Good afternoon, everyone. Welcome to the Crinetics Pharmaceuticals fourth quarter and full year 2024 financial results conference call. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we will hold a question-and-answer session. You may register to ask a question at any time by pressing star one on your telephone. Also, today's call is being recorded, and with that, I'll turn things over to Gayathri Diwakar, Head of Investor Relations. Please go ahead, ma'am. Thank you, operator. Good afternoon, everyone, and thank you for joining us to discuss the fourth quarter and full year 2024 results. Today on the call, we have Dr. Scott Struthers, founder and Chief Executive Officer, Isabel Kalofonos, Chief Commercial Officer, Dr. Dana Pizzuti, Chief Medical and Development Officer, Dr. Steve Betz, founder and Chief Scientific Officer, and Marc Wilson, Chief Financial Officer. Also joining us for Q&A is Dr. Alan Krasner, Chief Endocrinologist. Please note there is 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. Slide two. 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 can differ materially from those stated or implied in such statements due to risks and uncertainties associated with the company's business. 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 would also like to specify that the content of this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, February 27th, 2025. 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 good afternoon to everyone joining today's call. 2024 was a remarkable year for Crinetics. As you can see on slide three, we successfully executed on all of the key objectives we set out to accomplish. This set the stage for what we believe will be a transformative 2025. On today's call, we'll review some of these accomplishments and outline our plans for 2025 and beyond. Since our last earnings call, the FDA accepted the NDA for our investigational drug, paltusotine, for the treatment and long-term maintenance therapy of acromegaly. The PDUFA date is September 25 of this year. This is our first NDA filing, and I'm extremely proud of the team for its hard work in getting us to this point. We're continuing to prepare our organization for the anticipated launch of paltusotine later this year. As part of this, we are completing the build-out of our commercial and medical affairs teams, as well as the underlying administrative infrastructure. A very important part of this was hiring Isabel Kalofonos this past December as Chief Commercial Officer. She successfully launched many rare disease products at both large and small biopharmaceutical companies. Isabel has all the skill sets and relevant experience to lead us through our upcoming transition into a commercial-stage company. I'm happy to introduce her to you here today. Given the strength of the clinical data for our lead programs and the deep pipeline behind them, we continue forward with our stepwise regional growth strategy in Europe. We anticipate filing an MAA for acromegaly shortly. We have incorporated a hub in Zug, Switzerland, and brought a general manager and leadership for EU regulatory, market access, and medical affairs, and we're beginning to extend this organization into Germany. As a leader in endocrine innovation, we plan on leveraging this infrastructure in the coming years as we evolve into a fully integrated global pharmaceutical company. Last year, we made significant progress on multiple clinical readouts, including for paltusotine's second indication, carcinoid syndrome. In a phase II study, paltusotine treatment demonstrated rapid, sustained reductions in frequency and severity of flushing episodes and bowel movements. We have begun activating clinical trial sites for the phase III trial and expect the first patient to enroll next quarter. We also shared extremely positive data for our second candidate, atumelnant, in both congenital adrenal hyperplasia, or CAH, and in Cushing's disease. In a phase II study in adults with CAH, atumelnant achieved rapid, substantial, and sustained reductions of both biomarkers, A4 and 17-OHP. Importantly, significant clinical improvements in symptoms were also observed, which was impressive in a 12-week study. We believe that atumelnant can provide healthier hormone levels on both dimensions: adrenal androgens and exogenous glucocorticoids, and this profile has the potential to differentiate atumelnant and provide meaningful improvements to people living with CAH. With this in mind, we're progressing towards initiation of late-stage CAH studies in both adults and in children. These studies are designed to take advantage of atumelnant's very potent mechanism of action to provide benefits for a broad spectrum of patients with CAH. Atumelnant also demonstrated initial positive results in Cushing's disease. All participants in this phase I-A, I-B, II-A trial rapidly achieved normalization of urinary free cortisol, and that is the primary endpoint required for registrational studies in Cushing's disease. Lastly, we're making notable progress on our earlier stage programs, including 9682, our first drug candidate from a novel non-peptide drug conjugate, or NDC, platform. This year, we expect to submit four INDs in total, including 9682. Steve will discuss these in more detail toward the end of the call. With that, I'm pleased to introduce Isabel, who will tell you more about the progress in building our commercial capabilities. Thank you, Scott. I'm thrilled to have joined Crinetics to lead the commercial organization in this exciting new chapter for the company. Today, I will share more about how we are advancing our commercial capabilities and working diligently to be launch-ready ahead of our first potential FDA approval. We are building a best-in-class commercial and medical affairs organization with strong leaders across all functions: operations, marketing, market