Acadia Pharmaceuticals Inc (ACAD) Q3 2026 Earnings Call Transcript

Hello, and welcome to Acadia Pharmaceuticals' third quarter earnings call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, please press star 1 on your telephone keypad. I would now like to turn the conference over to Al Kildani, Senior Vice President, Investor Relations and Corporate Communications. You may begin.

Good afternoon, and thank you for joining us on today's call to discuss Acadia's third quarter 2026 financial results. Joining me on the call today from Acadia are Catherine Owen Adams, our Chief Executive Officer, who will provide some opening remarks, followed by Tom Garner, our Chief Commercial Officer, who will discuss our commercial brand's debut in New Placid. Also joining us today is Dr. Sanjit Patak, SVP and Head of Clinical Development, who will provide an update on our pipeline programs, and Mark Schneier, our Chief Financial Officer, who will review the financial highlights. Catherine will then provide some closing remarks before we open up the call for your questions. We are using supplemental slides, which are available on our website in the Events and Presentations section. On today's call, both GAAP and non-GAAP financial measures will be discussed, including non-GAAP New Placid net sales and non-GAAP total revenues. The non-GAAP financial measures that are also referred to as adjusted financial measures pertain only to New Placid sales in 2025 and their impact on total revenues. All references to non-GAAP are reconciled with the most directly comparable GAAP financial measures in our earnings press release and slide presentation, which has been posted on the investor's page of the company's website. Before proceeding, I would like to remind you that during our call today, we will be making several forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements, including goals, expectations, plans, prospects, growth potential, timing of events, future results, and financial guidance, are based on current information, assumptions, and expectations that are inherently subject to change and involve several risks and uncertainties that may cause results to differ materially. These factors and other risks associated with our business can be found in our filings made with the SEC. We were cautioned not to place undue reliance on these forward-looking statements, which are made only as of today's date, and we assume no obligation to update or revise these forward-looking statements as circumstances change, except as required by law. I'll now turn the call over to Catherine for opening remarks.

Thank you, Al, and good afternoon, everyone. Quarter 3 was another strong quarter for Acadia, one that demonstrates the strength of our commercial foundation. And the progress we are making to translate that strength into our next chapter of growth. In the third quarter, we delivered total revenues of $342 million, representing 22% year-over-year growth on an adjusted basis. Debut delivered record net sales of $140 million, up 39% year-over-year. Debut Styx is expanding our opportunity in several different ways. Current patients who want to switch to STICS, new patients who are trying debut for the first time, and patients who previously stopped treatment and are coming back to try again with STICS. Given this momentum, we are raising our 2026 debut guidance, and we remain confident that we can reach 700 million in debut sales by the end of 2028. We also achieved an important IP milestone during the quarter, receiving a U.S. PTO Notice of Allowance for an important new patent covering the weight-banded dosing regimen used in both Debut Oral Solution and Debut Stix. Following issuance with pediatric exclusivity, the patent is expected to provide U.S. protection for both formulations of Debut through March 2041, extending patent protections by nearly five years. Following the successful completion of our Phase 3 trial for DEBU in Japan, we are focused on identifying the right distribution partner while preparing for an expected 2027 regulatory submission to support market entry and remain committed to bringing DEBU to patients there. New Plaza delivered $202 million in net sales, up 12% year-over-year on an adjusted basis, with virtually all of that growth driven by patient demand through volume. As we approach the end of the year, we are narrowing our New Plazid guidance and remain confident that we are on track toward our ambition to reach approximately $1 billion in New Plazid net sales by the end of 2028. Tom will provide additional color on the commercial drivers behind our performance on both brands. Turning to our pipeline, the phase 2 portion of our radiant program of remnifantzerine in Alzheimer's disease psychosis narrowly missed statistical significance on the primary endpoint, but achieved our goals with the study to clarify the dose to advance into phase 3 and generate insights needed to optimize the phase 3 portion of the program. At the 60 milligram dose, efficacy was observed across all four psychosis scales assessed in the full study population. With increasing separation from placebo through the six-week treatment period on both the primary and key secondary endpoints, along with a favorable safety and tolerability profile similar to placebo. Based on these findings, we are focusing our Phase III program on the 60 milligram dose and taking additional steps designed to optimize for potential positive Phase III outcomes. The more we have learned from these data, the more we have learned from these data, the The more confident we have become in the path forward for the program. The findings from our Radiant Phase II in ADP also reinforce our confidence in the opportunity in Lewy body dementia psychosis. We remain excited about the potential for remlefanserin in this population and are pleased to announce that we expect Phase II results from the Illumera study in the fourth quarter of 2027. Taken together, Remlifantzerin represents an important potential growth franchise across both ADP and LBDP, both areas of huge unmet medical need, with an approximately $4 billion combined peak sales opportunity. Our priority now is to generate the clinical evidence needed to validate that opportunity. Beyond remlefanserin, we are advancing our broader pipeline of promising programs that we believe have the potential to address significant unmet needs and create long-term value. An additional data readout for our Norlite Phase 2 study of ACP211, our once-a-day oral deuterated form of arnal ketamine for the treatment of major depressive disorder, is now expected in the second half of 2027. We believe ACP 211 has the potential to address significant unmet need in major depressive disorder, specifically around the patient and clinician experience, and we look forward to sharing more on this program as we move into 2027. When you step back and look at the full picture, Ramnafanserin in ADP and LBDP, ACP 211 in MDD, and some of our earlier stage programs. We see multiple independent paths to add potential value across large, high-unmet-need markets, representing combined peak sales potential of approximately $11 billion. The opportunity is significant, but our conviction and investment will continue to be guided by the evidence each program generates. Before I hand over, a brief update on our R&D leadership. Today's pipeline update will be delivered by Dr. Sanjeev Patak, our Senior Vice President and Head of Clinical Development. Many of you will know Sanjeev from our R&D Day or from prior investor conferences, and I think you'll find his perspective as a double board certified psychiatrist on the remlefanserin data particularly valuable. As we indicated in April, Dr. Liz Thompson has now retired from her role as Head of R&D. Liz has made an extraordinary contribution during her tenure at Acadia, and we are deeply grateful for her leadership. She remains engaged with us as a valued consultant, and we wish her very well in her retirement. We do expect to announce our new head of R&D in the near term. In the meantime, R&D leadership responsibilities are being shared by Sanjeev, along with other members of our R&D leadership team. With that, I'll hand the call over to Tom to walk through our commercial performance in detail.

