Crinetics Pharmaceuticals, Inc.

Welcome to the Chronetics Pharmaceuticals First Quarter 2025 Financial Results Conference Call. At this time, all participants are in listen-only mode. Following the management's prepared remarks, we will hold a question and answer session. Please press star followed by one on your telephone keypad. If you change your mind, please press star followed by two. I would now like to turn the call over to Gayathri Diwakar, Head of Investor Relations. Please go ahead.

Thank you, Operator. Good afternoon, everyone, and thank you for joining us to discuss the first quarter 2025 results. Today on the call, we have Dr. Scott Struthers, Founder and Chief Executive Officer, Dr. Dana Pizzuti, Chief Medical and Development Officer, Isabel Calafonos, Chief Commercial Officer, and Toby Schilke, Chief Financial Officer. Dr. Alan Krasner, Chief Endocrinologist, will also be joining for the Q&A portion. 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 Crunetics website. In addition, a press release was issued earlier today and is also available on the corporate website. Slide two. As a reminder, we will be making forward looking statements and I invite you to learn more about the risks and uncertainties associated with these statements as disclosed in our SEC filing. Such forward-looking statements are not a guarantee of performance, and the company's actual results could differ materially from those stated or implied in such statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's news release. The company's other news releases and chronetics SEC filings, including its annual report on Form 10-K and quarterly reports on Form 10-Q. I would also like to specify that the content of this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, May 8, 2025. Kinetics takes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. With that, I'll hand the call over to Scott.

Thank you, Guthrie, and good afternoon to everyone joining in today's call. We're pleased to share our first quarter results and highlight the great progress we're making towards our mission of transforming the lives of patients with serious endocrine and endocrine-adjacent diseases. Turning to slide three, kinetics has never been stronger, and I want to emphasize that. We're strategically positioned for long-term, sustainable growth. Our immediate focus is on the anticipated commercial launch of our first product this year. This is a pivotal milestone for the company. We believe Peltucetin has the potential to deliver meaningful improvements for people living with acromegaly. Faced by an experienced team deeply embedded in the endocrinology community and driven by a strong commitment to patients and science, we're well on our way to becoming a fully integrated global commercial organization. We're advancing a robust pipeline in parallel, including two late stage candidates, one recently clearing IND, and three additional candidates in preclinical studies. With $1.3 billion on the balance sheet, we're able to continue to invest in our pipeline, support prospective launches, and thoughtfully pursue opportunities and enhance value across our portfolio. We have never been stronger. I'd like to take a moment to welcome Toby Schilke. who you'll be hearing from towards the end of today's call. Toby recently joined as Chief Financial Officer, and he brings over 25 years of global experience with a proven track record of guiding companies through the transition from R&D-focused ventures into fully integrated commercial organizations. Toby's extensive financial and operational experience will be invaluable as we accelerate our growth trajectory and position Krenetics for long-term success. I also wanted to reassure you that regulatory engagement with the FDA on the Caltucetine NDA for acromegaly, as well as our other clinical development activities, have been proceeding on track. We're grateful for the ongoing professionalism and commitment of the staff at FDA with whom we interact. We remain proactive in monitoring the evolving regulatory environment and maintaining active dialogue with key stakeholders, both in the administration and on Capitol Hill. As you'll hear from Isabel, we're laser-focused on preparing for the anticipated launch of Peltucetine in September. This will be our first product approval and a defining milestone for our ambition to become a fully integrated pharmaceutical company. On today's call, we'll walk through some of the launch initiatives we are executing and reflect on the progress the team has made to date. Turning to AstraZeneca, we remain very encouraged by its potential to establish an uncompromising adrenal hyperplasia. We're moving forward to the phase three study for adults with CAH that Dana will describe in some detail. At a high level, this study is designed to redefine the standard of care as the achievement of normal adrenal androgen levels with only physiologic levels of glucocorticoid replacement. We believe atumelan should be used to treat the disease and glucocorticoid should only be used for physiologic replacement, not treatment. With that, I'll hand the call over to Isabel to update on our Acromegaly launch preparations. Isabel?

