Q4 2024 Crinetics Pharmaceuticals Inc Earnings Call
Please stand by. We're about to begin.
Good afternoon, everyone. Welcome to the Kronetics Pharmaceuticals fourth quarter and full year 2024 Financial Results Conference call.
At this time, all participants are in a listen-only mode.
Following management's prepared remarks, we will hold a question and answer session. You may register to ask a question at any time by pressing star 1 on your telephone. Also, today's call is being recorded. And with that, I'll turn things over to Gayathri Diwakar, Head of Investor Relations. Please go ahead, ma'am.
Gayathri Diwakar: Thank you, Operator. Good afternoon, everyone, and thank you for joining us to discuss the fourth quarter and full year 2024 results.
Gayathri Diwakar: Today on the call, we have Dr. Scott Struthers, Founder and Chief Executive Officer.
Speaker Change: Isabella Calafonos, Chief Commercial Officer, Dr. Dana Pizzuti, Chief Medical and Development Officer,
Speaker Change: Dr. Steve Betts, Founder and Chief Scientific Officer, and Marc Wilson, Chief Financial Officer. Also joining us for Q&A is Dr. Alan Krasner, Chief Endocrinologist.
Speaker Change: Please note there is a slide deck for today's presentation, which is in the Events and Presentations section of the Investors page on the Kronetics website.
Speaker Change: In addition, a press release was issued earlier today and is also available on the corporate website.
Bye, Tim.
Speaker Change: As a reminder, we'll be making forward-looking statements, and I invite you to learn more about the risks and uncertainties associated with these statements as disclosed in our SEC filing.
Speaker Change: Such forward-looking statements are not a guarantee of performance, and the company's actual results can differ materially from those stated or implied in such statements due to risks and uncertainties associated with the company's business.
Speaker Change: 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 Prunetic's SEC filings, including its annual report on Form 10-K and quarterly reports on Form 10-Q.
Speaker Change: I would also like to specify that the content of this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, February 27, 2025.
Speaker Change: Connecticut takes no obligation to revise or update any forward-looking statement to reflect events or circumstances after the date of this conference call. With that, I'll hand the call over to Scott.
Scott Struthers: Thank you, Gayathri, and good afternoon to everyone joining today's call.
Scott Struthers: 2024 was a remarkable year for Kronetics. As you can see on slide 3, we successfully executed on all the key objectives we set out to accomplish.
Scott Struthers: This sets the stage for what we believe will be a transformative 2025.
Scott Struthers: On today's call, we'll review some of these accomplishments and outline our plans for 2025 and beyond.
Scott Struthers: The PDUFA date is September 25 of this year. This is our first NDA filing and I'm extremely proud of the team for its hard work in getting us to this point.
Scott Struthers: We're continuing to prepare our organization for the anticipated launch of Pal2Satine later this year.
Scott Struthers: As part of this, we are completing the build-out of our commercial and medical affairs teams, as well as the underlying administrative infrastructure.
A very important part of this was hiring Isabel Calafonas.
This past December as Chief Commercial Officer.
Scott Struthers: She successfully launched many rare disease products at both large and small biopharmaceutical companies.
Speaker Change: Isabel has all the skill sets and relevant experience to lead us through our upcoming transition into a commercial stage company.
I'm happy to introduce her to you here today.
Speaker Change: Given the strength of the clinical data for our lead programs and the deep pipeline behind them, we continue forward with our stepwise regional growth strategy in Europe.
We anticipate filing a DMAA for
Speaker Change: We have incorporated a hub in Zug, Switzerland and brought a general manager and leadership for EU regulatory, market access, and medical affairs, and we're beginning to extend this organization to Germany.
Speaker Change: As a leader in endocrine innovation, we plan on leveraging this infrastructure in the coming years as we evolve into a fully integrated, global pharmaceutical company.
Thank you very much.
Speaker Change: Last year, we made significant progress on multiple clinical readouts, including for peltucetine second indication, carcinoidin.
Speaker Change: In a Phase II study, L-16 treatment demonstrated rapid, sustained reductions in frequency and severity of flushing episodes in bowel movements.
Speaker Change: We have begun activating clinical trial sites for the Phase 3 trial and expect the first patient to enroll next quarter.
Speaker Change: We also shared extremely positive data for our second candidate, SMLNAT, in both congenital adrenal hyperplasia, or CAH, and in Cushing's disease.
Speaker Change: In a Phase II study in adults with CAH, Atumelan achieved rapid, substantial, and sustained reductions of both biomarkers, A4 and 17-OHP.
Speaker Change: Importantly, significant clinical improvements in symptoms were also observed, which was impressive in a 12-week study.
Speaker Change: We believe that AtomelNet can provide healthier hormone levels on both dimensions, adrenal androgens and exogenous glucocorticoids, and this profile has the potential to differentiate AtomelNet and provide meaningful improvements to people living with CAH.
Speaker Change: With this in mind, we're progressing towards initiation of late-stage CAH studies in both adults and in children. These studies are designed to take advantage of etaminon's very potent mechanism of action to provide benefits for a broad spectrum of patients with CAH.
FMLNA also demonstrated initial positive results in Cushing's disease.
Speaker Change: All participants in this Phase 1B-2A trial rapidly achieved normalization of urinary-free cortisol, and that is the primary endpoint required for registrational studies in Cushing's disease.
