commercial manufacturing capacity as well as the distribution and fulfillment costs of PALSONIFY. Our research and development expenses for the fourth quarter were $85.1 million, compared to $90.5 million in the third quarter. The decrease is a result of startup costs for our ongoing clinical studies that were recognized during the third quarter. Selling general and administrative expenses were $53.7 million for the fourth quarter, generally steady compared to the $52.3 million in the third quarter since our field force, commercial team, and corporate functions were already in place prior to approval. We used $326.2 million of total net cash for the full year 2025, reflecting continued clinical development and commercialization activities. This result was favorable relative to our guidance range of $340 million-$370 million, primarily due to working capital timing and a modest increase in cash flows from employee option proceeds during the fourth quarter. We ended 2025 with over $1 billion in cash equivalents, and investments. This does not include the net proceeds of $380 million from our January 2026 public offering. Immediately after our January 2026 public offering, our cash equivalents, and investments totaled approximately $1.4 billion. As of February 13th, 2026, we had approximately 104.7 million shares of common stock outstanding. On a fully diluted basis, we had 121 million shares outstanding. This includes our outstanding options, unvested restricted stock units, and shares expected to be purchased under our employee stock purchase plan. Moving to Slide 15. For 2026, we expect GAAP operating expenses to be between $600 million and $650 million. We expect non-GAAP operating expenses, which exclude cost of revenue, stock-based compensation, depreciation, and amortization to be between $480 million and $520 million. The anticipated increase in operating expenses relative to 2025 reflects the ongoing investment in the recently initiated clinical trials as well as the inclusion of a full year of commercialization activities supporting PALSONIFY. Based on our current operating plans and cash position, we believe that existing cash and investments will be sufficient to fund our operations into 2030. This provides us with significant runway to execute on the commercialization of PALSONIFY, pivotal readouts for the ongoing clinical trials in carcinoid syndrome, adult CAH, pediatric CAH, and ADCS, and to achieve proof of concept for 9682. I'll now turn the call back to Scott for some closing remarks. Thank you, Toby. To wrap up, Crinetics is well positioned for an exceptional 2026. We're simultaneously executing across our entire portfolio. We're driving the U.S. launch of PALSONIFY while actively advancing our global regulatory path. On that front, we're pleased to announce that today we received a positive CHMP opinion for PALSONIFY in the treatment of acromegaly, a milestone that reflects both the strength of our data and the potential benefit for patients in the E.U. In addition, we continue advancing clinical trials of paltusotine, Atumelnant, and our novel nonpeptide drug conjugate, CRN09682 across multiple endocrinology and oncology indications. Finally, in discovery, we're rapidly advancing our early-stage assets to fuel the next wave of growth. We remain committed as ever to transforming the lives of people with endocrine diseases and creating long-term sustainable value for all of our stakeholders. Finally, I'd like to say that 2025 was a great year. Thank you to everyone who helped us achieve our most substantial year yet. With that, I'll turn it back to the operator to begin Q. & A. Operator? Thank you. If you would like to ask a question, please press star followed by one on your telephone keypad. If you would like to withdraw your question, please press star followed by two. When preparing to ask your question, please ensure your device is unmuted locally. First question comes from Maxwell Skor with Morgan Stanley. Your line is open. Please go ahead. Great. Thank you very much for taking my question, and congrats on all the progress. Now that you've outlined the phase II/III design today, were there any key learnings from the Lancet, GRACE data or the FDA's relacorilant CRL that informed how you're thinking about clinically meaningful endpoints or just overall study structure? Thank you. Thanks, Max. I'll let Alan handle that question. Thank you. Well, you know, actually, the basic structure of a Cushing's disease study is well precedented. The primary endpoint, for example, is known to be normalization of urine-free cortisol for drugs in which you can measure cortisol as a, as the biochemical marker for Cushing's disease activity. Relacorilant and other glucocorticoid receptor antagonists actually prevent endocrinologists from using cortisol as a marker of activity because they block the glucocorticoid receptor and result in compensatory rises in cortisol. It's a different metric, I would have to say. In the case of the glucocorticoid receptor antagonist, you have to use sort of downstream surrogates like measuring the improvement in glycemia that can be seen when you treat Cushing's. In our case, I think we can measure both cortisol itself, as well as important corollary clinical outcome