Earnings Call Transcript - CRNX Q1 2024

Corey Davis, Moderator

Welcome to the Crinetics Pharmaceuticals First Quarter 2024 Earnings Conference Call. I will now turn the call over to Corey Davis of LifeSci Advisors. Please proceed.

R. Struthers, CEO

Thank you, Corey. Good afternoon, everyone, and thank you for joining us on our first quarter 2024 results call. I'll begin by spending a few moments summarizing our recent accomplishments, before turning the call over to Dr. Alan Krasner, our Chief Endocrinologist. He will discuss our clinical programs and recently reported data in more detail. Crinetics had an extremely strong start to 2024. Recently, we reported positive results from two late-stage clinical studies for paltusotine in patients with acromegaly and carcinoid syndrome. Behind paltusotine, we've built a remarkably deep pipeline. This includes our second internally discovered clinical stage compound, CRN04894, which will now be known as atumelnant. At the Endo Conference this June in Boston, we will present five abstracts from our clinical development programs, including four late-breaking abstracts. Two poster presentations will highlight initial data in each of the ongoing open-label Phase II studies, evaluating the safety and efficacy of atumelnant in patients with CAH and Cushing's disease. We are also hosting an in-person reception to review data from clinical studies of atumelnant in CAH and ACTH-dependent Cushing's syndrome at 6 p.m. on Monday, June 3, for those attending in person. Data from the entire PATHFNDR Phase III acromegaly program will be featured in a science and innovation theater, led by Dr. Kevin Yuen of the Barrow Neurological Institute on Saturday, June 1. Three posters from the paltusotine acromegaly clinical program will also be presented, highlighting results from PATHFNDR-2, the use of acromegaly symptom diary and PATHFNDR-1, and updates on the long-term safety and efficacy data from the ongoing open-label extension study. We've also made excellent progress towards new development candidates this quarter in all of our early-stage programs. These include a PTH receptor antagonist for the treatment of hyperparathyroidism; a TSH antagonist for the treatment of Graves' disease, including thyroid eye disease; and our programs for diabetes and obesity. Now let me take a few minutes to dive a little deeper into the progress made with the two paltusotine indications. We're extremely pleased to have completed our Phase III program in acromegaly, with a successful readout of PATHFNDR-2 in April. This study evaluated paltusotine in people with acromegaly who are not pharmacologically treated and was the second of two pivotal trials. PATHFNDR-2 achieved its primary endpoint of IGF control, and met all secondary endpoints with high levels of statistical significance. Together with the PATHFNDR-1 results we reported last year, we now have data from two Phase III studies to support an NDA filing for the treatment of acromegaly in the second half of this year. In anticipation of a potential 2025 launch of paltusotine, we're continuing to work on important aspects of commercial readiness. We have already held multiple advisory boards and conducted market research with physicians to gather their input on how to optimize the communication of the paltusotine program. We will continue to educate the medical community with data presentations at multiple medical conferences in the coming months. We will launch a campaign later this year directed towards health care providers to increase awareness of the unmet needs with the current standard of care, including injection site pain, breakthrough symptoms, and the month-long regimens required to identify the appropriate dosage for their patients receiving injectable depots. An accompanying campaign directed at patients will be launched early next year. Our market access team has also been in active dialogue with leading payers to understand the current marketplace and the dynamics for paltusotine to become a valuable treatment option for patients, if approved. PATHFINDER-1 data has already been well received and we are seeing a similarly enthusiastic response to our early conversations regarding PATHFNDR-2. We're also very pleased with the results from the open-label Phase II study in carcinoid syndrome patients that demonstrated meaningful reductions of both frequency and severity of flushing episodes and bowel movements caused by this disease. These effects were rapid, sustained, and consistent with the preliminary data we reported last December. Overall, we believe the safety and efficacy profile of paltusotine in this study supports progressing into a Phase III study as soon as we can. We plan to discuss these results with the FDA and align on a Phase III study design, which would enable us to begin a Phase III study by the end of the year. Finally, we strengthened our balance sheet with a $350 million private placement in February from new and existing equity investors. This additional capital has provided us with sufficient runway to fund operations into 2028 based on current projections for our pipeline of product candidates. In summary, looking to the rest of 2024 and 2025, we anticipate multiple upcoming milestones from our clinical candidates and continued advancement of our deep pipeline of emerging candidates that address increasingly higher prevalence indications. As has been our practice since inception, we continue to invest in our world-class discovery capabilities that provide the roots for our long-term success. With that, I'll hand it over to Dr. Alan Krasner, our Chief Endocrinologist, to talk about our clinical programs.

