Welcome to the Crinetics Pharmaceuticals Corporate Update 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 will now turn the call over to Gayathri Diwakar, Head of Investor Relations. Please go ahead. Thank you, Operator. Good morning, everyone, and thank you for joining us to discuss today's corporate update. On the call, we have Dr. Scott Struthers, Founder and Chief Executive Officer, and Dr. Alan Krasner, Chief Endocrinologist. Also joining for the Q&A portion will be Isabel Kalofonos, Chief Commercial Officer, Toby Schilke, Chief Financial Officer, and Dr. Garnett Howells, Global Product Leader. Please note there's a slide deck for today's presentation, which is in the Events and Presentations 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, slide two, 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, future performance, and other data about the acromegaly market, as well as plans for phase III studies for atumelnant, 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 reports on Form 10-Q. I'd also like to specify that the content of this conference call contains time-sensitive information that is 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 day of this conference call. With that, I'll hand the call over to Scott. Scott? Good morning. Thank you for joining us for today's update to kick off 2026. First, we're excited to share the great progress we've made on the Palsonify launch during its first full quarter after approval late in September. We hit the ground running, and the momentum we're seeing is exactly what this community needs. Second, atumelnant continues to demonstrate its potential to transform the treatment landscape for patients living with congenital adrenal hyperplasia, or CAH. Our goal has always been to set a new standard of care where patients do not have to choose between managing their excess adrenal androgens and enduring the side effects of high-dose steroids. The data we are sharing today brings us one step closer to making that reality for the thousands of people struggling with CAH. We believe the totality of the atumelnant data collected to date across healthy volunteers, Cushing's disease patients, and CAH patients demonstrates its robust benefit-risk profile. Today's update strengthens our conviction in the phase III CAH study and positions atumelnant to become the leading medical therapy for people struggling with CAH. We've proven that our discovery engine can deliver world-class science and that our development organization can deliver compelling data for regulatory approval. Now we're proving that we can deliver our products to patients across the U.S. and get reimbursed. Palsonify is just the first step in our journey to redefine endocrine care. atumelnant is the second step. As you'll see today, we are strongly positioned to turn this landmark year into sustained growth. Commercial execution remains our top priority for the company, so I want to take a few moments to review the exciting progress we've made on the first full quarter of the Palsonify launch. Turning to slide five, when we talk about 36,000 people living with acromegaly in the U.S., we aren't just looking at a market opportunity. We're looking at thousands of individual journeys that have been stalled by burdensome, inconsistent treatments. Many have abandoned medical care. Many more have not yet been diagnosed for the underlying cause of what has been troubling them. Our phase launch strategy for Palsonify is designed to meet these patients wherever they are, whether they're currently struggling with monthly injections or have been lost to the system entirely. At this point, we're early in the first phase. We're focusing intensely on the approximately 10,000 switch and treatment naive patients already actively managed by a healthcare provider. Succeeding here will bring experience, confidence, and voice to both patients and their care providers. In the second phase, we will identify and activate the approximately 9,000 patients who don't appear to be actively managing their acromegaly. We hope that some of these may have been surgically cured, but it's unlikely to be the case for most of them. This phase will begin later this year and build on the momentum from the first phase. Over time, our goal in the final phase is to accelerate the diagnostic process itself. It takes five to ten years to diagnose acromegaly, and during that time, damage accumulates. This is a daunting but very important challenge. We'll begin laying research groundwork this year to define potential approaches to solving this problem. Let us not forget that the success in these efforts will not just grow the markets for Palsonify. It will help thousands of people living with acromegaly get the care they need and deserve. Turning to slide six, our goal for Palsonify is to become the leading medical therapy for acromegaly. We believe that the metrics shown here demonstrate that we are off to a great start. From a patient perspective, the feedback has been strongly positive. Some patients were eagerly awaiting approval. They and others who were only more recently heard about Palsonify are starting to ask their HCPs for it. Others have heard about it from their HCPs and decided to give it a try. We are seeing people switching from injectable peptide depots and oral octreotide. We are seeing people receiving Palsonify as their first-ever medical therapy for their acromegaly. All of our 22 U.S.