benefits like improvements in glucose and improvements in blood pressure, et cetera. Great. Thank you. We now turn to Yasmeen Rahimi with Piper Sandler. Your line is open. Please go ahead. Good afternoon, team. Congrats on the EQUILIBRIUM study initiating and the very innovative design. Just wanted to ask a question on PALSONIFY. Would love to maybe get color around how maybe starting script shaped up into January and February and if you saw any trends, just as trends going from December to the beginning of the year. I'll jump back into the queue. Yeah. Thanks, Yas. Look, I'm super pleased with the launch of PALSONIFY. I'm particularly pleased by the stories we're hearing back from prescribers and patients and the real-world experiences that are starting to accumulate. I think you'll start hearing about those experiences now that people are out there starting to think about case series and other types of reports, and I look forward to that, you know, throughout the year and in the coming years actually. I don't really wanna get into quantitative comments on trends for the quarter. You know, it's still early days, and we have a lot of work to do. Generally, I'm very pleased that patients are starting to benefit from the hard work we've put into this for the last many, many years. Yes, and as Yasmeen. Thank you very much. We are very pleased because our strategy is really resonating. Efficacy first is an important message for us. What we are hearing back from physicians and patients is that particularly the patterns of action and the symptom controls are resonating. The fact that it works in two to four weeks is really allowing the physicians to have a early positive experience as well as the patients. We are focusing on execution across the board, activating the patients, activating the physicians, and continue to engage with payers successfully. Thank you. Thank you. We now turn to Alex Thompson with Stifel. Your line is open. Please go ahead. Hey, great. Thanks for taking our question and congrats on the quarter as well. Maybe as a follow-up here, could you comment as to whether you think sort of this 200 enrollment form, that you recorded in four Q is a reasonable run rate moving forward? Is that bullish, or are you seeing consistency with what you saw in four Q? If you're not able to sort of answer that, can you talk about the sort of time from enrollment form to commercial therapy? Thanks. Yeah. Toby, why don't you respond? I think, you know, it's premature to sort of comment on extrapolating that 200 enrollment form. We feel very pleased about that number, and just because there's a lot of headwinds and tailwinds that you have. You have at the beginning of a launch, there's some patients who were on our open label extension program who came on to commercial supply. You have kind of continued momentum through increased field interactions going forward. I think on your second question, you talked about the time it takes from the Quick Start patient program as well? Yeah. I guess, you know, from when you receive your enrollment form to when you're getting on reimbursed therapy or on Quick Start, how long is that? Yeah. You know, we haven't really guided to that. What we're really pleased to say right now is that at the initial point of kind of measurement, about 50% of patients are reimbursed for commercial or Medicare, Medicaid, and the other 50% go on to that Quick Start program. We have a few touch points along that way. Because it's relatively early days in the launch, it's difficult to kinda predict how long those patients will come off Quick Start and be on reimbursed care. The first bottle they get is for 30 days, and then we have check-ins every 15 days thereafter. Thank you. We now turn to Tyler Van Buren with TD Cowen. Your line is open. Please go ahead. Hey, guys. Thanks for taking the question. Congrats on the progress, and enjoyed the prepared remarks on ADCS. Just maybe I could fit in one more on the launch, but a little bit less, so on the near term, a little bit more on the medium term. Just over the course of the year, what do you expect the cadence to look like? Is it gonna be lumpy because it's kind of an orphan launch Or is it gonna be more linear or exponential as we exit the year? Curious to get your thoughts on that. A second, since you mentioned the zero cost inventory, can you tell us what level of sales that inventory equates to roughly? Yeah. Thanks, Tyler. You know, so I did a lot of biophysics earlier in my career, and we were trying to fit curves to data points. I can say I suspect it'll be lumpy, but I don't think there's enough data to start fitting an exponential or a linear curve to this yet. You know, the team's out there every day. We're getting great uptake around the country with a broad set of prescribers, and they're getting more comfortable with it. We've got other things coming up. It's, you know, we had a pretty good snowstorm this last week, and that showed up a little bit. I think it'll be lumpy and, you know, we're experimentalists at this point, not theoreticians. You wanna comment a little more, Isabel? Yes. You know, we are on target for our goal to become the number one acromegaly treatment in the future, and we are continued in our execution that