Alan Krasner, Chief Endocrinologist

Thank you, Scott. Today, I will provide updates on recently reported clinical programs, starting with paltusotine. As a reminder, the Phase III PATHFNDR program was designed to evaluate the safety and efficacy of paltusotine for the treatment of a broad spectrum of patients with acromegaly. Both PATHFNDR studies met all prespecified primary and secondary efficacy endpoints, and paltusotine was shown to be generally well tolerated. We, therefore, intend to seek approval for patients who might switch from injected SRLs to paltusotine as studied in PATHFINDER-1 and also in those who are not currently treated with medications and might start paltusotine as a first-line treatment, as studied in PATHFNDR-2. We reported most recently the top line results from the untreated patients in PATHFNDR-2. Besides meeting all key endpoints, it was notable that IGF-1 was reduced from elevated baselines in 93% of patients treated with paltusotine. These IGF-1 declines occurred rapidly, with most of the effect occurring in just two to four weeks. These reductions were durably sustained throughout the treatment period. Significant improvements in acromegaly symptom control associated with paltusotine compared to placebo have now been documented in two major independent controlled trials. As previously discussed, we are very excited to further explore our rich database into which patients reported their symptoms on a daily basis during the trials. With the database from PATHFNDR-1, we have already been able to perform additional interesting analyses, which we will be reporting at the Endocrine Society Meeting in June. We have wondered for a long time whether daily oral paltusotine might result in a difference in the frequency of day-to-day symptom exacerbations that plague many patients with acromegaly treated with long-acting injections, and we look forward to reporting on this soon at the meeting. We will also be presenting late-breaking updated data from our long-term open-label extension cohort from the Phase II ACROBAT advance study. A number of the participants in this study have now been treated with paltusotine for over four years. The overall data set suggests that paltusotine represents a lot more than just a user-friendly, convenient oral substitute for an injection. Unlike the current first-line agents, paltusotine has been rigorously demonstrated to control symptoms of acromegaly as well as biochemical markers of disease activity. The notably rapid IGF-1 response observed in PATHFNDR-2 could allow patients and physicians to reach the fully effective dose of paltusotine much faster than is the case for the current standard of care. A simple once-daily oral agent could prevent the pitfalls, pain, and unneeded expense associated with the current standard of care. People that are already dealing with the burdens of acromegaly might not need to schedule their lives around the next injection and dealing with the side effects that often occur after these injections. With paltusotine, one would not need to worry if the last injection was administered correctly, and whether or not it will last until the next one is due, nor would one need special equipment or to take a course on how to self-administer acromegaly medication at home. In short, paltusotine may represent a completely new paradigm for somatostatin receptor-based therapy. Paltusotine's second target indication, carcinoid syndrome, has also shown promising results. In March, we reported top line results from the open-label Phase II trial. This study enrolled participants with carcinoid syndrome who experienced one or both of the key symptoms of the disease: diarrhea and flushing. Participants were either naive to standard of care treatment or untreated and actively symptomatic or were controlled on SRL therapy and willing to wash out prior to entry. Paltusotine was generally well-tolerated at the doses evaluated in this trial with no severe or serious treatment-related adverse events. In addition, pharmacokinetics in this patient population was consistent with what we expected to see from prior experience. We observed significant and meaningful reductions in both the frequency and severity of bowel movements and flushing episodes, consistent with the initial results we reported last December. Importantly, the intensity of these symptoms was also reduced by paltusotine. These reductions occurred quite rapidly and were sustained throughout the eight-week treatment period. We intend to discuss the Phase II carcinoid syndrome data with the FDA to align on a Phase III study design. We look forward to updating you on the Phase III details, including dose, registrational endpoint, and timing once we've had these discussions. As Scott discussed, our second investigational compound in clinical development is atumelnant, which is a once-daily oral ACTH receptor antagonist in development for the treatment of both congenital adrenal hyperplasia, or CAH, and Cushing's disease. The adrenal glands are the sole source of excessive steroid that cause the clinical complications in both disease states, and the steroid production is driven by excessive exposure to ACTH. It is natural, therefore, to target the ACTH or MC2 receptor in order to fundamentally interrupt the pathologic progression of these diseases. That is because the receptor is the sole mediator of ACTH signaling, and it is found only in the adrenals. The lead indication for atumelnant is classic CAH, a genetic disorder that affects approximately 27,000 patients in the U.S. These patients lack a critical enzyme in the adrenals responsible for cortisol production. The hypothalamus and pituitary respond to these low cortisol levels by producing high levels of ACTH. This excess ACTH, in turn, causes overstimulation of the adrenal cortex, resulting in overproduction of cortisol precursors like 17-hydroxyprogesterone and adrenal androgens like androstenedione, also known as A4. The adrenal hyperandrogenemia causes many serious medical complications, beginning in utero, progressing through childhood and into adulthood. Because CAH patients cannot produce cortisol, exogenous glucocorticoid replacement is required for life, but replacement doses should be very low, and these low doses should not cause adverse effects. As a result, many physicians find it necessary to use high super physiologic doses of glucocorticoids in an attempt to suppress elevated ACTH levels and thereby, lower adrenal androgen production. These elevated glucocorticoid doses are frequently associated with adverse effects such as weight gain, elevated glucose, edema, bone loss, and a host of other serious medical problems. It is very difficult to find a dose of glucocorticoid, which effectively controls adrenal androgen production without causing these side effects. This highlights the fundamental challenge in treating this disease to strike the right balance between reducing adrenal androgens, yet minimizing the effects of excess glucocorticoids. We believe atumelnant is the right approach to achieve this balance and look forward to showing initial data from our Phase II studies in the coming weeks. Atumelnant was designed to reduce or eliminate ACTH stimulation at the level of the adrenal, thereby lowering adrenal androgen output. Once adrenal hyperandrogenemia is controlled, patients who are taking excessive doses of glucocorticoid should be able to lower their dose and reduce or even avoid steroid therapy-related adverse effects. Remember, the ACTH receptor in the adrenals is the only means by which ACTH drives the pathologic adrenal androgen output seen in CAH. And the ACTH receptor is a single chokepoint at which this overdriven system might be turned off. Our ongoing Phase II open-label sequential dose cohort study in CAH is evaluating safety and pharmacokinetics of atumelnant dosed for three months. In addition, we are evaluating pharmacodynamics. And in CAH, this is measured primarily using the androgenic biomarker, androstenedione, or A4, as well as the cortisol precursor 17-hydroxyprogesterone. The goal of treatment is to reliably and reproducibly eliminate excessive exposure to adrenal steroids as reflected by these biomarkers. The patients in our study continued their pretrial glucocorticoids at unchanged doses, so we can observe the time course and durability of any response to atumelnant itself. In future studies, we expect to evaluate glucocorticoid dose reduction once we know that the compound can reduce adrenal androgen output. As Scott mentioned, we will be presenting late-breaking atumelnant data at the upcoming Endocrine Society Meeting in June. This will not include the full cohort of patients in the CAH study, but will comprise initial data from a subset of the first two dose cohorts. We expect these early results will give us directional information that will help guide developmental plans for atumelnant in CAH. Initial data from the Phase II single-center trial in Cushing's disease will also be presented at the same meeting. With that, I will now hand it over to Marc to review the financials.

