Great. good morning, everyone. My name is Jess Fye. I'm the large-cap biotech analyst at JP Morgan, and we're delighted to be continuing the conference today with Karuna Therapeutics. A little different format this year. You don't need to change rooms for Q&A. We're gonna stay here for the Q&A session after the presentation. There's two ways to ask a question. You can raise your hand and someone will bring you a mic, or you can submit your questions electronically to the portal, and I can read them off upfront. With that, let me pass it over to Karuna's CEO, Bill Meury. Thanks, Jess. Good morning, everyone. Before we start today's presentation, please look at slide two of the deck and read our forward-looking statement. As you know, it's a riveting read if you haven't read it already. By way of introduction, my name is Bill Meury. I joined Karuna just last week as President and CEO. Clearly I've had plenty of time to get ready for this conference. To be fair, Steve Paul and I started talking back in 2021. Between then and now, I've learned a great deal about the company, and I've gotten to know Steve quite well, he and the rest of the management team. You'll hear from Andrew Miller and Troy as well as Steve very shortly. I think they're real professionals, I look forward to working with all of them. Some of you know me, others don't, I'll start with background very, very briefly. I started at a company called Forest Laboratories, which became Actavis, then Allergan, where I was the chief commercial officer for several years until 2020. Most recently, I was a partner at a New York City-based private equity firm focused on healthcare products and services. Having been an operator for many, many years, I will tell you it was an invaluable experience and perspective to be an investor for several years. Over the course of my career, I've run global operations with 8,000 people and $16 billion in revenue. I've been involved in countless BD&L transactions, M&A, and most importantly, 25 FDA approvals and new product launches. Eight of those were in CNS, S chizophrenia, depression, and Alzheimer's disease. I have a pretty good idea of what works and what doesn't work. Now, I joined Karuna after a great deal of careful consideration and because I believe, one, in what the company is trying to do. I believe in its mission and its vision. I believe the company, as you can see on this slide, has the necessary ingredients to be a successful business. The first of those is science. As you know, it's the key currency and lifeblood of any successful biopharma company, large or small. Our lead asset, KarXT, scientifically and pharmacologically is novel. It's a completely different approach to managing the symptoms of Schizophrenia, and there's a mechanistic reason to believe here. In psychiatry, that matters and it's key. Clinically, the benefit risk profile, which really came into focus with EMERGENT-3, or excuse me, EMERGENT-2, is fundamentally different, and for some patients may be superior. Finally, KarXT has the potential to be a platform, one product with multiple indications. That's number one, the underlying science. Number two is the company has a strong team in place. You know, no company is inherently valuable. It's a function of management, people, and culture. The team of people at Karuna have the skills and the experience needed to scale and build this business. There's really a shared commitment inside the company, and you can feel it, to deliver transformative therapies to patients and to physicians. Finally, Karuna operates in neuroscience, which I think is one of the most structurally attractive markets in biopharma in terms of innovation, unmet need, and commercial opportunity. There is somewhat of a renaissance going on in neuroscience. Karuna is right in the middle of it, and we're helping to lead it. It's for these three reasons right here that there's a unique opportunity to build a neuroscience company, a leading neuroscience company, a company defined by great medicines, great people, culture, and hopefully exceptional financial performance. Now, today, we're gonna talk about our NDA submission, our ongoing development work for new indications, and our plans to build the commercial organization to launch KarXT. 2023 is an important year. The company is approaching a transition point, shifting from an R&D organization to what is hopefully a fully integrated R&D and commercial organization. Before we get into all that, I wanted to touch on some of the highlights from the past year. A great deal was accomplished in 2022 from a development, organizational, and financial perspective. First and most importantly, we announced positive data from the EMERGENT-2 trial in Schizophrenia. The trial confirmed the positive findings from our first EMERGENT-1 trial and should provide a clear pathway to an NDA submission this year. We also made progress enrolling our ARISE trial, which is designed to assess the efficacy and safety of adjunctive KarXT in Schizophrenia, the second potential indication. We initiated a phase III program in psychosis-related Alzheimer's disease, the third potential indication for KarXT, an area which many of you know has no