This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk17: Good morning, and welcome to the Sarah Bell Therapeutics Second Quarter Financial Results Conference Call. At this time, all participants are in listen-only mode. Later, you will have the opportunity to ask questions during the Q&A portion of the call. Please note that this call may be recorded. I will now hand the call over to Matt Galastri, Vice President of Investor Relations.
spk08: Thank you. Good morning, everyone. We appreciate you joining us for our second quarter 2023 earnings call. On today's call, you'll be hearing from Ron Renaud, our president and chief executive officer, Dr. Ray Sanchez, our chief medical officer, Dr. John Renger, our chief scientific officer, and Dr. Susan Altshuler, our chief financial officer. During our call today, please refer to our press release from this morning detailing our second quarter 2023 financial performance, as well as our updated corporate presentations. both of which are available on our website. I would like to remind you that we will be making forward-looking statements that reflect our current views related to, among other things, the potential attributes and benefits of our product candidates and the format and timing of our product development activities and clinical trials. We strongly encourage you to review the information that we file with the SEC regarding specific risks and uncertainties. I will now hand the call over to Rob Renaud, President and CEO of Cerebel, to provide an overview of our achievements and outlook.
spk10: Good morning, everyone, and thank you for joining us for our second quarter 2023 business results call. I'm pleased to be here with all of you today as the new president and CEO of this exceptional company. In my time at Ceravel so far, I've seen immense passion and dedication from the team, and I'm incredibly enthusiastic about our science and innovation as we aim to build a world-class neuroscience company. Before getting into the specifics, let me share some of my initial observations of this organization. CeraVil is comprised of smart, energized, with deep experience in neuroscience drug, energized people with deep experience in neuroscience drug development and notable track records of success. We have an unparalleled pipeline with the potential to bring new treatments to some of the most challenging neuroscience diseases. We're also focused on discipline execution, aware that patients and loved ones are waiting for these important new treatment options. Before I joined the company, I was impressed with this enviable portfolio. Now that I've had an opportunity to work with this team and dive deep into the details of the science and the programs, I'm even more excited about all we have ahead of us. Turning to our lead programs, let me start with Imraclidine, our M4 selective positive allosteric modulator, or PAM. At Cerevel, we're exploring all aspects of the M4 muscarinic pathway as we seek to build a franchise that can address a broad range of diseases via this mechanism. Imraclidine is a highly selective for M4, and we believe it has the potential to change the way we do and treat schizophrenia, Alzheimer's disease, psychosis, and other serious mental illnesses. We announced this morning that our Imraclidine Phase II Empower program is now expected to read out in the second half of 2024, a change resulting from recent slower than expected enrollment. We are deploying measures to restore our pace of enrollment and I am personally working closely with Ray and the team on mitigation strategies. Ray will provide more details, including our go-forward approach and our reasons for confidence in our updated timing. As always, we're focused on ensuring the quality of Imraclidine data and will be thoughtful in our plans to add new sites or countries to ensure we maintain our rigorous standards. Moving now to Tevapidon, the first D1, D5 partial agonist in the development for treatment of Parkinson's disease. We believe our Registrational Phase III Tempo Program has the potential to establish Tavapadon as a backbone treatment across the spectrum of Parkinson's disease therapy. Tavapadon has the opportunity to serve as both the preferred monotherapy for newly diagnosed patients and the ideal adjunctive therapy to levodopa as the disease progresses. We expect Tempo III to be our first data readout of 2024, while data from Tempo I and Tempo II will read out in the second half of 2024. Turning now to DERIGABAT, our selective alpha-235 GABA-A PAM, currently in development for both epilepsy and panic disorder. Our phase two realized trial in focal epilepsy is designed to address an area of tremendous unmet medical need for patients who need better control of their seizures. We expect this program to be our second data readout next year, coming mid-year 2024. We also recently initiated the ADAPT trial of DERIGABAT, a Phase II proof-of-concept trial in panic disorder. We have confidence in the potential of DERIGABAT to treat anxiety-related disorders, given its selective receptor subtype profile and its avoidance of Alpha-1, the receptor subunit we believe is the main driver of side effects for benzodiazepines. On the financial front, we have a strong balance sheet that is expected to support all of our anticipated late-stage data readouts next year. Before I hand it over to Ray, I want to take a moment to welcome the newest members to the CeraVel executive team, Dr. Susan Altshuler, Chief Financial Officer, and Paul Burgess, Chief Business Development and Strategic Operations Officer. Susan brings financial management, investor relations, and business planning experience from leading biopharma companies. Paul brings deep experience in corporate development, business development, and operations, key skills during this important juncture for CeraVel. All three of us have been warmly welcomed by Cerevel senior leaders, seasoned leadership team. I'm proud of how in just seven weeks, we've come together as a new invigorated executive team. I'm energized by all that we will do together, along with all of our Cerevel colleagues to build a world-class neuroscience company with multiple commercial products. With that, I'll now turn the call over to Dr. Ray Sanchez, our chief medical officer to provide some added color about our lead programs.