Marc J. Wilson, CFO

Thank you, Alan. Crinetics continues to be in a strong financial position, having ended the first quarter with approximately $900 million in cash and investments. This includes proceeds from the $350 million private placement equity financing we completed in February. Our solid financial foundation is projected to fund our current operating plan into 2028. And this includes plans to commercialize paltusotine for acromegaly, the initiation of multiple later-stage clinical trials in additional indications with paltusotine and atumelnant as well as continued investment in our pipeline. With respect to the financial results, research and development expenses were $53.3 million for the quarter ended March 31, 2024, compared to $38.5 million for the same period in 2023. The increase was primarily attributable to higher personnel costs and manufacturing and development activities, both of which were driven by the advancement of our clinical programs and the expansion of our preclinical portfolio. For the quarter ended March 31, 2024, general and administrative expenses were $20.8 million compared to $12.2 million for the same period in 2023. These increases were primarily attributable to higher personnel costs to support the growth of the organization. Net loss for the quarter ended March 31, 2024, was $66.9 million compared to a net loss of $46 million for the same period in 2023. Revenues were $0.6 million for the quarter ended March 31, 2024, compared to $2.7 million for the same period in 2023. Revenues during the current year's quarter were primarily derived from our paltusotine licensing arrangement with our Japanese partner, SKK, and revenues for the prior year were associated with licensing arrangements for paltusotine and CRM-01941, another somatostatin-targeted development candidate. Net cash used for operating activities for the quarter ended March 31, 2024, was $52.9 million. We continue to expect our cash burn to be approximately $50 million to $60 million per quarter for the remainder of 2024. I will now hand it back to Scott for closing remarks before we begin Q&A.

