Hello, everyone. Thank you for joining us, and Welcome to the Crinetics Pharmaceuticals first quarter 2026 financial results. After today's prepared remarks, we will host a question and answer session.If you would like to ask a question please press star one to raise your hand, to withdraw your question, press star one again. I will now hand the conference over to Gayathri Diwakar, Head of Investor Relations. Gayathri, please go ahead.
Thank you, operator. Good afternoon, everyone, and thank you for joining us to discuss the first quarter 2026 results. Today on the call, we have Dr. Scott Struthers, Founder and Chief Executive Officer; Isabel Kalofonos, Chief Commercial Officer; Dr. Alan Krasner, Chief Endocrinologist; and Tobin Schilke, Chief Financial Officer. Please note there is a slide deck for today's presentation, which is in the Events and Presentation section of the Investors page on the Crinetics website. In addition, a press release was issued earlier today and is also available on the corporate website s lide 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 your SEC filings.
Such forward-looking statements are not a guarantee of performance, and the company's actual results could differ materially from those stated or implied in such statements due to risks and uncertainties associated with the company's business. In particular, today, we will be reviewing launch progress to date, our commercialization plans, future performance, and other data about the acromegaly market, which are all necessarily subject to a high degree of uncertainty and risk. These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's news release, the company's other news releases in Crinetics SEC filings, including its annual report on Form 10-K and quarterly reports on Form 10-Q. In addition, this call will include certain non-GAAP financial measures. A presentation of the most directly comparable GAAP financial measures and reconciliations thereto are included in today's news release, accessible from the Investor Relations section of our website.
I would also like to specify that the content of this conference call contains time-sensitive information that is accurate only as of this live broadcast. Crinetics takes no obligation to review or update any forward-looking statements to reflect events or circumstances after the date of this conference call. With that, I will hand the call over to Scott.
Thanks, Gayathri. Thank you for joining us on today's call, m oving on to slide four. This has been another strong quarter of executing our plan to make Crinetics the premier endocrine company. Crinetics is committed to translating the complexities of cutting-edge endocrinology into real value for patients. With the launch of PALSONIFY, we are delivering on that commitment every day. We've made great strides in building the business by consistently adding patients every week to the pool that will be helped by PALSONIFY for many years to come. The consistent positive feedback we continue to receive from both patients and HCPs is especially gratifying. We have also meaningfully advanced our deep clinical stage pipeline with four major trials running and recruiting nicely. These represent blockbuster opportunities across several areas.
We continue to grow the pipeline with multiple compounds and IND-enabling activities with more to come from our ongoing discovery efforts. We have built a company that has proven it can discover, develop, and deliver its own novel therapeutics, and we are well-capitalized to continue to execute this growth strategy and drive value creation. I'm very proud of our team's strong execution across all dimensions of the company's first launch. This collective effort has translated into 232 additional patient enrollments and $10.3 million in net product revenue for the quarter. We are making strong progress with access, including continually driving higher conversion from enrollment forms to patients starting PALSONIFY and growing reimbursement as coverage on formularies expand. We expect low discontinuation rates based on our clinical studies. Therefore, the number of patients on PALSONIFY should continue to compound.
We continue to see momentum build on all fronts in the second quarter. While it's early days, we are confident in our growth trajectory. PALSONIFY sets a new standard of care for the treatment of acromegaly and is on track to become the most prescribed brand. Over the last few weeks, we've continued to advance PALSONIFY globally, including the European Commission approval of our MAA, the JNDA submission in Japan by our partners at SKK, and our MAA submission in Brazil. These milestones underscore the strength of PALSONIFY's clinical data and the significant unmet need amongst patients around the world. As we expand internationally, we are taking a disciplined market-by-market approach, prioritizing geographies with clear regulatory and reimbursement pathways, and pacing investment in line with an increasingly dynamic global pricing and access environment.
All in all, it's clear that PALSONIFY is positioned to become the leading acromegaly treatment, and Crinetics has an exceptionally equipped team to bring it to the patients in need. With our early commercial success, continued clinical execution, and a robust balance sheet to support the advancement of our innovative pipeline, Crinetics is well positioned to generate value for all stakeholders in both the near and long term. I'll now turn the call over to Isabel to discuss the PALSONIFY launch in more detail. Isabel?
Thank you, Scott, t urning to slide six. The PALSONIFY launch continues to build on its strong momentum. I'm incredibly proud of our team. Their execution has led to a strong demand across all patient segments, expanding the breadth and depth of prescribing activity and solid reimbursement coverage. PALSONIFY is establishing itself as a newer standard of care in acromegaly, addressing a clear need for an effective, safe, and convenient treatment to control the disease, m oving to slide seven , starting with patients. As Scott mentioned it, in the first quarter alone, we secured 232 new patient enrollment forms. This performance reflects a strong execution in the field and demonstrates that we are expanding beyond early adopters and clinical trial transitions to reach the broader acromegaly population. As expected at this stage of launch, the majority of new enrollments continue to come from patients switching from existing therapies.