we had described before. First, we are focusing on the switching of the market and live patients, then we wanna focus on expanding the market. We don't only want to have patients on PALSONIFY, but we wanna help transform care and elevate care as a premier endocrinology company that we wanna be. We wanna be the partner of choice. Many patients have lost hope and are not on treatment that we think we can bring them back. As physicians and patients gain experience with our drug, and given that the drug is delivering even better in the clinical trials in the real world, we expect that we'll be able to continue to expand the marketplace. Maybe to your second question, Tyler, on the cost of product revenue. You know, I'm so glad you asked that question. It always makes the CFO happy. We have a little bit additional details on our Form 10-K that we just recently filed. As you note in our income statement, we have about $1 million of cost of product revenue noted in fourth quarter. In Page 72 and thereafter on our Form 10-K, we broke that down a little bit more, and we said that there was about $826,000 related to manufacturing readiness and a second slot supplier qualification. Another $250,000 of that $1 million allocated towards sort of packaging, distribution, fulfillment. We noted also that there was less than $100,000 related to the zero cost inventory that I referred to in my prepared remarks. Looking forward, we kind of expect cost of product revenue. If you were to do apples to apples, you would see of that $5.4 million, you would see about that $250,000, and that less than $100,000 of being cost of product revenue. That's awesome. Thank you. We now turn to Gavin Clark-Gartner with Evercore ISI. Your line is open. Please go ahead. Hey, this is Yash on for Gavin. Thank you for taking the question. Just a quick one on PALSONIFY. We were just wondering how payer dynamics are looking so far, and specifically if you're noticing any significant pushback on the payer side or new cadence in terms of step edits to get on PALSONIFY. Thanks. Thank you. We are very pleased with how market access is progressing, and we don't see real barriers to treatment. That's very positive. We have most of our coverage already based on our labels, so all our product authorizations are proceeding, and we're proceeding well with medical exceptions as well. We continue to monitor the marketplace and engage with the payers. If we ever have an accept edit, we move very quickly from the coverage of treatment to a clinical review, and that had moved very fast in the process. So far as we announced in fourth quarter, 50% of the claims have been pre-reimbursed and 60% of them moved into Quick Start, and we remain committed to move that Quick Start in less than the average of rare diseases, less than 67 days. Great. Thank you. We now turn to Brian Skorney with Baird. Your line is open. Please go ahead. Hi, team. Thanks for the question. This is Luke on for Brian. On the ADCS study, there's a mention that the phase III endpoints may change based on phase II 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? Yeah. Thanks for the question. I think one of the main purposes of the phase II part is to find the right dose for phase III. In phase III, it would be a traditional perspective, parallel group, placebo-controlled comparison trial. The primary endpoint is pretty much set by the FDA, and that is the% of patients who achieve a normal urine free cortisol at the end of treatment. This is a 24-hour urine collection which sort of measures the integrated output of cortisol. Over that period of time. The hurdle for the study is to show there's a statistically significant increase to proportion of patients who achieve that goal on drug versus placebo. Yes. What we will learn from phase II is the dose. It is very unlikely we would change that primary endpoint, however, for phase III. Our next question comes from Joe Schwartz with Leerink Partners. Your line is open. Please go ahead. Hello, for Cornetta Zins. Thanks for the update. I was actually curious on 9682, and wondering if you can give us any insight into how you're selecting patients for the BRAVESST2 trial. Are you Do you have a working hypothesis for particular biologies 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? How do you hope to put it relative to current options? Thanks. Thanks, Joe. I gotta say 9682 is currently the apple of my eye. The compound is, you know, it's something we worked so hard on both from a concept and from, you know, a development and an optimization point of view. The patient selection is really very simple. We have a basket study with all kinds of different patients with somatostatin two receptor expressing tumors. The core criteria is they have to have on a somatostatin PET scan a higher density in tumors compared to the liver. They have to have progressive disease or, you know, why would they come into a clinical trial like this? We're very pleased that the reception by the community has been strong and the screening queue of patients is always there. So we're just working our way through it. In terms of preclinical models, you know, we showed some fabulous data with essentially lung cell, small cell lung carcinomas, which are a high-grade lung