R. Struthers, CEO

Thank you, Marc. We will continue to build on the strong progress this quarter throughout the rest of the year and beyond. We look forward to sharing atumelnant data in the coming weeks as well as providing continued updates as we progress paltusotine to regulatory submissions and as we make continued advancements in the exciting new programs beginning to emerge from our discovery efforts. Thank you all for your attention. Operator, we are ready to take questions.

Operator, Operator

Your first question comes from Yasmeen Rahimi of Piper Sandler.

Yasmeen Rahimi, Analyst

Yes. I know we will discuss CAH's upcoming readout during the Q&A, but I would like to focus on the Cushing's dataset. It appears to be an interim look run by an NIH investigator who will share the data. We all understand that cortisol reduction is key. I would like to hear your thoughts on what we hope to learn from that study and what the potential next steps might be for Cushing's development. I will return to the queue.

R. Struthers, CEO

Thank you, Yas. Alan, can you take that question?

Alan Krasner, Chief Endocrinologist

Sure. Yas, we are collaborating with a leading KOL at the NIH in our Cushing's disease study. This is a study in which the compound is dosed for 10 days, while patients are in the clinical research center, and there is frequent monitoring of many parameters, but especially, pharmacodynamically speaking, of most interest would be cortisol. These are patients with Cushing's disease who start with high levels of cortisol excretion. And of course, we'll be interested to see if cortisol is reduced during this 10-day dosing period. That is the information we would get from this study that I think will be of interest. We expect that the data we would present at the Endocrine Society Meeting would give us directional kind of information to help guide our future development in Cushing's. Sort of like when we reported carcinoid syndrome data in December, it was directionally of interest. I would expect we would learn a great deal from what we've seen so far. Of course, it will be a subset of the patients as we discussed in our remarks. But still, again, I hope we have qualitative directional information.

Operator, Operator

Your next question comes from Jessica Fye of JPMorgan.

Jessica Fye, Analyst

What elements of atumelnant's profile do you think will best differentiate it from CRF antagonist in CAH?

R. Struthers, CEO

Well, thank you, Jess. As we've said over the course of discovery and development in this program, that if you look at the mechanisms by which the adrenal is controlled, they all converge on ACTH acting at its receptor on the adrenal, which is formed by the MC2 protein, but we'll just call it the ACTH receptor. It's the only way ACTH can act, and it's the only thing that the ACTH receptor does. And so by blocking that, we're blocking a single chokepoint of action of the whole hypothalamic-pituitary-adrenal axis on the adrenal. And we've always said we expect to achieve good blockade of adrenal activity, whether it's measured by adrenal androgens in CAH or by glucocorticoids in Cushing's patients.

Operator, Operator

Your next question comes from Cory Jubinville of LifeSci Capital.

Cory Jubinville, Analyst

I really like the new name for 04894: atumelnant. I'm quite interested in your Endo abstract title regarding the CAH data, which is "Atumelnant Induces Rapid and Profound Reductions of A4 in 17-OHP and Participants with CAH." The term "profound" stands out to me. Could you help us set expectations for the data we'll see at Endo? And if you can't provide detailed information, could you share at a high level how satisfied you are with the pharmacodynamics you're observing with atumelnant compared to the CRF1 antagonist? We've also noted mixed results recently from competitors' CAH readouts. Can you give us a better understanding of the types of patients you've been enrolling in this Phase II study?

R. Struthers, CEO

Yes. I think you'll have to wait until Monday, June 3 at 12 p.m. Eastern Time when the embargo lifts before we can go into detail on this. We look forward to seeing you at our poster presentations and welcome everyone to our Investor Relations event at the Omni Hotel on the same day at 6 p.m. Can you repeat the second half of your question, if you're still on the line?