currently approved therapy. We continue to build on our in-house capabilities. In 2022, we hired over 100 new employees from across the company, from discovery to development to commercial to HR and to finance. Finally, in mid-August, we announced the closing of a public offering, which generated gross proceeds of $862.5 million. With approximately $1.2 billion in cash on our balance sheet, we expect to be able to fund operations through 2025. On every level, 2022 was an excellent year. Now I'm gonna talk a little bit about 2023. Strategically and operationally, we're focused on these three areas right here. The first one is to build the core, which means maximizing the value of KarXT. That means filing the NDA in 2023, securing approval and launching in 2024, and then continuing to develop new indications and claims. That's the formula for value creation, and that's what we're gonna concentrate, of course, on today. The second area of focus is building the capabilities needed to commercialize KarXT. You know, it's often said that emerging biopharma is good at innovation and large cap pharma is good at commercialization. While I get that sentiment, I understand it. Building an R&D commercial organization, transitioning Karuna to that type of a company is infinitely doable. The company is well-capitalized and will have the management team and capabilities needed to scale this business. The third area of focus is building the pipeline. To be clear, there is no ambiguity inside of Karuna about where our time, attention, resources need to be placed. Filing the NDA, securing approval will be the single most important path to value creation. That said, we do have a drug discovery organization and a seasoned group of drug hunters to grow our pipeline organically and inorganically through licensing and partnerships. We're focused on novel mechanisms with validated targets, and we'll look for opportunities that provide much more than an incremental benefit to patients. Instead, we're looking for best in class medicines. We'll be disciplined in terms of where and how much we invest. For each opportunity, we'll consider the probability of technical and regulatory success and understand the full range of financial outcomes. We'll never start a project without understanding the value creating potential of that project and the downside risks. Now, the key point on this slide is that we see KarXT, we genuinely see KarXT as a platform. One compound with the potential for at least three different distinct indications: Schizophrenia, adjunctive treatment, and Alzheimer's disease. Platforms, if built effectively, can create strategic, operational, and financial advantages. Strategically, we can be more relevant to psychiatry and to the mental health community. Operationally, we can leverage our resources and capabilities. Financially, we can enhance and diversify our revenue stream and sources of growth. From a timing perspective, we're targeting a potential launch for KarXT in the second half of 2024, followed by adjunctive treatment in 2025, and then Alzheimer's psychosis in the 2026, 2027 period. If we're successful from a development and regulatory perspective, we'll be launching one new indication every 1- 2 years during this period of time. Let's talk more specifically about Schizophrenia, the first indication. For some of you, this will be a review and for others an introduction. I'm gonna be brief, Schizophrenia is a serious, complex mental health condition that affects how a person thinks, feels, and behaves. Symptoms can differ from person to person, but generally fall into three categories: positive, negative, and cognitive. Starting treatment early is important. Treatment is usually lifelong and involves a combination of supportive care and, of course, pharmacotherapy. Now, in terms of pharmacotherapy, the currently available atypicals have made a big difference in many patients' lives, but as you know, they're not without limitations. Response to atypicals is highly idiosyncratic. Response rates are low, failure rates are high, and a drug that works for one patient may not work for another. Beyond their limited efficacy, the safety and side effect profile of atypicals is problematic, including substantial weight gain, which can lead to comorbidities such as hypertension and diabetes, sedation, extrapyramidal symptoms, all of which can result in high rates of discontinuation, leading to relapse and hospitalizations. That is the cycle. In fact, 75% of patients will discontinue their first treatment in the first 18 months, and on average, take four to five different treatments over the course of their illness. Today, there are 10 million-15 million prescriptions being written for atypicals in the United States just for Schizophrenia. That's one prescription every three seconds in the United States. What's unique about this category is those 10 million-15 million prescriptions are for one class of medication. It's impossible to overstate the degree to which the condition is managed with a single pharmacological approach since every FDA approved option is a dopamine antagonist. In contrast, for example, in depression, there are eight different classes of