Thanks, Scott. As described on the slide 4, our mission with participating is to provide the next generation of care for people living with Acromegaly. While we have a long-term global vision, And we are building out our infrastructure to support commercialization of our whole pipeline. We are constantly focused on executing on the anticipated U.S. launch. We are making significant progress in building our infrastructure, educating and driving awareness among healthcare professionals and patients, and engaging with payers. We also have a strong longstanding patient advocacy partnerships in place as we continue to engage with the broader community. On the healthcare professional side, we have health advisory boards with nurses and endocrinologists, and they have provided positive feedback on the potential value proposition of Paltuzutin in both biochemical control of IGS1 and symptom control. We are working on the final Salesforce mapping, and we expect to have approximately 30 reps in place over the summer. We will co-work healthcare professionals in P230 treatment centers, academic centers of excellence, and in community endocrinology practices. We're making powerful strides in advancing awareness and visibility for Pac-12 team and our broader pipeline at conference attended by academic endocrinologists like Endo, and by community endocrinologists like ACE. We will share exciting new scientific data that reinforce the long-term value of paltricitin and the need for innovation in acromionic treatment. Notably, we'll present data from our four-year Acrobat Open Label Extension or OLE study, demonstrating that patients on paltricitin maintain biochemical control in IGES-1 over a 96-week period. Equally important, 87% of patients prefer partucetine over prior injectable SRL therapy, highlighting the patient-centric benefits of our one daily oral treatment. We will also share real-world evidence that current SRL therapies are associated with persistent breakthrough symptoms and low compliance and adherence. Patients experience symptom exacerbations more than one-third of days each month, and those days are not always concentrated in the week leading up to the next injection. Data from Pathfinder 1 demonstrate that patients treated with Paltuzutin experience decreased symptoms exacerbation rate over time. Additionally, based on real-world data compiled over a four-year period, 80% of patients with acromegaly who are newly treated either discontinue or switch from their initial treatment within their first year. This data highlights Paltucetin's scientific and clinical relevance in an area of significant to improve the lives of patients living with acromegaly. In slide five, education and awareness are critical elements of our plan to reach patients as part of our activate, adopt, access, adhere, launch strategy. We are focused on elevating awareness of the burden of disease experienced by patients, even those currently being treated. Our insights consistently show that while patients might achieve biochemical control, they often continue to experience persistent symptoms that impact quality of life. Our educational initiatives are designed to address both aspects of disease control to ensure patients are better informed, more empowered, and fully activated to advocate for treatment that addresses the need of the current standard of care. We recently launched our Kinetic Care Patient Support Service platform to act as a partner to patients on their treatment journey from the very beginning. We opened our hub before the anticipated approval because the acromegal community faces significant and med need in patient support. Kinetic Care connects patients with nurses to discuss their symptoms and offers interactive tools to help them locate experienced healthcare providers. The Krenetic Care platform will serve as a continuous connection between us and the patients we serve. Once TAL 215 is approved, Krenetic Care will provide a wide-gloved experience for patients from the time they receive prescriptions to initiation of therapy, all the way to long-term maintenance. We also recently revealed our unbranded disease stay education campaign. This campaign leveraged our learnings from our ongoing engagement with healthcare professionals, patients, and acromegaly community partners to amplify patients' voices and provide educational materials. Turning to slide six, we continue our pre-approval conversations with payers, and we are encouraged by their feedback. In particular, we anticipate that prioritization for participating will reflect the label which will help us drive the success of reimbursement. Altruistic value proposition is resonating with payers because their main needs with injectable SRL, long titration times, incorrect injections, and inconsistent symptom control collectively result in higher costs overall. First, patients starting on SRLs typically have their dose titrated every three months. With three different dose strands available, it might take patients up to nine months to get to the right dose where the disease is under control. Payers bear the cost of treatment for many months before the patient sees a benefit. In contrast, daily dosing of Paltucetin will allow titration to the optimal levels within weeks if titration is needed. SRS are not always correctly delivered, which can lead to higher costs to manage the resulting symptoms and side effects. For context, SRL injections are given with a large 18-19 gauge needle. The injections are unpleasant to receive and challenging to give. A research study conducted at MD Anderson, one of the leading centers, found that half of long-acting osteotype injections administered by experienced nurses were not injected into the intramuscular phase. The dipole of ultracite instead persisted in the subcutaneous layer where they formed nodules that sometimes became granular. It is important to note that if the drug is not administered properly, it might not achieve its intended ethics. Payers understand that injectable SRS often do not provide adequate disease control for the duration of the injection cycle. According to a real-world data analysis, one-third of acromegaly patients on injectable SRS received more than the 13 injections per year expected based on an approved dosing, which is every four weeks. Consequently, this increases costs substantially for payers. Furthermore, uncontrolled acromegaly is associated with comorbidities and additional procedures, which are costly for payers and very burdensome for patients. Lastly, L2-161 daily oral dosing offers an opportunity to improve patient adherence for more consistent control. In sum, there remains a significant and met need for safe, highly efficacious, easy-to-administer treatments that offer daily control, and the economic and clinical value that an option like Paltucetin could provide to all stakeholders is clear. These and other market insights continue to highlight meaningful and many and strong enthusiasm for Paltucetin. During early launch, we anticipate menstrual uptake as we educate both healthcare providers and patient communities. As with any new therapy, we expect coverage to build progressively, and we will work through the formulary review process with payers over the first six to nine months. Our team is highly prepared and confident in navigating this initial step to unlock the full opportunity of participating. As the value proposition continues to resonate with patients, healthcare professionals, and payers, We are optimistic that over time, paltuzatine could become the new standard of care in acromegaly. And now, Dana will share a regulatory update and additional detail on our CAH late-stage development strategy. Dana?