Cory Jubinville, Analyst

Yes. I guess at a high level, how satisfied are you with the pharmacodynamics you're seeing in comparison to some of the CRF1 antagonist. And we've also seen mixed results in competitors' CAH readouts. And can you help us understand the types of patients that you've been enrolling into this Phase II study in terms of whether it be compliance or whether it be severity of disease or degree of control the...

R. Struthers, CEO

Yes, I understand that many people are eager to establish benchmarks, but I have always advocated for focusing on treating the entire disease rather than setting limits based on a particular compound. Regarding our level of satisfaction, you will need to review the data presented at Endo. For now, I'll just say that we invite you to come and see us. We are excited about sharing our findings and discussing them with everyone.

Alan Krasner, Chief Endocrinologist

Maybe, Scott, I could address the question on what sort of patients are enrolled in this study, if that would be helpful.

R. Struthers, CEO

Yes. Please take it.

Alan Krasner, Chief Endocrinologist

These are adult patients with classic CAH, which means they have the most severe form of enzyme deficiency. They are born with this condition and generally need to take glucocorticoid replacement throughout their lives. All participants in the study are adults with this condition who are currently on glucocorticoid therapy. Typically, they will start the study with elevated adrenal androgen levels, and we are examining a range of disease severities to be as inclusive as possible. The study involves a three-month dosing period during which we will administer a fixed dose of atumelnant. The background pretrial glucocorticoid therapy remains unchanged during the study. Our primary goal is to evaluate how well 4894 reduces adrenal androgen output on its own, without any adjustments to glucocorticoid doses, for future studies. If 4894 is effective in managing adrenal hyperandrogenemia, we will also consider glucocorticoid dose reduction in subsequent studies, as many of these patients are on excessively high glucocorticoid doses and would benefit from a reduction to the appropriate replacement dose levels.

Operator, Operator

Your next question comes from Joseph Schwartz of Leerink Partners.

Joseph Schwartz, Analyst

Congrats on the progress. Given the Phase II CAH atumelnant study continues to enroll patients, I was wondering if you could talk about what more you hope to learn or demonstrate beyond the interim data, which you'll be reporting at Endo? Are there additional questions you need to answer before you can advance to Phase III? And when will the next look at the CAH trial be?

R. Struthers, CEO

Thanks, Joe. Alan, why don't you take that question?

Alan Krasner, Chief Endocrinologist

Yes. So we will be presenting, Joe, a subset of the study. The goal of the Phase II study is to fully evaluate the relationship between the dose of an experimental agent and the safety, of course, but also pharmacodynamic response at various doses. So this will be a subset. I think we will get good directional information from the doses tested, but we do want to complete the study to make sure we have a complete range of dose response evaluated to help us best design subsequent development for the compound.

Operator, Operator

Your next question comes from Jon Wolleben of Citizens JMP.

Jonathan Wolleben, Analyst

One more for me on 894 and then carcinoid syndrome. When we're thinking about the data at Endo, how do you balance the relative importance of a percent reduction in A4 versus achieving normalization as far as clinical development and also management of patients in the real world? And then wondering if you could give us some high-level thoughts on the Phase III preliminary design in carcinoid syndrome?

R. Struthers, CEO

We will skip the next two questions on that topic, but I'll address the first part, and Alan can discuss carcinoid syndrome. Generally, using percentages is just a simplified way of expressing things, and it really depends on the starting point when considering the effect magnitude. The goal of therapy is to reduce androgens as much as possible to eliminate their effects and adjust glucocorticoid levels to a normal state. While using percentages can be a useful and straightforward method for making comparisons, the primary focus should remain on the patients themselves. It's important to note that it's not only about biomarkers but also how changes in hormone levels can influence symptoms and disease expression in these patients. Alan, would you like to add anything regarding carcinoid syndrome?

Alan Krasner, Chief Endocrinologist

Sure. Yes. As we've reported Phase II data, we are actively designing the Phase III program for carcinoid syndrome. The plan, of course, is to review with the FDA the full data set from the Phase II study as well as our proposals for Phase III and to align with them on the design of Phase III. I can give you some sort of high-level thoughts about Phase III. Again, we have to remember that we haven't had those regulatory discussions yet. So it's not set in stone. But in general, based on regulatory history in this disease state, I would anticipate we're looking at a placebo-controlled trial. The most recent approval for carcinoid syndrome involved a three-month placebo-controlled trial. And I think that's kind of what we're anticipating here too. Of course, the key endpoints would have to do with the cardinal symptoms of carcinoid syndrome: diarrhea and flushing. And as we already reported in Phase II, we see reductions in both the frequency of these episodes but also the severity of diarrhea and flushing, too, with paltusotine therapy. And I think we will very likely, very carefully measure those things in Phase III as well. And in terms of sample size, historically, carcinoid syndrome pivotal trials, first of all, they're generally single pivotal trials for carcinoid syndrome. And the sample sizes in the past have ranged between roughly 80 and 150 patients. And based on our power calculations to date, I think that's right about the range I would expect for our Phase III trial as well. I hope that's helpful.