medications. The field of psychiatry, of course, wants and needs a new pharmacological approach that can be used alone or in combination with other compounds to improve functional outcomes. That's where we, of course, think KarXT can provide a solution. Mechanistically, KarXT stimulates the M1M4 receptors in the brain to exert its antipsychotic and pro-cognitive effects. The pharmacology opens up the possibility to not only treat positive symptoms as a mono or adjunctive treatment, but also negative symptoms and cognition, which if you talk to any psychiatrist, are the most disabling symptoms of the disorder. Clinically, KarXT's benefit risk profile appears fundamentally different. Across our trials, KarXT has demonstrated an early and sustained reduction of core positive and negative symptoms of Schizophrenia. Whether you focus on P values or effect size or response rate, the benefits were statistically significant, clinically meaningful, and while there are no head-to-head studies, the efficacy we've observed is at the upper end of the range that reported for the currently available products. Now in terms of safety and side effects, the profile is just as compelling. Common side effects were mostly cholinergic in nature, mild to moderate in severity, and occurred within the first two weeks of treatment, and resolved over time with repeated dosing. What we don't see with KarXT, which is important, is weight gain, sedation, abnormal motor movements, EPS, and elevated prolactin levels, some of the common side effects of current medicines. This is a unique profile compared to what is used today. We hear loud and clear from psychiatrists, this is what they're looking for. We continue to generate additional efficacy and safety data on KarXT in Schizophrenia through our EMERGENT program. As mentioned, we've completed our registration trials, two registration trials. These trials will contribute mainly to establishing long-term safety in a larger number of patients, which will be needed for the NDA data package, along with ongoing planned phase I and phase II... phase III trials not shown here. We've made great progress across the program, completing enrollment in EMERGENT-3, the second phase III efficacy and safety study last quarter, with top-line data expected in Q1. As a reminder, EMERGENT-3 shares nearly all of the design features of EMERGENT-2, namely inclusion/exclusion criteria, design and dosing endpoints, powering assumptions, to just name a few. We're generating long-term safety data through EMERGENT-4 and EMERGENT-5, which are both one year open-label studies. EMERGENT-5 continues to progress nicely, we feel confident in our enrollment projections and remain on track for submission in the middle of the year. Just a few comments on the NDA submission, which is the first and most important step that we're gonna take. This is a company-wide all hands on deck effort. Operationally, we've ring-fenced the groups that are critical to collecting and cleaning data, statistical analysis, and writing, of course, the NDA modules. This includes the groups CMC, Preclinical and Clinical Development, Clinical Operations, Regulatory and Program Management. The leaders of each of these groups have extensive experience and expertise with NDA submissions. In other words, they know what they're doing. In terms of the commercialization plan, briefly, we'll be focused on certain sort of strategic positioning and pricing research, medical education, working with policymakers and advocacy groups to continue to destigmatize the condition and ensure access at launch, and creating deployment plans for the MSLs and the field force, among many other things. All these efforts are intended to just simply lay the groundwork for a potential launch in the second half of 2024. There's a lot to do here, but we have plenty of time to do it. I've been through this many, many, many times. We'll talk about our commercial program in much more detail in the future. Now, an important development opportunity for KarXT is an indication for adjunctive treatment. As many of you know, most common and complex medical disorders require more than one agent to manage symptoms and improve outcomes. The concept of using two treatments that are mechanistically different, complementary, and additive is a well understood concept and accepted. Adjunctive treatments are available in depression, and Bipolar depression, and Alzheimer's disease, Epilepsy, Parkinson's disease, but not in Schizophrenia. Despite this, an estimated 30% of patients will receive two dopamine receptor antagonists during the course of their illness in an effort to achieve greater efficacy, even though the scientific rationale and clinical benefits of combining such similar drugs is lacking. An adjunctive treatment for KarXT could change the status quo in Schizophrenia. We're evaluating the opportunity through the ARISE program, which consists of a six week placebo-controlled trial and an open label long-term extension trial. The ARISE trial is enrolling patients who are on a stable regimen of antipsychotic medication, but have had an inadequate response and are still experiencing symptoms. Although we expect the severity of