Thank you, Catherine, and good afternoon, everyone. I'm pleased to walk you through what was another strong quarter for the commercial business. Starting with debut, Q3 marked yet another record quarter for the brand with $140 million in net sales, representing 39% growth year over year, with almost all of that being driven by volume. That's a result that we're particularly proud of, as it not only reflects the continued execution of our commercial team, but also the deepening position Debut holds as the foundational standard of care for Rett syndrome. Debut sticks continue to be an important contributor to growth in Q3. Now, with approximately six months of commercial experience, we're seeing increasing utilization across the patient base and continued adoption in both sense of excellence and community practices. Over 50% of all U.S. DEVU patients were receiving STICs by the end of Q3, with these patients generally utilizing doses consistent with, or somewhat higher than, what we have seen historically with DEVU liquid. We're also encouraged by the early experience with patient restarts, which expands the growth opportunity for debut beyond naive patients alone. Patients who previously discontinued therapy represent an opportunity for re-engagement, and STICS provides caregivers with a compelling reason to reconsider treatment with a different formulation. While the initial pace of STICS conversion will naturally moderate as the launch matures, We believe continued new patient uptake and restarts provide two distinct opportunities to drive sustained growth going forwards. Turning to debut outside the U.S., Q3 was a landmark quarter. We received European Commission approval to debut, making it the first and only approved treatment for the neurobehavioral symptoms of Rett syndrome in the EU. This is an important milestone for patients, families, and treating physicians who previously had no approved treatment options available. We launched commercially in Germany in early October, and the early response from RET treating physicians has been encouraging. We're already seeing that initial interest translate into new patients receiving commercial product, in addition to those patients converting from our Compassionate Use program. As a reminder, Germany allows us to launch at a freely set price while reimbursement negotiations are completed, so we were able to move quickly to make Debut available to these patients. Looking across the rest of the EU, we plan to submit reimbursement dossiers for our key planned launch countries before year-end to drive additional commercial access to Debut. In addition, our name patient supply programs have been important in markets where we do not yet have regulatory approval, and the continued momentum across those programs reinforces the breadth of interest in this therapy globally. As we look to the remainder of the year, we feel good about where we stand. The momentum with Deview 6 is real and building, and the EU launch adds a new dimension to the growth story that we're just beginning to realize. As Catherine noted, we are raising our full-year guidance for DEBU and reiterating our confidence in our previously stated $700 million sales ambition for 2028. We see 2028 as a milestone on a much longer growth path because of the recently announced patent allowance extends our U.S. exclusivity runway into 2041. That confidence is supported by multiple growth drivers. Beyond the U.S., our expansion into Europe and other international markets adds another meaningful source of future growth. Together, these drivers and our long-term exclusivity support sustained growth for Debut as the standard of care for patients living with Rett syndrome. Turning now to New Placid. Net sales in the third quarter were $202 million. Representing 12% growth year-over-year on an adjusted basis, with 11% of that growth coming from volume. New-to-brand prescription trends remain healthy, with MBRX growth continuing to at pace the prior year period, reflecting the underlying demand we're building in the Parkinson's disease psychosis market. Earlier this year, we made a significant investment in our New Plaza field force. To increase the reach and frequency of our engagement with neurologists, psychiatrists, movement disorder specialists, and PCPs. That investment has more than doubled our reach. We now engage a customer universe of over 10,000 physicians, including more than 5,000 that we are calling on for the first time. The results thus far are encouraging. Call volume and rep productivity have increased as expected. And when our highest-value customers are called on, their intent to prescribe new Plasid increases. It is now at its highest level in years. Our focus now is on converting this positive momentum into new-to-brand prescriptions through focused execution. As expected with a new group of physicians, building those relationships takes a few more calls, and our reps are moving up the productivity curve. We are confident in the trajectory, and we expect to realize the full benefit of the expansion through the back end of this year and into 2027. With one quarter remaining, we have narrowed our new plastic guidance within our prior range to reflect that timing. At the same time, our direct consumer investment is expanding awareness of PDP and encouraging patients and caregivers to talk about symptoms and treatment. An aided awareness of New Placid is at an all-time high, and awareness of hallucinations and delusions associated with Parkinson's disease has also increased significantly. That awareness is turning into action. Through September, our branded and unbranded campaigns reached more than 1.3 million qualified Parkinson's patients. Approximately one in ten subsequently visited a neurologist, with more than 1,500 having since initiated New Placid as a result. These campaigns complement our expanded field organization. They build awareness and intent among patients and caregivers, while our teams increase engagement with the healthcare professionals who diagnose and treat them. Together, they are building momentum towards sustained New Placid growth. Looking ahead, our confidence in reaching approximately $1 billion in net sales by the end of 2028 remains unchanged. The path to that ambition is clear. Expand awareness and diagnosis of PEDP among treating HCPs and people living with Parkinson's disease. Increase the number of appropriate patients who initiate treatment and support patients in remaining on therapy. With a larger and more productive field force now in place, we are well positioned to deliver on each of these priorities and drive sustained growth for New Placid. With that, I'll hand the call over to Dr. Sanjeev Patak to walk through our pipeline programs.