neuroendocrine tumor. We've done some other tumor models. You know, so many people have cured tumors in mice that we're now at the real point where we're looking at these different tumors in humans. The reason we designed this study is in such a broad way is we want to make sure we capture the different populations of patients who can benefit. As a reminder, it's not just neuroendocrine tumors, of which, you know, it'll range from relatively slow-growing neuroendocrine tumors, grade one or grade two, up to more aggressive grade two or three, and even up to neuroendocrine carcinomas or, like small cell lung is a very aggressive point of view. We'll also be looking for patients with meningiomas, which are almost always somatostatin receptor positive and often very difficult to treat. We'll be seeing perhaps some HR positive breast tumors, head and neck tumors. As we start working our way up the dose escalation, defining the tolerability profile, we may start to see some hints, but what we'll really look for is signals when we get into those expansion cohorts. It's, as you saw from the trial design, it really allows us to bring in any type of patient with SST2 positive tumors. Thank you. We now turn to Jon Wolleben with Citizens. Your line is open. Please go ahead. Hey, thanks for taking the question. A few on EQUILIBRIUM. Wondering how you're thinking about disclosure data from the phase II before the phase III, if the same patients are gonna be able to roll over. If you discussed at all with FDA a randomized withdrawal design and any advantages, disadvantages to it, what you landed on here. Thanks. Thanks for the question, Jon. Actually, the phase II part of the ADCS study is a three-month treatment experience, and when they finish that, they would be eligible to roll directly into an open label extension study, those patients. When we get into phase III, the same thing, it will be new patients who would also, when they complete that treatment period, be eligible to roll into the same open label extension. You know, we have certainly looked the history of development of drugs for Cushing's, and randomized withdrawal has been done in the past. For example, LINK-3 was one of the registrational trials for osilodrostat. A lot of methodologic problems with that kind of study design, I think, you know, most in the regulatory community would consider what we're planning here a prospective parallel group trial placebo-controlled as sort of the most definitive demonstration of drug safety and efficacy. There are carryover effects to worry about in randomized withdrawal designs that you do not have to confront here, I think this is just a cleaner study. Okay. When you have the phase II results, will we be learning just what dose you'll be moving forward, or will you guys be giving out data on the endpoints as well? I think it's a little early to be too specific, but I do think that we'll want to communicate phase II results at appropriate scientific conference. You know, it's important for the community to realize that the experiences we're seeing in phase II to help motivate investigators and patients to sign up for phase III. That makes sense. Thanks, Scott. Thanks, Alan. Thank you. We now turn to Katherine Dellorusso with LifeSci Capital. Your line is open. Please go ahead. Hi, team. Congrats on the quarter. Thanks for taking the questions. Maybe another one from us on the BRAVESST2 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. Then maybe on the bar for safety, what are your internal benchmarks that you're striving for? I guess how does that relate to whether or not you pursue a PRRT naive versus experienced patient populations going forward? Well, I'll take the last part. You want to take the first part, Alan? I don't think PRRT is a prerequisite or really that relevant for CRN09682. PRRT is great. It demonstrates that, you know, somatostatin targeted therapies are really important in these populations. It's not for everyone. It's not always easy to get. We're not requiring people to step through it or. Anyway, I just wanna remind folks that this is a much more democratic therapy than a radiotherapy. Let me just add, though, that, you know, in a phase I oncology trial, traditionally, you would be enrolling patients who've been through other therapies, including things like PRRT in the past. These are patients often who are sort of out of the conventional options at this point in time. I do agree, though, with time, in theory, this mechanism of action, it could be sort of a non-radioactive PRRT someday, where it is used sort of in at an earlier stage of treatment than we would test in a phase I trial. In terms of what we're looking for, you know, we're in a dose escalation phase now in this study, and, you know, traditionally in an oncology study, what we would stop when we get to a maximally tolerated dose. These days, you don't necessarily have to go that far. In general, we wanna see the primary sort of endpoint for this part of a study is safety and toleration. We hope this would be fairly well tolerated for all the reasons we've been through in terms of why this kind of approach might result in, you know, not only an effective, well targeted therapy but also a well-tolerated one. You know, of