Thank you, Isabel. Starting with paltuzatine, we continue to make progress in both the U.S. and EU, where our regulatory reviews remain on track. We have not experienced any disruptions with our interactions with the FDA and continue to expect a decision by September 25th. And as previously mentioned, we do not anticipate an advisory committee meeting as part of the NDA review. The European Medicines Agency has validated our MAA submission and granted orphan drug designation. We believe the orphan drug designation highlights the unmet need in acromegaly and the potential benefit that paltuzatine can offer patients compared to existing therapies. Our team continues to work with regulatory authorities in the U.S. and EU on all aspects of the review process. In preparation for launch, our growing medical affairs team has been connecting with the endocrinology community. Our experienced endocrinologists at Krenetics have been making warm introductions for our medical science liaisons to all the top KOLs. We've hosted roundtable discussions to deepen our understanding of the patient journey and gaps in treatment. As Isabel highlighted, we have submitted multiple abstracts to upcoming endocrinology meetings that showcase paltucetin's differentiation. Moving to carcinoid syndrome, we expect to initiate the CareFinder phase three trial in the second half of 2025. Turning to Adam Mellon on slide seven, we added a fourth cohort to our phase two study due to the significant amount of enthusiasm and interest from sites and investigators. Cohort four is just one part of our larger development plan for Adam Mellon and CAH. and it is an exploratory analysis in a small group of 6 to 12 patients to evaluate 80 milligrams with morning dosing as opposed to evening dosing in the prior cohorts and to allow for glucocorticoid reduction. As previously shared, we are also conducting an open-label extension study which will provide real-world insights into Adam Mellman's efficacy and safety over the long term. Investigators will have the opportunity to titrate both the dose of adamalnin and the dose of GCs as they see fit. Study participants from the Phase II study are given the opportunity to enroll in the OLE. This study is ongoing and will eventually also include patients who complete Phase III. Turning to slide eight. Our phase three study for adamelanin in adult CAH patients builds on the strong top line results we shared from cohorts one through three of the phase two study. It is designed to provide a potential new therapeutic paradigm for patients. As Scott mentioned, there is a significant need for new treatments in CAH that not only allow patients to lower their GC dose to physiologic levels, but also to control their androgens, which account for many of the signs and symptoms of the underlying disease. With this in mind, we are pursuing a novel primary endpoint that combines both goals. The proportion of participants with A4 levels less than or equal to the upper limit of normal and who are on physiologic doses of GC replacement at week 32. Patients should not have to sacrifice one or the other in treating CAH. In this study, we will enroll 150 participants who will be treated for 32 weeks. We will offer investigators two periods of time over which they can reduce GCs with four assessment visits in each period. Investigators are given additional flexibility for physician-guided reductions. We designed this individualized approach in response to feedback we received from investigators who prefer to use their discretion in titrating GCs as they would in a real-world scenario with the goal of reaching physiologic doses. Based on the early and profound decrease in A4 seen without a melanin treatment in the Phase II study, we are measuring A4 at just two weeks after the study initiation and allowing investigators to assess glucocorticoid reduction immediately thereafter. Midway through the study, participants will be on stable GC doses for several weeks so their A4 can be measured. Investigators will then have the option to titrate patients up to 120 milligram dose of adamilin if the patient needs more A4 control. Otherwise, participants will continue on 80 milligrams. The key secondary and other endpoints are designed to demonstrate potential benefits beyond what has been achieved with existing standard of care for CAH patients. In addition to reductions in key disease biomarkers such as A4 and 17-OHP and other androgens, we will study improvement in the clinical signs and symptoms of CAH including, but not limited to, restoration of menses, testicular adrenal breast tumors, or TARTs, and adrenal size. Our primary endpoint will use morning androgen measurement post-GC dosing, consistent with the previous regulatory precedent. However, in our secondary endpoint, measuring these hormone levels pre-GC dosing is a rigorous test of efficacy because the androgen levels can be influenced by morning GC administration. Consistent with our patient-centric approach to drug development, we will include a novel disease-specific patient-reported outcomes tool as part of the study design. The last piece of our CAH development program is the combined Phase 2-3 study in pediatric patients. We are finalizing our specific plans for integrating each age group into the registrational study, and we have already received helpful feedback from FDA and European authorities on our proposed study design. In summary, as illustrated on slide nine, we believe adimelanin has the potential to establish uncompromising treatment goals for people living with CAH by addressing both elevated androgens and reducing the need for supraphysiologic glucocorticoid dosing which could lead to negative side effects for patients. We believe glucocorticoids should ideally only be used to provide physiologic replacement, not to treat the underlying disease. Our phase three trial aims to provide a tailored approach to treatment for individual patients, enroll a broad patient population, inclusive of patients who could benefit from GC normalization, androgen normalization, or both, and measure clinical outcomes that are paramount to both HCPs and patients. Our vision is to lower the burden of disease overall and provide a new standard of care for the 17,000 plus people living with CAH. Moving to slide 10. We are making steady progress on the rest of our pipeline, and we are pleased to announce IMD clearance for 96A2, the first candidate from our non-peptide drug conjugate, or NDC, platform. 96A2 is being studied for SST2-positive tumors, including neuroendocrine tumors, or NETs, to complement our carcinoid syndrome indication with peltuzetine. Additionally, our discovery team continues to identify new ways to leverage the NDC platform for novel targets to address unmet needs in endocrine oncology. As mentioned in our press release, IND-enabling studies for the TSH antagonists are continuing as expected. Also, we continue to progress our SST3 agonist candidate. Based on emerging data from IND-enabling studies, Our PTH antagonist candidate, preclinical development, has been substituted with another candidate expected to exhibit an improved profile. This new candidate is an IMD-enabling studies, which we intend to complete next year. This decision is reflective of the rigorous process we followed with Paltucetin and adamilin, and that we applied to all our pipeline programs. We look forward to highlighting our early stage pipeline in more detail at our upcoming R&D day on June 26th. Of note, we will cover NETS and beyond with 9682 for SST2 expressing tumors and peltuzatine for carcinoid syndrome. We will also present our TSH antagonist for Graves and thyroid eye disease and our SST3 agonist for ADPKD. These programs represent the next generation of kinetics innovation and have the potential to positively impact the lives of patients and their caregivers across multiple communities. With that, Toby will now provide the financial update.