Thank you, Ta. Good afternoon, everyone. I'm Sanjeev Patak, and I'm very pleased to be speaking with you today in my role as Senior Vice President and Head of Clinical Development here at Acadia. By way of background, I'm board certified in both psychiatry and pediatric psychiatry and maintain an active medical license. In my clinical practice, I have treated children with Rett syndrome and related disorders, as well as patients with Alzheimer's disease and other dementias. That experience continues to shape my work and reinforces the importance of getting the science right. I've led development programs across pharma and biotech and joined Acadia five years ago. Remlifasrin sits at the intersection of my clinical background and the leaders I have focused on throughout my career. I'm honored to share leadership responsibilities for our R&D organization during this transition and look forward to engaging with many of you. As you can see on this slide, it's a great privilege to lead clinical development at a time when Acadia has such a broad and promising pipeline across neurological and rare diseases. Let me now turn to remlefanserin and the Phase II RADIAN study results in ADP. The Phase II portion of the seamless Phase II, Phase III RADIAN study had two important goals. First, to establish the appropriate dose to advance into phase three. And second, to generate the data and insights needed to optimize the design and execution of our ongoing registrational studies. The study achieved both of these goals. While it narrowly missed statistical significance on the primary endpoint, SAPS HND, with a p-value of 0.0603, the 60-milligram dose demonstrated a clear and consistent signal of activity. Efficacy was observed across all four psychosis efficacy scales that were assessed for the full study population evaluated. Including SAP H&D, CGIS ADP, CGII ADP, and NPI, with the key secondary endpoint CGIS ADP achieving nominal statistical significance with a p-value of 0.0077. Effect sizes were 0.26 on the primary endpoint and 0.37 on CGIS-ADP, and both measures showed increasing separation from placebo through the six-week treatment period. Taken together, we believe these findings support further evaluation of the 60-milligram dose in Phase III. There was evidence of a dose response relationship with minimum efficacy observed with 30 mg. Therefore, we plan to discontinue the 30 mg dose in Phase III for ADP. Importantly, the study also provided insights into the relationship between patient characteristics and efficacy. When we examine outcomes by baseline disease severity, we observe greater treatment effects among patients with higher baseline severity. This, along with other learnings from Radiant, directly informs the second goal of the study, optimizing the phase 3 program. That objective was particularly important because this was our first global parallel group randomized placebo-controlled study in ADP using biomarkers to identify patients with Alzheimer's disease. As you may recall, previous Pivomancerin ADP studies either used a randomized withdrawal design or were conducted exclusively in UK nursing homes using older clinical diagnostic criteria. Radian, therefore, provided valuable clinical and operational insights specific to remlefanserin as a new 5-phase T2A inverse agonist that we can now apply directly to phase 3. Safety and tolerability are another important part of what we learned, particularly given the vulnerability of this patient population. Adverse event rates were similar to placebo. We observed no negative impact on cognition, no motor adverse effects compared with placebo, no signal of QTC prolongation compared with placebo, and no deaths in the ramblifancin treatment arms. For a therapy intended to treat patients with ADP who are typically older, cognitively impaired, and often medically fragile, this safety and tolerability profile is particularly important. Together with the extensive clinical experience with penelanserin, we believe these findings reduce an important source of safety-related uncertainty as we move into Phase III. So while we continue to evaluate the full data set, the key takeaway is that Radiant has meaningfully reduced several important areas of uncertainty, given us greater clarity on how to optimize the Phase III program, and strengthen our confidence in the path forward towards potential registration. We look forward to sharing additional Radiant Phase II results at CTAT in Boston later this month. Moving to next steps, we are continuing enrollment in our Phase III program and updating the study protocols based on what we learned in Phase II. The most important change is the dose. We are removing the 30-milligram arm and focusing on 60-milligram where we observed the efficacy signals. We are also taking steps to potentially optimize the study for effect size and regulatory success. Some of these modifications we will share at a later date, while certain design elements will remain confidential to protect the integrity of the study. First. We are refining site selection based on site performance in phase two. Second, we are expanding the use of central raters, particularly at sites where we identified rating challenges or limited availability of qualified local raters. Finally, we will be making modifications to the statistical plan with the most promising potential to optimize the effect size. We are not disclosing those specific details at this time, but we are confirming there are no plans to make any changes to the current inclusion criteria. Together, these steps allow us to focus our efforts on the dose with the greatest potential to benefit patients while actively trying to optimize the Phase III program to generate robust registrational quality evidence. I'd now like to connect what we learned in ADP to our LBDP program because we believe this is another important part of the Reblich-Fansman opportunity. We are pleased to share today that we expect Phase II results from the Illumera study in Lewy body dementia psychosis in the fourth quarter of 2027. We also recently received FDA fast-track designation for remlefanserin in Lewy-Body Dementia Psychosis, recognizing the significant unmet need for new treatment options. The ADP results provide additional support for our confidence in the LBDP program. Importantly, a reminder that with PIMAvanserin, our approved 5-HT2A inverse agonist, We have observed greater efficacy in LBDP than in ADP, both within individual studies and across studies, although the LBDP sample size was small. Remlifanserin is, of course, a new and distinct molecule with different attributes and its own clinical profile, but it targets the same validated mechanism as a novel, highly selective 5-HT2A inverse agonist. We therefore believe the Pimavanserin experience, together with the activity observed with Remlifanserin in ADP, provides additional support for the potential of Remlifanserin in LBDP. In addition to the mechanistic and clinical rationale, the potential utility of Remlifanserin in LBDP is supported by the favorable tolerability profile observed with Remlifanserin in Radiant. Patients with Lewy body dementia can be particularly sensitive to adverse effects, including motor symptoms and cognitive burden. The absence of motor adverse effects and negative impact on cognition and similar rates of adverse events to placebo in Radiant is, therefore, an encouraging finding as we evaluate remlefansin's potential in LBDP. Beyond Rebley-Fanstein, in later stages of development, we have ACP-211, our investigational, oral, nucleated, or nor ketamine compound in major depressive disorder, or MDD. In phase one data thus far, with ACP-211, we have observed no sedation, limited dissociation, and no blood pressure liability in Supporting the potential for a differentiated profile and patient experience relative to existing treatments. We expect to share these Phase I data at medical conferences in 2027, followed by the Phase II readout in the second half of 2027. MDD remains one of the largest and most underserved markets in psychiatry. So we very much look forward to sharing more data as we try to optimize the treatment experience for patients. In Japan, we successfully completed our Phase III trial for DEBU, generating results consistent with the previous Lavender Phase III results that support filing for approval with Japan's... Pharmaceuticals and Medical Devices Agency, and we remain committed to bringing Debut to patients there, with a targeted launch in 2028. Taken together, these programs reflect the pipeline focused on areas of significant unmet need, where we believe we can make a meaningful difference for patients. We are encouraged by the opportunities ahead and remain committed to advancing the programs where the data are strongest. With that, I'll hand the call over to Mark to walk through our financial results.

