Good morning and welcome to the Jefferies 2025 Global Healthcare Conference. It is my pleasure to now introduce Catherine Owen Adams, CEO of Acadia Pharmaceuticals. Good morning, ladies and gentlemen. Thank you for joining us here this morning. We are a compact but bijou audience, and I look forward to sharing more about Acadia Pharmaceuticals. Today I want to share our progress in building a leading neurological and rare disease company with our intention of becoming a global biotech powerhouse. Today I'm going to be making some forward-looking statements, and I encourage you to look at our SEC filings to examine the risks and uncertainties relevant to our business. Acadia is building for long-term growth in both neurological and rare diseases. We intend to build on our strong foundation of history with NUPLAZID in the Parkinson's disease psychosis space, which is leading the way right now, and we continue to see that momentum strong into the future into 2038. Behind that, we have some really exciting pipeline opportunities, which I look forward to sharing more about today. We are specifically excited about our new 5-HT2A Agonist, ACP-204. In rare disease, we've made strong progress with DAYBUE, and we look forward to global expansion, already having approval in Canada and in the EU in Q1 2026 and beyond that into Japan. In terms of our pipeline focus in rare disease, we have some exciting opportunities to continue our focus in Rett syndrome, but also in Fragile X, in Huntington's disease, and in SYNGAP1 in terms of our collaboration with Stoke Therapeutics. In terms of our business development focus, we're looking forward to continuing our focus on rare disease and expanding into potential new areas such as endocrine, metabolic, nephrology, cardiovascular, and immunology. All of our strategy is building on our focus on precision medicine with a strong focus on using biomarkers in as many of our trials as possible. Data innovation, driving AI and machine learning into our development and commercial capabilities. Globalization, building our business beyond the U.S., now having a strong focus in Europe, Japan, and beyond. Finally, patient empowerment, having the patient and their journey at the center of everything we do so that when we deliver medicines, those medicines really are there to be their difference. In terms of our current portfolio, we have two commercial products, DAYBUE and NUPLAZID, with expected revenues this year in 2025 of over $1 billion. Their peak potential we estimate at between $1.5 billion and $2 billion. With the pipeline that I'm going to share with you and specifically the four programs I'm going to go through today, we believe our risk-adjusted potential for those programs is $2.5 billion. Should all of them be successful, the peak potential of all four combined up to $11 billion. Importantly, this is not guidance. As we all know, drug development carries inherent risks, but we're really excited to share with you today what we believe can become an exceedingly important and powerful pipeline. In terms of building momentum across our pipeline, we've had several recent milestones, including the start of our ACP-204 study in Lewy body dementia psychosis and initiating our phase III trial of trofinetide in Japan. We have several important milestones in the next six months, including the initiation of our phase II study with ACP-211 in major depressive disorder, and also our first in-human study of ACP-271, the first, we believe, GPR88 to go into humans. We also expect in Q1 of 2026 our CHMP opinion on trofinetide, and we have four major readouts by the end of 2027. We're particularly excited about our ACP-204 opportunity in Alzheimer's disease psychosis. Let me start by taking you through our product specifically and start by an overview of NUPLAZID. In terms of Parkinson's disease psychosis, there are over a million patients that suffer from this in the U.S., with over 50% of them experiencing hallucinations and delusions at some point during their disease. What we do know is that many caregivers and their families don't really understand the impact beyond motor symptoms of Parkinson's disease, and less than 10% of caregivers are actually aware that their family member could suffer from psychosis due to Parkinson's. Because of that, we have launched a large awareness campaign in the U.S., partnering with the actor Ryan Reynolds to raise the awareness of the hallucinations and delusions associated with Parkinson's disease. This campaign has helped us to raise that awareness and has been incredibly successful in terms of the progress we're now seeing with NUPLAZID. NUPLAZID is the first and only approved FDA treatment for hallucinations and delusions of Parkinson's disease. Since launch, we have treated over 93,000 patients. Within the U.S., we estimate to have about 25% market share of the 130,000 patients treated every year with an atypical antipsychotic that are treated off-label. We believe there is a lot of room for growth both now and in the future. With our IP taking us out for our capsule formulation beyond 2038, we have strong excitement about the growth potential for NUPLAZID. In Q3, we reported record sales of $177.5 million, which was 12% year-over-year growth, 9% delivered by volume, with very strong demand indicators, 21% year-over-year increase in referrals, and 23% increase year-over-year in prescriptions, the strongest growth since 2019. Because of that, we have decided to expand