We are seeing meaningful breadth and switching behavior with patients coming from all acromegaly therapies, including lanreotide, octreotide, cabergoline, oral octreotide, and combination regimes. We are very pleased to see that PALSONIFY is performing consistently across this diverse patient base, with physicians and patients experiencing its benefits regardless of prior therapy. Importantly, both controlled and uncontrolled patients have switched to PALSONIFY, reinforcing its versatility across different clinical profiles. We are also encouraged by the expansion within treatment-naive patients. From the fourth quarter in 2025 to the first quarter in 2026, treatment-naive patients increased from 5% to 15% of total enrollments. We believe this is a positive signal of growing physician confidence, and over time, we expect sustained growth in the share of naive patients. Providers are increasingly viewing PALSONIFY as a reliable solution across a broad range of patient profiles.
As previously discussed, our strategy remains focused on driving adoption among both treatment-naive and switching patients while expanding the overall market. PALSONIFY's differentiated profile, including rapid onset of action in as little as two to four weeks, sustained symptom and IGF-I control, and convenient once-daily oral dosing positioned it well to address key limitations of existing therapies. We are already seeing early signs of this potential. Approximately 15% of first quarter prescriptions came from patients reinitiating therapy after discontinuing prior treatment, which is an encouraging indicator of PALSONIFY's ability to expand the treatment population over time. Our patient strategy continues to focus on empowering the patient voice and ensuring early and seamless access to treatment, as described on slide eight. This includes rapid initiation through our QuickStart program and comprehensive hub support.
We also support patients with a robust suite of services designed to meet patients' needs throughout their treatment journey, including education delivered by our endocrine nurse educators and engagement through our patient ambassador program. Our ambassador program connects with patients through multiple digital and social channels, as well as live patient ambassador programs. The patient stories being shared reflect a diverse range of experiences on PALSONIFY, including individuals who were previously uncontrolled on existing therapies and who have achieved meaningful IGF-I reduction along with clinical important symptom improvement. We believe this will motivate patients to more proactively manage their acromegaly and to initiate informed conversations with their physicians about PALSONIFY. via CrinetiCARE, we are providing comprehensive support to help navigate insurance coverage and minimize friction in the prescribing process.
Together, these efforts reinforce our commitment to supporting patients, amplifying their voices, and helping them take a more active role in their care, t urning to slide nine. I am very pleased with our marketing and field execution. We continue to expand our prescriber base. As of March 31st, there were 263 unique prescribers, up from over 125 at the end of 2025. This represents an important and expanding foundation for future growth. At large treatment centers, we are seeing top prescribers begin with a gradual number of patients with highly positive responses. In many cases, broader adoption is currently limited not by interest, but by appointment availability, which reinforces our confidence in underlying demand. Consistent with the prior quarter, enrollments remain evenly split between academic and community settings, reflecting broad relevance across practice types.
Awareness of PALSONIFY continues to build, supported by targeted media outreach, a strong presence at major congresses, and a growing body of scientific publications. This includes a recently published indirect treatment comparison demonstrating PALSONIFY's value relative to other therapies, as well as two oral sessions at the American Association of Clinical Endocrinology, including a late breaker that presented the first six real-world cases highlighting PALSONIFY's efficacy in both treatment naive and uncontrolled patients. Our commercial execution continues to support educational programs and peer-to-peer engagement. Overall, we are very pleased with the positive experience prescribers had with PALSONIFY, which reinforces our confidence in continued adoption and growth. From an access standpoint, approximately 70% of patients on therapy at the end of first quarter were reimbursed, a meaningful improvement from last quarter, and patients are continuing to transition from QuickStart to reimbursed product.
Over time, we expect nearly all patients to have coverage for PALSONIFY, and we will continue to provide QuickStart when needed to ensure initiation of therapy as soon as possible. We are also seeing most prior authorizations approved for 12 months and aligned with the label, reflecting payer confidence in both the clinical profile and durability of benefit. Turning to slide 10. Payers appreciate PALSONIFY's unprecedented safety and efficacy, which continues to be reinforced with new research and publications. As I mentioned it, we recently published in the Journal of Clinical Endocrinology & Metabolism, a comparison of PATHFNDR-1 results against other approved acromegaly therapies. The analysis showed placebo-adjusted IGF-I normalization of 79.7% with paltusotine, more than double what has been reported for both subcutaneous or oral octreotide. This efficacy data, coupled with PALSONIFY's fast onset of action and symptom control, are resonating strongly with payers.
We continue to have highly productive discussions with top payers across the country, including regional and self-insured employer groups, supported by compelling clinical presentations that are resonating clearly. These conversations are translating into results. We are achieving formulary wins earlier than the typical decision timeframe, reinforcing the strength of PALSONIFY's value proposition. Moving to slide 11. Importantly, we have now achieved over 60% coverage and remain on track to exceed our 75% coverage goal by the end of third quarter of 2026. Our national account directors will continue to meet with payers in the next quarter to continue to accelerate coverage. We have delivered this progress with improved speed to therapy and continued operational efficiencies across prior authorization and appeals.
Collectively, this reinforces that payers recognize the meaningful clinical benefit of PALSONIFY and the value of keeping people living with acromegaly in sustained biochemical and symptom control. Overall, our experienced commercial team is executing extremely well. The value proposition is clearly resonating with all stakeholders, and we are encouraged by the trajectory of the launch as we continue to expand access and improve outcomes for patients. I will now hand the call to Alan to discuss the pipeline.