Thank you, Sanjeev. Good afternoon, everyone. I'll now walk you through our financial results for the third quarter of 2026 and provide an update on our full year outlook. Total revenues for the third quarter came in at $342 million, representing 22% year-over-year growth on an adjusted basis. Debut net sales were $140 million in the quarter, up 39% year-over-year, driven almost entirely by volume. The gross to net adjustment for debut in the quarter was 23.2%. As Tom described, the continued uptake of debut sticks in the U.S. was the predominant contributor to our growth this quarter. New Plaza net sales were $202 million in the quarter, up 12% year-over-year on an adjusted basis, with 11% of that growth attributable to volume. This volume-driven growth reflects continued expansion in underlying demand. The gross-to-net adjustment for New Plaza in the quarter was 22.7%. Turning to operating expenses, research and development expenses for the quarter were $76 million, compared to $88 million a year ago. The decrease was primarily related to reduced expenditures for ending studies that took place in 2025, partially offset by increased expenditures for remlifantorin and ACP 211. SG&A expenses were $159 million for the quarter, compared to $133 million a year ago. This increase reflects our investments to expand both the New Placid and Debut Field Forces and increased marketing investments supporting both brands. We continue to manage our cost base with discipline while ensuring we are making the right investments to support both near-term commercial execution and the longer-term pipeline programs Sanjeev described earlier. Our cash position at the end of the quarter was $976 million. We believe our balance sheet is a genuine strategic asset. It provides the flexibility to invest behind the strongest evidence in our pipeline, pursue business development where strategic fit and expected returns are compelling, and to continue to execute against our commercial ambitions from a position of strength. Turning to our full-year outlook, now that we are three-quarters into the year, we are narrowing our guidance ranges and providing several updates. We now expect total revenues of $1.265 to $1.295 billion. For DEBU, we are raising and narrowing our full-year global net sales guidance to $505 to $520 million. This reflects the strong performance we've seen from debut sticks in the U.S. And the momentum Tom described earlier. For New Placid, we are narrowing our full-year net sales guidance to $760 to $775 million, reflecting the timing of the field force impact Tom described. For gross to net, we now expect debut to be approximately 23 to 24 percent, and New Placid to be approximately 22 to 23 percent for the full year. Turning to operating expenses, we now expect full-year R&D expenses of $325 to $340 million. This reduced updated outlook reflects the timing of development spend, portfolio prioritization decisions, and reduced personnel costs. For SG&A, we now expect full-year expenses of $665 to $685 million. Overall, these updates reflect our latest expectations as we enter the final quarter of the year. We remain focused on executing against the continued growth opportunities for both commercial brands while maintaining disciplined investment across our pipeline. With that, I'll hand the call back to Catherine for her closing remarks.