Speaker Change: Thank you for watching. Please subscribe to my YouTube channel. I'm your host, Alan Krasner.
and many more. Thank you. Thank you.
Speaker Change: Lastly, we're making notable progress on our earlier stage programs including 9682, our first drug candidate from a novel non-peptide drug conjugate, or NDC, platform.
Speaker Change: This year, we expect to submit four INDs in total, including 9682. Steve will discuss these in more detail towards the end of the call.
Speaker Change: With that, I'm pleased to introduce Isabel, who will tell you more about the progress in building our commercial capabilities.
Thank you, Scott.
Isabel: I'm pleased to have joined Creanetics to lead the commercial organization in this exciting new chapter for the company.
Isabel: Today, I will share more about how we are advancing our commercial capabilities and working diligently to be launch-ready ahead of our first potential FDA approval.
Isabel: We are building a best-in-class commercial and medical affairs organization with strong leaders across all functions, operations, marketing, market access, medical affairs, and sales.
Isabel: Separately, our Medical Affairs team has talented endocrinologists leading the effort to liaise with healthcare professionals and KOLs.
Isabel: Our MSL team has already reached out almost 100% of our core academic targets to solidify relationships and refine our understanding of the unmet needs in acromegaly treatment.
Isabel: We also have a strong partnership with the broader endocrinology community, which we believe will be instrumental for a successful launch.
Isabel: There is significant unmet need in the acromegaly market. Healthcare professionals and patients want therapies with a rapid onset of action, sustained effect, favorable adverse event profile, and ease of use.
Isabel: We are building our commercial and medical organizations to drive educational efforts in a market that has not seen any meaningful innovation for a long time.
Isabel: Slide four outlines the four imperatives of our commercial strategy. Activate, adopt, access, and adhere.
Isabel: First, we want to activate healthcare professionals and patients to demand more from their acromegaly therapy. For example, we want them to realize that they can achieve better disease control and don't have to settle for frequent breakthrough symptoms.
Isabel: Across the Phase III program, PASTU-13 demonstrated rapid, reliable control of biochemical markers, decreased symptom severity, and reduced the frequency of breakthrough symptoms.
Isabel: Second, after approval, we want to drive adoption of BANTUSU team by clearly articulating its differentiated efficacy and safety profile to patients and healthcare professionals.
Isabel: Our efforts will be focused on pediatric treatment centers as well as the community.
Isabel: And since patients tend to visit their health care professionals only one or two times per year, we expect a more gradual adoption at the outset.
Isabel: We are actively developing strategies to motivate patients and health care professionals to accelerate this timeline. Over time, we are confident in the potential of Paltus team to become the new standard of care.
Isabel: Third, we want to ensure access to Palticitin. Our market access team has continued to engage with the top U.S. payers, and they have been very receptive to the value proposition of Palticitin.
Isabel: We're extremely confident that we'll be able to provide optimal access for all acromegaly patients that could benefit from participating.
Lastly, we want patients to adhere to their PASC-216 regimen.
Isabel: Patient support goes far beyond financial co-pay assistance, and our comprehensive patient support center will include a full suite of services to provide unparalleled support for patients at every step.
Isabel: starting at Initiational Therapy and throughout the course of their long-term treatment regimen.
Isabel: In summary, the Pantusa team profile we are sharing in market research is resonating with all key stakeholders, healthcare professionals, payers, and most of all, patients.
Isabel: We look forward to sharing more details on our launches strategy in the coming months.
Isabel: Lastly, it is important to note that the work that we do today will serve as a solid foundation for anticipated future launches.
Isabel: We will leverage the infrastructure we are building today in the U.S. and Europe across additional indications for participating as well as the other candidates in our pipeline.
Dana: With that, I will hand the call to Dana to discuss our clinical development progress.
Dana: Thank you, Isabel. This is a very exciting time for chronetics. Turning now to slide five, the NDA for caltuzatine was accepted last quarter.
Dana: We have a productive relationship with the Endocrine Division at the FDA, and our NDA review is proceeding normally. In addition, we expect to file our MAA for acromegaly to the EMA in the first half of this year.
Dana: Separately, the Committee on Orphan Medicinal Products of the EMA has issued a positive opinion on our application for orphan designation for acromegaly.
Speaker Change: based on the committee's judgment that it has a potential to provide significant benefit over the currently available therapies.
Speaker Change: We are continuing to activate sites for the Phase 3 study of paltuzatine in carcinoid syndrome. We are planning to run this study globally and expect to enroll our first patient in the second quarter.
Speaker Change: For Adam Mellman in CAH, we are putting the finishing touches on our Phase 3 adult protocol after productive interactions on its design with the FDA and two European health authorities. I'll provide more detail on this in a moment.
Speaker Change: We've also had important and supportive discussions with FDA and EMA regarding a proposed Phase 2.3 pediatric study for CAH.
Speaker Change: We are completing protocol development and will provide more details on the design and plan to begin this study before the end of the year.
Speaker Change: We are continuing to pursue development of antimelanin in ACTH-dependent Cushing syndrome, or ADCS.
Speaker Change: We are finalizing a proposed seamless Phase 2-3 study design, which we developed after review of our NIH study data and in close collaboration with external experts and regulatory advisors.
Speaker Change: In the near future, we will provide our proposal to the FDA and European agencies for discussion. We will then finalize the protocol and would expect to enroll our first patient late this year or early next year.