access, medical affairs, and sales. Separately, our medical affairs team has talented endocrinologists leading the effort to liaise with healthcare professionals and KOLs. Our MSL team has already reached out almost 100% of our core academic targets to solidify relationships and refine our understanding of the unmet needs in acromegaly treatment. We also have strong partnerships with the broader endocrinology community, which we believe will be instrumental for a successful launch. There is significant unmet need in the acromegaly market. Healthcare professionals and patients want therapies with a rapid onset of action, sustained effect, favorable adverse event profile, and ease of use. We are building our commercial and medical organizations to drive educational efforts in a market that has not seen any meaningful innovation for a long time. Slide four outlines the four imperatives of our commercial strategy: activate, adopt, access, and adhere. First, we want to activate healthcare professionals and patients to demand more from their acromegaly therapy. For example, we want them to realize that they can achieve better disease control and don't have to settle for frequent breakthrough symptoms. Across the phase III program, paltusotine demonstrated rapid, reliable control of biochemical markers, decreased symptom severity, and reduced the frequency of breakthrough symptoms. Second, after approval, we want to drive adoption of paltusotine by clearly articulating its differentiated efficacy and safety profile to patients and healthcare professionals. Our efforts will be focused on pituitary treatment centers as well as the community. Many patients see their doctors in the community setting, where adoption of new therapies tends to lag behind academic centers. And since patients tend to visit their healthcare professionals only one or two times per year, we expect a more gradual adoption at the outset. We are actively developing strategies to motivate patients and healthcare professionals to accelerate this timeline. Over time, we are confident in the potential of paltusotine to become the new standard of care. Third, we want to ensure access to paltusotine. Our market access team has continued to engage with the top U.S. payers, and they have been very receptive to the value proposition of paltusotine. As with any new drug, there will be a standard formulary inclusion process that will need to be followed, but we are working towards having comprehensive coverage as soon as feasible after launch. We're extremely confident that we'll be able to provide optimal access for all acromegaly patients that could benefit from paltusotine. Lastly, we want patients to adhere to their paltusotine regimen. Patient support goes far beyond financial co-pay assistance, and our comprehensive patient support center will include a full suite of services to provide unparalleled support for patients at every step, starting at initiation of therapy and throughout the course of their long-term treatment regimen. In summary, the paltusotine profile we are sharing in market research is resonating with all key stakeholders: healthcare professionals, payers, and most of all, patients. We look forward to sharing more detail on our launch strategy in the coming months. Lastly, it is important to note that the work that we do today will serve as a solid foundation for anticipated future launches. We will leverage the infrastructure we are building today in the U.S. and Europe, across additional indications for paltusotine, as well as the other candidates in our pipeline. With that, I will hand the call to Dana to discuss our clinical development progress. Thank you, Isabel. This is a very exciting time for Crinetics. Turning now to slide five, the NDA for paltusotine was accepted last quarter. We have a productive relationship with the endocrine division at the FDA, and our NDA review is proceeding normally. In addition, we expect to file our MAA for acromegaly to the EMA in the first half of this year. Separately, the Committee on Orphan Medicinal Products of the EMA has issued a positive opinion on our application for orphan designation for acromegaly, based on the committee's judgment that it has the potential to provide significant benefit over the currently available therapies. We are continuing to activate sites for the phase III study of paltusotine in carcinoid syndrome. We are planning to run this study globally and expect to enroll our first patient in the second quarter. For atumelnant in CAH, we are putting the finishing touches on our phase III adult protocol after productive interactions on its design with the FDA and two European health authorities. I'll provide more detail on this in a moment. We have also had important and supportive discussions with FDA and EMA regarding our proposed phase II-III pediatric study for CAH. We are completing protocol development and will provide more details on the design and plan to begin this study before the end of the year. We are continuing to pursue development of atumelnant in ACTH-dependent Cushing's syndrome, or ADCS. We are finalizing a proposed seamless phase II-III study design, which we developed after review of our NIH study data and in close collaboration with external experts and regulatory advisors. In the near future, we will provide our proposal to the FDA and European agencies for discussion. We'll then finalize the protocol and would expect to enroll our first patient late this year or early next year. Before I leave atumelnant, I realize there may still be some lingering discussion about the one case of elevated liver enzymes in the CAH phase II study. As we have previously described, one patient in the 120-milligram dose cohort had liver enzyme elevations at the final study visit at 12 weeks, and those levels returned to near normal within two weeks. The patient did not show any