Thanks, Isabel. As we launch PALSONIFY, we continue to advance our deep homegrown pipeline. This pipeline continues in the PALSONIFY tradition of using novel and meticulously designed small molecules to interact with therapeutic endocrine receptors to improve the health and lives of our patients. Like PALSONIFY, we work to create truly new and needed treatments, which are easy to use for the patients and for their healthcare providers. As a clinical endocrinologist, I have long been frustrated by what I call no better option inertia, and the history of acromegaly care is a great example of this. For decades, we have been telling our acromegaly patients treated on depot injections that their blood tests look okay, therefore they are okay. Even if the patient wasn't feeling okay, there was very little we could do about it anyway.
We knew that there were a lot of unsolved problems, not the least of which was unstable control of acromegaly symptoms, even when blood test results suggested normal or close to normal IGF-I levels. That's where PALSONIFY came in. It was long past time to break the inertia and create a better option. One that, for the first time, was approved with a rigorous demonstration of IGF-I normalization and symptom control. The patients don't have to wait a long time to achieve these goals. PALSONIFY for acromegaly is only the first candidate on this pipeline slide, and the potential patient impact across our pipeline is enormous. atumelnant is another great example of a Crinetics' pipeline candidate. It has a novel mechanism of action that has already resulted in unprecedented biomarker and clinical responses in short-term phase II studies.
The phase III CALM-CAH adult and phase II/III BALANCE-CAH pediatric studies are actively enrolling with a great deal of patient and investigator interest. We are also excited to begin enrollment into the phase II/III EQUILIBRIUM ADCS study in the near future. Additionally, we will report interim data from our phase II CAH open label extension later in the year. When I look at slide 13, I see a lot of scientific creativity addressing long-standing inertia in clinic, and plenty of opportunities for significantly better therapies to address many endocrine and endocrine oncologic disease states. We don't settle for the status quo at Crinetics. We don't do inertia. I'd like now to update you on our activities at major medical conferences. I recently returned from the American Association of Clinical Endocrinology meeting, where PALSONIFY data were featured in two well-received oral presentations.
As Isabel mentioned, one of these was the first description of real-world experience using PALSONIFY presented by a prescribing physician. There is no better way for practicing healthcare providers to learn about a new product than discussing with each other personal observations of how patients do with the treatment. We have heard many powerful anecdotes from patients. These real-world results are very consistent with what we are hearing. Diligent study and follow-up does not stop just because a product is approved. The annual Endocrine Society meeting is coming up in June. There will be several Crinetics data communications, three of which are oral presentations. One of these oral presentations will summarize results of up to two years of long-term safety and efficacy data from the phase III PATHFNDR OLE studies.
Another oral presentation will detail final results from the phase II TouCAHn study results for atumelnant in the treatment of adult congenital adrenal hyperplasia or CAH. The third will present new dosing data from the ongoing single center study evaluating atumelnant in patients with ACTH-dependent Cushing's syndrome. With the great potential across the Crinetics pipeline, I expect we will be presenting at these and other meetings for many years to come. With that, I will hand the call to Tobin for a financial update.
Thank you, Alan. Turning to slide 16, our financial results for the first quarter 2026 demonstrate a balance of disciplined execution and strategic investment as we advance the development of our pipeline and commercial launch of PALSONIFY. In the first quarter, we recognized $10.7 million in total revenue, consisting of $10.3 million in net product revenue from PALSONIFY and $0.4 million from our licensing agreement with our Japanese partner, SKK. Cost of product revenue in the first quarter was $0.2 million. prior to PALSONIFY's approval last September, manufacturing costs were expensed through R&D at zero cost inventory. If we were to include the cost of product sold that was previously expensed at zero cost inventory, the cost of product revenue would have increased by less than $0.1 million.
To date, we have only distributed zero cost inventory and expect to continue to do so for the near term. Our research and development expenses for the first quarter were $100.1 million compared to $85.1 million in the fourth quarter. The increase compared to the fourth quarter is primarily due to the ramp-up of ongoing phase III trials as well as the initiation of the phase II/III pediatric study of atumelnant in CAH. selling, general, and administrative expenses were generally steady at $50.8 million for the first quarter compared to $53.7 million in the fourth quarter. The fluctuation compared to the fourth quarter reflects timing variability of commercial investment. We ended the quarter with $1.3 billion in cash equivalents, and investments.
As of April 23rd, 2026, we had approximately 105.4 million shares of common stock outstanding. On a fully diluted basis, we had 123.5 million shares outstanding. This includes our outstanding options, unvested restricted stock units, and shares expected to be purchased under our employee stock purchase plan. Moving to slide 17. We are maintaining our guidance for GAAP and non-GAAP operating expenses in 2026. We expect GAAP operating expenses to be between $600 million and $650 million. We expect our non-GAAP operating expenses, which exclude cost of product revenue, stock-based compensation, depreciation, and amortization, to be between $480 million and $520 million.