spk05: Ray. Thank you, Ron. And good morning, everyone. Let me start with Imraqidine, our highly selective M4 positive allosteric modulator, or PAM, which we are currently developing in both schizophrenia and Alzheimer's disease psychosis, or ADP. In ADP, our phase one healthy elderly volunteer trial is ongoing, and the results of this trial will guide our clinical development plan as we advance in this important indication. Turning to schizophrenia in our phase two EMPOWER program. As a reminder, EMPOWER 1 and EMPOWER 2 are two adequately powered three-armed trials that each include 372 adults living with schizophrenia and experiencing an acute exacerbation of psychotic symptoms. The first trial is studying and bracketing 10 milligrams and 30 milligrams once daily versus placebo. And the second trial, 15 milligrams and 30 milligrams once daily versus placebo. We designed these trials to potentially meet criteria necessary to serve as pivotal trials based on what we expect the FDA will evaluate in a registrational package. We're also enrolling in Power 3, our 52-week open-label safety extension trial, and prioritizing the completion of non-clinical and clinical pharmacology studies to accelerate a potential registrational package for a miraculous unit of schizophrenia. As Ron discussed, we have seen a recent slowdown in enrollment. Enrollment in this program had strong momentum at the outset, but we've observed a slowing of that initial pace in recent months, with some ex-U.S. sites taking longer to stand up than planned and several U.S. sites yielding slower enrollment. We are responding accordingly with mitigation measures, including increased site and investigator outreach and plans to enhance enrollment in existing sites. We will also look to add additional high-quality sites in the U.S. and one to two more countries without going beyond a total of 30 sites per trial to preserve data quality and mitigate the placebo response risk. We will continue to stay laser-focused on executing these trials while maintaining the quality of the data. We recognize the central importance of Imragladine to Cerovone, our investors, and the patients we seek to serve, and we are acting with deliberate speed to address these potential headwinds and restore our prior pace of enrollment. With the strong efforts of the team, I am highly confident in our ability to deliver within these revised timelines. Turning now to terapinon, our D1, D5 partial agonist. Our phase three trials known collectively as the TEMPO trials are ongoing, along with the corresponding open label extension in which we are encouraged by a high rollover rate of 90% or more. We expect data for TEMPO3 to be our first data readout in 2024. with data for Tempo 1 and 2 coming in the second half of 2024. I'll now discuss DERIGABET, our selective GABA-APAM, which is currently in development for epilepsy and panic disorder. We believe DERIGABET has the potential for both anti-epileptic and anxiolytic activity comparable to currently available benzodiazepines, but with reduced side effects. DERIGABET's novel mechanism of action and expected tolerability profile provide the potential for a new treatment option that may be used chronically. Our Phase II realized and focal epilepsy is progressing, and we expect results in mid-year 2024. Here, we also are encouraged by a continued high rollover rate into the realized open-label extension. Beyond epilepsy, we're excited about expanding the potential applications of DERIGABAT through the initiation of the ADAPT trial, a Phase II trial in panic disorder. The ADAPT trial will evaluate DERIGABAT 25 milligrams twice daily versus placebo and enrolled 228 patients with panic disorder. The primary endpoint will be the proportion of subjects who are free of panic attacks during the last two weeks of the maintenance period. And key secondary endpoints will be the change from baseline in the panic disorder symptom scale or PDSS total score at week 14 and the change from baseline in panic attack frequency during the last two weeks of the maintenance period. A new drug has not been approved in panic disorder in nearly 20 years. So we are excited about the potential of providing DERIGOVAT to patients in need of new therapies. With that, let me turn it over to Dr. John Renger, our Chief Scientific Officer, to provide an update on our early stage portfolio. John?
spk09: Thank you, Ray. Good morning, everyone. I'm very pleased with the progress that we've made in discovery research and early clinical development. Let's begin with our CAP opioid receptor antagonist, or CORA program, also known as CBL354. We recently completed both our single and multiple ascending dose trials in which a broad range of doses were administered and considered well tolerated. These trials will enable us to interrogate a wide range of receptor occupancies of both the kappa and mu opioid receptors. This dose range will provide us with the potential for the selection of doses that can either preferentially target the kappa receptor or provide a dual inhibitory activity at both kappa and mu receptors simply by increasing exposures. We anticipate that this dose flexibility will enable us to explore efficacy and better understand tolerability across a number of populations of interest, which include major depressive disorder, post-traumatic stress disorder, and substance use disorder. Our results to date demonstrate pharmacokinetics as support for today's administration and the ability to dose without regard for meals. In addition, we've demonstrated a predictive dose-related change in serum biomarkers that are consistent with opioid antagonists. We are also pleased to announce that we've received additional NIDA National Institutes of Drug Abuse or NIDA grant funding of up to $8.1 million over three years to support the ongoing clinical development of CVL354, including our recently initiated phase one PET receptor occupancy trial that will include determination of both kappa and mu receptor PET tracer displacement to further characterize selectivity across compound exposures. We anticipate providing updates on our internal phase one data and plans for next steps in the future. Moving to other exciting news in our early stage pipeline, we recently received a grant from the Michael J. Fox Foundation for Parkinson's Research to advance our internally initiated TMEM 175 program, which is aimed at slowing and or stopping the progression of Parkinson's disease. As context, TMEM 175, or transmembrane protein 175, is a recently identified and structurally unique protein which is believed to be an endolysisomal potassium and proton channel. This target has been of particular interest to our team because of its strong genetic relationship to idiopathic Parkinson's disease. Our TMAM-175 program consists solely of internally identified compounds that have been discovered by our cerebellar chemists and scientists. It represents one of our initial efforts to develop potentially disease-modifying therapies intended intended to stop the progression of debilitating neurodegenerative disease. We look forward to working closely with the Michael J. Fox Foundation. This grant will support our program's research efforts and enable progress to be made in finding promising new chemical matter. I look forward to sharing more details of the compelling science behind this effort as we continue to advance this program. With that, I'm now going to turn it over to Cerebell's Chief Financial Officer, Dr. Susan Altshuler, who's going to review our financial performance for the second quarter. Susan?