elevation in bilirubin nor any associated symptoms. It is also important to note that we have seen no concerning signals nor unexpected safety findings in the preclinical work or in the phase I healthy volunteer studies. We have shared all preclinical and clinical data, including the details on this patient, with the FDA and global health authorities as part of the consultation process for our proposed phase III design. After reviewing all the data and the proposed phase III protocol, the FDA has not recommended any changes to the safety monitoring in the ongoing open-label extension study, nor any additional testing on top of routine hepatic safety monitoring in our proposed phase III protocol. We remain very enthusiastic about the strength of the overall phase II efficacy and safety results, and we believe this favorable benefit-risk profile will be confirmed in our phase III trial. This enthusiasm is reflected in our phase III protocol, which we will share in detail when final, but our intention is to use a novel endpoint. Based on the entirety of the clinical program and atumelnant's unique mechanism of action at the MC2R receptor, atumelnant should be capable of reducing androgens into a normal range and allow for lowering glucocorticoid doses to physiologic replacement levels. Our proposed endpoint would capture this differentiating aspect of atumelnant and will allow for broader phase III inclusion criteria than was used for the currently approved CAH therapy. In particular, patients with normal glucocorticoid doses but high A4 levels could potentially benefit from atumelnant and will be included in our phase III study. 2025 is an exciting year for paltusotine and atumelnant as we continue towards registrational studies for these candidates in multiple indications. We will soon have four late-stage clinical programs underway, which is a new high-water mark for Crinetics. As we make progress on our preclinical pipeline, we look forward to potentially initiating additional early-stage trials. With that, I will hand it to Steve to describe our upcoming INDs. Thank you, Dana. As you can see highlighted on slide six, Crinetics has an innovative pipeline of drug candidates with IP into the 2040s, with 10 wholly-owned programs currently disclosed and more innovation happening within our discovery team. Our core expertise is in targeting G-protein coupled receptors, or GPCRs, with small molecules that have specifically tailored pharmacology and properties. To reflect the breadth of opportunities within the GPCR space, we have organized our discovery team into three main focus areas: endocrine disease, metabolism, and what we call targeted therapeutics. Since our inception more than 15 years ago, Crinetics has focused on developing innovative non-peptide drug candidates that target specific endocrine pathways to modulate abnormal hormone secretion. Most of the candidates currently in our pipeline have come from our endocrine group, and we continue to explore additional GPCR targets within the endocrine system, focusing, as always, on key areas of unmet need. Relatedly, metabolic disorders, including diabetes and obesity, impact the lives of hundreds of millions of people around the world, and their effects on patients are significant and varied. We feel that many of these disorders can be addressed by appropriately activating or blocking the receptors of key metabolic hormones, including insulin, glucagon, GLP-1, and GIP. Crinetics' understanding of these hormonal pathways and the GPCRs that control them is driving us to create new molecules with the chance to improve the lives of these patients. Lastly, I'd like to cover targeted therapeutics. Our efforts in this space began with the development of non-peptide GPCR targeted radioligands for the imaging and treatment of a broad range of endocrine receptor-driven cancers. This work ultimately led to the formation of Radionetics Oncology in 2021. Following that, we continue to explore this concept of using non-peptide ligands to target endocrine GPCR as relevant to oncology, but with non-radioactive payloads. This work has led to the development of a new modality that we call non-peptide drug conjugates, or NDCs. NDCs are a novel therapeutic approach that are conceptually similar to ADCs but use a non-peptide ligand instead of an antibody to selectively target and deliver payloads to tumor cells expressing GPCRs. We feel NDCs possess multiple advantages, including straightforward production by standard synthetic methods and tailored in vitro and in vivo properties that allow us to optimize half-life, tumor penetration, and payload. Four early-stage programs from these discovery efforts are currently in IND-enabling studies. The farthest along of these is CRN09682, our NDC for SST2-expressing neuroendocrine and solid tumors. The SST2 agonist ligand for 9682 has been optimized to promote internalization so that its payload can be efficiently delivered intracellularly to induce tumor cell death. We are on track to submit an IND for this program early this year. The other candidates with INDs planned for 2025 include a PTH antagonist for hyperparathyroidism, a TSH antagonist for Graves' hyperthyroidism and thyroid eye disease, and an SST3 agonist for autosomal dominant polycystic kidney disease, or ADPKD. Similar to what we have seen in our development of both paltusotine and atumelnant, one advantage of several of these programs listed on this slide is that we can get early mechanistic proof of concept in phase one trials. The first in human studies of 9682 will be in oncology patients, so we can measure progression of disease. In hyperparathyroidism and hyperthyroidism, there are hormonal biomarkers that should demonstrate whether we are having our desired pharmacological effect. These early insights ensure that we can optimize our potential for success across each of