symptoms to be slightly less than our monotherapy program, what we are looking for is a clinically meaningful improvement in the reduction of symptoms by the end of the study, which has not been observed by combining two currently approved agents. The data from this trial are expected in the first half of 2024, prior to our potential launch in Schizophrenia. To sum up the profile, every therapeutic area eventually undergoes a scientific base shift, and that's what KarXT represents. An FDA approval could start a changing of the guard in the treatment of Schizophrenia, which most would say is long overdue. I liken the potential shift from atypicals to potentially muscarinic receptor agonists in schizophrenia to the shift that we observed in depression from TCAs to SSRIs. Even what we're seeing today, for example, in the migraine market, triptans to CGRPs. It's conceptually no different. While our data set is still evolving, we have a compound with a differentiated pharmacology. Antipsychotic activity at the upper end of the range and side effects at the lower end of the range, with potential use as a mono or adjunctive therapy. We're in a pretty good spot right now. Turning our efforts with KarXT and Alzheimer's disease. Many of us have first-hand experience with Alzheimer's, whether it's a family member or a friend. Memory loss and confusion are the better-known symptoms of Alzheimer's. Behavioral symptoms such as hallucinations, delusions, agitation, aggression, are common and present in up to 50% of patients. These behavioral symptoms can present a significant burden for patients, family members, caregivers, are often a key factor in the transition from living at home to a full-time care-based setting. Today, there are no FDA-approved treatments, as you know, for psychosis related to Alzheimer's, despite its prevalence. We believe KarXT, if successfully developed could be the first. As I mentioned earlier, we're currently evaluating KarXT as a treatment for hallucinations and delusions associated with Alzheimer's disease in our Phase III ADEPT program. The program is designed to generate data on KarXT's efficacy as a maintenance and as an acute treatment via ADEPT-1 and 2, as well as a long-term safety study through ADEPT-3. Recalling the earlier Lilly trial of xanomeline in Alzheimer's, both acute and maintenance benefits were observed. The first trial in our program, ADEPT-1, is underway, and we're planning to start the remaining studies this year. We expect the ADEPT-1 and ADEPT-2 trials will complete around the same time towards the end of 2025, and we'll refine that guidance once both trials are up and running. While this trial is focused on KarXT's effect on hallucinations and delusions, we're also gathering data on prominent symptom domains such as agitation and aggression, where we saw xanomeline show a benefit in the earlier Alzheimer's trial by Lilly. To wrap up here, the need for a new treatment option for serious mental health in both psychiatry and neurology has never been higher. Our country was in a mental health crisis before the pandemic, and it only worsened after the pandemic, affecting virtually every demographic group, regardless of age, race, and gender. While the discovery and development risks in this field are real, the need for new treatment options is clear, and we'll be smart and disciplined in where and how we invest. 2023 will be a pivotal year for Karuna as we aim to submit our NDA, build platform capabilities, and develop our pipeline. Thank you very much. Thank you. I'd like to introduce and ask Steve Paul, our President and Head of R&D and Chief Scientific Officer, Andrew Miller, Chief Operating Officer, and Troy Ignelzi, CFO, to join the Q&A portion. Great. As a reminder, if you guys wanna ask a question, just raise your hand and someone will bring you a mic. It's a pretty small room, so we could also just repeat the question. I will start. First one's for Bill. You know, you're coming in as CEO of the company, what's your long-term vision for Karuna? Look, I think, our long-term vision is gonna be a function of the short term. Right now we have a job to do, and we have to focus on what I would say is the single most important path to value creation, and that's filing the NDA, securing approval, and launching the product. That being said, if the narrative around the company in several years is we have a broad and deep product line with novel compounds in both psychiatry and neurology, financially, we have durable revenue, earnings, and cash flow, and it's a place that employees wanna work, I'd say we'd be in a pretty good spot. You mentioned the EMERGENT-3 results are gonna come out this quarter. What level of kinda detail should we expect when those top-line results come out? Steve or Andrew, you wanna answer that? I'll start, and Andrew can embellish. We expect really the same top-line details that we had for EMERGENT-2 and EMERGENT-1. It'll be pretty much the same. We get the efficacy data and some of the safety data pretty quickly when we analyze the data. There are some additional things that we measure, blood levels and certain serum analytes, et cetera, that take a little longer. Once we have the initial