course, we also, as part of the clinical care for these patients with sort of advanced cancers, they will also be having regular imaging studies, CT scans or MRI scans, to measure the size of their tumors. We follow formal RECIST criteria to understand if there is stable disease, partial responses or any, you know, according to the standard RECIST criteria, we would classify this. This is kind of a long-term prospect, though. Many of these tumors are on the slow-growing side. That kind of response data will take time to evolve over time. Certainly, we hope to have enough information coming out of this dose escalation study to go into the expansion part of the protocol, where we would kind of enroll more patients with the most likely to respond tumors, including some of these non-neuroendocrine tumor SST2 positive kind of tumors that we know of, such as meningioma. I hope that's helpful. Yep, absolutely. Thank you. We now turn to Dennis Ding with Jefferies. Your line is open. Please go ahead. Hi. Thanks for taking my questions. I have two on the NDC. Number one, what's the big picture strategy here? 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 you would move aggressively into, or is your priority to remain mainly in endocrinology and in endocrine-related tumors? Number two, for the phase I, I'm assuming you'll get a lot of NETs. How does SST2 expression change in the second and third line? If there's any difference in patients who have had experience with Lutathera versus those who didn't? If you can comment on the ORR for chemo in this late line setting, that, you know, we should be thinking about once you go into dose expansion, that'd be helpful. Thank you. Thanks, Dennis. Yeah. This is Scott. I'll take the big picture and then hand it off to Alan for more about expression. I'm really interested in this whole notion of using small molecule targeting for a variety of payloads. I think it offers just some core benefits compared to antibody targeting or peptide targeting, for example. As you know, with an antibody targeting, you're always going to be limited to a relatively long time in circulation, you're going to be limited by the types of epitopes you can address, you're gonna be limited by bioconjugation reactions to the linkers and payloads that are suitable. All that goes away when you just stay with small molecule chemistry like 9682. We first pioneered this idea in the radiotherapy space and spun out Radionetics, which is doing very well, thank you very much. Now we're continuing in the non-peptide space for first neuroendocrine tumors, as you say. I do think because of the way the radio imaging is used and radiotherapies are used, the bulk of those patients in routine care are neuroendocrine tumor patients, but that's growing pretty rapidly outside of that. The general strategy is to see where the science and the medicine takes us. I expect this to take us outside of our core neuroendocrine tumors, which is 100% synergistic with the carcinoid syndrome program. As I think about it in discovery, we are just beginning with this platform, so I can imagine additional types of payloads, maybe targeting SST2 first, 'cause it may be that this payload may not be for all SST2 expressing tumors. We're also exploring other types of targeting because GPCRs that recognize these peptide hormones are often very difficult to target with antibodies. We're looking at various different types of payloads. What else can we do? It's a blue sky area of research, and I'm very excited to see where it goes. I talked for a little while, Alan, but maybe you wanna address about line of therapy and expression and things like that. Yeah. Yeah. It's a, it's a really good question. Is there any change in SST2 receptor expression over time as patients receive various treatments? What I can say is that one of the eligibility criteria for this phase I study is positive SST2 receptor expression as documented on clinical receptor nuclear medicine imaging studies, that DOTATATE kind of scan. We know- As part of the screening, not just historical. Correct. Patients have to have known SST2 expressing tumor at the time of enrollment into our study. We know they're still there in our patients. I think as a general rule of thumb, it may depend on what kind of tumor you're talking about, but certainly the well-differentiated neuroendocrine tumors, generally, the SST2 receptors hang around for a long time. Thanks. We now turn to Catherine Novack with JonesTrading. Your line is open. Please go ahead. Hi. Good afternoon, everyone. Thanks for taking my questions. Thinking about CAH, you know, now that prescribers have had about a year of experience with Crinetics, 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? Similarly, do you anticipate having different price points for pediatrics and adults? I just wondering what we can learn from their launch so far? Thanks, Catherine. I think it's premature to really think about pricing at this point in the game. We're definitely doing our work to make sure we illustrate the full potential value of the molecule in our clinical program. What I can take away from the Crinetics launch is it's the first new drug for CAH since glucocorticoids, and it's been doing quite well. I think there's a