spk12: Thank you, John. For the second quarter of 2023, operating expenses were approximately $97 million, comprised of $74 million of research and development expenses and $23 million of general and administrative expenses. We ended the second quarter with roughly $825 million in cash and marketable securities on the balance sheet, which provides us runway comfortably into 2025. Opportunistically bolstering the balance sheet remains a priority for the company to ensure we maintain the financial strength to maximize the value of our broad pipeline. As our track record shows, we will be thoughtful about how we access capital and will consider a variety of options, including evaluating partnerships and regional collaborations in service of meaningful value creation for our patients and our shareholders. With that, I will hand the call back over to Ron for his concluding remarks.
spk10: Thanks, Susan. At Cerevil, we believe we have an unparalleled pipeline in neuroscience. We're thinking big, and as I start my tenure as CEO, I can tell you that the potential of this company is inspiring. We are committed to bringing important new treatment options to patients facing some of the most devastating neuroscience conditions, including schizophrenia, Alzheimer's disease psychosis, Parkinson's disease, epilepsy, and panic disorder. I am pleased and honored to be at the helm of this company and to be part of the incredible work we're doing together here. I've gone under the hood and I've taken a close look at our operations, and I can assure you we are focused on execution. Our entire executive team is working together to deliver on promises to bring new medicines to patients as quickly as possible. With our Tevapidon Tempo 3 data expected in the first half of 24, followed by DERIGABAT realized data mid-year, and a busy second half of 24 with the Empower and remaining Tempo readouts. I look forward to updating you as we advance this robust portfolio. I'd like to conclude with my sincere thanks to our employees and to the patients and investigators in our clinical trials who graciously make everything we do possible. With that, let's open the call for questions.
spk17: As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. At this time, I would now like to turn the conference back over to Ron Renaud for closing remarks.
spk08: Operator, I think there should be some folks in the queue. I see them on here, so could you double-check, please?
spk17: One moment. Ah, yes, our first question. One moment for our first question. Our first question comes from the line of Amir Rafat from Evercore ISI.
spk11: Hi, this is Mike DeFiore on for Ulmer. Thanks so much for the question. Welcome, Ron. I'm looking very forward to working with you. A few for me. I just want to better understand the drivers of the schizophrenia trial delays. Second, if you can, what is the CRO that you're using? And, Ron, just as an outsider coming in with a wealth of experience, does something seem to be that different in the conduct of CROs psychosis or schizophrenia studies, what do you think it is that, in general, is causing them to be more delayed, maybe reasons outside of COVID? Thank you.
spk10: Yeah, so thanks for the questions. You know, I'll let Ray provide some color on some of the logistical issues. But, you know, basically, you know, we said this in our prepared remarks. We'll say it again. We know the importance of Imraclidine. We know the potential for this to be a truly transformative therapy for patients. And I think you can hear in our comments that we're moving to bring this ahead as quickly as possible. But while we do this, we're going to continue to be incredibly rigorous in our site selection with an eye towards minimizing variability and some of the other factors that Ray can talk about in terms of things that play a role in placebo effect. We're not going to compromise on this at all. To your point, yes, undeniably, we've reported delays in the past with some of our other programs, to Vapidon, to Rigabat, and now Miraclidene. And I think, you know, what I would tell you here is, as I'm new, Susan is new here, Paul is new here, we're taking a fresh look at everything. We're putting a fresh set of eyes on how we do everything. And, you know, how can we do a better job at forecasting these enrollment timelines? We know that this is critical, given the importance of Imoraclidine, Tavafidone, and Zergabat and their respective indications. And what I can tell you is we do need to do a better job at this, and we're committed to getting this right. And these are some of the things that we're looking at right now. With regard to some of the specific issues around the factors driving delay in the CRO, I'll let Ray take that.