Operator, Operator

Your next question comes from Leland Gershell of Oppenheimer.

Leland Gershell, Analyst

Congratulations on the progress. Also a couple for me on carcinoid, maybe for Alan. With the benefit now of a few months since the reveal from the Phase II, I want to hear of any feedback you've received from physicians with respect to their interest in using paltusotine in patients who are untreated on SRLs, given the large population segment who is not currently on therapy. And then I'll have a follow-up.

R. Struthers, CEO

Go ahead, Alan.

Alan Krasner, Chief Endocrinologist

Thanks for the question. We, of course, work closely with a number of specialist physicians, oftentimes oncologists who specialize in neurologic patient care and also themselves usually treat those patients with carcinoid syndrome. A lot of them are our investigators and our study steering committee. And the feedback has been generally very positive from them. They're very excited about the data we have, and I would say pleased to be helping us think about what's coming up in Phase III. And probably many of them would participate in Phase III as well. I think it's recognized by many of the physicians who treat this that there are some shortcomings with these injections that are the standard of care for the control of carcinoid syndrome. And we went through many of those limitations in my prepared remarks, but these are just very burdensome from patients in many ways. They're also technically difficult to deliver in a reproducible way. And this has actually been shown in the literature in this patient population, in particular. So I think both the patients and the physicians have expressed, to me, at least, positive thoughts that this would be a real contribution to the field.

Leland Gershell, Analyst

And then further to the point of the data you've shown. So the 5-HIAA levels in serotonin were pretty well-reduced by paltusotine. It seems like that was much better than we've seen with the SRLs. Wondering if that particular finding has resonated with respect to maybe longer-term efficacy beyond, I think, the eight weeks that you've shown with the Phase II for longer-term control of the cardinal symptoms.

Alan Krasner, Chief Endocrinologist

It's a thought-provoking question. Unfortunately, I don't have the answer. I'm uncertain if it's even documented in existing literature. The ability of the biomarker response to predict long-term responses regarding these tumors or symptoms is not well established. Typically, these biomarkers are used in clinical settings mainly to diagnose carcinoid syndrome, but their effectiveness in monitoring therapy is unclear. However, I appreciate you bringing that up. We did observe some promising responses, although finding such information in older literature is challenging. This may, in part, be due to advancements in the methodologies used to measure these biomarkers. We are utilizing the latest assays, which I believe could have contributed to the noticeable symptom and biomarker responses we observed. We certainly aim to leverage this for our Phase III program as well.

R. Struthers, CEO

Just to follow up a little bit, I wanted to mention your comment about potentially reaching those patients who are currently being treated. I find it surprising that a significant number of patients with carcinoid syndrome are not receiving treatment when they clearly should be. It seems there must be a judgment being made regarding the burden of treatment compared to the burden of the disease and/or access to medications. This has resulted in too many patients lacking access to treatments that could benefit them. We look forward to exploring ways to provide this to more patients than are currently using the injectable depot therapies.

Operator, Operator

Your next question comes from Douglas Tsao of H.C. Wainwright.

Douglas Tsao, Analyst

I was wondering, Scott, about the early-stage pipeline. You have several therapeutic areas you're focusing on, with candidate selections for this year. I believe you mentioned diabetes and obesity for next year. Is there any prioritization among these? How do you view the pace at which they will enter the clinic and begin to show results? You have a history of conducting innovative early-stage studies that provide significant pharmacodynamic data early in development. I’m curious if you expect similar outcomes for these candidates.