-based open-label extension patients have switched to commercial supplies. To date, we have processed more than 200 enrollment forms. On the provider side, we have healthy uptake across a broad base of prescribers in all regions of the country. Our messages of efficacy and speed of onset of action are resonating. Built on the strong execution of our commercial and medical teams, we now have more than 125 unique prescribers, with roughly 50% of them in smaller community-based practices and the rest practicing in pituitary treatment centers, or PTCs. This reflects our approach of deploying the field force both in the community and to the centers from the start. Over time, we expect this ratio to tilt further towards community prescribers, of which there are many more than prescribers in the PTC setting. Finally, our payer-facing team has been very active, meeting with all key payers. We've already secured early formulary inclusions. These were sooner than expected, given that this is not the typical time of year for payers to update their plans. Currently, we are pleased to see that with the help of our patient support program, Crineti Care, that roughly 50% of filled prescriptions are rapidly reimbursed before needing to ship a bridging supply through our QuickStart program. We are also pleased to see that the vast majority of prior authorizations are for 12 months, so the patients have a full year without worrying about their insurance for Palsonify. Finally, we're pleased to report that this activity has resulted in over $5 million in unaudited net Palsonify revenue for the fourth quarter. On slide seven, you'll see that while we're very pleased to have achieved the metrics of success above, it's the individual stories of how people have benefited from our efforts that resonate the most with us here at Crinetics. I've personally known some of these patients for years and seeing the clinical development of Palsonify translate into life-changing results for them is extremely meaningful. On this slide are stories of Megan, David, and Ashley. They are the first three ambassadors in our Palsonify Patient Ambassador program. At the start, ambassadors will have been on Palsonify anywhere from a few weeks to up to four years, and they are all excited to share with others about their experience both with Palsonify and navigating their healthcare journey as someone living with acromegaly. Patients want to hear from other patients, and we will ramp up this activity in 2026 as more and more patients have treatment experience on Palsonify and qualify to become ambassadors. Building on the success of the discovery, development, approval, and launch of Palsonify, now let's turn to our second candidate, atumelnant. On slide nine, a reminder that we designed atumelnant to transform the CAH treatment paradigm. Since CAH was first characterized, people living with this genetic disease have been trapped in a zero-sum game between the consequences of uncontrolled adrenal androgens and the Cushing's syndrome-like adverse consequences of exogenous excess glucocorticoids. The data we are sharing today demonstrates with atumelnant this trade-off could no longer be necessary. As a reminder, we added Cohort 4 to the phase II study to evaluate atumelnant's ability to lower A4 while tapering glucocorticoids to physiologic dosing levels and to assess dosing of atumelnant in the morning versus the evening. Alan will share the details, but at a high level, the findings from Cohort 4 are what we expected from our prior phase I and II results. Because of atumelnant's unique mechanism of action, it can block excess production of adrenal androgens even in the context of low physiologic replacement doses of glucocorticoids. These results, together with confirmatory results from the first patients reaching 13 weeks in the open-label extension of phase II, reinforce our conviction in the phase III Calm study in adults with CAH. All data so far point towards a highly differentiated profile that we anticipate will propel atumelnant to become the preferred medical therapy for the treatment of CAH after it is approved. Importantly, atumelnant continues to be well tolerated with a growing safety database, including more than 750 weeks of adult CAH patient exposure. To date, we have well over 200 participants exposed to atumelnant in a combination of healthy volunteer, clinical pharmacology, Cushing's, and CAH studies. We continue to be encouraged by the very favorable benefit-risk profile across the board. With that, I'll turn the call over to Alan to discuss today's atumelnant results in more detail. Alan? Thank you, Scott. Before we get into the data, I'd like to take a moment to briefly review atumelnant's unique mechanism of action and why it is an attractive approach for the treatment of CAH. For decades, the only way to reduce excess adrenal androgen production in this disease was to increase glucocorticoid doses to suppress ACTH production. Glucocorticoid treatment, though, is an inefficient means of reducing adrenal androgen, and unfortunately, many patients end up on high doses of glucocorticoid and still have high androgen levels. atumelnant is the first and only agent tested in humans that selectively blocks the ACTH receptor found only in the adrenal glands. The ACTH receptor is a single choke point in the system, which likely explains the potency seen with atumelnant to date. Data from the first three treatment cohorts from this phase II CAH study demonstrated that treatment with atumelnant results in marked androgen reductions when baseline glucocorticoid doses remain fixed. In addition, data from healthy volunteers in the phase I study showed that the ACTH antagonism provided by atumelnant could withstand huge surges of ACTH exposure. Based on the totality of data, we hypothesize that when glucocorticoid doses are reduced in the presence of atumelnant, the reduction in adrenal androgen levels would be sustained, and Cohort 4 is the first test of this hypothesis. In contrast, CRF1 antagonists, one of which is approved, can be circumvented through other pathways, most notably stimulation of ACTH production by arginine vasopressin. Slide 11 shows published phase III data from the study, which evaluated the approved CRF1 antagonist, crinecerfont, in adults with CAH who prior to the trial took high doses of glucocorticoid. We can see that androgens, as measured by androstenedione, or A4 levels, were reduced at one month when glucocorticoid doses were fixed. This reduction in androgen nearly evaporated after a period of glucocorticoid dose reduction from weeks four to 24, although A4 levels were still improved compared to placebo. Slide 12 shows our vision for atumelnant. We believe atumelnant will represent another level of care in which patients and their healthcare providers can pursue both goals of medical therapy and CAH, that is, achieving low physiologic doses of glucocorticoid replacement without losing the reduction in androgens. Furthermore, we believe atumelnant could be a treatment for the broadest possible spectrum of people with CAH who need treatment, for those who happen to be on high doses of glucocorticoids, but also those who have