Good afternoon, everyone. Welcome to the Crinetics Pharmaceuticals Fourth Quarter and Full-Year 2024 Financial Results Conference Call. [Operator Instructions] Also, today's call is being recorded. 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 to the 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 2. As a reminder, we'll be making forward-looking statements. And I invite you to learn more about the risks and uncertainties associated with these statements as disclosed in our SEC filings. Such forward-looking statements are not a guarantee of performance. And the company's actual results could differ materially from those stated or implied in such statements due to risks and uncertainties associated with the company's business. 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 27, 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 3, we successfully executed on all of the key objectives we set out to accomplish. This sets 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 the EMA 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…

Thank you, Scott. I'm pleased 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 their effort to liaise with health care 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 a strong partnership with the broader endocrinology community, which we believe will be instrumental for a successful launch. There is significant unmet need in the acromegaly market. Health care 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. And Slide 4 outlines the 4 imperatives of our commercial strategy: activate, adopt, access and adhere. First, we want to activate health care professionals and patients to demand more from their acromegaly therapy. For example, we wanted 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 health…

Thank you, Isabel. This is a very exciting time for Crinetics. Turning now to Slide 5. 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 applications for Orphan's 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 the 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 2 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 we'll 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 advisers. In the near future, we will provide our proposal to the FDA and European agencies for discussion. We will then finalize the protocol. And we'd expect to enroll our first patient…

Thank you, Dana. As you can see highlighted on Slide 6, 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 3 main focus areas: endocrine disease, metabolism and what we call targeted therapeutics. Since our inception more than 15 years ago, Crinetics is 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 a 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 target radio ligands for the imaging and treatment of a broad range of endocrine receptor-driven cancers. This work ultimately led to the formation of -- Oncology in 2021. Following that, we continue to explore this concept of using non-peptide ligands to target endocrine GPCR is…

Thank you, Steve. Turning to Slide 7. 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 3 months ended December 31, 2024, or the 3 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 the 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 3 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 3 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…

Thank you, Marc, and thank you for your leadership over the past 7 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 date. 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 Tobin Schilke, who will succeed Marc as Crinetics CFO. Tobin 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 8. I'm very bullish on the bright future before Crinetics. The array of opportunities for us to help patients with endocrine-related diseases with the pipeline we've created from scratch is breath-taking. With the progress I have described today, we have made great strides on our path to becoming a 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?

[Operator Instructions] We'll go first this afternoon to Tyler Van Buren of TD Cowen.

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 want 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 and your global strategy in particular?

Thanks, Tyler. I totally agree with you with how strong the data has been for acromegaly. And as we talk to the KOL community, I think there's an emerging consensus that this really is the next level of care. And 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 orphan designation. So I think we've built something that is going to give Isabel and the rest of the team something very strong to work with. And 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 hired 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 patients. 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 has stated, we have a treatment that has fastened set of action, 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 health care 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 chains 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 international 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 are preparing and advancing that as well, so really exciting times and the commercial organization is full engagement and making sure that we advance towards a successful launch.

We'll go next now to Yasmeen Rahimi at Piper Sandler.

This is [Dominic] on for Yas 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 '25? 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?

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.

Yes. 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 is proceeding normally. And there's a very productive relationship with the agency.

We'll go next now to Joe Schwartz of Leerink Partners.

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 health care 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 in 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 time line. How should we think about how long it might take for atumelnant in Phase III?

Nice working in a compound question, Joe. So let me answer the latter and then I'll hand it off to Isabel. But 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 chronicity 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. And in fact, 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. And so I see 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 we show that only 35% of the patients, the 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 from fatigue, sweating and other symptoms as well that are impairing 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 health care community.

We'll go next now to Jessica Fye of JPMorgan.

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.

Thanks, Jess. Yes, 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 tox. So all the patients had come off of drug and now they're coming back on under physician care. And yes, I look forward to seeing how that plays out. And I think it will be a valuable source of information.

We'll go next now to Cory Jubinville of LifeSci Capital.

This is [Kate] on for Cory. 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 carcinoid launch in CAH has gotten some early momentum. And we're just curious what were the learning 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.

We'll go next now to Gavin Clark-Gartner at Evercore ISI.

Congrats on the progress. For atumelnant, can you share any additional details on Cohort 4 in the TouCAHn study? And when we may be able to possibly see that data?

Yes. Thanks, Gavin. We haven't really started talking about Cohort 4. Remember, it's just one cohort and 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 4. 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.

We'll go next now to John Wobel at Citizens.

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 just kind of a general kind of question on the endpoint and a differentiated endpoint from the one that was kind of previously used. So what is the kind of rationale from a regulatory standpoint as well as a commercial standpoint on changing up the endpoint, if you could give a little bit more color on that?

Yes. Thanks. I think the thing to recognize is that -- sorry, we're 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, yes. And I think as Scott mentioned, we -- 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.

We'll go next now to Dennis Ding of Jefferies.

We just had one on atumelnant. Can you -- from a timing perspective, can you commit to sharing additional data this year, whether it's from CAH 14 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?

Well, I try never to commit to any time lines 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 if patients are on.

Yes. So I think that the most relevant data there is what we saw with the adrenal sizes in a 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.

We'll go next now to Catherine Novack of JonesTrading.

My question is around how are you prioritizing the 3 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?

Catherine, I'll answer that the same way I often do, which is I'm now up to 4 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.

We'll go next now to David Lebowitz at Citi.

John on for David. For the atumelnant and Phase II data, just curious, what is the current thinking behind the lack of observed dose response in the 17OHP decrease across all the doses? I understand that A4 was the primary endpoint. But just given the fact that 17OHP plays an important role as an intermediate hormone, just interested to hear what the latest thinking is on that data point.

Thanks very much for the question. 17 hydroxyl 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-hydroxyprge 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 unprecedented magnitude compared to other therapies in the past. And it's very difficult to achieve those kinds of reductions with glucocorticoids alone, which is why we'd like to think of atumelnant as ultimately, hopefully, the treatment for CAH, whereas glucocorticoids 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 said, 17-OHP is a bit more variable.

We'll go next now to Rohan Mathur at Oppenheimer.

This is Rohan on for Leland Gershell. Just one for me on paltusotine. Just given the use of adrenal steroidogenesis and 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?

Yes. Thank you. I think there's, a couple of 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 is, 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 U.K. 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 the 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.

We'll go next now to Andy Chen of Wolfe Research.

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 are the most excited about? So especially now that we know that Cipla will be back to the U.S. 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 nonfactors in the grand scheme of things?

Yes. I do think that in general, the generics or 501 equivalents are really just the next generation. And 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 the 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 tend to lag towards the last week of the 4 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 surveys and continue to have pain. So overall, the payers see this as an improvement on the standard of care. They are very positive about the sustainability of effect. The rapid action because we also see an injectable that sometimes it takes a long time to find the right dosage, which is not the case which is other case. And this is really transforming the standard of care. So we are very pleased with how they are appreciating the value proposition of the drug.

We'll go next now to Brian Skorney of Baird.

This is Charlie on for Brian. 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 incident cases. How many of those would you expect to be addressable with this compound?

Alan?

Thanks very much. Yes, 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 treatment, medical option for the treatment of this disease. And in theory, a PTH antagonist could help all of the end organ damage that we see in this condition.

Yes. And I think this is the 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 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 had 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 first-hand experiences and challenges that they're facing, which always bring 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.

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.