Thank you, Mark. Before we open the call for questions, let me briefly step back and highlight what this quarter says about the CAGE's trajectory. We had an excellent quarter commercially and expect to finish the year with continued momentum across both Debut and New Plaza. At the same time, we are making important progress across our pipeline, creating multiple opportunities to drive our next phase of growth. Remlifanthrin is central to that opportunity. The phase two radiant results show a clear efficacy signal at 16 milligrams and a favorable safety and tolerability profile. While providing important insights into how to optimize Phase 3. We are moving forward with conviction in ADP and will present more data at CTAD later this month. Results have also reinforced our confidence in the LBDP opportunity, where Phase 2 results from Illumera are expected in the fourth quarter of 2027. Beyond Remlafanserin, we are advancing additional programs that can broaden our portfolio and create new growth opportunities, led by ACP 211, with Phase 2 results in MDD expected in the second half of 2027. Together, these programs give us multiple potential paths to value creation in large, high-unmet-need markets. With a strong commercial foundation and the financial flexibility to invest behind the opportunities where the evidence and our conviction is strongest, we are well positioned to advance this pipeline and build momentum across several important clinical programs. Thank you all for your continued support of Acadia. And with that, we're happy to take your questions. Operator?

Thank you. If you would like to ask a question, please press star 1 on your telephone keypad. If you would like to withdraw your question, simply press star 1 again. Your first question comes from Ritu Barrel with TD Cowan. Your line is open. Good afternoon, everyone.

Thanks for taking the question. Two quick questions. One is on the optimization of the phase three design for remosanserin and ADP. Previously, you had mentioned potentially tweaking the inclusion criteria for more severe patients, as I think some of the additional analysis suggested a greater effect size in more severe patients. Will that also be part of forward optimization to improve probabilities of success? And then on the continued strength of DEBU, specifically DEBU STIX, congratulations. Have you guys found in your post-marketing experience any evidence of improved tolerability with the STIX formulation? This was a very hot topic of patient groups and… The MOMS at the IRSF conference a few months ago.

Thanks, Ritu. I'm going to take those questions in order. So, in terms of optimizing in the ADP trial and referring to the inclusion criteria versus statistical modifications, I'm going to ask Sanjeev to take you through the thinking and help sort of illustrate what we're thinking right now. Sanjeev?

Thank you, Ritu. You're asking a very relevant question. Our goal of optimization is to potentially increase the effect size, and what we are going to do is statistical modifications. I wanted to clarify that we are not changing the inclusion or exclusion criteria. The analysis of the data has informed us about various patient characteristics that are linked to most robust efficacy, and we will utilize them in the statistical modifications. The severity criterion is an important one, which we will be including as part of the statistical modification. I also want to take the opportunity to guide through what other Optimization approaches we would be taking. We also plan to modify the protocol where we will be dropping the 30 milligram arm. And once again, no change in inclusion exclusion criteria. We are also going to We will optimize the study conduct. Key among them approach would be increased use of central raters. You may recall with the PIMA-VANCIN PDP pivotal program, when we went from phase two to phase three, we had increased use of central raters. It led to a better effect size and successful registration. So we will be doing that. We'll also have enhanced training of these sites. We are also refining the site selections based on the performance in the phase two. Taken together, we are feeling much more confident about the effect size and the robustness of the results that we hope to deliver in our Phase III program.

Thanks for clarifying that, Sanjeev. Tom, why don't you address the question around STIX and post-marketing and tolerability?