our field force in the U.S. and increase our customer-facing roles by 30%. We are starting that increase now and looking forward to getting those people in place by the first quarter of 2026. If we move now to rare disease, I want to start by talking about Rett syndrome. Rett syndrome is a highly debilitating disorder affecting predominantly females due to MECP2 gene disruption. These young girls develop normally for the first two years of their life, and then their parents notice developmental deterioration. They lose their cognitive abilities, they lose their motor abilities. It's a devastating disease. Over 5,500 patients in the U.S. are diagnosed with Rett syndrome. Since we've launched DAYBUE, we've seen an increase actually of about 20% in that diagnosis rate. We estimate the prevalent population to be somewhere between 6,000-9,000 patients in the U.S. and 9,000-12,000 in the EU. DAYBUE is the first and only treatment for Rett syndrome. Since its launch in 2023 in the U.S., we've treated over 2,000 patients. We have strong efficacy data, but we also have strong persistency data, with over 50% of patients remaining on treatment at 12 months, showing that sustained benefit that their families are seeing. Importantly, we have a large real-world evidence study ongoing, our LOTUS study, in which we have more than 300 patients who we're tracking over time and continue to produce data to show the long-term efficacy and safety of DAYBUE. Looking ahead, we're really excited to anticipate a CHMP opinion in Q1 2026, and we're building our team in Europe to be there to support that launch immediately, with our first launch country going to be Germany. In Q3, we recorded record sales of DAYBUE of over $100 million, with over 1,000 patients now treated globally. We've seen the highest quarter-over-quarter referral of patients, with now over 950 doctors in the U.S. having prescribed DAYBUE. We're evolving our strategy from focusing on centers of excellence to now focusing outside those centers of excellence into the community. In Q3, we saw 74% of our prescriptions now coming from doctors treating patients in the community. In terms of the international demand for DAYBUE, it has been extremely strong. As a result of that, we've put in place name patient supply programs in countries where that's possible due to the regulatory and legal framework. We now have patients sourcing DAYBUE in the EU, in Israel, in the Middle East, and Latin America. We expect our meaningful field force benefits to continue to increase as we head into Q4 and in 2026 and beyond. Now let's look at our pipeline. I'm going to start by showing you an overview of our pipeline. As you can see, this is split into our neurological diseases and our rare disease programs. With some big phase II and phase III readouts coming in the next few years, I wanted to share a little bit more about some of these programs to give you an insight of why we believe so strongly in our pipeline and our ability to deliver. I'm going to start with ACP-204. We're very excited about this opportunity and this program. It's our next 5-HT2A agonist, which we believe has the potential to transform Acadia if our clinical development program is successful. Now, this molecule has been developed based on the understanding that we have on pimevanserin. Structural differences specifically have been designed initially to minimize or eliminate QT prolongation. Why that's important is that we can now, in this more frail elderly population, take ACP-204 to higher doses than we have been able to with pimevanserin. We're also seeing a faster onset of efficacy. Altogether, we're excited about the possibility to differentiate with ACP-204. Our first focus area is Alzheimer's disease psychosis, an area of huge unmet medical need with no approved treatments. About 30% of patients with Alzheimer's disease do experience hallucinations and/or delusions during their disease process. It can actually occur at any stage of the disease, sometimes even before the dementia starts. About 800,000-850,000 patients in the U.S. are treated for this hallucination or delusion or psychosis associated with Alzheimer's, but they're treated with off-label therapies. Again, there's substantial unmet medical need in this area. ACP-204 is being tested in global double-blind placebo-controlled trials. Currently, our phase II trial is underway, looking at two doses, the higher dose at 60 mg and a dose similar to that of the approved pimevanserin dose at 30 mg versus placebo. The primary endpoint for this trial is SAPS-H+D at six weeks. The master protocol has been developed as a seamless design between phase II and phase III, allowing us for more seamless execution and hopefully faster timelines. Our top-line results of our phase II study are expected in mid-2026. We're also excited to study ACP-204 in Lewy body dementia psychosis. Lewy body dementia is a progressive brain disorder that affects thinking, movement, mood, and behavior, and it's associated with abnormal alpha-synuclein pathology within the brain. There are over 1 million patients who suffer from this in the U.S., and the psychosis associated with Lewy body dementia is actually higher than Alzheimer's disease, with 50%-70% of patients with Lewy body experiencing this psychosis during their disease process. There are no approved therapies for Lewy body dementia psychosis. Patients are treated with off-label antipsychotics, often causing sedation and cognitive decline. There