spk05: Thank you, Ron. And good morning, Mike. So, Mike, what I can tell you is that all the principal investigators that I continue to talk to in the Imracadine program are extremely excited about this new class, specifically Imracadine, because of its one daily and dosing and no need for titration. So there's a lot of excitement there. We are continuing to understand the root cause of some of these delays at the site level. Importantly, because we strive to use the best sites, we're not going to compromise on data quality, data integrity, trying to manage and mitigate placebo response. But you have to understand that each of the sites also, they rely on referrals to ensure that we get the right patients. And that's the key thing, getting the right patients. And so in doing so, some mumps are better than others. But collectively, those are some of the bottlenecks that really hold getting the right patients into the trial. But again, because we are so focused, so laser focused, as I said in the call earlier, on getting this right, making sure that we just don't exacerbate the placebo response, that we work closely, which we are with the investigators. We're heightening our communication plan with them to ensure the greatest likelihood of success for these trials. So that's really our main focus. And those are some of the challenges that we're up against in terms of the sites and what they're experiencing.
spk11: Got it. Thanks so much.
spk02: Thank you. One moment for our next question. Our next question comes from the line of Mohit Bansal from Wells Fargo.
spk14: Great. Thank you very much for taking my question and welcome, Ron, Susan, and Paul. Looking forward to working with you. So my question is also the same line because So Ron, I mean, in the limited time you have spent with the company so far, when you look at the timelines, I mean, there could be one or two reasons. Like one is obviously, was this a case of, you know, a little bit providing aggressive timelines to investors and now realizing that's probably not fair or it is the other way around where there is something fundamentally changing in the marketplace where, uh where it is hard to enroll these patients i'm asking this because i mean like this these these especially the schizophrenia trials this looks i mean like it is a short trial so it is still we are still ways away from uh from the point where we can say that the child is fully enrolled so just trying to understand if it is like what what exactly is the underlying causes uh and then the second part of my question is like uh so you mentioned that you are doing some more work in terms of figuring out the right data package for the filing for schizophrenia trials. So, how should we think about the timeline for schizophrenia in terms of filing timelines and how much data you need to generate there?
spk10: Thank you. Yeah. So, thanks for the good words. You know, first of all, again, I'll keep coming back to this, and you'll hear us say this over and over again. Our focus remains on ensuring the quality of data, and we're going to be rigorous in our site selection. We're going to be rigorous in the investigators that we work with and our focus on placebo variability reduction strategies. You've seen in the industry what happens as the number of sites increase, as the number of patients increase, that variability increases, and that is something that we are really focused on minimizing. we're just not going to compromise in any way, shape, or form on the quality of the sites that we work with. I know there's going to be a natural, there's always a natural inclination as a sponsor to want to speed things up, to want to hurry up and meet the timeline. And it's unfortunate that we've pushed this out. On the other hand, again, we're not going to compromise the quality of of the sites that we're using here. And so we're going to continue to stay focused on that. And so with that data reading out in the second half, you know, I don't want to point towards exactly when we would file, you know, anything with the agency. That being said, we're putting all of the pieces in place and we've been putting all of the pieces in place to be prepared to file an NDA for for Imraclidine here. And so, you know, we're working down that pathway at the same time that we're focused on execution of this program. And that's all happening, you know, in conjunction with each other. Thank you.
spk17: Thank you. One moment for our next question. Our next question comes from the line of Greg Souvenal from Mizuho Securities.
spk13: Hey, thanks. Thank you for taking my question, and Ron, Susan, and Paul, my congrats on the new positions, and I look forward to working with and partnering with you. I have two questions, if I may. First, Ron, just bigger picture as you step in as new CEO, maybe just a broad question on whether you're coming in with a view that you know, you need to do a review of the business and you need six months before making any changes, any kind of thoughts on like overall strategy, just bigger picture thoughts. And then my second question, maybe it's best for Ray with regards to this Emrakladine trials. And I just wanted to ask in light of the phase three negative readout for the Synovion and Otsuka TAR-1 program where it was ascribed to a very large placebo response. Could you just remind us the measures that you're putting in place in order to best minimize the chance that you'll potentially see a high placebo response in order to ensure that we minimize the risk of a negative trial outcome? Thanks.
spk10: Yeah, so thanks for the question, and I'll take the first part of that, and then I'll, as you asked, let Ray take the second part. So absolutely, you know, coming in, we're, you know, seven or eight weeks into this. Obviously, you know, I want to turn over as many stones and make sure from an operational perspective we're working as efficiently and as effectively as we possibly can. There's a lot going on here. We have, you know, more than 2,000 patients on CeraVelt studies right now. where, you know, double-digit number of studies, not to mention the number of those studies that are part of registrational pathways. And so, I will tell you my initial views on everything here at Cerevel is that our company, our fundamentals are very strong. I believe we have an unparalleled pipeline of neuroscience assets. I think you'd be, I think you'd struggle to find another portfolio of neuroscience assets in the industry that looks as broad and as robust as what we have here in Cerevel. But we've got to continue to focus on the progress of these clinical trials, the execution of these clinical trials, and making sure that, you know, we can forecast these enrollment timelines, you know, much more effectively. Obviously, we know that that helps all of the folks in the investment community as they try to figure out what we're doing, but it's also helpful for us. It's important for us in our planning as we think about how we roll these programs out. And so, you know, we're looking at that. We continue to prioritize the progress of these trials, and we're preparing for multiple pivotal trial readouts next year. And I want to make sure we execute very well on all of those.