Absolutely. So, hi, Ritu. Hope you're doing well. Yeah, so as we shared on the call, we continue to be very pleased with the performance of STIX and the role it's playing in really fueling this next stage of growth that we're seeing for debut. Clearly, the reception from both the clinical community and the patient community remains very encouraging, and it's establishing, obviously, a multiple front that we can now continue to grow from, both in terms of naive patients, but also patients who may have discontinued previously. In terms of your questions around tolerability, I mean, this is something that we are continuing to monitor very closely. What I would say is, if we look at kind of ongoing persistency across the two brands, across the two formulations at the moment, they look fairly similar. What we do hear from families is that the ability to use a lower volume is actually seen as very meaningful. It means that they're spending less time administering the Manson in comparison to the liquid formulation. But on the whole, you know, we're not hearing or seeing any major differences between the two formulations, because obviously they do both have trofinetide as the active ingredient. So continuing to monitor closely, but we continue to be pleased with the progress that we're Thank you.

Thanks for taking. Your next question comes from Tessa Romero with J.P. Morgan. Your line is open.

Hi, team. This is Caroline Poacheron for Tessa Romero with J.P. Morgan. Thanks so much for taking our questions. So just first, how does the new U.S. patent that extends the patent protection for Debut and Debut Sticks change how you think about the long-term trajectory for the brand out to 2041? And then I just have a follow-up.

Yeah, I think for us, it really gives us confidence now that we can continue to invest and grow the brand out to Q1 of 2041. The weight banded dosing was something we felt very strongly about. We were very pleased to be issued the patent. We're also prosecuting that same patent in Europe and hope to see a similar result there. So overall, the pattern allows us to really have a strong commercial outlook through 2041 and make the appropriate investments to drive that. In terms of the potential upside to any forecast for debut moving forward, just to say that we do look forward to updating our conviction around that. We're not going to do that on this call, but I would probably say that we're likely to do that in Q1 of next year in terms of restressing what we think the peak sales opportunity will be for debut. Thanks for the question.

And yeah, if I can just squeeze one more in kind of along those lines, can we expect you to guide in February as per usual, or will you consider perhaps guiding at a small conference that may be taking place in San Francisco in January?

We will likely guide in February during our usual time, but thanks for the opportunity.

Thank you.

Your next question comes from Brian Abrahams of RBC Capital Markets. Your line is open.

Hi, good afternoon. Thanks for taking our question, and congrats on the quarter. Just on REMLI, I'm curious if you can give us a sense of what the effect size would have been with the use of the optimized sites, the central raters, and the most, the more optimal population, which it sounds like is going to be what's statistically analyzed in the phase three portion. And then secondarily, just on the debut restarts, just wondering if you could speak to how sustainable that is, how many more patients are out there on the sidelines that could potentially come back over time. Thanks.

Thanks, Brian. I'm going to ask Sanjeev to have a go at the sense of effect size, although, as you can probably imagine, we're not going to give you specifics around that. But, Sanjeev, why don't you give Brian some thoughts on that?

Thank you, Brian, for your question. As you can imagine, we want to keep some elements of our statistical methodology and our analysis confidential to ensure the integrity of the trial. So, we are unable to share those specific effect sizes of the analysis that we have done. At a future date, when we have agreed upon the plan with the FDA in the first quarter of 2027, we would be in a better position to discuss some of it. Of course, some aspects of this will remain confidential, as you can understand.

Thank you, Sandy. And Tom, debut, restart.

Absolutely. So, thank you for the question. So, just as a reminder, you know, we kind of think about the market in two distinct buckets. There's the naive patient population, which we've been pursuing ever since we launched Debut, and now we have Debut Styx. It's opened up an additional front in terms of patients who may have discontinued the therapy previously, who we are now reengaging with Styx. If we think about that second bucket of patients and you think about kind of how well penetrated we are, there's still significant headroom there. I mean, over 80% of those patients are yet to retry debut sticks. Obviously, that's an area that we continue to work closely with the patient community and the HCP community to educate. Well, not only the benefit the debut can bring, but now we have the new formulation, why it remains a viable option as the only approved treatment for patients living with RET. So we remain excited. You know, Q3 was another standout quarter for the brand. We continue to reach new highs, especially on the restarts front, and we still have significant headroom to grow. So look forward to sharing more information in due course.

Thanks, Tom. Appreciate it. Thanks.

Your next question comes from Yagel Natchamovic with Citi. Your line is open.

All right. Thank you. Just one additional question on Radiant. You mentioned a few of the ways you're going to optimize the effect size. What about the primary endpoint? In the downstream analysis of the top line, the CGIS ADP looked very good. Just wondering if that's something that you would change in the protocol to be the primary endpoint or if that's something that you're going to leave as it is currently. Thanks.

That's a good question, Yagal. I'll let Sanjeev share our thoughts on the endpoint analysis that we're looking at.

Good question, Yagal. Our primary endpoint remains SARS-CoV-2 as our preferred endpoint, and you're right to point out that if we look at the totality of the evidence, including CGI, SADP, you can see that 60 milligrams performed well. And when we look at the totality of the data, some additional information that we'll share at CTAD, we are seeing good activity with 60 milligrams. We are also seeing a dose response. And as has been pointed out by Dr. Liz Thompson at the top-line results call, that there was greater efficacy in patient population with higher severity. We typically see these with active medications, and so it is giving us more confidence in our approach forward. But to go back to your primary question, SAPS-H&E remains our primary endpoint. We will be developing a dossier and submitting to the FDA and meeting with the FDA in the second quarter of 2027, And we will also be developing additional information to support the additional endpoints that we have.