Based on our current operating plans and cash position, we project that our existing cash and investments will be sufficient to fund our operations into 2030. This provides us with significant runway to execute on the commercialization of PALSONIFY, pivotal readouts for ongoing clinical trials in carcinoid syndrome, adult CAH, pediatric CAH, and Cushing's, and continued advancement of our early pipeline, including proof of concept for CRN09682. I'll now turn the call back to Scott for some closing remarks.
Thank you, Toby. Turning to slide 19. PALSONIFY sets a new standard for the medical treatment of acromegaly. I'm very pleased with the progress we have made on the launch. We are optimistic that the trajectory ahead of us will make it the most prescribed treatment for these patients. As we approach the halfway point of 2026
Crinetics is in a unique position of strength with fully integrated capabilities, a deep pipeline, and robust balance sheet. We are nicely advancing this innovative portfolio of clinical programs. The site activations and enrollment trends in all studies are positive. I look forward to sharing meaningful data from these programs as they mature. Beyond our late-stage trials, we're continually innovating on our early-stage programs and moving them forwards towards the clinic, as well as beginning new discovery efforts. We've also taken a new step for the company in establishing a collaboration with Dr. John Kopchick at Ohio University for the discovery of oral nonpeptide growth hormone antagonists. Dr. Kopchick is a leading innovator in the field and discovered pegvisomant, the only commercially available growth hormone antagonist. We look forward to working with him to potentially create a new oral add-on therapy.
As you've seen today, we are not just executing a launch, we're building the premier endocrinology company. With PALSONIFY setting a new standard of care in acromegaly and ongoing phase III studies for carcinoid syndrome, atumelnant advancing toward two important indications, CRN09682 exploring the potential of an entirely new platform, a discovery engine that keeps replenishing what comes next, and a uniquely experienced team to carry it forward. We are well on our way to transforming the lives of people living with serious endocrine diseases and creating lasting value for all stakeholders in the near and long term. Thank you for listening, and we look forward to your questions.
We will now begin the question and answer session. If you would like to ask a question, please press star one on your telephone keypad. Please limit yourself to one question and one follow-up. To withdraw your question, press star one again. Please pick up your handset when asking a question. If you are muted locally, please remember to unmute your device. Please stand by while we compile the Q&A roster. Your first question comes from the line of Joe Schwartz with Leerink Partners. Your line is open. Please go ahead.
Hi. Thanks for taking my questions. I have one on atumelnant and one on CRN09682. First, we noticed that you've added a BALANCE-CAH update for 2026. What will that entail? Can you give us a sense of the quantum of data you'll report and what you hope to demonstrate there? Second, where are you now in terms of enrolling the BRAVESST2 study dosing cohorts, and when do you think we might get our first taste of data out of that program? Also, at what point do you make the investment decision to expand the range of tumors you might target?
Thanks for both questions, Joe. Let's see. Taking them in order, let's talk about the BALANCE-CAH study. A reminder, this is a cohort-based study starting first in 12 to 18-year-olds, looking at doses and confirming the translation of our expected doses in pediatrics from the adults. There's 2 cohorts there that are mandated and then a possible third cohort. We're not changing our guidance. We hadn't said it wasn't coming this year. We're just reminding folks it may come this year. Especially if we don't need that third optional cohort, we will have data on the 12 to 18-year-olds as we begin going down the age groups. In terms of CRN09682, you know, we are in the dose escalation phase, marching up the doses.
We don't think it's prudent to give guidance as to when that may or may not come about. But the enrollment and enthusiasm in both that and all the CAH programs and the Cushing's program and the carcinoid syndrome program are very high. CRN09682 will make the decisions on the additional cohorts as we get to an effective or a tolerated dose. But we've already set out some key cohorts we're going to be expanding in the expansion phase.
Thanks for the insights.
Thanks, Joe.
Your next question comes from Gavin Clark-Gartner from Evercore ISI. Your line is open. Please go ahead.
Hey, guys. Great to see the progress. For PALSONIFY, I just wanted to confirm. For the cumulative enrollment, that pie chart you showed with 15% of naive patients, that's cumulative since launch, right? What was the percent of naive patients that came in specifically in the first quarter?
Thanks, Gavin. Let me hand that over to Isabel. We are pleased with the overall execution across all dimensions of this launch. You know, I've got a lot of questions over the years. "Where do you think the primary group is going to be?" I think the answer I've given is everybody. Our source of business is every single group. In addition to those naïves, the folks who are coming back to care represents an early victory on our planned phase II of the launch when we start focusing more heavily on them. Maybe, Isabel, you want to comment a little bit more about the naïve population.
Yes, Scott. Just to clarify, the 15% is specific to 1st quarter. Our market research showed that basically the messages on PATHFNDR-2 are resonating really well with the community. We're helping shift longstanding perceptions. We are successfully reframing orals as a true first-line option rather than a second-line alternative. The efficacy story is landing really well. As Alan mentioned it, three of the six patients highlighted at the AACE poster were naive patients who had remarkable results. We see this group really expanding in the future. We expect to be actually dominating in this group.
Yeah, just to add onto that, remember, this comes back to our overall strategy of laying the groundwork, getting people experience, and then starting not just to focus on switching market, but growing the market, and bringing people back to the care that they need, that they gave up on because of the problems associated with the current level of care, like Alan was talking about. You know. The inertia is not something that we wanna do. We need to move past that.