Thank you, Dana. Turning to slide 11. I am pleased to be participating in my first earnings call at Kinetics. It is a privilege to join a team with a patient-centric mission and leading-edge science. We are poised for growth and importantly, well capitalized to execute on our ambition. Now I will present the financial results for the first quarter of 2025. I will not read aloud the full results as they are available in our press release and on our form 10 Q filing beginning with our income statement. We recognized $0.4 million of revenue during the first quarter of 2025 compared to $0.6 million during the same period in 2024. As a reminder, this revenue is non-cash and is based on amortization of payments we received in connection with our Paltucetin licensing arrangement with our Japanese partner, SKK. Our research and development expenses in the first quarter of 2025 were $76.2 million, a 43% increase compared to the same period in 2024. Excluding depreciation, amortization, and stock-based compensation, R&D expense was $64.4 million. The increase in R&D expenses was primarily due to additional personnel, increased manufacturing costs, and higher outside services costs to advance our clinical programs and expand our preclinical portfolio. We expect quarterly R&D spend to increase sequentially through the remainder of the year, primarily driven by Phase III clinical trials for Paltuzatine and Atumelna. Our selling, general, and administrative expenses for the first quarter of 2025 were $35.5 million. a 71% increase compared to the same period in 2024. Excluding depreciation, amortization, and stock-based compensation, SG&A expense was $26.2 million. The increase in SG&A expense was primarily driven by growth to support our ongoing programs and the planned commercial launch of Paltuzatine. We expect quarterly SG&A investment to increase sequentially through the remainder of the year as we continue to build our commercial infrastructure and prepare for the anticipated launch of Paltuzitine. Our cash used in operations for the three months ending March 31st, 2025 was $88.5 million compared to $52.9 million for the same period in 2024. For 2025, we continue to anticipate are cash used in operations to be between $340 and $380 million. This compares to $226 million of cash used in operations in 2024. Approximately 60% of the increase relative to 2024 is due to R&D investments with the balance due to SG&A. Turning to slide 12. We ended the first quarter of 2025 on strong financial footing with approximately $1.3 billion in cash, cash equivalents, and investments, which we continue to expect to fund our operations into 2029. As a reminder, we could potentially receive up to $250 million if Lilly exercises its option to acquire Radionetics. Krenetics has always been disciplined with capital allocation, and we continue to take a prudent approach to execute on the compelling opportunities ahead of us. We believe our strong balance sheet positions us to deliver on our near-term milestones, including the anticipated approval and launch of Paltuza Team, and advance our deep and rich pipeline in parallel. I'll now turn it over to Scott for closing remarks. Scott? Thank you, Toby.

Moving on to slide 13. At Krenetics, our core mission is to improve patients' lives and transform the treatment paradigm in areas of serious unmet need like acromegaly. For over 10 years, we have partnered with patients for their direct input on our discovery effort, clinical designs, and patient resources. We design our therapies to allow patients to live their best lives instead of letting their disease define them. With our strong pipeline of late and early stage candidates, and the support of our robust balance sheet, we are well positioned to deliver on our clinical, regulatory, and commercial priorities in 2025 and beyond. With that, I'll hand the call back to the operator to begin the Q&A. Please limit yourselves to one question each in the interest of time. Operator?