Speaker Change: Before I leave Adam Melnick, I realize there may still be some lingering discussion about the one case of elevated liver enzymes in the CAH phase 2 study.
Speaker Change: As we have previously described, one patient in the 120 mg dose cohort had liver enzyme elevations at the final study visit at 12 weeks.
And those levels return to near normal within two weeks.
Speaker Change: The patient did not show any elevation in bilirubin nor any associated symptoms.
Speaker Change: It is also important to note that we have seen no concerning signals nor unexpected safety findings in the preclinical work or in the phase one healthy volunteer studies.
Speaker Change: We have shared all preclinical and clinical data, including the details on this patient, with the FDA and global health authorities as part of the consultation process for our proposed phase three design.
Speaker Change: After reviewing all the data and the proposed phase 3 protocol, the FDA has not recommended any changes to the safety monitoring in the ongoing open label extension study.
Speaker Change: nor any additional testing on top of routine hepatic safety monitoring in our proposed phase 3 protocol.
Speaker Change: We remain very enthusiastic about the strength of the overall Phase 2 efficacy and safety results, and we believe this favorable benefit-risk profile will be confirmed in our Phase 3 trial.
Speaker Change: Thank you for watching. I'm your host, Dana Pizzuti. Be safe out there.
Speaker Change: This enthusiasm is reflected in our Phase 3 protocol, which we will share in detail when final, but our intention is to use a novel endpoint.
Speaker Change: Based on the entirety of the clinical program and Adam Melnick's unique mechanism of action at the MC2R receptor,
Speaker Change: Atomelanin should be capable of reducing androgens into a normal range and allow for lowering glucocorticoid doses to physiologic replacement levels.
Speaker Change: Our proposed endpoint would capture this differentiating aspect of Adamelnut and will allow for broader Phase III inclusion criteria than was used for the currently approved CAH therapy.
Speaker Change: In particular, patients with normal glucocorticoid doses but high A4 levels could potentially benefit from Adamelnut and will be included in our Phase 3 study.
Speaker Change: 2025 is an exciting year for Paltusatine and Edelman as we continue towards registrational studies for these candidates in multiple indications.
Speaker Change: We will soon have four late-stage clinical programs underway, which is a new high-water mark for Chronetics.
Speaker Change: As we make progress on our preclinical pipeline, we look forward to potentially initiating additional early-stage trials. With that, I will hand it to Steve to describe our upcoming INDs.
Steve Betts: Thank you, Dana. As you can see highlighted on slide six, Kronex has an innovative pipeline of drug candidates with IT into the 2040s, with 10 whole yield programs currently disclosed and more innovation happening within our discovery team.
Steve Betts: Our core expertise is in targeting G-protein coupled receptors, or GPCRs, with small molecules that have specifically tailored pharmacology and properties.
Steve Betts: To reflect the breadth of opportunities within the GPCR space, we have organized our discovery team into three main focus areas endocrine disease, metabolism, and what we call targeted therapeutics.
Steve Betts: Since our inception more than 15 years ago, Trinetics is focused on developing innovative non-peptide drug candidates that target specific endocrine pathways to modulate abnormal hormone secretion.
Steve Betts: Most of the candidates currently in our pipeline have come from our endocrine group, and we continue to explore additional GPCR targets within the endocrine system, focusing as always on key areas of unmet need.
Steve Betts: Relatedly, metabolic disorders including diabetes and obesity impact the lives of hundreds of billions of people around the world and their effects on patients are significant and varied.
Steve Betts: We feel that many of these disorders can be addressed by appropriately activating or blocking the receptors of key metabolic hormones including insulin, glucagon, GLP-1, and GIP.
Steve Betts: Chronetic's understanding of these hormonal pathways and the GPCRs that control them is driving us to create new molecules with a chance to improve the lives of these patients.
Steve Betts: Lastly, I'd like to cover targeted therapeutics. Our efforts in this space began with the development of non-peptide GPCR target radioligands for the imaging and treatment of a broad range of endocrine receptor-driven cancers.
Steve Betts: This work ultimately led to the formation of Radionetics Oncology in 2021. Following that, we continue to explore this concept of using non-peptide ligands to target endocrine GPCR as relevant to oncology, but with non-radioactive payloads.
Steve Betts: This work has led to the development of a new modality that we call Non-Peptide Drug Conjugates, or NDCs.
Steve Betts: NDCs are a novel therapeutic approach that are conceptually similar to ADCs but use a non-peptide ligand instead of an antibody to selectively target and deliver payloads to tumor cells expressing GPCRs.
Steve Betts: We feel NDCs possess multiple advantages, including straightforward production by standard synthetic methods and tailored in vitro and in vivo properties that allow us to optimize half-life, tumor penetration, and payload.
Steve Betts: Four early-stage programs from these discovery efforts are currently in IND-enabling studies. The farthest along of these is CRN09682, our NDC for SST2-expressing neuroendocrine and solid tumors.
Steve Betts: The SST2 agonist ligand for 9682 has been optimized to promote internalization so that its payload can be efficiently delivered intracellularly to induce tumor cell death. We are on track to submit an IND for this program early this year.
Steve Betts: The other candidates with INDs planned for 2025 include a PTH antagonist for hyperparathyroidism, a TSH antagonist for grave hyperthyroidism and thyroid eye disease, and an SST3 agonist for autosomal dominant polycystic kidney disease, or ADPKD.