Great. That's super helpful. Super quick follow-up. What's the scope of the CAH data that's coming at end of this year? Thank you.
I think you'll just have to wait and see for the abstracts, but, you know, it's a beautiful molecule and we very much like it.
Great. Thanks, guys.
Your next question comes from the line of Yasmeen Rahimi with Piper Sandler. Your line is open. Please go ahead.
Hi, team. This is Liam on for Yasmeen Rahimi. Congrats on another outstanding quarter. Just looking forward at the PALSONIFY launch, could you provide some color on how you think 2Q will compare to 1Q? How do you really see starting forms evolving over the next fourth quarters? I guess, like, what would be considered a steady state starting form number?
I'll let Tobin take that one.
Thanks, Liam. You know, when you step back and zoom out, you know, as Scott mentioned, you know, we've accomplished a lot in the first quarter. You've seen the growth of the naive patients, as the first question answered. The penetration into the discontinued patients, and sort of just the depth and breadth from, you know, payer coverage and the increasing number of accounts that we've penetrated over time. There's always puts and takes. For instance, we had the momentum in the fourth quarter of 2025, where we had some patients who had joined and became enrolled from the OLE, and some kind of early adopters and a handful of hand-raisers there. That it's really tricky to kind of forecast where we're going to be.
We like the momentum that we're building, and we're really confident in our trajectory.
I think something that has been very nice to see is just how well the team across all the dimensions of the company, whether it’s sales or medical affairs or even the back office stuff, it’s all working very smoothly. The engine’s humming and we’re building momentum.
Thank you so much.
Your next question comes from the line of Maxwell Skor with Morgan Stanley. Your line is open. Please go ahead.
Great. Thank you very much for taking my question. Regarding PALSONIFY, with 70% reimbursed, what's the form to paid conversion rate, and how should we think about timing for the remaining 30%? Thank you.
Well, first let me compliment the market access team. 70% at this early point in the launch is really superb for a molecule in the rare disease space like this. Do you want to comment a little bit more on some of the dynamics, Isabel?
Yes. Thank you for the question. As Scott pointed out we're very pleased that 70% of the bottle dispense on the patients are getting reimbursed. We are working to moving those QuickStart into reimbursed patients. That's moving at a good pace. I'm not gonna mention the specific metric, but we're expecting all of them will eventually be converted to reimbursed drugs.
Great. Thank you.
Your next question comes from the line of Jonathan Wolleben with Citizens JMP. Your line is open. Please go ahead.
Hey, guys. Thanks for taking the question. Just for one from me on PALSONIFY. When we think about the unique prescriber base, do you have a sense of how many acromegaly patients those prescribers have under their care? Just looking for some commentary about kind of the deepening of the prescribers, as well as the broadening over time. Thanks.
Yeah. John, thanks. As we've said in our overall strategy the last couple times, you know, we're trying to get a broad set of experience so that we can then begin to expand the market and get people in and focus then on depth. I think we're succeeding on both aspects of that. We're getting a broad set of prescribers at the top tertiary centers and out in the community, and those are starting to show depth in some of those prescribers, and some are just new to the drug. Maybe you wanna add a little bit to that, Isabel.
Yes. We are very pleased with the results. As I mentioned earlier in the call, you know, 50% of the prescriptions are coming from community, and 50% are coming from ATCs. The 50% from community are coming from 70% of our total prescriber base. That's really promising because it means we're expanding the market, building a broad base of prescribers that are having really positive experience and are starting to put the second, third, and fourth patient on drug. Answering your question on how many patients those doctors represent today, approximately 1,400 patients.
Our next question comes from the line of Jessica Fye with JP Morgan. Your line is open. Please go ahead.
Hey, guys. Good afternoon. Thanks for taking my question. I was curious, as you enrolled the registrational atumelnant trials, do you anticipate being able to provide the street with commentary on the ongoing safety profile, maybe based on like blinded safety data as it accrues? Thank you.
Thanks, Jess, and welcome back. Yeah, let me just say that, you know, every day we're accruing patients, or every week, and the safety profile continues to be what we've always communicated it to be, which is, you know, very, very favorable. Maybe I should let Alan give a more position-oriented answer to that.
Well, yeah, Jess, I mean all trials especially major phase III, phase II/III trials are carefully monitored for safety. Sometimes the efficacy results, of course, are blinded. There are always medical monitors following both safety and efficacy as well as external data monitoring committees. In general, when these trials continue, that means the risk-benefit profile has been analyzed, it has been found to be safe to go forward. I don't know that we would come back to make public announcements, you can be sure that this is when the trials continue, things are going along as expected.
Maybe just to be absolutely clear, with continued experience, we see a continued good safety profile with nothing that has changed our mind or perspectives on that whatsoever. As we add more patients, anything in the past that might have been a concern to some, not so much us, continues to be diluted by more and more experience, both in the adult, ongoing phase III in the rapidly recruiting pediatric study where everybody's super sensitive to safety, of course, and in the ongoing OLE experience. That experience base grows every day, and we continue to be pleased with the profile of atumelnant, both on a safety and efficacy point of view.
Great. Thank you.
Thanks, Jess.