these programs while maintaining a capital and resource-efficient development strategy. We look forward to sharing some of the early results from these programs with you as they become available in the future. With that, I will hand it over to Marc to review the 2024 financial results. Thank you, Steve. Turning to slide seven, 2024 was an outstanding year that demonstrated the strength of our strategy and our team's execution capabilities. Crinetics entered 2025 with strong momentum across all programs, and the company remains focused on discovering and developing novel therapies for patients, as well as generating value for its co-owners. The tremendous progress made over the course of last year has enabled the company to continue investing in the pipeline as we prepare to launch the first drug candidate emerging from our own R&D efforts. Now I will walk through the financial results for the fourth quarter and year. Revenues were $1 million for the full year ended December 31, 2024, compared to $4 million for the same period in 2023. There were no revenues in the three months ended December 31, 2024, or the three months ended December 31, 2023. Revenues in both years consisted of the amortization of payments we received in connection with our paltusotine licensing arrangement with our Japanese partner, SKK. Revenue in 2023 also included approximately $2 million associated with a development candidate that we licensed to Loyal to explore extension of lifespan in large and giant breed dogs. Research and development expenses were $66.6 million and $240.2 million for the three months and full year ended December 31, 2024, compared to $45.6 million and $168.5 million for the same periods in 2023. The increases were primarily attributable to higher personnel costs and increased development activities associated with the expansion of our pipeline. G&A expenses were $28.2 million and $99.7 million for the three months and full year ended December 31, 2024, compared to $17.1 million and $58.1 million for the same period in 2023. These increases were primarily driven by increased personnel costs and commercial planning activities. Our net loss for the three months ended December 31, 2024, was $80.6 million, compared to a net loss of $60.1 million for the same period in 2023. For the year ended December 31, 2024, the company's net loss was $298.4 million, compared to a net loss of $214.5 million for the prior year. For 2025, we anticipate our cash burn to be between $340 million and $380 million. This increase reflects our plans to initiate four late-stage trials in 2025, so we expect our R&D spend to grow in 2025 as those trials start to ramp up. SG&A will also increase this year as we continue to build our commercial infrastructure and prepare for the potential launch of paltusotine in the fourth quarter. We ended 2024 on strong financial footing with approximately $1.4 billion in cash and investments, which is expected to fund our operating plan into 2029. Before I turn it back to Scott, I'd like to take a moment to thank my fellow Crinetics for their support during my tenure, particularly since I announced my plan to transition out of the CFO role a number of months ago. I would also like to thank those of you in the investment community who have been outstanding colleagues over the years. I truly believe in the work that is being done at Crinetics. It is a genuinely unique company, and I am honored to have been a small part of what the organization has accomplished. I am optimistic about the future and am confident that Toby will be an exceptional steward of the company's resources through its next phases of growth. I'll now turn it over to Scott for closing remarks. Scott. Thank you, Marc, and thank you for your leadership over the past seven years. You've been instrumental through these years of incredible growth. With your help, we have grown from a pre-Series B private company to the public company we are today, with operations around the world and on the verge of our first PDUFA day. I speak for everyone here when I say that we are deeply grateful for your dedication and contributions. We're also very excited to welcome Toby Schilke, who will succeed Marc as Crinetics CFO. Toby brings over 25 years of global pharmaceutical experience and has led several biotech companies through the transition to fully integrated commercial enterprises. He brings a wealth of experience and a unique perspective, and we're excited to have him on board as we prepare for our first commercial launch. Turning to slide eight, I'm very bullish on the bright future before Crinetics. The array of opportunities for us to help patients with endocrine-related diseases with a pipeline we've created from scratch is breathtaking. With the progress I have described today, we've made great strides on our path to becoming the premier fully integrated global pharmaceutical company. The combination of our best-in-class in-house discovery capabilities, proven clinical development, and our ongoing build of commercial capabilities strongly positions us to execute on a number of key milestones in 2025. We plan to leverage our growing infrastructure across multiple programs and therapeutic areas while recognizing economies of scale along the way. I believe this strategy will propel us to maximize patient reach and drive long-term value growth for all our stakeholders. With that, I'll hand the call back to the operator to begin Q&A. Please limit yourself to one question each in the interest of time. Operator. Thank you, Dr. Struthers. Ladies and gentlemen, at this time, if you do have any questions or comments, please press star one. If you find your question has been addressed, you may remove yourself from the queue by pressing star two. Once again, star one for questions. We'll go first this afternoon to Tyler Van Buren of TD Cowen. Great. Thanks, guys. It's