spk05: Greg, thanks for the question. And as you know, we've underscored how we're trying to mitigate the placebo response, and no doubt that the data that you outlined just a few moments ago was quite sobering, I think, to the field. So what we're doing and what we've mentioned before, as you know, is ensuring that we get the right patients. And how you do that is really critical. And so we have a process in place to do that that really looks at the patient qualification because, as you know, and others know that the patient profile really drives the outcome of these trials, as does the quality of the raters at the site. When we say quality sites, we're talking not just about the ability to access the right patients, but their ability actually to have competent, really robust raters. And so, we have a plan in place to address that. Other things that we're doing is we have a placebo mitigation protocol at each of the sites that allows for certain interventions to be made or not be made. to ensure that the placebo response is kept at bay as much as possible, but also limiting the number of sites and limiting the number of countries. And when you do that, invariably you're going to see waxing and waning of the enrollment. However, at no point do you dilute the data and you position your trial for the greatest likelihood of success. So collectively, that's the confidence that we have, that these trials are positioned for the greatest likelihood of success and outcome.
spk02: Thank you. One moment for our next question.
spk17: Our next question comes from the line of Tizina Mon from Bank of America.
spk01: Hi. Good morning. And also, Ron and team, congrats on the new roles, and we look forward to working with you. I just wanted to clarify, you've mentioned now on the call several times that you need to find the right patients for the schizophrenia program. Can you maybe give us a little bit of color on what the right patient looks like and how that might translate into what you ultimately think the market opportunity would be in schizophrenia? Would it be for the broader population, or are you thinking that there is a subset of the population, which could still be quite large, that might be best suited for your drug? And then secondly, can you just remind us what your cash runway is? Thanks.
spk10: So I'll turn the first part of your question over to Ray and Susan on the second part.
spk05: Good morning. Thank you for that question. So the trials are meant for the generalized schizophrenia population. When we talk about the right patient, remember, we're conducting clinical trials. So we're trying to detect the signals this therapy has. And so in order to do that, you need to refine the patient population in terms of the severity of disease. So as you know, we have a PAM score of at least 85 up to 120. and a variety of other criteria. It's really to define the patient population that's going to really give you the best opportunity to detect the signal of the miraculous and to be a robust therapeutic in the population. However, it doesn't mean that you're restricting the population in any way to suggest that it only works in certain patients and not others. It's really for the general schizophrenia population, but Because you are conducting a clinical experiment, you have to have certain controls in place to ensure the greatest likelihood of success.
spk12: Great. Thank you. As noted, we are well capitalized and ended the second quarter with $825 million on the balance sheet. So that funds us through all our key data readouts next year and comfortably into 2025. So we'll continue to be thoughtful about resource allocation and opportunistic in bolstering the balance sheet, but we feel very good about our cash position.
spk02: Thank you. One moment for our next question. Our next question comes from the line of Paul Matisse from Stifel.
spk16: Hey, thanks so much for taking my questions. On Imraclidine, we noticed that a drug-drug interaction study was put on clinicaltrials.gov. Is that just a typical study, check the box for an NDA, or are you actually expecting to elucidate an interaction that could be significant as it relates to how people prescribe the drug? And then separately, I had a couple pipeline questions on the CAPA program. I was curious in your perspective now that it seems like we have a couple external studies suggesting this target has an antidepressant effect. I guess, do you agree with that? And do you plan on moving more quickly now in depression? And then, John, to your point on a dose range as it relates to kappa and mu, do we want to be targeting mu as well? I was under the impression that that produced more side effects. So maybe you could just kind of speak to that. scientific hypothesis behind your compound and how you're thinking about it. Thanks so much.
spk10: It sounds like John can take all of these.
spk09: You don't want to try, Ryan? Thanks, Paul. Appreciate the plethora of questions here. So, yeah, the DDI profiling is standard for a registrational package, and so As you know, you have to inform the label on potential for DDI and any kind of dose adjustments so the physician can make the right decision for each patient based on their background therapies. And so these are pretty much standard. For CORA, yeah, so we're really excited. So now, as you mentioned, the second company is shown. So as you know, the first colleague company, I'll say, showed a nice potential for looking at the core mechanism of action as an adjunct on the standard of care in MDD, the major depressive disorder. And now recently we've seen another colleague company showing that monotherapy also showed a nice effect, a positive benefit in the MDD as a monotherapy. So we think this is very consistent with the mechanism of action that's been published quite extensively in preclinical models. As you know, there's a lot of potential for this mechanism to actually go beyond MDD. And so that's gonna lead into the answer to the next one, which is, you know, as you know, we've been working closely with NIDA and we received, like I mentioned this morning, an additional funding to go forward with even more studies there in the clinic, PET receptor occupancy being one of them. And so, you know, when you think about what it is that you wanna achieve, So both, if you look at the both competitor molecules, you know, the first one is a very kind of non-selective approach that we've seen as the adjunct. And what you've seen with the more recent data is one that we consider to be highly selective to kappa. And so you have, in both cases, you have a nice demonstration that either a mixed activity or highly selective activity is effective. However, as you think across what the different potential indications could be, Some of those may actually benefit from having some new activity. And so what we want to do is be able to think about how we take this particular molecule and actually look at dose ranges that are appropriate for different indications. And so as an example, if you went into substance use disorder study in opioid patients, you definitely do not want to have new activity because you could induce withdrawal, which is extremely unpleasant for the patient. And so in that, it would be a different dose range than potentially another indication where you would actually benefit from having some new activity. I think with this molecule, knowing that we can cover a very broad range in a well-tolerated fashion, it gives us the potential to actually look at those ranges that are appropriate for different indications based on what we know about the etiology of the disease and what would benefit each group. It's a really exciting molecule, really exciting science.