Your next question comes from the line of Dennis Ding with Jefferies. Your line is open. Please go ahead.
Hi. Thanks for taking my question, and congrats on a strong first quarter. I had one on PALSONIFY. It seems like each doctor so far is prescribing it to one, maybe two patients. What's the feedback from them who have used it so far, and what's preventing them from prescribing PALSONIFY to more patients? Is it just confidence in getting these scripts approved, or maybe penetration is just gated by the timing of patient visits? Thanks.
Thanks, Dennis. Let me correct your premise. It is not true that they've only prescribed to one or two patients. It depends on how many patients they have and how often they're able to see them. We have some who, you know, routinely are switching patients or adding to new patients. It's, you know, just as we've said since the beginning, the major challenge is just getting that darn appointment. We're hearing tons of positive feedback in an anecdotal sense that we're now starting to publish as evidence. We're getting good coverage, good reimbursement, everything is moving along just as we expect. Nothing is getting in the way other than a little bit of time and a little bit of finding those darn appointments.
Got it. If I can have a follow-up, for your preclinical oral TSHR antagonist, how do you think about this approach going after the receptor versus going after the autoantibodies? I mean, one might say that completely hitting the receptor might get patients to go into a hypothyroid state that might require levos supplementation. Just how are you thinking about that? Thanks.
Just like our other programs, we're really going after the core target of the disease. It's super specific to go after the receptor. Remember, there's this whole other branch that are going at things downstream of the receptor, like the anti-IGF-1R antibodies. At its core, what we've shown in a preclinical setting is a great degree of specificity, ability to achieve dose response, and if necessary, we could take add-back approaches like levothyroxine, which almost every endocrinologist is familiar with. Alan, maybe you wanna elaborate on the, on how we're thinking about developing this drug.
Yeah, no, I mean, I agree with Scott. It's the fundamental driver of the disease states in multiple organ systems. It's mediated by the TSH receptor, so that's where we really wanna target the therapy. You know, the autoantibodies in Graves' disease are very, they come and go. They wax and wane with time. It's unpredictable as to when antibodies are even there versus how much antibody is there and what form of antibodies are there. These are polyclonal antibodies. They're very heterogeneous. Even measuring them in a laboratory isn't necessarily predictive of clinical things. It's very hard to react to autoantibodies and chase them, especially in a disease state, which the natural history is for these things to kind of appear and disappear.
I think targeting the TSH receptor is much more reliable and, I hope will prove to be much more effective and a long-term solution for patients.
Perfect. That's very helpful. Thank you.
Your next question comes from the line of Kate Dellorusso with LifeSci. Your line is open. Please go ahead.
Hi, team. Congrats on all the progress this quarter, and thanks for taking the questions. Just a quick one on PALSONIFY. I know it's early days, but I was wondering if you had any insights on real world compliance or adherence thus far that might be captured through your patient resources like the CrinetiCARE platform.
Yeah. Thanks, Kate. You know, just a reminder, we've had great compliance and persistence throughout the clinical trials, open-label extensions, and that trend continues as we go into a real-world setting. Maybe you want to comment, Isabel?
Yes. We are very pleased with the positive experience that patients are having on PALSONIFY. You see a faster set of action in two to four weeks. You see symptom control and IGF-I control, and that had led to the patients to continue in therapy. The patients that started in fourth quarter are on therapy today. We see a very positive trend on adherence and compliance.
If I just extrapolate from, you know, these anecdotes we're hearing about how patients feel better, the converse of that is when you stop, you know what good is like, and you are reminded what bad is like again. As we think about these enrollment forms each quarter and the natural history of acromegaly, it's important to remember that this is a lifelong disease, and we've developed a lifelong treatment. Each quarter we're adding hundreds of people who I think we can help, not just through providing a good drug, but providing a whole ecosystem through CrinetiCARE and our other services to help them manage their healthcare, help them get reimbursed for their drug, and help them stay on the care that they need.
Great. Thank you so much.
Thank you, Kate.
Your next question comes from the line of Alex Thompson with Stifel. Your line is open. Please go ahead.
Hey, great. Thanks for taking our question. You know, I guess, you know, when might you be in a position to give us some more clarity around timelines for the paltusotine carcinoid phase III and the atumelnant adult study? I guess asked another way, both of those trials have primary completion dates for 2027 on clinicaltrials.gov at this point. Is it possible we see data next year, or are we gonna have to wait till 2028? Thank you.
Well, look, as I said earlier, Alex, it's not prudent to comment on timelines at an early stage of a trial like this. You have to throw an estimate in clinicaltrials.gov. We've done a whole bunch of different things as we've grown the company to help ensure that we can maximally recruit our studies, and these go from things like internalizing our U.S. clinical operations. Those are relationships at sites where we've had studies before, and now it's with our own Crinetics staff who have low turnover and stay as a relationship for the duration of the study. Those people are also then, of course, the likely prescribers of the drug. We've seen an acceleration in site activations. We've also put in various structures to help make sure that the sites are screening effectively.