Thank you, Scott. To ask a question, please press star followed by one on your telephone keypad now. If you change your mind, please press star followed by two. When preparing to ask your question, please ensure your device is unmuted locally. First question comes from Yasmine Rahimi with Piper Sandler. Your line is open. Please go ahead.

Good afternoon, team. Thank you so much for all the great updates. Two quick questions. The first question is, could you talk about the powering of your very innovative primary endpoint, which is a co-primary? And then short question for cohort four. Have you been able to collect any data from that cohort yet? And I'll jump back in the queue. Thank you again.

Thanks, Jeff. I'll hand that over to Alan to answer.

Well, yes. So with regard to powering of the study, I would say very highly powered to detect statistically significant differences between the treatment arm and the placebo arm. across a range of potential deltas between groups. And I think that Dr. Melvin is well situated to achieve this endpoint that Dana discussed earlier, showing both normalization of A4 and physiologic dosing of glucocorticoid. With regard to cohort four, this is enrolling, and I can't speak I can't speak yet to timing of data. I think what we would do, of course, is show new data at scientific meetings, but the timing of that I can't comment on quite yet. One other lexicon thing I'd like to mention is the kind of primary endpoint we're talking about. I think it's better described as a composite endpoint rather than a co-primary endpoint. There are two components to the endpoint. A co-primary, though, is something else where you kind of have to, each component has to statistically stand by itself, whereas a co-primary is, it's basically a responder analysis where a responder is defined as having both normal glucocorticoid doses and normal A4 levels.

Our next question comes from Jessica Fye with J.P. Morgan. Your line is open. Please go ahead.

Hey, guys. Good afternoon. Is the COM-CAH study design fully signed off on by FDA as a trial that could support registration? And what indication statement would you hope to secure assuming the trial is successful? Do you think you'd need one or two trials to get approved for CAH? Thank you.

Thanks, Jess. I'll let Dana answer that one.

Yeah, sure, Jess. Thanks for the question. The protocol was, you know, put together. based upon input from FDA as well as other health authorities, and they are aware of the final study design. I think that, you know, the other parts of your question were about the indication state. Yeah, it's hard to say right now an indication, but I think what, you know, and the data, of course, you know, we'll define what we can, you know, talk with the agency about. But, you know, the basic, you know, difference that we have is what we are trying to develop here is a drug that will treat the disease, the CAH, right, and will only need glucocorticoids for a prevention of adrenal insufficiency, right? So, if you look at the chronicity indication, it's as an adjunct to glucocorticoids for the control of androgens. And so that implies that the glucocorticoids are necessary to control the androgens. In our situation, based upon our Phase II data, it's the added melanin that's really going to drive the, you know, reduction in androgens. And therefore, you don't need glucocorticoids to treat that part of the disease. And as I mentioned, you know, when we did the call, we really only expect that the glucocorticoids will be used for, you know, physiologic replacement. So we expect that that could, you know, result in a slight difference in how the indication is, you know, granted.

Our next question comes from Gavin Clark-Gartner with Evercore ISI. Your line is open. Please go ahead.

Hey, guys. Thanks for taking the questions. First, just on the primary endpoint for the phase three, what's the rationale to test the endpoint at a single point in time at 32 weeks as opposed to averaging across multiple time points? Is there any risk that A4 variability may lead to some non-responders who maybe shouldn't be non-responders?

Thanks for the question, Gavin. I think generally responder analyses are conducted at single points in time rather than averages. There is always variability with biochemical markers. Before, I think of all the choices in this disease state is one of the least variable. And again, there's a lot of confidence that this compound can achieve both components of the composite primary endpoint. And therefore, the odds that variability would...variability might explain, you know, one of these endpoints hitting it once in a while on an occasional patient, but hitting both is quite, I think, specific, and I would anticipate, you know, pretty strong results that are clearly delineated from placebo.

Our next question comes from Tyler Van Buren with TD Securities. Your line is open. Please go ahead.

Hi, this is Frances on for Tyler. So just one question about the fourth acumen cohort.

So what is the rationale for looking at the morning dosing versus the evening dosing?

Yeah, thanks. Thanks for the question. This is Scott. You know, I think for many of us, you know, it would be more convenient to perhaps take the drug in the morning rather than in the evening, and we just wanted to explore that to provide future optionality for patients. And maybe just to clarify a little bit, reminder that there's a strong diurnal rhythm in this axis, including in the CAH patients. And so you just want to be sure that the timing of the drug in respect to the diurnal rhythm doesn't have a significant effect.