efficacy and safety data, we'll issue some top-line results. You talked about the KarXT submission in the middle of this year. Can you walk us through what any of the remaining gating factors are between kind of where we stand today and that submission going in? Yeah. Go ahead, Andrew. You're running that. Yes, sir. I can speak to that. You know, from a submission perspective, I think we've consistently stated that the long-term safety data is fundamentally the time-limiting factor. That guidance around middle of the year really takes into account where we are from a long-term safety perspective. I remain confident in that. There are, of course, many activities that go into the NDA. The Emergent-3 study will be a part of that data package. Bill mentioned briefly there's a number of other phase I studies ongoing and, of course, CMC and preclinical work as well. None of those do we expect limiting from a timing perspective at this point. I think there have been some investor questions about, ambulatory blood pressure monitoring. Have you done that work? Is that something Karuna needs to do? Where do you stand with that, as it relates to kind of the filing if that might be needed? Go ahead, Andrew. Yeah, I can speak to that as well. I think an ambulatory blood pressure monitoring study is something that we are seriously considering. You know, just to recap, across our program, our data does not suggest that there's any meaningful chronic blood pressure increases associated with KarXT. It's not something that the agency has requested that we do, but simply something, I think, as we think about where we are from a company and development perspective on the back end of our second positive efficacy study in EMERGENT-2, that an ambulatory blood pressure monitoring study would offer the opportunity to simply provide a confirmatory and more definitive data point towards the lack of any blood pressure increases associated with KarXT. That's something that we're considering. It's not something that we would put in advance of the anticipated submission of the NDA at this point. Should we choose to do it wouldn't have any impact on our projected timelines of submission and review, but something that we think could be a prudent step for us. Maybe we can talk about where you see KarXT fitting in the schizophrenia treatment landscape. For example, how early on in treatment might KarXT be used, and how do reimbursement and payer dynamics factor into that? Yeah, I can start, then I'm sure Steve will have a comment about positioning. I'll start at the end. Of course, this is all subject to our labeling, or an approval on a labeling. There's certainly a version of this where it's first line, first switch, and first adjunctive. If this was a D2 antagonist that looked like the other dozen D2 antagonists that are available on the market, I wouldn't expect the positioning of the use to be as broad. If you think about in this category, they've been cycling through three or four different products that are actually more similar than different in managing each patient. They have not had a what could be both a monotherapy and adjunctive treatment. When you look at the benefit risk profile of this product, whether it's placebo-adjusted effect on the PANSS, which is literally at the upper end of the range if you were to rank all the atypicals from high to low. If you look at side effects, you're only dealing with what I would call SSRIs-like side effects, anticholinergic side effects, as opposed to things, as I've mentioned, like weight gain, sedation, and in EPS. I think there's gonna be a lot of anticipation by psychiatrists in the United States to work with this compound. You know, Steve has said many, many times, if you give someone an antihypertensive or an anti-diabetes agent or dyslipidemia drug, it'll lower their millimeters of mercury, HbA1c, or LDL in 90% of the cases. You give someone an antipsychotic, and you're lucky to get a 20% or 30% or 40% response rate, and there's no such thing as remission. To date, there's been no polypharmacy approach in Schizophrenia, unlike virtually every other CNS condition. I think that the psychiatry community, this could trigger a changing of the guard. I don't mean that just sort of conceptually, but a real change from how they're dealing with the condition today. You know, not much to add, except as an old psychiatrist who once used to treat patients with Schizophrenia, as Bill said, again, contingent on getting this drug approved and all of that, this is a potential game changer because when you have patients come in and you wanna offer them something. Today, you're offering them drugs that produce immediately akathisia and extrapyramidal side effects. They increase your risk of tardive dyskinesia. Many of the better ones cause very significant weight gain, which leads to diabetes and hypertension, metabolic syndrome. Life expectancy for this group due to cardiovascular disease is greatly reduced. When you're putting all that into the equation, you have something now that doesn't cause any of that, but also has robust efficacy on positive symptoms, quite likely on negative and cognitive symptoms as well. We can talk a little