elevated levels of adrenal androgens regardless of glucocorticoid dose. Slide 13 explains why there are two goals for the treatment of CAH. Excess androgen can cause a host of problems, including infertility, acne, and polycythemia, or elevated red cell counts in males and females. In females, it is associated with menstrual disorders and hirsutism, or excessive hair growth. On the other hand, glucocorticoids, when used at supraphysiologic doses to treat high androgen levels, can cause their own panoply of medical problems, including diabetes, weight gain, osteoporosis, and cardiovascular disease. We have previously reported improvements in menstrual function and resolution of polycythemia even within the three-month treatment period of this phase II study. We will be carefully documenting clinical outcome improvements in the longer-term phase III CAH study getting underway. Here we see the phase II TouCAHn study, which was designed primarily to evaluate safety and to identify the doses of atumelnant which best lowered A4 levels in adult patients. The study evaluated three different atumelnant doses in patients with classical CAH who had elevated A4 levels while using supraphysiologic doses of glucocorticoid before the trial. Unfortunately, as we mentioned, patients suffering with high androgen levels despite high glucocorticoid doses are all too common in clinical practice. During the three-month treatment period, patients in cohorts one through three stayed on fixed doses of glucocorticoid based on the dose they were taking prior to the study. We have previously reported results from cohorts one through three, and we will review those results shortly. In Cohort 4, we are again using 80 mg per day of atumelnant as we did in cohort one. However, in Cohort 4, the protocol required glucocorticoid dose reductions to the physiologic range if tolerated. A major objective of Cohort 4 was to assess if A4 reductions seen with atumelnant would be sustained in the face of these glucocorticoid dose reductions. We also explored in this study whether the timing of the atumelnant dose affected A4 lowering. atumelnant was dosed in the morning in Cohort 4 and given in the evening in cohorts one through three. More on this later when we review the design of the phase III study. Today, we are newly reporting top-line results from Cohort 4, the final group to complete this study. 10 patients enrolled in this cohort, two withdrew consent after enrollment and therefore discontinued early. The A4 data in this cohort will be from the eight completers, but the safety data always include data from all dosed patients. Slide 15 shows the robust A4 declines we saw in all four cohorts despite all patients starting with very high A4 levels of baseline. It is notable that the A4 reduction we see in the new Cohort 4 is similar to what we saw at the same dose of atumelnant previously, despite the fact that glucocorticoid doses were reduced in Cohort 4. When looking across all four cohorts, we see the magnitude of response increasing with increased dose, which we will leverage in phase III, as we will see later. Furthermore, there was no discernible effect of dose timing on the magnitude of effect in this small set of patients. I'd also like to point out a technical factor which is very important when interpreting these data. The A4 blood samples in phase II were obtained before the morning glucocorticoid doses. These therefore represent the maximum A4 values that would be seen in the course of the day since they are furthest in time from the patient's previous glucocorticoid dose. In phase III, we will be measuring A4 after the morning glucocorticoid dose when these levels are lower. We'll review this further when we discuss phase III design. Slide 16 shows mean glucocorticoid doses and mean A4 levels over time in the Cohort 4 patients. A4 responded dramatically to atumelnant in the first two weeks, as we have seen in all the cohorts. Further, the A4 reduction in Cohort 4 did not rebound despite seven of eight patients having their glucocorticoid doses successfully reduced to the physiologic range. Mean glucocorticoid doses at baseline by chance happened to be a bit lower in this cohort compared to the others, but these glucocorticoid dose reductions are meaningful and represent yet another stress test that atumelnant passed. We previously shared data shown in this figure from the published CRF1 antagonist phase III trial. The lowered A4 achieved by crinecerfont during the first four weeks when glucocorticoid doses remained fixed were largely lost as GC doses were reduced from weeks four through 24. In slide 17, we can qualitatively see that the A4 reductions achieved with atumelnant within two weeks are sustained through 12 weeks. The baseline A4 levels in the atumelnant study were higher than those in the crinecerfont studies, so quantitative comparisons should be made with caution. However, the shapes of these curves appear to be very different, and if this holds true in the phase III trial, this could translate to a highly differentiated product profile for atumelnant. We also want to share an early data snapshot from the atumelnant open-label extension trial with you. Please note this is an ongoing study that has not yet completed enrolling participants. Participants were eligible for this trial if they completed one of the cohorts in the core phase II study, which includes Cohort 4. The starting dose of atumelnant was the same dose assigned in the core study. However, there was a gap between the end of the core study and the start of the OLE for most participants. As is the case with most OLE studies, here we are trying to simulate real-world clinical practice scenarios in which investigators would have control over both atumelnant and glucocorticoid doses. However, like the core phase II study, this protocol instructs investigators to lower glucocorticoid doses to the physiologic range as tolerated. Slide 19 shows A4 levels over time in the seven individual subjects who had at least 13 weeks of treatment in the OLE as of the data snapshot from last month. Please note all seven of these participants are continuing in the OLE. So far, across the three doses used at initiation, we are seeing a median 72% A4 reduction and impressive glucocorticoid dose reductions occurring within the