Our next question comes from Corey Chauvinville with LifeSci Capital. Your line is open. Please go ahead.

Good afternoon. Thanks for taking our questions. You know, you folks have recently received acceptance for your marketing application for Paltucetin in Europe. Curious how you're thinking about launch strategy in these different geographies. You know, you previously discussed patient concentration in the US is largely at these pituitary centers of excellence. Is patient concentration similar to those in Europe and or Latin America? What, if any, are some of the material differences in the way that acromegaly patients might be treated in those geographies that might be important to consider for a launch?

Yeah, that's a great question, Corey. So, yeah, I was going to hand that off to Isabel, who's on the line here. Go ahead, Isabel. Sorry.

Sure. Hi, Kerry. Yes. So we are very excited to have the filing approved, and we are preparing for the launch in Germany, where also there is a significant unmet need for patients with acromegaly. So to your question, the European markets tend to be more concentrated in terms of even more patients are part of the centers of excellence. There is a little bit more of community in Germany than the rest of the markets, but still, you know, a ratio of about 70 to 30%, 70% of key centers. We continue to research to confirm that. And so highly concentrated. We are working extensively in our market access strategy and in our discussions with GBA and the different markets. And we are going to be very progressive and be very thoughtful about how we continue to expand there. So right now, we have a footprint in Zug. We have our team in place in Germany. And it's a very small group of resources that we think will help us maximize the opportunity there and help as many patients as possible. Regarding Latin America, you had seen also that there is a high unmet need and a lot of patients that have been identified. So the one country that we had considered as a country for expansion is Brazil. As you had seen in our clinical trials, over 30 patients in our acromegaly studies were recruited there. We had very good relationships with the different centers and it's also concentrated. So we see the opportunity there to also serve the patients beyond the United States. So it's a commitment for for kinetics to actually serve patients not only in the US, but in as many countries as possible. But we will be very gradual about our geographic expansion.

Our next question comes from John Wallivan with Citizens. Your line is open. Please go ahead.

I just Catherine on for John, a quick question about the 9682 program and the phase one to trial on the treasure about to, I guess, speak with your plan to begin soon. Any details you could share on the trial design and kind of what you want to learn? And also any state particular safety kind of issues that you're going to be looking out for in this trial? Thank you.

Yeah, this is Dana. And, you know, we look forward to actually sharing a little bit more about this at the R&D day that we're going to have in June. And so that'll be sort of, you know, front and center, you know, for those discussions. But our general approach is that it's going to be a fairly standard, you know, dose escalation design protocol for oncology. And obviously... you know, when you're treating patients as opposed to healthy volunteers in your phase one, you have additional safeguards and, you know, sort of parameters that you're looking at, particularly around safety. But, you know, we'll be very excited to share more details on that later.

Our next question comes from Alex Thompson with Stifel. Your line is open. Please go ahead.

great uh thanks for taking our question another on the cah phase three just wondering if you could talk a little about your your uh design here in the context of glucocorticoid reduction and investigator discretion are there any overall guidelines for for how to do this or how confident are you that you're not going to see a significant amount of variability here in the study thanks well i think part of the uh um sort of overall um you know sort of

mindset that we were trying to convey in the trial conduct here was that we wanted it to be as similar as possible to the real world in what investigators would want to do in terms of reducing glucocorticoids. Obviously, patients can come in with quite a lot of differences in what their glucocorticoid levels are, and some may have very high levels of And so what we wanted to do was allow enough time in the first part and the second part of the trial so that that can be done judiciously and carefully with, you know, the investigator deciding what increments they want to use in, you know, decreasing that. We have some general guidances that we put in the protocol about, you know, what the limits on those increments should be. But in general, we like to leave it up to the, you know, the PIs to decide what's best for their patients that are in the trial.

Our next question comes from Maxwell Score with Morgan Stanley. Your line is open. Please go ahead.

Great. Thank you for taking my question. I was just wondering, I recognize you're not interacting directly with CBER for palitocetine. But I was wondering if you'd comment on the evolving regulatory environment overall and how you're thinking about any potential implications for the rare disease space. Thank you.

Yes. You know, as you know, we're working with the CDER part of FDA. And so far, we really haven't seen much of a difference in terms of how things are progressing. and across all of the programs, not just with paltuzatine. So it's, you know, right now it seems like regular order for the way that, you know, FDA is working, particularly with programs like ours. And most of our programs are rare disease programs. So, you know, we don't really see, you know, any differences at this point.

Our next question comes from Joseph Schwartz with LeRinc Partners. Your line is open. Please go ahead.

Hey, all. This is Will Onford, Joe. Thanks for taking our question. Grats on the progress this quarter. So one on Peltucetin. Now that we're getting closer to the eventual commercial launch, could you provide any preliminary comments on how you might be thinking about pricing? And then with the recent MFN pricing headlines, does this change your thinking around the general strategy at all? And finally, can you just remind us of where the drug is manufactured? Thanks so much.