bit more about that. It really has an ideal profile. I would think that starting patients out on this drug will be quite common. Taking patients who are on atypicals that are partial responders and adding this drug will also be quite common. Then taking patients off existing agents because of those side effects and adverse events that I alluded to will be very common as well. In all three categories of patients, I think we're gonna see a lot of utilization. Jessica, as it relates to reimbursement, you can never underestimate the macro pricing environment in biopharma. I think the Inflation Reduction Act actually provides a little bit more predictability. I wouldn't get too naive about how anything can change. In mental health, there is still a balanced conversation taking place between manufacturers, health plans, PBMs, and even CMS with Medicare or Medicaid. There is a real motivation to enable access, especially in the area of Schizophrenia. If you just look at the last four atypicals that have been introduced, and they started with Schizophrenia, and some of them are being used predominantly in mood disorders, but their formulary coverage rates right now are between 70% and 85%. They were all D2 antagonists. Their benefit risk profiles actually look more similar than different. I think in introducing this into the payer world, we are in a very good position in terms of being able to enable access to it. Of course, we have a responsibility to achieve access at a price point that makes sense for the company and a price point that makes sense for payers. We, of course, have 18-24 months to do that, but I like how this could shape up over the next two years. Bill, you said the P word, price. Maybe we can talk on that thread a little bit more. You've got really compelling efficacy, differentiated side effect profile going into a market with a lot of generics. What is the price that you anchor to? Is it those branded atypicals or kind of what are we indexing off of? Yeah, look, we're of course 18-24 months away. I would say there is a pricing corridor in this market. You know, one of the benefits of introducing KarXT into Schizophrenia is it's novel, but this is a very well-established category. If you're thinking about it, there is a corridor out there. We of course have to do a lot more work, and I put out a price now and then UnitedHealth plan will call or Aetna, and that would not make a great deal of sense. We would do something that is intuitive. You kind of, mentioned the possibility of polypharmacy, and I think with the differentiated mechanism, that makes sense. Is a single efficacy trial sufficient to support registration for an adjunctive Schizophrenia label? Yeah, Andrew, why don't you answer that? I mean, it's our anticipation that a single study would be sufficient. given actually other examples in psychiatry, particularly in mood disorders, where one adjunctive study and one monotherapy study are combined into a single application that results in labeling for both. Obviously, that's contingent upon us being a marketed product already in Schizophrenia, but that is what we anticipate, as an outcome from the ARISE program. Can you also walk through the ADEPT program trial designs and your overall strategy in psychosis and Alzheimer's disease? Sure. I can comment on the trial design aspect. Steve and Bill can add on from there. We have three studies in Alzheimer's. One of them has already been initiated. That's the ADEPT-1 study. That is a 38-week randomized withdrawal study, 12 weeks of open label treatment and patients are asymptomatic, hopefully getting to a degree of therapeutic response, and then entering a 26-week double-blind randomized withdrawal study design. That's actually a common design used across psychiatric indications. Primarily, it's been used in mood disorders, it is also a common study in Schizophrenia for getting a maintenance therapy indication, for instance. ADEPT-2 is really kind of the not the reverse, but kind of the other side of the coin. Rather than starting with 12 weeks of open label treatment, you start with 12 weeks of double-blind placebo-controlled treatment, and then patients would be eligible to enter the long-term maintenance study or open label study, ADEPT-3. Patients who complete either ADEPT-1 or ADEPT-2 will be eligible to go into that long-term safety study. We think this really gives us the opportunity to demonstrate and hopefully replicate the acute and maintenance benefit that was observed in the original Lilly Alzheimer's study, where the antipsychotic benefits of xanomeline were first discovered. It also, I think, gives us a great chance to demonstrate clinically meaningful benefit in patients with Alzheimer's, where, as Bill mentioned, there are currently no approved treatments for that indication. I think that was well said. Well, I have not much to add. Mm-hmm. Thanks, guys. Great presentation. Steve, Andrew, I think a few people debate that the class is a major step forward, kind of above the D2, D3, and D3 kind of class. One question that we've been thinking about is on receptor pharmacology, how does agonizing M1, M4 vary potentially in both ADP and Schizophrenia from the alternative