short time of treatment covered so far. I would note that one patient treated with 80 mg seen in this slide is the first one who has been treated with atumelnant for longer than three months. I am intrigued by what appears to be a progressive decline in A4 after week 13 because this pattern is consistent with the idea that efficacy may improve with time. Recall that we have previously presented MRI data from this study showing adrenal gland volume reductions even within three months in these patients who have long-standing hyperplasia of the adrenal glands. This could translate to less androgen-producing capacity over time. Although we cannot make a conclusion from one patient curve, I eagerly await longer-term treatment data from this study and from the phase III study. Overall, the OLE data so far are quite convincing or quite encouraging, showing these patients are well along the way to achieving both goals of CAH treatment. This slide shows the most common adverse events reported in the four completed cohorts of the phase II core study. Overall, headache and fatigue were among the most common reported adverse events. These symptoms are commonly reported in this patient population. There were no hepatic transaminase adverse events in Cohort 4 or in the OLE. Not unexpectedly, in Cohort 4, two cases of glucocorticoid deficiency were reported. These reflected nonspecific symptoms believed to be a result of insufficient glucocorticoid dosing, which can be seen when these doses are reduced. One case of adrenal insufficiency in Cohort 4 also reflected similar symptoms with the addition of the objective finding of orthostatic changes in blood pressure. Across the cohorts, no adverse events were classified as serious. With greater than 750 weeks of combined patient exposure so far and over 200 individuals dosed, atumelnant has been well tolerated. There were no serious adverse events or discontinuations due to adverse events in the phase II core or OLE studies to date. As we have shared previously, the phase III Calm-CAH study is designed to evaluate the safety and efficacy of atumelnant. It is a 32-week randomized double-blind placebo-controlled trial with a targeted enrollment of 150 patients. This is the first major study in CAH in which the eligibility criteria include all patients with CAH who need therapy, including those who have elevated levels of adrenal androgens, elevated glucocorticoid doses, or both. The sample size is well powered to demonstrate a statistically significant difference between atumelnant versus placebo in the proportion of participants who achieve normal levels of A4 while being on a physiologic glucocorticoid dose. Quite simply, this primary endpoint reflects the real goals of medical therapy in CAH: sustained androgen reduction and low replacement doses of glucocorticoid. Like all Crinetics drug candidates, we aim to show that atumelnant is not only safe and uniquely effective but also a simple-to-use drug for the broadest possible spectrum of people who need treatment. This slide summarizes the many reasons why we have confidence in phase III. Firstly, based on the totality of clinical data, the starting atumelnant dose of 80 mg once per day is expected to achieve the primary endpoint therapeutic goals in many patients. However, the study does allow for an up-titration to 120 mg once per day for those who may need some additional A4 control. This relationship between dose and response is very reminiscent of the situation we encountered emerging from phase II with paltusotine, and we are employing a similar single-step up-titration option used successfully in the PATHFNDR phase III studies. In addition, the longer duration of the trial should allow plenty of time for patients to reduce their glucocorticoid doses to the physiologic range with the goal of avoiding glucocorticoid withdrawal symptoms. Also, atumelnant will have more time to reduce glandular hyperplasia, which, as we discussed, might translate to extended androgen lowering even after the acute effect we've already seen in our short-term trial. Participants in the phase III study will take their atumelnant dose in the evening to best match the timing of the maximal concentration of drug exposure to the normal ACTH surge that occurs early in the morning. The data from Cohort 4 presented today indicate that many patients would also succeed with morning dosing. However, it is possible that some individuals in a large group could see further benefit from nighttime dosing. As discussed earlier, in phase III, we will be measuring A4 after the participants take their morning glucocorticoid dose, which literature suggests should allow full androgen reduction to be seen. To summarize the clinical data, in Cohort 4, we have demonstrated a 67% reduction in A4 consistent with our earlier 80-milligram cohort. This A4 reduction was sustained while seven of eight participants reached physiologic glucocorticoid doses. There was no discernible impact of morning versus evening atumelnant dosing. The overall safety database shows that the drug continues to be well tolerated. Needless to say, we are all very excited about the phase III program that is already underway. With that, I'll turn it back to Scott for closing remarks. Thanks, Alan. You know, we often talk about the inflection point of a company transitioning to a commercial stage, but today you're looking at what it actually looks like in practice for Crinetics. 