So I'll answer the manufacturing and then leave it to Isabel to not answer your question on pricing directly, but give you some thoughts about how we're thinking. In terms of manufacturing, the final tablets are made here in the U.S. and packaging here in the U.S., although we get precursors and final API from Europe and originally in India. So that answers that part. But maybe, Isabel, can you talk just a little bit about the value we're hoping to deliver?

Yes, of course. As I mentioned before, the value proposition of participating is resonating really well with fairs, you know, fast and safe actions, durable effects, easy to use one daily dosage for patients. And also the fact that they don't have to deal with the greater symptoms and the wastage currently associated with injectors. At this time, we're not commenting on price. Of course, it's something that we're looking at very closely. We're conducting market research, advisory boards were there. As I mentioned, what is very positive for us is that the value proposition is resonating very well, and we are tracking on that. We don't see at this point, answering your second question, any impact in our strategy based on the recent dynamics, but of course we're closely monitoring that with our government affairs group as well, and we'll continue to do so considering the About 40% of the population is in Medicare and Medicaid, 30% Medicare, 10% Medicaid, and we want to continue to monitor the potential impact in the future. But for now, there are no analysis.

Our next question is from Dennis Ding with Jefferies. Your line is open. Please go ahead.

Hi, this is Anthea on for Dennis. Thank you for taking our questions. On CAH, the long-term extension, can you give an update on enrollment and follow up there? And what is the critical mass that you need to give another update to investors? Thank you.

Well, enrollment is proceeding. And we will, of course, once we have a critical mass, we would present to the scientific meeting. I can't really comment on numbers and exact timing at this time. But again, the OLE is another way for us to assess how the compound performs in sort of a more real-world setting, which the doctors have control over the dosing of the compound as well as over the dosing of the glucocorticoids. It's always very valuable data for us, and we look forward to reporting that when we can.

Our next question is from David Lebowitz with Citi. Your line is open.

Please go ahead. Thank you very much for taking my question. The new primary endpoint seems to be a higher bar, and I am curious, do you reserve the ability to maintain also the same primary endpoint as clonassar font to potentially use if needed for FDA approval?

So I think you're right. It is a higher bar. We're asking the study to see if etzumelanine can really be the treatment for CAH and give patients an option so that they don't have to compromise on either glucocorticoid levels or the adrenal precursors that are being produced. And so it's intentionally a high bar, but I think it's designed specifically for Atunoma because that's the type of study that this drug deserves. And maybe I'll let Dana talk about the endpoint cascade.

Well, yeah, and I think, you know, just along the lines of what Scott was just saying, the patient population is also different from what Chronicity studied in that we have a broader patient population. And as you recall in their study, basically what they were looking at was trying to reduce GCs, and A4 was sort of a side issue. It had to be roughly where it started, which could have been normal, could have been sort of above normal. And so what we'd like to do is be able to address the full population of patients who have CAH, who may have high A4s and not so high GCs, high GCs and normal A4 and high both. And so in order to do that, you really can't have the same endpoint as chronicity had. Okay? So now we also have a cascade, as I mentioned in the call, of secondary endpoints. And some of those are looking at certain aspects of how quickly we work and then, you know, sort of other combinations of particular, you know, sort of endpoints of interest. But we also... will look in the same way that they did at, you know, somewhat, you know, similar, you know, endpoint for theirs too. But that's not what we, you know, intend to use for the FDA. And you can't, you know, so if we make the primary endpoint this broader endpoint, that's what it is required to have to get approved. So we can't change the endpoint.

And I think it's maybe important to remind all of us that we're building a study that measures a variety of different parameters of the impact of etzumelan on the lives of CAH patients. And it's that whole package that will be the basis for guiding physicians about how this might be used should it be approved. And so we're interested in developing a broad profile, and that's The primary endpoint is one thing, and I know we'll all focus on that, but also getting to how much do we reduce the A4 levels or 17 OHP, which are a couple of our first secondary endpoints, because those lowering is important too, even if you only get to slightly above the upper limit of normal. So the goal of the study is to capture all of this to provide ability to guide physicians and then eventually to use in our commercialization efforts.

And we also intend to look closely at the other clinical endpoints and, you know, adrenal size as well.

Yes.

Our next question comes from Brian Scorney with Baird. Your line is open. Please go ahead.

Good afternoon. Thanks for taking the question. Just also on CAH study, in terms of enrollment criteria, how do you kind of compare exclusion, inclusion criteria to the catalyst study? Are there differences in criteria around GC dose, A4, 17-OH, beta, et cetera? And the pediatric plan you have filled as a phase 2-3, is this just nomenclature? Is there a dose-finding portion for the PEAD study that precedes full phase 3 enrollment?