R. Struthers, CEO

Thanks, Doug. Yes, the emerging pipeline is really super exciting. And we are really committed to what I call the craft of drug discovery. So we want to make sure that these are really the best possible molecules we can make before we invest in development. And so those programs are now really starting to get close to molecules that might be good enough. PTH is probably first. We've been doing some non-GLP tox studies on multiple candidates, and it looks like the team is getting close to selecting the best one out of several good ones. And then the other programs are successively behind that. Fortunately, we've been in a financial position where we don't need to make difficult prioritization decisions about which good molecule to slow down over the other good molecules. And I do think there's a little bit of just internal prioritization we have to do as we balance workloads between some of the different projects. But largely, all projects are moving forward as fast as we can. And I'm optimistic that that's going to leave a whole sequence of upcoming clinical information on these programs over the next 12, 18, 24 months.

Douglas Tsao, Analyst

Okay. Great. That's really helpful. Congrats on the progress.

Operator, Operator

Your next question comes from Catherine Novack of Jones Research.

Catherine Novack, Analyst

I'm just wondering, when it comes to commercialization, what's the overlap in terms of treatment centers and prescriber base for CAH and acromegaly? And then was there any overlap extended to carcinoid syndrome? Is that a completely different institution that you're looking at?

R. Struthers, CEO

Thanks, Catherine. There's a high degree of overlap. And maybe, Jim, you could get into some more detail there.

James Hassard, Chief Commercial Officer

Yes. Thanks, Catherine. In terms of acromegaly and especially carcinoid syndrome, when we look at the 35 to 40 pituitary treatment centers, typically, they are academic centers that also overlap with the National Comprehensive Cancer Center network. So when we're doing some sales force sizing, we see a lot of overlap between acromegaly and carcinoid syndrome. Even in terms of endocrinologists, there's a high degree of overlap with acromegaly and Cushing's disease, of course, because it's pituitary, but we're also seeing the same for congenital adrenal hyperplasia. So a lot of the specialist endocrinologists are seeing all three pituitary or adrenal diseases.

R. Struthers, CEO

And I'll just add that, that was really part of our long-term strategy when we started getting into these indications. So that not only from a commercial point of view do we start building into the same centers and same prescribers, but also from a development point of view so that we start using the same investigators and centers again and again and again, and trying to find synergies and ways of working well together as those relationships go for the long term.

Operator, Operator

Your next question comes from Jeffrey Hung of Morgan Stanley.

Michael Riad, Analyst

This is Michael Riad on for Jeff Hung. Circling back to the Phase III design for carcinoid syndrome. Is there any ability for the study design to accommodate or potentially show the ability to prevent like breakthrough symptoms in the typical waxing and waning versus SRLs, maybe during the initial screen or wash out? Just wondering if there's any potential for that analysis.

R. Struthers, CEO

Thanks. I think that's an important question, and we are asking ourselves that. Alan, you might want to comment a bit on it.

Alan Krasner, Chief Endocrinologist

Yes, it's an important concept because, as I mentioned earlier regarding the limitations of current injection therapy for carcinoid syndrome, this is a significant issue. When patients receive long-acting injections more often than once a month, they may still experience days with active breakthrough symptoms like diarrhea or flushing, sometimes extending beyond a single day. This often leads them to take additional medications, such as antidiarrheals or even short-acting subcutaneous boluses of octreotide in addition to their long-acting octreotide. The reasons for these breakthrough episodes are not completely understood, but I suspect they may relate to variations in drug exposure from month to month. There is known variability in the technique used to deliver octreotide accurately to the intramuscular space, which I believe contributes to this phenomenon. In our trials, we plan to ask patients daily about how they are feeling through an electronic diary, similar to what we did in Phase II and Phase III for acromegaly. I am hopeful that we will discover whether the issues seen with long-acting injections could potentially be addressed with a daily oral dose of a simple oral agent.

Operator, Operator

Your next question comes from Brian Skorney of Baird.

Charles Moore, Analyst

This is Charlie on for Brian. So just wanted to switch gears a little bit towards the PTH asset or assets. Just kind of wanted to ask what from the presentation earlier this year at the Bones and Teeth Gordon Research Conference really gave you confidence in the profile of the molecules you're developing. And if maybe you could kind of walk us through what excites you about it as well as if this is kind of the profile that you're looking for from the other assets that you're selecting from.