2025 was a landmark year for us, not just because we conceived, discovered, developed, and received approval for our first drug, but because we are now proving that we can deliver it to the patients who need it and get reimbursed. As we enter 2026, we're operating to advance our mission on all fronts. Our commercial engine is humming. The launch of Palsonify is winning because it treats the whole patient: biochemical control and symptom control. But look at the breadth of the pipeline behind that. It will follow the path built by Palsonify. Today's results from the TouCAHn study and its OLE illustrate the impact we can make for people living with CAH. Our phase III Calm-CAH and BALANCED-CAH trials target one uncompromising goal: healthy hormone levels for every patient, adult, and pediatric. We believe atumelnant will redefine the standard of care for CAH because we are treating the malfunctioning adrenal itself, reserving steroid use for physiologic replacement only. In parallel, paltusotine is advancing in phase III for the treatment of patients with carcinoid syndrome, and we're pioneering the next wave of targeted therapeutics with our NDC program led by CRN09682, currently in a phase I-2 trial for patients with SST2-expressing cancers. Today isn't just about one drug or one launch. It's about the emergence of a sustainable, independent, creative leader in endocrinology and the adjacent fields that endocrinology can impact. This is just our beginning. Thank you all for your continued support. Operator, we're now ready to start the Q&A portion of the call. Thank you. Absolutely. If you would like to ask a question, please press star followed by one on your telephone keypad. If for any reason you would like to remove your question, please press star followed by two. Again, to ask a question, please press star one. We do ask that you limit yourself to asking only one question. As a reminder, if you are using a speakerphone, please remember to pick up a handset before asking your question. Our first question will go to the line of Yasmeen Rahimi with Piper Sandler. Yasmeen, your line is open. Good morning, team. Congrats on the outstanding launch matrix as well as the CAH atumelnant data. I think that my first question is on the really remarkable 200 starting forms. The danger sometimes becomes that analysts and investors take the 200 over the quarter reported and think about linearity as we go into 1Q 2026 and beyond. Would really appreciate Isabel's and Toby's color and thoughts from Scott on how we should be thinking about sort of uptick in the first few quarters of this year, and I'll jump back in the queue. Thanks, Yas. Appreciate the comments. Yeah, let me let Toby take this for a second. Thanks, Yas. You know, we're really pleased to achieve this enrollments. You know, it's difficult at this point in time to extrapolate going forward. However, it is a really strong start, and it reflects the execution of the field team. It reflects the messaging that we've delivered upon leading with efficacy and the onset of, you know, symptom control for Palsonify, and we're really encouraged by what we're seeing in the first quarter launch. Thank you, Yasmeen. Our next question will go to the line of Gavin Clark-Gartner with Evercore ISI. Gavin, your line is open. Hey, guys. Congrats on the really great updates. Thanks for taking the question. I was just hoping for atumelnant and CAH that you could synthesize the case for why you believe that you will be able to drive commercial switches from Crinetics down the line. Like, what are the key attributes in the data here that will enable that? What other data will you be generating in phase III to make this case? Thank you. Yeah, well, thanks, Gavin. You know, it's still a little early, but the profile that's emerging is really a very strong case for atumelnant. In many ways, it's very reminiscent of the emergence of Palsonify in its class. If you look at, you know, what Palsonify was facing, it was a standard of care that really wasn't there. It wasn't where it could be. The one other oral competitor was BID. The things that have stood out for Palsonify, I think, also will stand out for atumelnant. First, we're seeing rapid, rapid decrease in adrenal androgens. Two weeks. Second, it's sustained. This not having to compromise between glucocorticoids and adrenal androgens, I think, is something that's really important. Third, we're measuring in phase II and in phase III. We didn't talk so much about it today, but when we reported the earlier data, we noted a whole bunch of different ways in which patients were feeling the effects of the drug and getting benefit even in this short 12-week period, and I think that will only continue to be an important factor in the phase III program where it's longer and larger numbers of patients, so you can start to see these, so not just treating the biochemistry, but the symptoms and the impacts of the disease. And finally, just a fairly mundane thing, but it sure is easier for me to take a drug once a day than twice a day, so I think that's just a simple little thing. Thank you, Gavin. Our next question will go to the line of Tyler Van Buren with TD Cowen. Tyler, your line is open. Hey, guys. Good morning. Congratulations on two great updates to kick off the new year. Tough to ask just one, but I'll ask one on, again, the Cohort 4 atumelnant data. So given that you tested a relatively rapid tapering of the GC dosing in Cohort 4, can you elaborate more on the transition to phase III when there's a more gradual GC tapering, what impact that might have, and also just the evidence suggesting a reduction in adrenal gland volume may result in further A4 lowering? Alan? Yeah. Thanks for the question. So, you know, three months, you're right to say, is kind of a short time to get a large group of people to reduce doses of glucocorticoid in this situation. Remember, these are patients who've been taking high doses of glucocorticoids for many, many years, if not all their lives. And we know that when you start out at a high dose and reduce that dose, patients' bodies who are used to the higher exposure to glucocorticoid, they can start to feel these nonspecific glucocorticoid withdrawal symptoms. And I was, even in this three-month study, a little worried that we might run across a lot of that in this period of time. However, as we see in our data, it actually was doable in most of these patients. Now, remember, this is a fairly small group of patients just in Cohort 4. When we get to phase III and we have 150 patients, we might need to go slower on that taper in order to get everyone used to the lower doses of glucocorticoid. But I'm quite confident the duration of the phase III trial, I think, leaves us plenty of time to do that safely and in a well-tolerated way. Yeah, you know, another thing I was surprised that we saw within three months with this ACTH antagonist that we reported previously is sometimes very dramatic reductions in the adrenal gland volumes. Remember, these are, by definition, overgrown hyperplastic adrenal glands, and they've been that way pretty much for the whole lives for these patients, and the fact that we can see structurally