Steve Betts: Similar to what we have seen in our development of both Paltusatine and Atromelanet, one advantage of several of the programs listed on this slide is that we can get early mechanistic proof-of-concept in Phase I trials.
Steve Betts: The first in human studies of 9-6-8-2 will be in oncology patients so we can measure progression of disease. In hyperthyroidism, there are hormonal biomarkers that should demonstrate whether we are having our desired pharmacological effect.
Steve Betts: These early insights ensure that we can optimize our potential for success across each of these programs while maintaining a capital and resource-efficient development strategy. We look forward to sharing some of the early results from these programs with you as they become available in the future.
Steve Betts: With that, I will hand it over to Marc to review the 2024 financial results.
Thank you, Steve. Turning to slide 7.
Marc Wilson: 2024 was an outstanding year that demonstrated the strength of our strategy and our team's execution capabilities.
Marc Wilson: Chronetics entered 2025 with strong momentum across all programs and the company remains focused on discovering and developing novel therapies for patients as well as generating value for its co-owners.
Marc Wilson: The tremendous progress made over the course of last year has enabled the company to continue investing in the pipeline as we prepare to launch the first drug candidate emerging from our own R&D efforts.
Marc Wilson: Now I will walk through the financial results for the fourth quarter of the year.
Marc Wilson: Revenues were $1 million for the full year ended December 31, 2024, compared to $4 million for the same period in 2023.
Marc Wilson: There were no revenues in the three months ended December 31, 2024, or the three months ended December 31, 2023.
Marc Wilson: Revenues in both years consisted of the amortization of payments we received in connection with our Peltucetine licensing arrangement with our Japanese partner, SKK.
Marc Wilson: Revenue in 2023 also included approximately two million dollars associated with a development candidate that we licensed to Loyal to explore extension of lifespan and large and giant breed dogs.
Marc Wilson: Research and development expenses were $66.6 million and $240.2 million for the three months and full year ended December 31, 2024, compared to $45.6 million and $168.5 million for the same period in 2023.
Marc Wilson: The increases were primarily attributable to higher personnel costs and increased development activities associated with the expansion of our pipeline.
Thank you.
Marc Wilson: G&A expenses were $28.2 million and $99.7 million for the three months and full year ended December 31, 2024, compared to $17.1 million and $58.1 million for the same period in 2023.
Marc Wilson: These increases were primarily driven by increased personnel costs and commercial planning activities.
Marc Wilson: Our net loss for the three months ended December 31, 2024, was $80.6 million, compared to a net loss of $60.1 million for the same period in 2023.
Marc Wilson: For the year ended December 31, 2024, the company's net loss was $298.4 million, compared to a net loss of $214.5 million for the prior year.
Marc Wilson: For 2025, we anticipate our cash burn to be between $340 and $380 million.
Thank you. Thank you.
Marc Wilson: This increase reflects our plans to initiate four late-stage trials in 2025, so we expect our R&D spend to grow in 2025 as those trials start to ramp up.
Marc Wilson: SG&A will also increase this year as we continue to build our commercial infrastructure and prepare for the potential launch of Peltuzatine in the fourth quarter.
Marc Wilson: We ended 2024 on strong financial footing with approximately $1.4 billion in cash and investments.
which is expected to fund our operating plan into 2029.
Speaker Change: Before I turn it back to Scott, I'd like to take a moment to thank my fellow Kronetizens for their support during my tenure, particularly since I announced my plan to transition out of the CFO role a number of months ago.
Speaker Change: I would also like to thank those of you in the investment community who have been outstanding colleagues over the years.
Speaker Change: I truly believe in the work that is being done at Chronetics. It is a genuinely unique company, and I am honored to have been a small part of what the organization has accomplished.
Speaker Change: I am optimistic about the future and am confident that Tobii will be an exceptional steward of the company's resources through its next phases of growth.
I'll now turn it over to Scott for closing remarks.
Scott.
Scott Struthers: Thank you, Marc, and thank you for your leadership over the past seven years. You've been instrumental through these years of incredible growth.
Scott Struthers: With your help, we have grown from a pre-Series B private company to the public company we are today with operations around the world and on the verge of our first Hadoopa day.
Scott Struthers: I speak for everyone here when I say that we are deeply grateful for your dedication and contributions.
Speaker Change: We're also very excited to welcome Toby Schilke, who will succeed Marc as Chronetic CFO. Toby brings over 25 years of global pharmaceutical experience and has led several biotech companies through the transition to fully integrated commercial enterprises.
Speaker Change: He brings a wealth of experience and a unique perspective, and we're excited to have him on board as we prepare for our first commercial launch.
Speaker Change: Turning to slide eight, I'm very bullish on the bright future before Chronetics. The array of opportunities for us to help patients with endocrine related diseases with pipeline we've created from scratch is breathtaking.
Speaker Change: With the progress I have described today, we have made great strides on our path to becoming the premier fully integrated global pharmaceutical company.
Speaker Change: The combination of our best-in-class in-house discovery capabilities, proven clinical development, and our ongoing build of commercial capabilities strongly positions us to execute on a number of key milestones in 2025.