great to be back in coverage of Crinetics here again, and congratulations on all of your achievements, Marc. I wish you the best. I wanted to ask about Paltu. The data with Paltu and acromegaly are clearly strong, and the likelihood of approval in September is very high, but expectations for the launch seem conservative or even modest from some of your investors. So can you elaborate on the ongoing launch preparations for Paltu? What might surprise people in your global strategy in particular? Thanks, Tyler. I totally agree with you at how strong the data has been for acromegaly. As we talk to the KOL community, I think there's an emerging consensus that this really is the next level of care. We're super pleased with the announcement from the EMA that we've been granted orphan drug designation, which in part recognizes that because they felt that paltusotine constitutes a clinically relevant advantage over currently approved therapies, and that's part of their process in making the orphan designation. I think we've built something that is going to give Isabel and the rest of the team something very strong to work with. Let me let her talk to you about the ongoing preparations. Yes, thank you, Scott. Yes, we are in a really good place in preparing the organization, the market, and the product. In terms of the organization, we hire a very talented team, and we're very pleased to welcome our VP of sales as we continue to build our customer engagement model, including not only the sales team, but field reimbursement managers to facilitate the onboarding of the patient. In addition to that, we are preparing the market, and that involves very successful engagement right now with the payers that are responding very well to the value proposition of the drug. As Scott stated, we have a treatment that has a fast set of actions, sustainable effect, less breakthrough symptoms, has a very good tolerability profile, and of course, it's a once daily, which really resonates not only with the payers, but also with the physicians and the healthcare professionals. We continue to drive educational activities to engage with the doctors in disease awareness as well as with the patients. In terms of the product, we are in a very good place when it comes to our supply chain and distribution, and we continue to develop our training modules and launch materials consistent with the expected label. So we are in a very good place, and the product really offers the opportunity to really change the standard of care. In terms of the international organization, we think it's very important that this product is not only for the U.S. patients, but it starts really making a difference internationally as well. So we're starting in Europe, where we have hired a very talented team that, as in the U.S., has significant experience in product launches and in rare diseases. We have a general manager, market access, medical affairs, and regulatory in place, and it's our goal to now focus on building Germany. Similar to the U.S., the model is very fit for purpose, really with a significant value concentrated in centers of excellence, and we're preparing and advancing that as well. So really exciting times, and the commercial organization is in full engagement and making sure that we advance towards a successful launch. Thank you. We'll go next now to Yasmeen Rahimi at Piper Sandler. Hi, this is Dominic on for Yaz. Thank you for taking our questions and congrats on continued strong execution. Our question is just how do you envision your disclosures as you continue your dialogue with the FDA between now and September 25th? And are there certain topics of interest that could come up at your mid-cycle review? And also, have you had your mid-cycle review yet, and what was the outcome if you had? Thank you. Let me let Dana answer that. But just in general, I'm pleased with the overall cadence of our communications. And from a communications point of view, I think that will be simply as an as-needed basis. But let Dana just say a little bit more. Yeah. Well, we haven't had the mid-cycle yet, but we are scheduled to do that. And we're awaiting further interactions with the FDA as we go along. But as I mentioned in my initial remarks, everything's proceeding normally, and there's a very productive relationship with the agency, so. Thank you. We'll go next now to Joe Schwartz of Leerink Partners. Thanks very much, and congrats on all the progress. I was wondering if you could talk about the strategies you're working on to motivate acromegaly patients to see their healthcare providers, such as those in the community we heard you say often lag in the uptake of new treatments, and in a related sense, how long do you think phase III enrollment for atumelnant and CAH may take, recognizing that there's a new treatment option for the first time in a long time and could be a bit competitive. But also, I think you've already had a lot of experience with clinical development now for paltusotine, so I'm just wondering, relative to that phase III enrollment timeline, how should we think about how long it might take for atumelnant in phase III? Thank you. Nice working in a compound question, Joe. Let me answer the latter, and then I'll hand it off to Isabel. CAH, look, we've got quite a bit of experience now in that community. In many cases, it's the same institutions as we did with acromegaly. The fact that now there's an approved drug on the market in Crinetics is fabulous for these patients, but I don't think it's going to significantly impact our enrollment, especially since we're in a global clinical trial. In fact, as has been our past experience, and I think the past experience of most other companies, recruitment tends to be higher outside the U.S. than inside the U.S. So I've seen no effect. And then compared to prior trials of CAH that were underway during the pandemic, where