Yeah, I think the key to that is our discussion with the FDA in the first quarter, and we'll update you on the output of those meetings. But as Sanjeev says, our preference is still around SAPs H&D. And with that, we'll take the next question, operator. Oh, sorry, Yaghal, I've got something else.

I just was going to ask, thanks. I'm just going to ask quickly on 7-Eleven in Essential Tremor. You know, you have three, I believe you have three metrics there. They're slightly different. The Tetris performance scale at week four, there's an ABL score at week four, and then there's a change in CGI. Are those kind of all kind of be bundled together in looking at the efficacy picture, or is there one that's kind of the standout that you're going to focus on more?

Good question. So, we have 7-Eleven still in Phase 1 right now. So, Sanjeev, is there anything you want to add to Yugal's question around the endpoints we're looking at potentially to move into Phase 2?

Yes, Catherine, Yugal. We are currently in Phase 1. Our Phase 2 study design is in development. The endpoints that you mentioned seem all reasonable endpoints, but our protocol is not final yet.

So, we will share that with you next year and confirm that Phase II program.

Got it. Thank you.

Your next question comes from Amy Sadia with Needham. Your line is open.

Hi. Good evening. Thanks for taking my question. I wanted to sort of go back to the comment that you made. As you analyze the data for the Rennie study, you found some patient characteristics that you're going to reflect in the new statistical modifications. Can you elaborate a little bit about that? Is that, you know, kind of the baseline patient severity based on which you might modify the statistical analysis? And then also... You know, given the modification that you're making to your approach here for this indication, are there any implications for the Lewy body dementia trial analysis? Thank you.

Thanks, Ami. I'll let Sanjeev answer further on those characteristics that we're looking at.

Great question. Yes, we have looked at several patient characteristics. Of course, disease severity remains one of the key ones, and this is a finding not only in our trial, but also studies with other active medications, so we would likely incorporate that into our statistical modifications. There are other characteristics that we have identified, which we are not sharing, we are keeping these confidential, as I said, to maintain the integrity of the tribe. In regards to Lewy Body Dementia Psychosis Program, it has increased our confidence in that program, as I shared in the prepared remarks, that when we looked at the Pimavanserin program, despite small sample size, we had seen greater efficacy in subpopulations of LBDP. Now, remdesiviracin is a distinct molecule, but it does give us greater confidence, and we will be looking at the LBTP study design, and if there's an opportunity to optimize, we will do so. So far, we are progressing as planned.

I think this might be a good place to hit the 30 milligram, but that will continue in the LBD program.

Yes. So we are studying 30 milligrams and 60 milligram doses in the LBDP program. And as you know, LBDP is a distinct disease state and also has distinct efficacy and safety. Outcomes with off-label treatment. These patients are very sensitive to adverse effects. So therefore, we are studying both these doses. And also, given that the Pimavanserin data is with 34 milligrams, which is deemed equivalent to 30 milligrams of Remlifanserin, it makes sense to continue the experiment with both the doses in the LBDP study.

Thanks, Sanjeev. Thanks for your question, Omi.

Your next question comes from David Huang with Deutsche Bank. Your line is open.

Hi there. Thanks for taking the questions, and congrats on the strong quarter. I had two, so maybe first with debut. I know in the past you had talked about how the uptake and penetration was going in academic versus community practices, and so I was just wondering what the latest is there in terms of how penetration is looking in those segments and where there might be more room to grow. And then secondly, with ACP-211 and MDD, could you just kind of frame out what you're looking to see from the Phase II Neuralite trial? You know, what signal efficacy there would be compelling and where could 211 fit into the treatment paradigm? Thank you.

Thanks, David. I'll let Tom start on DB penetration, and then we'll go to Norline.

Thanks for the question, David. I hope you're doing well. Let me just give you a snapshot as to what we saw in the third quarter in terms of referrals and where they were coming from. So I think that that's always a useful point to start. So in Q3, Nearly 80% of our referrals came from the community. About 20% of those came from COEs, and I think that that's a reflection of the fact that we're now through the immediacy of the STIX launch, and obviously the team is now focused on educating the broader community on the benefits that STIX can offer, both for naive patients and for patients who discontinued. So that's been a full-court press from the team through Q3, and we'll continue into the end of this year. In terms of overall penetration, I mean, we still have significant headroom within the community setting. Remember that, that's about two-thirds of our overall volume falls outside of COEs. At the moment, we're about 30% penetrated there. So again, significant headroom, and now we have sticks in hand. We believe that that could be a true enabler to help us unlock future growth through the back end of this year and into 2027, which we're really excited by. So look forward to sharing more as we progress.