Speaker Change: We plan to leverage our growing infrastructure across multiple programs and therapeutic areas while recognizing economies of scale along the way. I believe this strategy will propel us to maximize patient reach and drive long-term value growth for all our stakeholders.
Speaker Change: With that, I'll hand the call back to the operator to begin Q&A. Please limit yourself to one question each in the interest of time.
Operator.
Speaker Change: Thank you, Dr. Struthers. Ladies and gentlemen, at this time, if you do have any questions or comments, please press star 1. If you find your question has been addressed, you may remove yourself from the queue by pressing star 2. Once again, star 1 for questions. We'll go first this afternoon to Tyler Van Buren of TD Cowen.
Speaker Change: Great, thanks guys. It's great to be back in coverage of Chronetics here again, and congratulations on all of your achievements. Marc, I wish you the best. I wanted to ask about PAL-2. The data with PAL-2 and acromegaly are clearly strong, and the likelihood of approval in September is very high. But expectations for the launch seem conservative or even modest.
Speaker Change: from some of your investors. So can you elaborate on the ongoing launch preparations for PAL-2? What might surprise people in your global strategy in particular?
Speaker Change: Thanks, Tyler. I totally agree with you at how strong the data has been for Acromegaly.
Speaker Change: which in part recognizes that because they felt that Peltucetine constitutes a clinically relevant advantage over currently approved therapies, and that's part of their process in making the orphan designation.
Speaker Change: So I think we've built something that is going to give Isabel and the rest of the team something very strong to work with, and let me let her talk to you about the ongoing preparations.
Isabel: Yes, thank you, Scott. Yes, we are in a really good place in preparing the organization, the market, and the product.
Speaker Change: In terms of the organization, we hired a very talented team, and we're very pleased to welcome our VP of sales as we continue to build our customer engagement model, including not only the sales team, but field reimbursement managers to facilitate the onboarding of the patient.
And in addition to that, we are preparing the...
the market and that involves
Speaker Change: Very successful engagement right now with the payers that are responding very well to the value proposition of the drug, as Cody stated. We have a treatment that has fast and slow action, sustainable effect.
Speaker Change: Let's break through symptoms has a very good tolerability profile and of course it's a once-daily which really resonates not only with the payers but also with the physicians and the health care professionals.
Speaker Change: We continue to drive educational activities to engage with the doctors in disease awareness as well as with the patients.
Speaker Change: In terms of the product, we are in a very good place when it comes to our supply change and distribution. And we continue to develop our training modules and launch materials consistent with the expected label.
Speaker Change: So we are in a very good place, and the product...
Speaker Change: really offers the opportunity to really change the standard of care.
Thank you. Thank you. Thank you.
Speaker Change: In terms of the international organization, we think it's very important that this product is known only for the U.S. patients, but it starts really making a difference internationally as well.
Speaker Change: We have a General Manager, Market Access, Medical Affairs, and Regulatory in place, and it's our goal to now focus on building Germany.
Speaker Change: Similar to the U.S., the model is very fit-for-purpose, really with a significant value concentrated in centers of excellence, and we are preparing and advancing that as well. So really exciting times, and the commercial organization is...
Speaker Change: you know, in full engagement and making sure that we advance towards a successful launch.
Yasmeen Rahimi: Thank you. We'll go next now to Yasmeen Rahimi at Piper Sandler.
Dominic Ambriaz: Hi, this is Dominic Ambriaz. Thank you for taking our questions and congrats on continued strong execution.
Speaker Change: Our question is just how do you envision your disclosures as you continue your dialogue with the FDA between now and September 25th?
Speaker Change: And are there certain topics of interest that could come up at your mid-cycle review? And also, have you had your mid-cycle review yet, and what was the outcome, if you had?
Thank you.
Speaker Change: communications point of view I think that will be simply as an as-needed basis but let Dana just say a little bit more. Yeah well we haven't had the mid-cycle yet but you know we are scheduled to do that.
Speaker Change: And, you know, we're awaiting, you know, further interactions with the FDA as we go along. But as I mentioned in, you know, my initial remarks, everything's proceeding normally and there's, you know, a very productive relationship with the agency.
Thank you. Bye.
Thank you. Thank you.
and more. Thank you. Thank you.
Speaker Change: Thank you. We go next now to Joe Schwartz of Leering Partners.
Joe Schwartz: Thanks very much and congrats on all the progress. I was wondering if you could talk about the strategies you're working on to motivate acromegaly patients to see their health care providers such as those in the community we heard you say often lag in the up
Joe Schwartz: uptake of new treatments. And in a related sense, how long do you think phase three enrollment for Atum Elnit and CAH
Joe Schwartz: may take, recognizing that there's a new treatment option for the first time in a long time and could be a bit competitive, but also I think you know you've
Joe Schwartz: already had a lot of experience with clinical development now for Peltucetine. So I'm just wondering, relative to that Phase 3 enrollment timeline, how should we think about how long it might take for Atomelanin in Phase 3? Thank you.
Well, nice working in a compound question, Joe.
Joe Schwartz: We've got quite a bit of experience now in that community. In many cases, it's the same institutions as we did with Acromegaly.
Joe Schwartz: The fact that now there's an approved drug on the market and chronicity is fabulous for these patients.
Joe Schwartz: But I don't think it's going to significantly impact our enrollment, especially since we're in a global clinical trial, and in fact has been our past experience, and I think the past experience of most other companies.