reduced volumes is impressive. We don't know that that correlates yet with biochemistry, but in theory, we will have less tissue manufacturing androgen over time of exposure with the drug when the adrenal glands do shrink. So we shall see with greater exposure and greater time and greater numbers of patients in phase III. But certainly, what we're seeing so far is very encouraging. Thank you, Tyler. Our next question will go to the line of Leland Gershell with Oppenheimer. Leland, your line is open. Great. Good morning. Thanks for the question and congrats from us also on the progress, both commercial and pipeline. Just one question on atumelnant. Great to see the GC reductions while maintaining androgen suppression, but just wondering, you know, with that one patient who wasn't able to, Scott, do you think that's just a question of dose response that if you used, you know, a bit more atumelnant, that the patient would be able to, or do you think that there'll just simply be some patients who, because of biology, perhaps because of high levels of ACTH, that those will outcompete the drug and maybe prevent them from being able to taper their glucocorticoids? Thanks. Yeah, thanks. And I think you're referring to that OLE patient who had a minimal effect, but notice they're on 40 mg. So. Was it about the patient who wasn't able to get the physiologic GC? Oh, is that what you meant, Leland? Sorry, I wasn't quite sure. Out of the seven out of eight. It's a seven out of eight. Yeah, exactly right. Yeah. Okay. Yeah, yeah, yeah. So now on that particular one, I think that's more just a timing issue than as much as anything else. But maybe you want to comment on? Yeah, this was a patient who had difficulty with symptoms of low glucocorticoid exposure, and it was determined the patient really shouldn't rapidly titrate down. We're following that same patient in the open-label extension, and we're already seeing with time the patient's been able to significantly reduce their glucocorticoid doses. So yeah, I mean, I think that's an example of why three months is a little bit short, even for everybody in a small group. Yeah. And so back to the mechanistic side of your question, that's why I thought you were talking about the OLE data where you noticed that one of the patients is, you know, had a very modest decline in A4 and they're only on 40 mg. So as part of that protocol, they'll be able to go up to 80 mg and then 120 mg if they need it. But mechanistically, there's no reason to believe that any patient with CAH should be somehow resistant to atumelnant. The adrenal gland, the adrenal cortex is dependent on ACTH signaling. atumelnant blocks that very effectively. And so that should lower activity of the ACTH signaling into the adrenal for anybody with CAH. And the question about, you know, are there just some patients with so much ACTH that they'll overcome this antagonism? I think we answered that very clearly in phase I, and I keep reminding people of it. But remember in phase I in our MAD portion of the study, also on 80 mg, that we saw a rise in ACTH with time as you lowered glucocorticoid negative feedback. And then we gave them this whopping dose of ACTH as an ACTH challenge test, which is far more than any CAH patient's going to see and probably even more than any ectopic ACTH secreting tumor's going to make. And we're still able to keep those patients adrenally insufficient. And so that's why I've guided all along that we were not worried about the ability of atumelnant to maintain adrenal suppression in the face of glucocorticoid lowering. But it's also nice to see the actual data. Thank you, Leland. Our next question will go to a line of Joe Schwartz with Leerink Partners. Joe, your line is open. Great. Thank you and congrats as well on the strong updates across the board. I was wondering if you could talk for a moment about the endpoints you're using to document potential clinical improvements for the patients who are being enrolled in CAH, which clinical manifestations might have the greatest potential to improve and which ones might be expected to be more challenging to impact or document in CAH? Hey, Joe. Thanks for the question. You know, we've already shown in phase II improvements in menstrual functioning. And I expect with a greater sample size, we'll be able to talk about more of that, I hope, in phase III. We also showed biochemical resolution of polycythemia. This is something that's not often thought about here, but it's well known that excess androgen exposure stimulates the growth of red blood cells. And these patients with polycythemia, by definition, have excess red cell mass. This is not necessarily a good thing because it can predispose to thrombosis and blood clotting problems. This was resolved in all the patients who came into the phase II study with polycythemia within the three-month period. So I expect more of that as well. We shall see. The other manifestations of hyperandrogenism, for example, now these are more long-term issues to try to document. Things like hirsutism and excess hair growth can take time. But we will be looking at some interesting features of this disease in phase III that we haven't explored yet, including, for example, fertility in males, which is a problem in this patient population that we hope we can help with. So there's a lot. TARTs, you know, and TARTs and. Yes. And there's the testicular adrenal rest tumors that are not uncommonly found in men. We will follow the size of those by ultrasound very carefully. And we'll be doing that in the pediatric CAH study too, where there is, I would hope we might be able to help children or adults with that problem as well. These are painful tumors in the testes, which can also cause and promote infertility in males. Yeah. The other thing I think we are hopeful that we may see in the longer-term studies is some of the effects of reducing the glucocorticoids, which are not something you can see in the very short term. But remember, excess glucocorticoids drive weight gain, elevated HbA1c. I think there's some opportunities there as well. Thank you, Joe. Our next question will go to a line of Cory Jubinville with LifeSci Capital. Corey, your line is open. Good morning and congrats on these updates and thanks for taking our questions. You have here in a footnote on