So, the question around ACP-211 and major depressive disorder, I think you are wanting to understand what signals we would view as compelling as we move into the Phase II study. So, Sanjeev, why don't you share a little bit more about what we're looking for with that trial?

Yeah, sure, Catherine. So, ACP211 is our oral norketamine, which is deuterated, and what we are hoping to see in this phase two trial is an evidence of a dose response to enable dose selection for phase three. We also want to learn about the efficacy operational characteristics of the study design, per se, and execution and conduct to inform the phase three design. Our TPP is about a better patient experience, so we are assessing the safety thoroughly, and also we do want to see an evidence of efficacy. So taken together, our study design is well-suited to answer these questions. I do want to underscore that what we currently know from phase one is that There has been no cases of sedation and limited dissociation, as well as no psychotomimetic effects, no blood pressure signal. So, so far, we are feeling good about our Phase II program as well, and the totality of the evidence that we have.

Yeah, and I just think from an overall perspective, we are looking for a patient experience that is a little bit different to the current patient experience, taking, for example, something like Spravato, where they're monitored for a long period of time. We're hoping that these sedation and dissociation indicators that we're currently seeing in phase one are something that would carry through to phase two and phase three and therefore allow the patient to have a different experience when they're dosed with our oral product.

Yes, and allow limited or better monitoring for the patients, as well as in the clinic setting, that they could go home after administration early relative to what is being done with other treatments.

Yep, so great. A lot of excitement around this trial to see what we can see within both the efficacy and the safety parameters of ACP 211. Thanks for the question.

Your next question comes from Rudy Lee with Wolf Research. Your line is open.

Thanks for taking my question. Just a quick follow-up for LBDP Phase II readout. Can you talk about the powering difference of this study versus the Phase II ADP trial? And should we think that Parkinson cohort will drive stronger efficacy, I mean, any color on the data stratification for Parkinson versus Lew's body and your own strategy for different subtypes? Thanks.

Yeah. Thanks, Rudy. I think just at a high level, we haven't shared the powering assumptions around the LBDP study. Yeah, but I will ask Sanjeev to talk about the stratification of the two groups of patients that we're looking at within that study.

Yeah, first I would like to point out that the LBDP population has Parkinson's disease, dementia psychosis population, as well as the dementia with Lewy body psychosis population. Both have the same underlying pathology of the alpha-symuclein. Pathology. And that is why we are studying them together. And we... We'll be evaluating the efficacy in totality as well as in these two subgroups as well, and as you may be aware that this is, again, a phase two study with two doses with a sample size of around 180, but it should give us good information to inform phase three.

Thanks, Sanjeev. Thanks for the question, Rudy.

Your next question comes from Ash Burma with UBS. Your line is open.

Hi, this is Soyeon on for ASH. Thanks for taking our question. I wanted to ask about the New Placid patent appeal by Aurobindo at the circuit court. There is an oral argument coming up on November 9th, next Monday, related to the 721 patent. Based on the briefing, Aurobindo appears to be challenging the district court's claim construction and its interpretation of the patent claims. Can you talk about your level of confidence in the IP position here and how you're thinking about the risk that the circuit court could reverse the district court's decision? Thank you.

Yeah, I'm going to ask Mark to take that question.

Yeah, I think at this point, I mean, as you just, as this, you know, oral arguments are right in front of us, you know, at the beginning of next week, appreciate the question, but we're not going to get into the details of the case, other than to say that we remain, continue to remain confident in our position related to the appeal, which is supported by the win that we earned at the district court level last year.

Thanks for the question. Your next question comes from Jack Allen with Baird. Your line is open.

Great. Thanks so much for taking the questions, and congrats on the progress made over the course of the quarter. I wanted to ask one real briefly on the upcoming CTAD update. I know you guys had data in the Phase 2 from both the 30 and the 60 milligram, and I'm just curious if you're going to have any exposure-related analyses at CTAD so we can better understand the underlying drug exposures within those two arms and how it correlates with effect.

I thought somebody might ask about exposure. So, Sanji, why don't you share a little bit more?

Yeah, we are working on the exposure response analysis, but it will not be ready for CTAD. This is to inform our future thinking for the entire program, and perhaps it will be available in 2027.

Yeah, CTAP will really be sharing a little bit more around the overall effect size that we've seen across the four psychosis scales. We were showing you a little bit more data around the efficacy over time and some other subcuts of data, but the exposure response, to Sanjeev's point, is just going to take us a little bit more time to work through. So we look forward to sharing that data when we have a good summary of that that we can share with you with a focus on the meaningfulness behind it.

What I will underscore is that we have seen a dose response, which gives us confidence in the activity of the model.

Thanks, Sanjee. Okay.

That is all the time we have for questions. Sorry, I'll turn it back to you, Catherine.

No, that's fine. Thank you so much, Operator. So, thank you all for your time and attention. We appreciate the questions and look forward to following up with many of you in the next 48 hours, and then no doubt following up after our CTAD presentations. Thank you again for supporting Acadia.

This concludes today's conference call. Thank you for joining.