people were late to the international markets, I expect us to do significantly better than previous experience. But Isabel, maybe talk a little bit about activating patients. I think they're highly motivated already, but we want to make sure they're empowered, not just motivated. Yes, Scott. Indeed, we are engaging with the patients through different venues, including our disease awareness campaign, really to highlight the significant unmet need that is happening in the marketplace. Today, the data will show that only 35% of the patients are uncontrolled. So many of the patients have significant unmet needs, and the majority of the patients have breakthrough symptoms. So even though the IGF-1 level might look like normal, they continue to experience significant effects with fatigue, sweating, and other symptoms as well that impair their quality of life. So we are making them aware of that, and there are different educational events and a disease awareness campaign, as well as our media outreach that is starting right now throughout the country. In addition to that, we have a patient hub that we believe is going to really help patients reach out, and we will support them not only through co-payments and additional activities, but also helping with their mental health and other things that will provide support to them. So overall, sorry, we are in the process of activating not only the patients, but the healthcare community. Very helpful. Thanks for the insights. Thank you. We'll go next now to Jessica Fye of JP Morgan. Hey, guys. Good afternoon. Thanks for taking my question. I was curious if there's any update on where things stand with the open-label extension for the CAH phase II trial. I'm just trying to think about if that's something we could see data from prior to getting those phase III results. Thank you. Thanks, Jess. Yeah, the sites are activating, and patients are switching into the open-label extension and eager to see how they do. It's a little bit of a second bite at the apple since we had a bit of a delay in starting the OLE to finish up the long-term talks. So all the patients had come off of drug, and now they're coming back on under physician care. And yeah, I look forward to seeing how that plays out, and I think it will be a valuable source of information. Thank you. We'll go next now to Cory Jubinville of LifeSci Capital. Hi there. This is Kate on for Cory. Thanks for taking our questions, and congratulations on the amazing progress this year. Just one from us related to the CAH program. It's, of course, still early days, but it seems like the crinecerfont launch in CAH has gotten some early momentum. And we're just curious, what are the learnings you've taken from the launch thus far and how you might be considering that for atumelnant in the future? And is there anything thus far that surprised you? Thanks, Kate. I think it's really a little early for us to draw any conclusions, but our friends and neighbors down the street have proven themselves as very good commercial pharmaceutical companies. So I expect they'll do a good job, and we're watching closely to learn from them and wish them well. Thank you. We'll go next now to Gavin Clark-Gartner at Evercore ISI. Hey, guys. Congrats on the progress. For atumelnant, can you share any additional details on cohort four in the Toucan study and when we may be able to possibly see that data? Thank you. Yeah, thanks, Gavin. We haven't really started talking about cohort four. Remember, it's just one cohort in a large overall program. But I think one thing we will be telling you about in the not-too-distant future is the overall study design details for the phase III program. And maybe at that time, it's relevant to talk about cohort four. But I'll try and get that out as soon as we have the final pieces in. I just don't want to tell you something that might have slight revisions. So we're very close to finalizing that and starting to activate sites and things like that. So I think we'll be able to provide clarity by our next earnings call at the latest. Great. Thank you. Thank you. We'll go next now to Jo hn Wolleben at Citizens JMP. Hi, this is Catherine on for John. I have kind of a follow-up question on CAH as well. I know that you just mentioned that you're going to be discussing the design details of the phase III program going forward. But it's kind of a general kind of question on the endpoint and a differentiated endpoint from the one that was kind of previously used. So kind of what is the kind of rationale from a regulatory standpoint as well as a commercial standpoint on changing up the endpoint to give a little bit more color on that? Yeah, thanks. Sorry, are we getting some feedback? I think the thing to recognize is that this is a completely different mechanism of action with a different pharmacologic profile. And we've shown in both the phase II and CAH patients deep suppression of A4. We've shown in healthy volunteers that even under conditions of very low glucocorticoids and extremely high levels of ACTH, that we can maintain suppression of the adrenal gland and keep those patients even to the point where they still need glucocorticoid add-back. And so our vision for the drug is not one, which is just helping glucocorticoids manage the adrenal. We think that atumelnant should be the treatment for CAH, and then glucocorticoids are not used for treatment. They're simply used for replacement. And so maybe Dana can elaborate a little bit more. We're trying to be not completely specific because there's still a few things to work out, but let me let her talk about principles. Well, yeah. And I think, as Scott mentioned, and as I mentioned earlier on the call, we feel that the drug is capable of doing more than just helping manage the disease with glucocorticoids, right? We feel, as Scott says, that this should be able to do