Joe Schwartz: Recruitment tends to be higher outside the U.S. than inside the U.S. and so I see no effect. And then compared to prior trials
Joe Schwartz: of CAH that were underway during the pandemic where people were late to the international markets. I expect us to do significantly better than previous experience.
Speaker Change: But Isabel, maybe talk a little bit about activating patients. I think they're highly motivated already, but we want to make sure they're empowered, not just motivated.
Thank you.
Speaker Change: Yes, indeed we are engaging with the patients through different venues including our disease awareness campaign really to highlight the significant unmet need that is happening in the marketplace.
Today, the data will show that only
Speaker Change: The 35% of the patients are uncontrolled, so many of the patients have significant unmet needs, and the majority of the patients have breakthrough symptoms.
Speaker Change: And as normal, they continue to experience significant effects in fatigue, sweating, and other symptoms as well that impair their ability to function.
Speaker Change: and the quality of life. So we're making them aware of that and there are different educational events and the Disease Awareness Campaign, as well as our media outreach that is starting right now throughout the country.
Speaker Change: In addition to that, we have a patient hub that we believe is going to really help patients
Speaker Change: reach out, and we will support them not only through co-payments and additional activities, but also helping with their mental health and other things that we provide support to them.
Speaker Change: So overall, sorry, we are in the process of activating not only the patients but the healthcare community.
Speaker Change: and many more. Thank you for watching. I'm your host, Dana Pizzuti.
Very helpful. Thanks for the insights.
Speaker Change: Thank you. We go next now to Jessica Fye of J.P. Morgan.
Jessica Fye: Hey guys, good afternoon. Thanks for taking my question. I was curious if there's any update on where things stand with the open label extension for the CAH Phase 2 trial. I'm just trying to think about if that's something we could see data from prior to getting those Phase 3 results. Thank you.
Speaker Change: Thanks, Jess. Yeah, the sites are activating and patients are switching into the open label extension and eager to see how they do. It's a little bit of a second bite at the apple since
Speaker Change: We had a bit of a delay in starting the OLE to finish up the long-term talks so all the patients had come off of drug and now they're coming back on under physician care and Yeah, I look forward to seeing how that plays out and I think it will be a valuable source of information
Thank you.
Corey Jubinville: Thank you. We go next now to Corey Jubinville of Lifesci Capital.
Corey Jubinville: Hi there, this is Kate on for Corey. Thanks for taking your questions and congratulations on the amazing progress this year.
Speaker Change: This one from us related to the CEH program. It's of course still early days but it seems like the Conecity launch in CEH has gotten some early momentum and we're just curious what are the learnings you've taken from the launch thus far and how you might be considering that for Atum Elnit in the future and is there anything thus far that surprised you?
and many more. Thank you. Thank you.
Speaker Change: Thank you. We go next now to Gavin Clark-Gartner at Evercore ISI.
Gavin Clark-Gartner: Hey guys, congrats on the progress. For Atumelment, can you share any additional details on Cohort 4 in the Toucan study and when we may be able to possibly see that data? Thank you.
and many more. Thank you. Thank you.
Speaker Change: Yeah, thanks, Gavin. We haven't really started talking about Cohort 4. Remember, it's just one cohort in a large overall program.
Thank you.
Speaker Change: But I think one thing we will be telling you about in the not-too-distant future is the overall study design details for the Phase III program.
Speaker Change: You know, maybe at that time it's relevant to talk about Cohort 4, but I'll try and get that out as soon as we have the final pieces in. I just don't want to...
Speaker Change: tell you something that might have slight revisions. So we're very close to finalizing that and starting to activate sites and things like that. So I think we'll be able to provide clarity by our next earnings call at the latest.
Great, thank you.
John Lobel: Thank you. We go next now to John Lobel at Citizens.
John Lobel: Hi, this is Catherine, on for John. I have a kind of a follow-up question on CIH as well. I know that you just mentioned that you're going to be discussing the design details of the Phase 3 program going forward. It's kind of a general, general kind of question.
John Lobel: and a differentiate endpoint from the one that was kind of previously
Speaker Change: So what is the kind of rationale from a regulatory standpoint as well as a commercial standpoint on changing up the endpoints, to give a little bit more color on that?
Yeah, thanks. I think the thing to recognize is that...
Sorry, we're getting some feedback.
Speaker Change: I think the thing to recognize is that this is a completely different mechanism of action with a different pharmacologic profile.
Speaker Change: We've shown in both the Phase II and CAH patients, you know, deep suppression of A4.
We've shown in healthy volunteers.
Speaker Change: that even under conditions of very low glucocorticoids and extremely high levels of ACTH, that we can maintain suppression of the adrenal gland and keep those patients even to the point where they still need glucocorticoid advect.
Speaker Change: And so our vision for the drug is not one which is just helping glucocorticoids manage the adrenal. We think that Atumelnant should be the treatment for CAH. And then glucocorticoids are not used for treatment, they're simply used for replacement.
And so maybe Dana can elaborate a little bit more.
Speaker Change: Trying to be not completely specific because there's still a few things to work out, but let me let her talk about principles Well, yeah, I think as Scott mentioned we and as I mentioned earlier on the call
Speaker Change: We feel that the drug is capable of doing more than just
Helping manage
Scott Struthers: the disease with glucocorticoids, right? We feel, as Scott says, that this
Scott Struthers: should be able to do both, right? And so when we put together an endpoint, it has to have both dimensions in it. Now, we haven't...