R. Struthers, CEO

Got it. How about Alan, I'll talk about the preclinical and you can talk about why we're excited about it clinically. But very much, this is like many of our programs where the endocrinology in animal model species is almost identical to the endocrinology in humans. And we know that it's very robust way in rats, for example, to induce hyperparathyroidism by infusing excess of parathyroid hormone, and we can watch calcium go up. And then we can introduce one of our antagonists and watch calcium normalize, and also take normal rats and we give them PTH antagonist and see their PTH levels rise. So this type of pharmacodynamic response in a model system is very much the same type of thing we would do in a healthy volunteer. And it goes up and down our pipeline. And it's a reason why, from a business perspective, endocrinology is just such a great field because you do so much derisking so early on, whether it's in animal models which closely mimic humans, or its early healthy volunteers or early patient studies where you're measuring biomarkers that are completely objective and well defined. But maybe, Alan, you can comment on clinical need and why we're excited about a PTH antagonist for these different patient populations.

Alan Krasner, Chief Endocrinologist

Yes, sure. This is a novel mechanism of action for that could potentially help a great number of patients who have parathyroid hormone excess for any number of reasons. And by the way, also parathyroid hormone-related protein excess. So beginning with hyperparathyroidism. This is a fairly common endocrine disease, primary hyperparathyroidism in which one of the parathyroid glands in the neck typically overgrows and causes unregulated excess secretion of parathyroid hormone. That results, as Scott mentioned, in hypercalcemia, high calcium levels in the blood, but it's really a multi-organ systemic disease that also damages the bones and the kidneys, in particular. And the hypercalcemia itself can cause sometimes very serious symptoms. Now fortunately, for patients with primary hyperparathyroidism, there are very, very effective surgical options available, and many of these patients are cured surgically. However, there is a very important subset of patients who don't get cured by surgery, sometimes because more than one gland actually enlarges in some patients. And there is really a great number of patients who could benefit from having a medical option to control hyperparathyroidism when surgery has not worked. And the other thing I would point out is even with patients who potentially could have surgery, it turns out, a lot of them don't have surgery for any number of reasons, including the fact that they may not be surgical candidates. And so therefore, I see a lot of potential for a medical option in this area. That's just one potential. It's probably the most straightforward indication, but there's also something called hypercalcemia malignancy, which is caused by parathyroid hormone-related protein, which also binds to the PTH receptor. Those patients could also use a new option. There are treatments available, but they all have limitations, and these patients can be quite ill. And I think it's an exciting prospect also potentially for the future for a PTH antagonist. And then there's more, but we don't have time to talk about more.

Operator, Operator

Your next question comes from David Lebowitz from Citi.

David Lebowitz, Analyst

With respect to the data being presented for CAH, how should we benchmark it versus what we've seen from other therapies? And what should we expect? And conversely, what should we not expect?

R. Struthers, CEO

Alan, maybe you want to reiterate that.

Alan Krasner, Chief Endocrinologist

Yes, I believe we are looking for trend information in the biomarker responses. As discussed, it's not just about the percentage reduction in biomarkers but also about how many patients return to normal levels. We also need to carefully evaluate all the clinical features of the disease when analyzing our data. Therefore, our Phase II interim data will not be purely a statistical exercise. However, I am optimistic that we will receive valuable directional insights regarding which doses may be effective and which designs we should consider for future development beyond Phase II.

Operator, Operator

Your next question comes from Dennis Ding of Jefferies.

Yuchen Ding, Analyst

Congratulations on all the progress. If I can ask on CAH, maybe just talk about how you're thinking about having to go to the high 160-milligram dose as it was an optional cohort. And just wondering if that cohort has started enrolling or not or do you even plan to.

R. Struthers, CEO

Alan, do you want to talk about how we think about cohorts and dose selection?

Alan Krasner, Chief Endocrinologist

Yes. This is a sequential dose cohort study. The first cohort of patients with CAH receives an 80-milligram once-per-day dose of atumelnant. This is based on Phase I data from healthy volunteers indicating that this dose appears to be effective. Once we finish the first cohort's dosing, all the data will be reviewed by a safety review committee, which will then recommend the dose for the next cohort. The next cohort may involve a higher or lower dose. We will share that information at the Endocrine Society Meeting during the scientific presentation. It is also reasonable to expect that we will have patients from both the first and some from the second cohort.

Operator, Operator

There are no further questions at this time. I would hand over the call to Dr. Scott Struthers, Founder and Chief Executive Officer, for closing comments. Please go ahead.

R. Struthers, CEO

Thank you, everybody, for being with us today, and we look forward to seeing many of you in Boston in the beginning of June and throughout the year, as more and more interesting things start coming out from the pipeline. Thanks again for your time. Good night.

Operator, Operator

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation, and you may now disconnect.