Okay, just to make sure that I understand, like, the... You asked about the entry criteria for our trial, right, first, for the adult trial. And, you know, I think that, you know, as I mentioned before, what we're trying to do is adapt for a broader population than, you know, the previous trial, you know, from, you know, . Now, in terms of our pediatric program, we've also received feedback from health authorities on that, and we're going to try to achieve the same things that we're doing for the adult program, and we just need to make sure that we have the doses right for the right size kits. And so we'll be gradually working through that. But, you know, we don't plan to do it differently. And as you recall in the, you know, the cronostrophon trial, they didn't, they held the GCs constant, right, in that one. So there was no GC reduction. So that's, you know, sort of one of the big differences.

Our next question comes from Douglas Sal with HC Wainwright. You're allowing this open. Please go ahead.

Hi. Good afternoon. Thanks for taking the questions. And welcome to Toby to the Craniotics College School for Real Hearing. I'm not on a recent call. But maybe just as a follow-up on CAH and the pediatric study, I'm just curious how you think about that program moving forward. Do you anticipate sort of You know, Dana, you referred to sort of need to do some dose exploration. Would you anticipate needing potentially to do two studies there, or do you think there's an opportunity to do an adaptive design which would enable you to only run one study? And, you know, again, would you anticipate, you know, you just said that you anticipate sort of having the same goals as with the COM-CAH study. Does that imply that you would think about the same endpoint? in terms of normalization A4 and physiologic GC, or is there some other potential sort of similar endpoint, but perhaps a slightly different one for targeted for the pediatric population? Thank you.

Well, I think, you know, to answer your first part of your question, and maybe Alan can comment on the, you know, sort of treatment objectives. But, you know, as far as the first question, the way we've designed this study is to be sort of a seamless design, right, as opposed to two separate trials. And so the way that it will work is the phase two part will guide the phase three part. And so we don't, you know, plan on doing separate trials on that. But I think, you know, maybe if Alan could comment on, you know, the treatment objectives for pediatricians on this.

Yeah. The reason I'm really excited and very supportive of this endpoint that we're talking about, normal GCs and normal A4s, is because this really is the treatment goal for this disease. And by the way, it's the same for pediatric patients and adult patients. This is what you want to achieve in clinic. It's very hard to do that these days with available treatments. really think at the moment has a lot to offer here to achieve that binary, you know, two-part goal. So, yeah, I think it would be very similar in pediatric patients ultimately.

Our next question comes from Andy Chen with Gould Research. Your line is open. Please go ahead.

Hey, thank you for taking the question. And back to your Phase III trial design. So I understand that the speed of reduction is individualized, but is it mandatory reduction at each stage of GC reduction, or is it optional reduction for patients? If it's optional, does that make the primary endpoint very wonky and highly dependent on baseline characteristics of patients? Is that a worry here or no? Thank you.

Well, maybe just as a quick reminder, we may have patients in who have physiologic replacement, but their A4 levels are already high, so they don't need a glucocorticoid reduction. So you have to account for that in the way you design the protocol. But maybe you want to explain a little bit more. Right.

That's a good point, Scott. And those who do come in on high glucocorticoid doses, I want to be clear that, yes, this is not optional. The protocol... requires, particularly at certain predefined visits, glucocorticoid dose reductions. Of course, the investigator has to individualize these dose reductions based on toleration and safety, but these dose reductions are expected and would be very carefully monitored and followed. And I agree, it's important to reduce the doses of glucocorticoid in those who come in on high gluc doses in order to achieve this endpoint and also to achieve the goal and clinic, which is the same. So, yeah.

As a reminder, to ask a question, please press star followed by one on your telephone keypad. Our next question comes from Catherine Novak with Jones. Your line is open. Please go ahead.

Hi. Afternoon, everyone. I just wanted to ask one question about So based on Pathfinder 2, we know you can go into treatment naive patients, but do you anticipate any possible step-through requirements for payers based on price? How are you thinking about that?

Isabel?

Thank you. Thank you for the question. Well, as you know, we had Pathfinder 2 was looking at naive patients, also washout patients, and patients that had discontinued continuing therapy. Our current discussions with payers don't anticipate any step therapy and so far the feedback is that they will really just hold us to the label in terms of prior authorization which in general is a very positive sign for us and at this point we don't anticipate that.

We currently have no further questions so I'll now hand back to Scott Struthers for closing remarks.

Thank you, everybody, for being with us today. And maybe I'll just take a brief moment to also thank our colleagues at the FDA for their hard work on multiple different programs we're working on and keeping up the normal course of business, at least as far as we've seen. So thank you all, and have a great afternoon and weekend.

This concludes today's call. Thank you for joining. You may now disconnect your lines.