both, right? And so when we put together an endpoint, it has to have both dimensions in it. Now, we haven't finalized exactly how that's going to work from a statistical point of view, but we think that the basis for that belief in terms of the mechanism of action could lead to a different potential indication for the drug, right? Because we feel that this is the treatment for the disease, and glucocorticoids are just a safety mechanism to prevent adrenal insufficiency. Thank you. We'll go next now to Dennis Ding of Jefferies. Hi. Thanks for taking our question. We just had one on atumelnant. From a timing perspective, can you commit to sharing additional data this year, whether it's from CAH like a cohort four or longer-term extension data or Cushing's? And then for the long-term extension, how do you think efficacy would evolve with longer treatment? I try never to commit to any timelines around things until we're absolutely certain about it. So just have to stay tuned. Sorry to keep you in suspense. But in terms of, sorry, the second part of the question was? Just around the long-term extension and how do you think efficacy could evolve in patients over longer-term? Yeah, sorry. Yeah. So I think that the most relevant data there is what we saw with the adrenal sizes in the very short 12-week study. So ACTH is trophic for the gland. In CAH, when these patients are experiencing high ACTH levels from birth, they end up getting larger adrenal glands. As my friend Dr. Krasner says, they become angry. Certainly, they're very active. And we're showing shrinkage of those glands in only 12 weeks. So I would expect that to continue with time. And if anything, then the ability to suppress the adrenal should increase or remain with time. There's no mechanistic reason to believe that any sort of tachyphylaxis should develop. Thank you. Thank you. We'll go next now to Catherine Novack of JonesTrading. Hi. Good afternoon. My question is around how are you prioritizing the three non-oncology assets that you're moving forward into IND filing this year? If you had to pick, which indication is most exciting to you at this time? Thanks. Hi, Catherine. I'll answer that the same way I often do, which is I've now up to four grandkids, and they each have their wonderful traits, and I love them all. But the prioritization, we're in a fortunate position where, because of our strong balance sheet and our build of the company, that we're not at a position where we have to prioritize them. We are able to move all of those forward at their natural pace. And at the moment, well, clearly, 9682 is in the lead. We'll be filing that IND very shortly. There's a bit of a race between the PTH antagonist and the TSH antagonist, and it looks like TSH is catching up a bit. And then ADPKD is working in the background. I just saw you wrote a note about ADPKD, and it hit my inbox as this was starting, so I'm looking forward to reading it. Thank you. Absolutely. Thanks, Scott. Thank you. We'll go next now to David Lebowitz at Citi. Hey, guys. John on for David. Thanks for taking our question. For the atumelnant phase II data, just curious, what is the current thinking behind the lack of observed dose response in the 17-OHP decrease across all the doses? Understand that A4 was the primary endpoint, but just given the fact that 17-OHP plays an important role as an intermediate hormone, just interested to hear what the latest thinking is on that data point. Thanks. Thanks very much for the question. 17-hydroxyprogesterone is a very variable biomarker, even in the clinical care of these patients, and particularly when you use it to try and assess adequacy of care in clinical practice. I feel like both biomarker responses, including the more variable 17-hydroxyprogesterone, are pretty impressive. And I take a lot of learnings from the fact that we actually, in this very short study, see clinical outcome benefits. And in that kind of situation, we no longer need to rely on the exact amount of surrogate biomarker reduction. We know it's of unprecedented magnitude compared to other CAH therapies in the past, and it's very difficult to achieve those kinds of reductions with glucocorticoids alone, which is why we like to think of atumelnant as ultimately, hopefully, the treatment for CAH, whereas glucocorticoids are just used at low doses for replacement. But I will say, I was looking earlier this week with the group at some of the exposure response modeling, and I don't think I agree with you. I think there is a nice exposure response with both 17-OHP and A4. So although, as Alan says, 17-OHP is a bit more variable. Thank you. We'll go next now to Rohan Mathur at Oppenheimer. Hey, this is Rohan Mathur from Oppenheimer. Thanks for taking the question. Just one from me on paltusotine. Just given the use of somatostatin receptor agonists in acromegaly in patients with neuroendocrine tumors, how do you think about carcinoid from a commercial standpoint, as there may be some overlapping call points and complementary dynamics once it's potentially made available in both indications? Thanks. Yeah, thank you. I think there's a couple areas of synergy there. One, from a geographic point of view, the oncology centers of excellence and the pituitary centers of excellence are geographically overlapping. And so there are some efficiencies there. I also think that our growing experience in acromegaly provides additional safety confidence for the patients with neuroendocrine tumors, which I'll remind folks are things that are really becoming a chronic disease in many ways. So long-term safety is, of course, important. There's an interesting dynamic to note outside the U.S., which is, in many of the countries in Europe, unlike the U.S., the prescribers who manage the acromegaly patients overlap more frequently with those that are managing neuroendocrine tumors. So for example, investigators