spk19: Stay tuned and we'll share more as we can. Thanks, John. Thank you, Paul.
spk02: Thank you. One moment for our next question. Our next question comes in the line of Joseph Sohn from TD Cowan.
spk03: Hi there. Good morning and thank you for taking my questions. Maybe the first one, as we're thinking about Imroclidine and ADP, I guess what would you be looking for in that Healthy Volunteer Study to advance the next level? And I guess how tied are the EMPOWER results to advancement in ADP? Do you want to wait for the EMPOWER studies to read out before committing to the next step? And then maybe just a quick one on the Deregabat Panic Disorder Study. Can you comment a little bit on how severe patient symptoms are at baseline? in terms of pretreatment or, I guess, just baseline severity. And then when we think about through the titration and maintenance period, can patients use any rescue medications if they do have an attack? Thank you.
spk09: I'll turn that over to John and Ray. Sure. So I'll speak to the ADP questions first, and then Ray can address the second step. So, you know, as you know, the population for ADP is – differentiated from the schizophrenia population primarily by age. And so what we have to do is a healthy elderly TK study. And then what you want to do is then go into the patient population. And so what will we be looking for? What we want to demonstrate is that we can achieve the exposures of drug that we have related previously to PET receptor occupancy data so that we're confident that we're able to achieve CNS receptor occupancies that will test the mechanism of the M4 in ADP patients. And so what we're looking for is safety and tolerability at the exposures that we want to achieve to take forward into the ultimate patient population. And so as you know, what we were in the middle of is a multiple ascending dose study to do that. And so that data will help us then demonstrate that we have a path forward. And so what we're looking for is really just to see that we have the same kind of well tolerated profile that we've demonstrated previously. As you know, it's a very different population than the schizophrenia population. So it's difficult, I think, to make any conclusions about whether one would inform on the other at this point. Obviously, there's rationale to believe it will be effective in both. And so that's the question that we need to answer. But we are going as quickly as we can, and we're not waiting for anything else to gate our decision to progress in this indication or potentially others. And so I think it's not a wait and see type of approach. It's go as fast as we can and as safely as we can. Thank you, John.
spk05: Good morning, Joseph. So listen, we're really excited about the potential to come up with a new therapy, which is much needed in the landscape for panic disorder with nearly 20 years ago that was the last medication approved for that. So the population that we're using is a moderate population and so we're looking at the panic disorder symptom scale severity of 12 or greater, 12 being the threshold of moderate disease. They also have to have at least eight panic attacks with no free week of panic attacks in the month prior to the screening visit and in the two weeks leading to the baseline visit have at least four panic attacks. And so, you know, that's something that, as you know, that severity does drive, and so appreciate that question, severity does drive the outcome in a lot of these studies. So we're using the right population to ensure the greatest likelihood of success. No rescue medication is allowed in the trial, as you know, that potentially could confound the outcome. So rescue medication is not allowed. And we're also, at every visit, doing screens to make sure that they're not using other therapies as rescue. So, those patients would be censored or discontinued appropriately. So, all in terms of how do you design the trial with the right methodology to ensure the greatest likelihood of success, and that's what we're trying to achieve.
spk18: Great. Thank you very much. Thank you.
spk17: Thank you. One moment for our next question. Our next question comes from the line of Jeff Hung from Morgan Stanley.
spk15: Thanks for taking my questions, and also my congrats to Ron, Susan, and Paul on the new roles. Two questions for me. First, can you talk about the challenges for identifying the appropriate patient population for dementia-related apathy? And in the context of challenges identifying appropriate patients, what is your latest thinking on the size of the market opportunity for this indication? And then second, for the ADAPT study and panic disorder, how's enrollment going? And can you remind us of what you need to see to consider the proof of concept of success? Thanks.
spk09: Again, John and Ray.