is a significant unmet medical need. We recently initiated our phase II study in Lewy body dementia with psychosis, and we arrived at this decision to move in this direction based in part on data, although limited, from our previous pimevanserin withdrawal study, which suggested the potential for targeting 5-HT2A for these patients. Lewy body dementia is an umbrella term that includes dementia with Lewy bodies as well as Parkinson's disease dementia. The difference in dementia with Lewy bodies is that cognitive decline is often the first symptom, with movement disorders coming after that. In Parkinson's disease dementia with psychosis, it begins as a movement disorder and then cognition changes over time. We're recruiting patients with both of these types of Lewy body dementia with psychosis into our clinical trials. The clinical trials are designed to ensure that we have strong stratification. We're capping our enrollment of Parkinson's disease dementia psychosis at 50%. We're also using biomarkers in this study as an exploratory endpoint, using skin biopsy. The doses here are the same as in our Alzheimer's disease psychosis study, 60 mg and 30 mg versus placebo. The primary endpoint is SAPS- LBDP at six weeks. We're very excited about our next molecule, ACP-211, in major depressive disorder. Major depressive disorder is characterized by pervasive loss of interest, sadness. There are multiple symptoms. I think we're all fairly familiar with major depressive disorder. Current treatments are out there, but they tend to be limited by their efficacy and/or their onset of action requiring extensive monitoring. ACP-211 is being designed as an oral therapy, and we are hoping to achieve minimal in-office monitoring to address this significant treatment gap. In terms of the unmet need, it is a very large burden across global populations. In the U.S. alone, 21 million adults are diagnosed with MDD, but only 9 million of those are currently treated. Of that, about 3 million have treatment-resistant depression, having failed on two or more therapies. I think we all understand the high cause of disability and also economic burden to most countries. A significant unmet medical need and large commercial opportunity. The design of the clinical trials here are going to be initiated in a phase II study. We're studying at a low dose and a high dose. We'll give more details about that in due course. It's going to be a four-week randomized double-blind placebo-controlled multicenter study, 153 patients, looking at the primary endpoint at four weeks of the change in MADRS score. We look forward to starting this trial soon and updating you on our future progress. Our next area for exploration is ACP-711 in essential tremor. Essential tremor is a movement disorder with a high frequency of kinetic tremor, mainly affecting the upper limbs and the upper body. It represents a huge unmet medical need. There have been no approved or effective therapies launched for the last 50 years. ACP-711 was acquired from Saniona and is a selective alpha-3 modulator targeting the GABA system. We are looking to start phase—we've started phase I data, which supports the potential absence of cognitive side effects, something that's pretty pervasive right now in the current treatments. In terms of essential tremor and the market opportunity, there's around 7 million patients in the U.S., but relatively fewer of those are actually treated for the essential tremor, those who are sort of moderate or severe or beyond, up to 1 million. Whilst high unmet medical need, older drugs approved and fewer patients actually treated because of the side effects associated with the current treatments. In terms of our focus, we have currently a phase I program underway, specifically also looking at an elderly cohort, which we believe is important to understand before we move into phase II. We are looking to start our phase II in the fourth quarter of 2026. The plan for that study is to enroll 150 patients in a double-blind placebo-controlled study. We look forward to discussing more details on this program as we move into next year. Finally, turning to our ACP-271 program, this is a GPR88 agonist, which we believe has an effect on modulating D1 and D2 signaling without affecting dopamine levels. This is a really exciting molecule that we believe is the only one about to go into clinic and the first time in humans. We are about to initiate our Healthy Volunteers study in Q1 2026 and plan to develop this candidate for both tardive dyskinesia and Huntington's disease. Finally, in terms of our milestones and our lookout to 2026, we're very proud of our accomplishments in 2025. We, as I've said earlier, plan to deliver over $1 billion in U.S. sales. As we look into next year, we're excited for our major readout for ACP-204 in the middle of next year, as well as our CHMP opinion for DAYBUE and our start of our phase I trial for ACP-271 and our phase II trial for ACP-711. We also have a strong financial balance sheet. We're cash flow positive, and we have a strong focus on business development. We're looking forward to sharing more about our focus on partnerships and acquisitions as we move into next year. At Acadia, our mission is to turn scientific promise into meaningful innovation for underserved neurological and rare disease communities and to be their difference. With that, I thank you for your attention and look forward to speaking to many of you while we're here at this conference.