Scott Struthers: finalize exactly how that's going to work from a statistical point of view, but we think that the basis for that belief in terms of the mechanism of action could lead to a different
Scott Struthers: potential indication for the drug, right? Because we feel that this is the treatment for the disease and glucocorticoids are just a safety mechanism to prevent, you know, adrenal insufficiency.
and many more. Thank you. Thank you.
Speaker Change: Hi, thanks for taking our question. We just had one on...
on a two-minute, can you?
Speaker Change: And from a timing perspective, can you commit to sharing additional data this year whether
Speaker Change: It's from CAH, so it's a 4.4 or longer-term extension data or Cushing's, and then for the long-term extension, how do you think efficacy would evolve with longer Trugan?
Speaker Change: Well, I try never to commit to any timelines around things until we're absolutely certain about it. So just have to stay tuned. Sorry to keep you in suspense. But in terms of, sorry, the second part of the question.
Thank you. Thank you.
Speaker Change: just around the long-term extension and how do you think efficacy could evolve patients are on?
Speaker Change: Yeah, so I think that the most relevant data there is what we saw with the adrenal sizes in a very short 12-week study.
So, ACTH is trophic for the gland.
Speaker Change: In CAH, when these patients are experiencing high ACTH levels from birth, they end up getting larger adrenal glands, as my friend Dr. Krasner says, they become angry, and certainly they're very active.
Speaker Change: and we're showing shrinkage of those glands in only 12 weeks.
Speaker Change: So I would expect that to continue with time and if anything then the ability to suppress the adrenal should increase or remain with time. There's no mechanistic reason to believe that any sort of tachyphylaxis should develop.
Thank you.
Katherine Novak: Thank you. We go next now to Katherine Novak of Jones Trading.
Katherine Novak: Hi, good afternoon. My question is around how are you prioritizing the three non-oncology assets that you're moving forward into R&D filing this year? You know, if you had to pick which indication is most exciting to you at this time. Thanks.
Hi, Gayathri, and I'll, uh...
Speaker Change: I'll answer that the same way I often do, which is I've now up to four grandkids and they each have their wonderful traits and I love them all, but
Speaker Change: The prioritization, we're in a fortunate position where because of our strong balance sheet and our build of the company, that we're not at a position where we have to prioritize them.
Speaker Change: We are able to move all of those forward at their natural pace.
Speaker Change: And at the moment, well, clearly, 9682 is in the lead. We'll be filing that IND very shortly.
Speaker Change: There's a bit of a race between the PTH antagonist and the TSH antagonist, and it looks like TSH is catching up a bit.
Speaker Change: and then ADPKD is working in the background. I just saw you wrote a note about ADPKD and it hit my inbox as this was starting so I'm looking forward to reading it. Thank you.
Absolutely. Thanks, Scott.
and many more. Thank you. Thank you.
David Leibowitz: Thank you. We go next now to David Leibowitz at Citi.
David Leibowitz: Hey guys, John on for David. Thanks for taking our question. For the At-Rim Internet Phase 2 data, just curious, what is the current thinking behind the lack of observed dose response and the 17 OHP decrease?
David Leibowitz: across all the doses. I understand that, you know, E4 was the primary endpoint, but just given the fact that, you know, 17-OHP plays an important role as an intermediate hormone, just, you know, interested to hear what the latest thinking is on that data point. Thanks.
Thank you very much for the question.
David Leibowitz: 17-hydroxyprogesterone is a very variable biomarker even in the clinical care of these patients and particularly when you use it to try and assess adequacy of care and clinical practice.
David Leibowitz: I take a lot of learnings from the fact that we actually, in this very short study, see clinical outcome benefits.
David Leibowitz: And in that kind of situation, we no longer need to rely on the exact amount of biosurrogate biomarker reduction. We know it's...
David Leibowitz: which is why we would like to think of etomelanid as ultimately, hopefully, the treatment for CAH, whereas glucocorticoids are just used at low doses for replacement.
David Leibowitz: But I will say, I was looking earlier this week with the group at some of the exposure response modeling, and I don't think I agree with you. I think there is a nice exposure response with both 17-OHP and A4, although, as Alan says, 17-OHP is a bit more variable.
and many more. Thank you. Thank you.
Rohan Mathur: Thank you. We go next now to Rohan Mathur at Oppenheimer.
Speaker Change: Hey, this is Rohan An for Lea Linger Show. Thanks for taking the question. Just one for me on paltusetine. Given the use of somatostatin receptor agonists in acromegaly in patients with neuroendocrine tumors, how do you think about carcinoid from a commercial standpoint as there may be some overlap in call points and complementary dynamics once it's potentially made available on both indications? Thanks.
Speaker Change: Yeah, thank you. I think there's a couple areas of synergy there. One, from a geographic point of view, the oncology centers of excellence and the pituitary centers of excellence are geographically
overlapping.
Speaker Change: And so there is some efficiencies there. I also think that our growing experience in acromegaly provides additional safety confidence for the patients with neuroendocrine tumors.
Speaker Change: Which I'll remind folks are things that are really becoming a chronic disease in many ways So long-term safety is of course important
Speaker Change: There's an interesting dynamic to note outside the U.S. which is in many of the countries in Europe.