spk05: Yeah, so I'll start with, thank you, Jeff, with the dementia-related app. If you know that This is a new path that we're carving forward. We received fast track designation from the FDA in order to do so. So we'll be working very closely with them. But it is an experiment that the trial that we're conducting is truly experimental. We're looking at various primary endpoints and so forth in terms of scales, but there's no formal hypothesis testing per se. One of the challenges, of course, the landscape recognizing who these patients are. So the families, the caregivers, the practitioners, really understanding what apathy is. So we've been working very closely with the ISCTM group, which FDA has been involved with, in order to understand the criteria to identify these patients. You know, that's the biggest challenge is really to identify the patients that are out there because we know that half of the patients with dementia suffer from apathy. It's a leading neuropsychiatric syndrome and a predictor of disease progression. So we're continuing to stay laser focused on that trial and also helping the sites identify the right patients. In terms of the panic disorder trial, So, as you know, it's a 14-week trial, really with a 12-week maintenance phase. It's 80% power to detect a difference of 20% in the proportion of patients, meaning between active and placebo, in the proportion of patients who are free of panic attacks during the last two weeks of the maintenance phase. And why that endpoint? Because that's the endpoint that the precedent has been set and that the FDA has historically wanted to understand. And As you know, it takes time for patients to respond to therapy, so that seems like an appropriate endpoint. So those are the parameters, and so we are excited about continuing that trial. As you know, it was just initiated within the last few weeks, so we have not provided any timelines at this point, but we're excited about the progression of the program moving forward, and so stay tuned as the program continues.
spk02: Great. Thank you. Thank you. One moment for our next question. Our next question goes in the line of Michael Yee from Jefferies.
spk17: Pardon me, Michael Yee from Jefferies, your line is now open.
spk06: Hello, can you hear me?
spk17: We can.
spk06: Can you hear me?
spk19: Yep.
spk06: Great. Following up on the questions around the enrollment for schizophrenia, we wanted to ask around clarification and color. You know, you go up to the CT.gov, you've got a lot of sites listed up there. I think some of them overlap at the major centers as some of the competitor enrollment center. And so I just wanted to understand, is it sites getting up? Is it, hey, we've got the sites, but we don't really like the criteria or the patients that are coming in, and we're not really happy with some of that? Maybe just shed a little bit of light on that, because what we see is a lot of centers, and we're just trying to think about what the actual logistical issues are. And then related to that, I know that you are running non-clinical studies and other studies that are related to the NDA. I know that the competitor is taking many months, but typically it's standard to file an NDA around six months after a completion of the data set. So do you feel comfortable, based on the timelines, that if your data comes out in second half of 24, of all the non-critical studies and all that should have a filing in first half of 25. Thank you.
spk05: Yeah. Ray? Yeah. So, Michael, good morning. So, as you know, we are always seeking the best sites. And, of course, everyone else, potentially, they are as well. So, there are going to be some overlapping sites with other sponsors. To that end, it's really around, to your point, really looking at getting the right patients. We have a method by which we help the site achieve that. That's independent of the actual site, you know, proposing the patient exclusively. So we have another independent committee that looks at the criteria to make sure we have the right patients in the trial. And that waxes and wanes over time. And it's really patient accessibility that sometimes can be a bit of the bottleneck. We're working with the sites closely to measure that and continue to understand the root causes of what's holding them up in certain cases. But just to remind you that we started with a bolus of patients, really an exciting, you know, very ahead of schedule type of enrollment initially. In the last few months, we've seen this slowing down in the U.S. Secondly, for ex-U.S. sites, and of course we choose countries where historically we've had good data that we know the sites well, there's been also a slowing down of getting those protocols approved Really, and the bottleneck there is really at the country level, at the IRB level in those countries, and I do think it's just a volume issue that they're grappling with. But we have all the sites that we need currently up and running, and we're looking at new countries and new sites potentially in the future. And again, always focused on data quality, not diluting the data in any way, not exacerbating placebo response. know we want to get this therapy out to the patient sooner than later but we also know in order to do that we need very robust data and that's what we're trying to achieve as well and mike i'll speak to the second question so in reference to our in reference to our preparedness for for submission um so
spk09: obviously we are all over the timelines to make sure that we have all of the preclinical data, the CMC data for the CMC module and the NDA, and also all the required ClinPharm studies to inform on dosing and those types of things. And so we will definitely, I'm not going to commit to how much time it is, but we will definitely position to have the data in hand when we get the readouts. We are very focused on minimizing that timeline from data readout to submission, and we're doing all the work necessary to make sure that we get the NDA completed as quickly as possible.
spk06: I think that can't be underemphasized. It's a pretty important part of the package besides the Phase III data.
spk09: Thank you.
spk17: Thank you. One moment for our next question. Our next question goes to the line of Charles Duncan from Cantor Fitzgerald.
spk04: Good morning, Ron and team. Thanks for taking our questions. Congrats to the new joiners on the call on the opportunity. I had a question on Imraqlidine and then actually one on Darigabat. With regard to Imraqlidine in the sites where you see overlap with a direct agonist, I guess I'm wondering if you have any feedback to share with regard to investigator interest. And then in addition to enrollment rate, can you provide any color on dropouts from that study? And then also in power three, Do you have any patients that have rolled over to that open label?
spk10: Thanks for the questions, Charles. I'll let Ray take those.