slide six that 81% of prior auths are a minimum 300-day duration, which seems really impressive. For the 20% of scripts that aren't, I guess, can you speak to the expected duration there? Are these six-month reviews? Are they monthly reviews with each new script? And I guess, are there any pre-specified clinical criteria required to allow patients to renew their prior auth, like achieving certain IGF-1 thresholds? And I guess just to be clear, have you received any pushback at all from payers on the availability of generic depot injectables, whether it be step-through edits or otherwise? Thanks, Cory. I'll remind folks it's still a little bit early days, but maybe Isabel, I think you're on the line. Can you address Cory's question? Sorry, Cory, I couldn't hear your question. He was asking about. Go ahead, Cory. Repeat yourself a little bit. Yeah. So on slide six, you have this footnote that 81% of prior auths have this minimum 300-day duration. You know, the 20% of scripts that aren't, what are the duration there? Are they six-month reviews? Do they need to be reviewed each renewal cycle? And are there any pre-specified criteria required for patients to renew their script, whether it be achieving a certain IGF-1 threshold, etc.? And then have you received any pushback at all from payers on the availability of generic depot injectables, whether it be step-through edits or any other prior auth requirements? Thank you, Cory. Yes, we're very pleased that over 80% of the prior approvals are coming over 12 months. And the other ones are coming primarily at six months, over 10% of them, and a few are coming at three months. So a really good initial response from payers. And a few of them actually came from indefinite time, particularly Part D. In terms of any requirements, no. They are being prescribed to label. So that's great news. You know, and there are no restrictions or prior authorizations, oh, I'm sorry, step edits that are required. So we are seeing a really good patient dynamic, and we haven't gotten any pushback related to generic use. Overall, it's going really well, and we continue to meet with payers, deliver on our value proposition messages, and we are executing to target when it comes to getting those prior authorizations moving as fast as possible. Thank you, Cory. Our next question will go to a line of Alex Thompson with Stifel. Alex, your line is open. Great. Thank you, and congrats on the updates as well. I guess maybe on atumelnant, you know, obviously with all the caveats of shorter duration and small numbers, I wonder if you could comment on, you know, the proportion of patients across Cohort 4 and the OLE that were able to achieve functionally your phase III primary endpoint of GC normalization as well as A4 control. Thank you. We did have some patients who met that criteria, even though in the phase II study, as I mentioned, we are looking at a different perspective of A4 control. Remember, in phase II, we're measuring the androstenedione levels before the morning glucocorticoid doses that the patient takes. That's kind of the worst-case scenario, A4. And in phase III, based on regulatory precedent, we will be looking at it at a time after glucocorticoid dosing when we expect even lower levels of A4. When we look at the totality of data, we're quite confident we will be able to show that difference between patients on drug versus placebo. And we're getting underway, and we're excited. Yeah. And maybe just more directly, in Cohort 4, already 25% hit the primary endpoint despite these caveats. It's not exactly the primary endpoint, but they're at full control. And the rest are headed there. And same thing in the OLE. Everybody's heading in the right direction. So with a little more time, I think there'll be an ability to dose titrate. We're super confident in the way this is playing out. Thank you, Alex. Our next question will go to a line of Jon Wolleben with Citizens JMP. John, your line is open. Hey, thanks for taking the questions and congrats on these updates. Just kind of piggybacking on the prior question, can you discuss in the phase III protocol the glucocorticoid reduction? Is this a forced reduction, or is it only once patients achieve normal A4 levels? Just wondering if you talk through kind of what those two different reduction periods look like and the differences between that and what you did in phase II. So in phase II and in phase III, the glucocorticoid dose reductions will not be based on A4 levels. They will be based on protocol instructions to, at certain visits, reduce the dose as long as the patient tolerates it from the standpoint of glucocorticoid withdrawal. And so it will be, in a way, a similar set of instructions to what we did in phase II, which we already saw in three months was pretty successful. So I expect with the additional time, even in more patients, reducing the vast majority of patients to the physiologic range will be very doable. Thank you, Jon. Our next question will go to a line of Maxwell Skor with Morgan Stanley. Maxwell, your line is open. Hello, this is Lena on for Max. On CAH, how does the positive Cohort 4 data help to inform dosing? Specifically, in Calm, would you expect more patients to be maintained on the 80-milligram dose at week 20 versus titrated to 120 mg? Yeah, I think broadly we've seen that 80 mg should be good for the majority of patients, if not all, eventually. It's a little bit of a question of time versus dose as well, right? As Alan was mentioning, we expect the efficacy to improve with time as these, as he calls it, angry adrenals calm down with the blanket of atumelnant on them. So I think it's also similar to what you've seen in the Palsonify program, right? So 80 mg should be good for most. If for some reason not, then they can go up to 120 mg. Thank you, Lena. Our next question will go to a line of Brian Skorney with Baird. Brian, your line is open. Hey, good morning. Thanks for taking my question. Just on the Palsonify launch, just trying to back out some things from the $5 million figure. I think this would imply something on the order of 250 prescriptions if it was a pure demand number. Was there any inventory build in the quarter to think about impacting next quarter, or is 250 prescriptions in the quarter a reasonable way to think about building out from in