hunger for new agents. I think that, you know, based on the pharmacology we've seen so far, Atumelnant will be able to do things that no other agents can do for these patients. I'm excited to expand this in the open-label extension we have going now, where we should have, you know, 20 something patients, be able to talk about them at some point in the not too distant future. I'm got great enthusiasm from the investigators I've met and the patient communities I've met for our phase III program in CAH, I really look forward to being able to complete that enrollment and start talking about data as soon as we can. Fantastic, Scott. Thank you. We now turn to Douglas Tsao- Thanks. We, We, you know, we have some more juice to squeeze from that orange. We now turn to Douglas Tsao with H.C. Wainwright. Your line is open. Please go ahead. Thank you very much. Thanks for taking the question. Maybe Isabella, just as a start, I think you've indicated that about 50% of patients are initiating therapy on the Quick Start program. I'm just curious if you have any insight or perspective on how we should think about how that might evolve over the next year or a couple of years. You know, would you anticipate we sort of stay at that level or should it trend down? I have a follow-up on 9682. Thank you. Yes. You know, over time, the Quick Start program will be less prominent as we get more access, direct access, where in formularies. We're expecting that, you know. Perhaps for the next like 18 months we'll have the program, but eventually, you know, to transition to just paid treatments. That's how I see the evolution of the plan. Okay, great. Then, Scott, to your point that sort of 96 to 82 is sort of now the apple of your eye, and I think this is the most you've talked about sort of an interest in terms of expanding on this platform. I guess I'm just curious, you know, how we should think about or how you're thinking about sort of the pace of innovation on this side of the business versus, sort of your initial focus on sort of endocrinology. No, thanks, Doug. Great question. We are still really committed to endocrinology. Don't take this as anything other than, you know, the newest and shiniest drug in our pipeline, and I'm really looking forward to seeing something come from it. We are working very hard to expand the endocrine side of the business. One of the things I've been learning as we've launched and I've been doing ride-alongs with some of our salespeople and our MSLs is how useful it will be in the future for us to walk into an office and be able to talk to them about their various types of patients, their acromegaly patients, their Cushing's patients, their CAH patient. You know, some of them even see neuroendocrine tumor patients. I think there's a huge synergy there. Now as we start moving from neuroendocrine tumors into and carcinoid syndrome into perhaps treating the tumors themselves, you know, I just do wanna see where this technology can take us. It's early days. We're waiting to see how 9682 performs and what we can learn from it. It's a whole new platform, but, you know, we're planting seeds, and this tree should bear fruit one of these days. Okay, great. That's really helpful to hear. Thank you. Congrats on the progress. Thanks, Doug. Our final question today comes from Andy Chen with Wolfe Research. Your line is open. Please go ahead. Hey, thank you for taking the question. 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? If you have any commentary on whether you think certain patient segments are tougher to capture, that'd be great. Thank you. Yeah, no. I mean, we don't have a field force out there talking to docs about CAH. I think that's more a question for the folks out there with that drug. I will say that I do think the things we're learning about acromegaly and the acromegaly prescribers and the community endocrinologists, many of whom do see CAH patients, and the capabilities we're building are directly transferable to the CAH patient population. It's part of a whole synergy that we've sought to build both in our pipeline and then later in the marketplace by focusing on endocrinology, which is something that, you know, Alan and I have done our whole careers and many others here in the company have spent their whole careers on. We've consistently talked about we are not just a sponsor coming in with a new molecule and plan to be gone from endocrinology. We're a part of that community, both as sponsors of clinical trials and now selling drugs and also in research and collaborations. Yes, you know, for me, PALSONIFY is the beginning of the story, and you can see it's a highly differentiated profile all around. If you start looking at the competitive market in acromegaly, for instance, today, we published in the Journal of Clinical Endocrinology & Metabolism our indirect treatment comparison, where we show superiority, even a statistically significant superior to a place. We are prepared to deliver as well in our future molecules as well. This is just the beginning. Thank you. Ladies and gentlemen, this concludes our Q&A and today's Crinetics Pharmaceuticals fourth quarter and full year 2025 financial results. We'd like to thank you for your participation. You may now disconnect your lines.