spk05: So, Charles, yes, we've seen, yes, we have patients rolling over. That's the way the program is set up, that patients have the opportunity when they complete the six-week trials to roll over into the 52-week open label extension. And, of course, that is for us to continue to gather the exposure data, the long-term exposure data that we need when we do file that NDA. Okay. In terms of Imraclidine and the investigators, as I mentioned earlier in the call, that one of the things that I've been really comforted by and excited by is really the level of enthusiasm that the investigator community has for Imraclidine, but specifically for this new class, really giving patients a better alternative to treat the psychotic symptoms. So, you know, again, we're working closely with them to ensure we get the right patients as we've been mentioning through the morning. And so I hope that answers your question. Is there anything else you'd wanna know about that?
spk04: No, I think that's clear and appreciate all the color that you've provided on your efforts for enrollment. Just moving on quickly to the Rigabond, I guess I'm wondering about the high rollover rate that you mentioned in the open label extension. I'm quite intrigued with that. To me, in an epilepsy patient, that perhaps reflects enthusiasm about the therapeutic profile. So I guess I'm wondering if you could provide any further color on that.
spk05: Yeah, so, you know, it's always difficult to predict the rollover rates in terms of patients rolling over. So, when you see robust rollovers, as we're seeing, you know, we get excited about the potential of the therapy in that patient population. And they're quite eager, as you know, to try to come up with a therapy that will really suppress their seizure activity. So, you know, we continue to be, you know, excited about the rollover rate and we're monitoring it closely. We're getting the exposures ultimately over time that we'll need when we do file after our Phase III program. So it speaks to all of that.
spk04: Might the rollover rate as well as persistence within open labels speak to the tolerability as well, differentiated tolerability?
spk05: You know, it may. At this point, you know, it'll be conjecture because we obviously have to look at the data. Obviously, if somebody rolls over and stays on your therapy for a long period of time, then it puts tolerability in a good light. But in terms of what that would look like, I think we should just wait for the data to read out. Okay. Thanks for taking that question. Thank you, Charles.
spk17: Thank you. One moment for our next question.
spk07: our next question comes from the line of douglas so from hc wainwright hi good morning and thanks for taking the questions and congrats to everybody for for joining the team um maybe to start with the miraculodine um not to beat a dead horse but ray i'm just curious in terms of finding the right patient so you taking any sort of logistical or any additional screening issues? I mean, obviously we have, you know, the patient inclusion and exclusion criteria to get the right patients, but are there any logistical things that are perhaps slowing down the process a little bit? And, you know, what benefits might those provide?
spk05: So, Douglas, you know, there's nothing that's slowing down the process. Remember that We started with great momentum and the process hasn't changed from that to what we've seen in the last few months. We have a very robust kind of safety net to make sure that, as I mentioned earlier, that the investigators stay true to form to make sure that we get the right patients and ultimately drive the success of the trial. So that's not slowing the trial down. I think it's really around that. It's really around finding the right patients, and that waxes and wanes over time. But we have to stay steadfast, and we've got to stay very committed and focused to ensuring that at no time we get the wrong patients. And again, that's what we're doing in positioning these trials to the greatest likelihood of success based on those parameters and that quest.
spk07: Okay. Great. Thanks. And then just as a follow-up, Just given some of the moving parts with the pipeline, and obviously some studies are now reading out later than was originally planned, does that affect how you think about moving some of the earlier stage assets into later stage development, just as you think about sort of managing your cash runway? Thank you.
spk10: Yeah, you know, I'll take that one. You know, look, we're very conscious of the balance sheet, and we pay close attention to that. And as Susan mentioned, We're going to do what we need to do to be opportunistic to make sure that that balance sheet can continue to support not only the late-stage programs that we spent most of our time talking about today, but many of these really interesting and important early-stage programs. And so, you know, the early stage program, you know, we won't shortchange that as well. And so, this is something that is equally as important as making sure we get the late stage program right.
spk07: Okay, great. Thank you so much, Ron.
spk10: Yeah, you bet.
spk17: Thank you. At this time, I would now like to turn the conference back over to Ron Renaud for closing remarks.
spk10: So I want to, first of all, thank everybody for the questions this morning, but also for the warm welcomes. You know, I know that Susan and Paul and I are super excited to be here, to be part of, you know, one of the most exciting pipelines in neuroscience, and to really be part of building this world-class neuroscience company, you know, is something that I'm incredibly excited about. We're well-funded with the resources to maintain, you know, all the work we're doing well into 2025. You know, we're looking at things with a fresh set of eyes, and we'll have lots of discussions with all of you and many more over the coming months as to, you know, the things we're learning along the way. But I think on balance, what you're going to find is there's a lot of incredibly important work going on here at Cerevel. Two late-stage programs, two NDA registrational programs underway here, and then a significant number of programs right behind that that's going to keep us busy, not only with these NDAs for the next 12 to 24 months, but for the foreseeable future after that, and that's incredibly exciting. So, I look forward to having more discussions with all of you on all of these programs as we move ahead. Thanks a lot, and I hope everyone has a great day.
spk17: This concludes today's conference call. Thank you for participating. You may now disconnect.
Disclaimer