of ours in the UK and some in Germany and some of the other countries have many more neuroendocrine tumor patients than they do acromegaly patients, but they see both. So they're beginning experience in one population to help them understand how they might use it in another later. So I think overall that people are used to using somatostatin analogs for both, and paltusotine is a next-generation somatostatin analog or ligand, excuse me. Thank you. Thank you. We'll go next now to Andy Chen of Wolfe Research. Hey, thank you for taking the question. I think it was Isabel during the prepared remarks that mentioned that payers are very supportive of the value proposition of paltusotine. Can you discuss which features of the product they're the most excited about? So especially now that we know that Cipla will be back to the US market against Ipsen in this quarter, and then I hear that generics will launch in Europe in the second quarter. Wouldn't payers be more excited about those generics a lot more, or do you think those are just basically non-factors in the grand scheme of things? Thank you. Yeah, I do think that in general, the generics or 505(b)(2), the equivalent, are really just the next iteration in the long-term small changes to the injectables, and I don't think that that provides the next generation of care that paltusotine provides, so let me let Isabel answer in a little more detail, though. Yes, Scott, that's right. Currently, with injectables, you see a significant discontinuation rate and lack of adherence to treatment, which many of the payers consider almost wastage. Because in theory, you are reimbursing for those treatments, but you are not getting the efficacy you are expecting to get. Also, the coverage, whether it's a generic or whether it's a branded product, the injectables tends to lag towards the last week of the four weeks of treatment, and many of the patients continue to have breakthrough symptoms, and we have done some economic analysis that shows that many of those patients end up having to have surgeries and continue to have pain and evolution, so overall, the payers see this as an improvement on the standard of care. They are very positive about the sustainability of effects, the rapid action, because you also see in injectables that sometimes it takes a long time to find the right dosage, which is not the case with paltusotine, and this is really transforming the standard of care, so we are very pleased with how they are appreciating the value proposition of the drugs. Thank you. Thank you. We'll go next now to Brian Skorney of Baird. Hey, this is Charlie on for Brian. Thanks for taking the question. Just touching on the PTH antagonist, it would be great if you could tell us more about the landscape there in terms of how patients are usually treated, as well as what you believe the antagonist could offer over that. As well as when you think about the 200,000 incidence cases, how many of those would you expect to be addressable with this compound? Thank you. Alan? Thanks very much. Yeah, a PTH antagonist for clinical use would be a very novel opportunity for patients with primary hyperparathyroidism. Right now, the major treatment option is surgical removal of the overgrown parathyroid adenoma, which usually causes this disease. That is curative much of the time. However, unfortunately, there are a lot of patients with this disease, as you mentioned, and many of them do not get surgery. There is really not a true medical option for the treatment of hyperparathyroidism. There is cinacalcet, which is approved. Cinacalcet, however, has only been shown to resolve or improve one aspect of this condition. That's the hypercalcemia or elevated calcium levels. But hyperparathyroidism is a multi-organ disease that affects the bones and the kidneys adversely. Cinacalcet, although approved, has never been shown to help the kidneys or the bones. We really need a medical option for the treatment of this disease. In theory, a PTH antagonist could help all of the end-organ damage that we see in this condition. Yeah, and I think this is a case also as we start thinking more about PTH, where I want to spend some time talking to the community in more detail about these programs so that people can begin to appreciate it. I know most of our conversations with the various investors and analysts have to typically stop at the atumelnant phase. But we are planning on putting together an R&D day this spring or early summer to try and provide more clarity. And I think the other thing about PTH, it's one of the ones together with neuroendocrine tumors that has started to become more personal. So as we address more and more of these diseases, I'm meeting employees or family members that are suffering from these. And we're starting to hear some of the firsthand experiences and challenges that they're facing, which always brings this home. And so as we think about PTH, I think it's a great example where you got to think of us as trying to really transform the treatment paradigm for the disease. And maybe there's a better way to manage patients while they're either waiting for surgery, or maybe they're not the best surgical candidate, or maybe there's just not a good surgeon nearby. So I think we can do something special with PTH. Thank you. And ladies and gentlemen, that's all the questions we have today. Dr. Struthers, I'd like to turn things back to you, sir, for any closing comments. No, thank you, everybody, for your questions and your hard work. We appreciate all of you and look forward to talking to folks in the coming hours and days. Take care. Thank you, Dr. Struthers. Again, ladies and gentlemen, that will conclude Crinetics Pharmaceuticals' fourth quarter and full year 2024 financial results call. Again, thanks so much for joining us, everyone, and we wish you all a great remainder of your day. Goodbye.