terms of demand in subsequent quarters? Toby? Yeah, thanks. It's a great question. I think that what we're seeing from our specialty distributors and our specialty pharmacy is a healthy level of channel mix and that what we're seeing is all of those, there have been reorders within the quarter and that they're managing within the prescribed inventory levels, which are typical in the industry. So, you know, the numbers you talk about there in terms of you have to think about monthly bottles versus sort of scripts per se. But when you do that, what we're seeing is healthy signs in the trade that the $5 million reflect the demand that's being generated from Palsonify. Yeah. And just to clarify, I think I heard something about 250, but we reported more than 200 enrollment forms. Thank you, Brian. Our next question goes to a line of Dennis Ding with Jefferies. Dennis, your line is open. Hi, good morning. Thanks for taking our questions. I had two real quick. For CAH, one biomarker that was missing was 17-OHP. So here's why that was left out. If you can comment, you know, if the changes in Cohort 4 were similar to what was presented before. And then number two, with regards to the OLE study, I think there was a footnote that said two out of the seven patients have not yet had their GCs reduced yet. Can you confirm that and, you know, any thoughts on why that is? Thank you. Yeah. Thanks, Dennis. Despite our tendencies to want to produce a presentation on the treatment of CAH for each data release, we kind of held back some things for scientific meetings. But the 17-OHP looked a lot like it did before. We'll report out testosterone levels and hydroxy steroid levels and other things at upcoming meetings. Alan, you want to talk about the OLE? Yeah. So the OLE is a very early data snapshot. And yeah, patients, remember, the doctors have control over exactly when either atumelnant or glucocorticoid doses are changed. And yeah, there were a couple patients who haven't had a change yet. But again, this is based on investigator judgment as to when it's the right time for an individual patient. Overall, we do see in the group as a whole significant reductions. And again, all these patients are well on track to achieving both therapeutic goals of CAH. Thank you, Dennis. Our next question will go to a line of Rich Law with Goldman Sachs. Rich, your line is open. Hey, guys. Happy New Year's, and congrats on data. Can you discuss the CAH composite endpoint in terms of what are the criteria for the A4 reduction there to meet and also what proportion of patients are needed for success? And then also based on today's Cohort 4 data, what proportion of patients do you think could achieve that A4 reduction within that first period and do not need that second period of GC reduction? Thank you. Maybe I'll let Garnet take this one. Garnet is our global product lead for atumelnant. Can you answer him, Garnet? Yeah, of course. For the phase III, it's actually not a composite, it's a responder endpoint. Patients need to have achieved both a physiologic dose of below 11 mg per meter squared per day of GC, hydrocortisone equivalent, as well as A4 below the upper limit of normal. We're very highly powered to detect a delta between placebo and active. In fact, the study is actually sized to account for the overall safety database requirements. That's the phase III component. As far as the second question goes, I mean, I think we're very encouraged by the phase II Cohort 4 data, as you've heard from Alan and Scott. I'd be confident that we would see a large number of patients hitting the primary endpoint even after that first period of, you know, 12 weeks of GC reduction, which is slightly longer. So it's 10 weeks of actual GC tapering in phase III relative to the eight weeks that was conducted in the phase II study. Thank you, Rich. Our next question will go to a line of Douglas Tsao with H.C. Wainwright. Douglas, your line is open. Hi, good morning. Thanks for taking the question and congrats for progress. On atumelnant, I'm just curious. We saw in the initial phase II data some patients had some early clinical responses in terms of resumption of menses. Have you seen sort of that occur more broadly in the open-label extension? If you could just sort of provide some color on what you're seeing clinically from patients who have had sort of longer exposure to the drug beyond just the sort of the biochemical measures that we're obviously focused on. Thank you. Yeah, no, Doug, it's a great question. I would hope and expect to see further clinical outcome improvements with longer-term exposure. You just need to remember that so far on the OLE, we've only had one patient who's gone a longer period of time than three months with dosing. So give us some time. But we certainly fully intend to report at scientific meetings updates on the OLE. And of course, it's the phase III trial. We'll be doing a placebo-controlled evaluation of safety and efficacy for a significantly longer period of time. Thank you, Douglas. We have one more question. Yes, one last question goes to the line of Catherine Novack with JonesTrading. Catherine, your line is open. Hi, good morning. Congrats on all of the fantastic data. Thanks for taking my question. Just a quick question on the reimbursement approval for Palsonify. Obviously, very early days, as you said. Do you get a sense if it's improving over time? And what is your ultimate, you know, realistic target in terms of percent approvals for prior auths? Thanks. Great. Let's let Isabel take that question. Isabel, you there? Yes. Thank you, Catherine. First of all, Catherine, our goal is to start getting into formulary. And as we had shared in the past, we hope that after six to nine months, most of the formularies will have been approximately 95%. And given our strong value proposition and the demand that we are generating, we are expecting that those formularies will be primarily reimbursing us based on our labels. So first-line and second-line use without any additional step edits. Of course, we are working towards that, and our goal is to be at over 75% in the next nine months. Thank you, Catherine. And with that, we will conclude both the Q&A session as well as today's corporate update conference call. Thank you for your participation and enjoy the rest of your day.