mechanism, which is a PAM? What was the question again? M1, M4 agonist versus- Yeah. We have KarXT is a dual M1, M4. xanomeline is a dual M1, M4. It's an orthosteric agonist, so it directly stimulates the receptor as opposed to allosteric compounds, which indirectly stimulate the receptor. We think the drive here is gonna be quite substantial, and there's evidence that M4 and M1 both contribute to the antipsychotic effects. There's evidence that both also contribute to the pro-cognitive effects. I won't go through the literature on this in any great detail, but lots of data suggesting that the M1 adds a very significant pro-cognitive pharmacology to the agent. We think this is exactly what we need to treat this disease holistically, as Bill pointed out, positive, negative, and cognitive symptoms. We're gonna have to come back and demonstrate that for certain, but we think that the pharmacology makes really good sense based on 30, 40 years of literature. I hope that answered the question. I couldn't quite hear it. Yeah, maybe to just take it one step further, just in regards to the differentiation versus an M4 PAM, just on Schizophrenia, but also I would say just in the acute Alzheimer's psychosis studies that you're running. Well, you know, again, I'd just say what I just said. M4 agonism is important. There's no question that contributes substantially to the antipsychotic properties. There's a difference between a drug that stimulates the receptor at the same site that acetylcholine does, that's the orthosteric site, versus an allosteric site. You need acetylcholine to be released for an allosteric compound to be active. My guess is that we're gonna see very significant activity at the M4, but also the M1 receptor, which is one of the other five muscarinic receptors. There's reams of data supporting its role, excuse me, in cognition, and I think that's gonna be a beneficial feature of this, of this agent. I would just add to that quickly. I mean, I think with KarXT and specifically with xanomeline, we have the benefit of four different placebo-controlled studies being conducted across Alzheimer's and Schizophrenia. I think with respect to M4 PAMs, we've yet to see any large scale multi-site registrational studies be conducted or see data readouts from those. It's a little premature to comment exactly about what the clinical profile of those are going to be. Obviously, I think as Steve mentioned, you know, feel like we're in a very strong position. Yeah. given the broad pharmacology across M1 and M4 that we think is really driving the benefits that we see clinically. Yeah. Historically, just to amplify what Andrew said earlier, when we were developing xanomeline back in the Lilly days, we were developing it as a cognitive drug, as a pro-cognitive drug to improve cognition in patients with Alzheimer's when we discovered its antipsychotic properties, the behavioral effects on hallucinations, delusions, agitation, aggression, all the bad behavioral effects. We also saw a significant improvement in cognition. The ADAS-Cog improved in that study. It's all been published. You can, you know, get you the references if you like. I think the two features that we have in this drug are ideal for treating Schizophrenia. As many of you know, once positive symptoms are dampened down, it's the negative and the cognitive symptoms that become the most disabling. In fact, Schizophrenia used to be called dementia praecox, dementia of the young. Sorry for that. Look, we get a lot of questions about how one compound could compare to another compound in development, and one point I think is important to make is, especially in this area, I don't think we see or anyone should see this as a zero-sum game, a fight to the death between compounds or market share battle. I just think that it's unique in this area as opposed to other areas where multiple options, even in the same class, does not mean there's not clinical value and of course, commercial opportunity for a company. Yeah. Exactly. With our remaining minute here, can you just remind us of your cash runway and maybe not just a point in time, but what the current cash balance is gonna enable the company to accomplish? Sure. Hopefully you guys can hear me. First, you know, going back to that last question, what an exciting time, I think, to be in psychiatry and psychiatric drug development for patients and caregivers. As Bill alluded to in his opening, you know, we're at the forefront of this, it is an exciting time. On the cash position, you know, we ended Q3 with $1.2 billion, and that's after the follow-on that was done in August from the EMERGENT-2 data. That gets us through 2025, and to your point, that allows us to get through the ARISE dataset, which we expect in the first half of next year, the NDA submission middle of this year, which we define middle as Q2 and Q3, the anticipated launch and approval or approval then launch in the second half of 2024 in both ADEPT trials, the one and two. Really a lot of clinical and meaningful milestones in the development side, but also that transition to a commercial organization, hopefully. We're out of time. We'll leave it there. Thank you. Thank you. Thank you. Yes.