We've been very pleased in the CAH study that almost every site, as soon as it's activated, starts screening immediately. You don't always see that in these types of clinical trials, but it's great evidence about the enthusiasm of the investigator and the patient community. Similar in carcinoid syndrome, remember what a tough disease this is and what really solid data we showed in the phase II program. We'd recently had investigators meeting there, again, a ton of enthusiasm and, you know, a very positive response. We are working hard to make sure we can bring in these timelines at their fastest possible pace, and we built the company to do that. You know, we had a discovery engine I think most people recognize.
The development engine, there's a lot of stuff behind the scenes that most people forget about, but it's complex, and it's really running well. Now we've built the commercial engine, and the commercial engine's humming too.
Thank you.
Thanks.
Your next question comes from the line of Tyler Van Buren with TD Cowen. Your line is open. Please go ahead.
Great. Thanks very much. This is Nick on for Tyler. Congrats on the progress and on the quarter. Can you discuss what proportion of revenue came from new patients this quarter compared to patients rolling over from last quarter? Also, what was the overall growth of the patient enrollment forms month-over-month in Q1 and as you moved into Q2? Thanks.
Let's let Tobin take that one.
Yeah. I don't think we were gonna comment on the, on the revenue from new patients versus carryover patients. When you step back, I think that
As we look at this data and sort of the growth that we've had in enrollments, we're feeling very good about the trajectory of things. The team, like as Scott and Isabel have mentioned, are building the relationships, and they're doing it in a very steady fashion. We're quite pleased with the progress and, you know, just the response to PALSONIFY in the field.
Thanks.
Your next question comes from the line of Douglas Tsao with H.C. Wainwright . Your line is open. Please go ahead.
Hi. Good afternoon. Thanks for taking the questions, and congrats on the progress. I'm just curious if you could provide a little bit more on the 15% of patients who are returning to therapy. I'm just curious if you have a sense of, you know, were they in the system still and routinely seeing a clinician but chose not to be receiving sort of, you know, injectable therapy and were very quick to come on as soon as PALSONIFY was available? Were these patients who somehow heard about the drug and then decided to sort of reenter sort of treatment? Thank you.
Yeah. Thanks, Doug. Let me give some credit to the team. They've been piloting some of the programs they're planning on deploying more widely to do exactly this and bringing these patients back to care. Some of it is from that, and some of it's spontaneous. Maybe you wanna comment, Isabel.
We are very pleased because we are bringing hope back to patients that have given up on their treatment even though they have a chronic disease where symptoms continue to advance. These patients that had discontinued therapy remain in the system. They were primarily discontinued due to the burden of the treatment and the fact that those treatments don't deliver, right? You continue to have symptoms at the end of the cycle. You have painful injections. After a while, you just give up. For us, it's great. Some of them have discontinued for more than two years, some of them just a few months ago, and we have re-engaged them. That re-engagement takes our media programs, our participation on the Ambassador Program, and also some specific tools where we are working to identify them with the practice.
These are very early outcomes in a group that has given up, but it's very encouraging for us because it means that we can expand the market.
Okay. That's really helpful. Just maybe on the switch patients, I'm curious, do they generally just come in, I mean, how many visits to see the doctor do they need? Are they generally coming in, talking with their clinician and saying, "Yep, I would like to do this," and they sort of get the ball rolling with the patient start form? Do some patients need a couple visits to sort of go through an education process? Thank you.
Yeah. There's a, there's a little bit of a mix. Before we hand it to Isabel, let me just tell you one anecdote I heard recently I had recently firsthand, where I was talking to a couple HCP friends of mine, and they were telling me about a couple different patients they, that had come in and asked for PALSONIFY. Their initial reaction was, "Well, this is a You're on a second-line therapy. I'm not sure a first-line therapy will be what you need." Yet it worked anyway, much to their surprise. Everybody was happy with that, and that story is propagating as well. You wanna comment, Isabel?
Yes. When it comes to the switching patients, I would first comment that we're very pleased that they are coming from all kinds of previous therapies, octreotide, lanreotide, combination therapy, cabergoline, MYCAPSSA. We are taking share from pretty much all those switches. The beauty of PALSONIFY is that it's performing really well across the board. That shows the versatility of our drug, and that confirms the efficacy, fast onset, and, you know, the benefit also having a once daily therapy. When it comes to how long it takes to convince patients, it's like everything in life. Some patients are more ready to do the change because they are having the symptoms, because they feel uncontrolled, because they hear about the convenience of our treatment. All of that makes them, you know, ready to switch.
Other patients want to hear from other patients. That's why we have our ambassador program to hear peer-to-peer stories. Other patients want to have a second opinion with their doctor. That's what we are seeing across the board, that patients have interest in learning more, and many patients are joining our ambassador events.
That's really helpful. Scott, can I just ask a quick follow-up in terms of your anecdote? I mean, just given their reaction, I mean, does that suggest that even very well-educated clinicians with PALSONIFY don't necessarily have a full appreciation of the data and the strength of it? Just given, you know, the PATHFNDR results, I mean, I don't think anybody should be surprised that the drug would work, or that it wouldn't be applicable to everybody.