Speaker Change: overlap more frequently with those that are managing neuroendocrine tumors. So, for example, investigators of ours in the UK and some in Germany and some of the other countries.
Speaker Change: have many more neuroendocrine tumor patients than they do acromegaly patients, but they see both. So the beginning experience in one population to help them understand how they might use it in another later.
Speaker Change: So, I think overall that, you know, people are used to using somatostatin analogs for both and paltucetine is a next generation somatostatin analog, or ligand, excuse me.
Thank you.
Speaker Change: Thank you. We go next now to Andy Chin of Wolf Research.
Andy Chin: Hey, thank you for taking the question. I think it was Isabel during the prepared remarks that mentioned that payers are very supportive of the value proposition of Paltusatine.
Andy Chin: Can you discuss which features of the product they're the most excited about?
Andy Chin: So, especially now that we know that CIPLA will be back to the U.S. market against Ipsen.
Andy Chin: in this quarter, and then I hear that generics will launch in Europe in the second quarter. Wouldn't payers be more excited about those generics a lot more, or do you think those are just basically non-factors in the grand scheme of things? Thank you.
and many more. Thank you. Thank you.
Andy Chin: Yeah, I do think that, you know, in general, the generics or 501B, the equivalents, you know, are really just the next generation in the long term.
Andy Chin: small changes to the injectables and I don't think that that provides the next generation of care that Paltucetine provides. So let me let Isabel answer a little more detail though.
Speaker Change: Currently with the injectables you see a significant discontinuation rate and lack of adherence to treatment, which many of the payers consider almost wastage, you know, because in theory you are reimbursing for those treatments but you are not getting the efficacy you are expecting to get.
Speaker Change: Also, the coverage, whether it's a generic or whether it's a branded product, injectables.
Speaker Change: Tends to lag towards the last week of the four weeks of treatment and many of the patients continue to have greater symptoms and we have done some economic analysis that shows that many of those patients end up having to have certain babies and continue to have pain and
Speaker Change: So overall, the payers see this as an improvement on the standard of care. They are very positive about the sustainability of effects.
Speaker Change: The rapid action, because you also see in injectables that sometimes it takes a long time to find the right dosage, which is not the case with adenosine, and this is really transforming the standard of care. So we are very pleased with how they are appreciating the value proposition of the drugs.
Thank you.
Brian Skorney: Thank you. We go next now to Brian Skorney of Baird.
Brian Skorney: Hey, this is Charlie on for Bryan. Thanks for taking the question. Just touching on the PTH antagonist, it would be great if you could...
Brian Skorney: tell us more about the landscape there in terms of how patients are usually treated as well as what you believe the antagonist could offer over that as well as when you think about the 200
Speaker Change: How many of those would you expect to be addressable with this compound? Thank you.
Oh
Thanks very much.
Speaker Change: Yeah, a PTH antagonist for clinical use would be a very novel opportunity for patients with primary hyperparathyroidism. Right now the major treatment option is surgical removal of the overgrown parathyroid adenoma, which usually causes this disease.
Speaker Change: that is curative much of the time. However, unfortunately, there are a lot of patients with this disease, as you mentioned, and many of them do not get surgery.
Speaker Change: There is really not a true medical option for the treatment of hyperparasitosis, and there is Sinocalcite, which is approved. Sinocalcite, however, has only been shown to
Speaker Change: or improve one aspect of this condition, that's the hypercalcemia or elevated calcium levels.
Speaker Change: But hyperparathyroidism is a multi-organ disease that affects the bones and the kidneys adversely. Stenocalcite, although approved, has never been shown to help the kidneys or the bones. We really need a treatment, a medical option for the treatments.
Speaker Change: and, in theory, a PTH antagonist could help all of the end-organ damage that we see in this condition.
Speaker Change: Yeah, and I think, you know, this is a case also as we start thinking more about PTH where I want to spend some time talking to the community in more detail about these programs so that people can begin to appreciate it. I know most of our conversations
Speaker Change: with the various investors and analysts has to typically stop at the at the moment is
Speaker Change: But we are planning on putting together an R&D day this spring or early summer
Speaker Change: And I think the other thing about PTH, it's one of the ones,
Speaker Change: So, as we address more and more of these diseases, I'm meeting employees or family members that are suffering from these, and we're starting to hear some of the firsthand experiences and challenges that they're facing, which always brings this home.
Speaker Change: And so as we think about PTH, I think it's a great example where
Speaker Change: You've got to think of us as trying to really transform the treatment paradigm for the disease.
Speaker Change: and maybe there's a better way to manage patients while they're either waiting for surgery or maybe they're not the best surgical candidate or maybe there's just not a good surgeon nearby. So I think we can do, I think we can do something special with PTH.
Thank you.
Thank you, and ladies and gentlemen,
Speaker Change: Ladies and gentlemen, that's all the questions we have today. Dr. Struthers, I'd like to turn things back...
Thank you, sir, for any closing comments.
Speaker Change: Thank you, everybody, for your questions and your hard work. We appreciate all of you and look forward to talking to folks in the coming hours and days. Take care.
Speaker Change: Thank you, Dr. Strellers. Again, ladies and gentlemen, that will conclude Chronetic Pharmaceutical's fourth quarter and full year 2024 financial results call. Again, thanks so much for joining us, everyone, and we wish you all a great remainder of your day. Goodbye.