Yeah. No, it's not that it wouldn't be applicable to everybody. It's just that we're seeing kind of even more than we expected in the real world setting than what we saw in the PATHFNDR studies. Remember we, the PATHFNDR had two parts of the spectrum, two ends. The patients who were untreated at all in PATHFNDR-2 and the patients who were very well controlled on the injectable depots. What was missing was all those patients in the middle. Who aren't that well controlled, who might be on combination therapy, and we only had a small amount of data on that from phase II. What we're learning in the real world setting is that even if you're on a combination therapy, some patients are getting better on PALSONIFY.
Even if you're on a something like pasireotide, which is a mixed receptor that people advance to after they fail on lanreotide, which has a variety of different problems associated with it, even those patients are getting switched and doing well. I think we're all just a little bit surprised at how well this has done in the real world setting, which is why it's so critical that we capture the real world evidence and start to get that out there, not just through word of mouth, which is already happening, but through publications and formal presentations of evidence.
Okay, great. That's really helpful.
Thanks, Doug.
Your next question comes from the line of Richard Law with Goldman Sachs. Your line is open. Please go ahead.
Hey, guys. Congrats on the results and progress so far, t wo questions for me. The first is, we saw sales from other products from many other companies impacted by the severity of weather in Q1. Was there any seasonal effects that could have impeded PALSONIFY sales or momentum in Q1? Do you believe there's a pent-up demand as a result in Q2? I have a follow-up on atumelnant.
Look, we're very pleased with just the overall consistent launch and the way the team's performing and, you know, I couldn't be happier. I think we've got enough time for the atumelnant question. Was that your follow-up?
Yeah. Also Yes. I think just following up to what you said earlier about safety monitoring, stuff like that. Can you discuss what data sets that you believe could help de-risk the safety profile related to atumelnant ahead of that phase III CAH study? Then I think in the ongoing trials you mentioned that you guys do monitor the safety or the data monitoring will monitor safety. If there's a lower grade, like, liver toxicity, would that get reported to you? What level and what quantity of that signal gets communicated to you guys?
I'll let Alan answer the technical part of that, but in my view, there's not really anything to de-risk anymore. We're at a normal phase III, and it's moving forward in a very nice fashion. Alan, maybe you wanna give people some comfort with the specificity of the rigor that goes into our overall safety monitoring, including the phase III.
Yeah, you know, all clinical trials, including phase III clinical trials, contain within it extensive safety monitoring, which generally includes regular visits with healthcare professionals for physical examinations, as well as a battery of routine safety blood tests, EKGs, and other important things too that are generally routine for clinical trials. All these safety data are very carefully monitored by well-trained professionals all the time. All the safety data is available in real time to the medical monitors in particular, and this is followed very carefully. As I said earlier, generally, when a trial is continuing, that means all the safety checks are as expected.
I feel very confident in our compounds and in our trials, including the ongoing trials.
Yeah. Maybe to even put a finer point on it. Do you really think IRBs around the world would let us start dosing 12-year-olds, or soon even younger, if they had any question about the safety or risk-benefit of this drug? I don't think they would, especially as we get into kids.
Our next question comes from the line of Catherine Novack with JonesTrading. Your line is open. Please go ahead.
Hi. Thanks for taking my question. Just one on PALSONIFY in Europe. Can you give me your thoughts on potential pricing dynamics here, and when you expect to see revenue from individual countries, and which countries may be first? Thanks.
Yeah. Thank you. Look, we're focused on executing on the U.S. launch, and I'm really pleased that we've received the approval in the EU. We've submitted in Brazil, we've submitted in Japan, you know, all of this is building options for us around the world, and I think showing the strength of the drug with the receptions we're getting from these global regulators. Like everybody else in pharma and biotech, we're monitoring rapidly how all the pricing and access situations are evolving, and we're navigating this uncertainty in a very disciplined market-by-market approach. We'll be prioritizing geographies with clear regulatory and reimbursement pathways. Also importantly, we're pacing the investment in these international activities, again, to preserve the option value without over-committing too much capital.
Just to be clear, we're not preparing for revenue from international operations this year, but we will be prepared for early launch in 2027.
Got it. Thank you.
Thanks.
Your next question comes from the line of Brian Skorney with Baird. Your line is open. Please go ahead.
Hey, good afternoon, guys. Thanks for taking the question and congrats on the quarter. Also wanted to get some thoughts maybe on the ex-U.S. launch you mentioned, sort of thinking about prioritizing where reimbursement may be favorable given sort of the IRA dynamics. How do you think about where there might be higher value areas through either genetic clustering or just diagnostic clustering being a driver of early demand? Like, I think in Northern Ireland there's a genetic cluster of the R304 mutation. Maybe Brazil seems to have better diagnostic infrastructure than other areas. Were there any areas that you'd kind of point to where the pool of identified patients might be particularly meaningful?
Yeah. First, there's not really a genetic clustering to acromegaly except, as you say, in the Irish Giants, which is one of a relatively small population where there is a genetic component to the acromegaly. The distribution of incidence is pretty much global, but some healthcare systems are better at identifying patients and/or keeping them under care. We need to balance that against also the reimbursement landscape and, you know, the regulatory certainty in those regions. All those things we're taking into account, but it's a little too early to comment in detail on the specificity of our international plans.
Okay. Thanks.
There are no further questions at this time. This concludes today's call. Thank you for attending. You may now disconnect.