Time has come, so we will now begin 2024 R&D Day of Nxera Pharma. Thank you very much for taking time out of your busy schedule to join us today. I am Nomura, CFO. I will be the moderator. Today we have Chris Cargill, CEO, Dr. Matt Barnes, President of Nxera Pharma U.K. and Head of R&D, and Dr. Makoto Sugita, President of Nxera Pharma Japan. Simultaneous interpretation is provided. Please click on the Earth icon in the lower right corner of the screen and select either Japanese or English. If you choose Off, you will hear the speaker's original voice. Today, we will explain the progress of our business using the materials in the first half, followed by a Q&A session in the second half. The presentation materials will be shown on the screen and are also available on our website. If you want a copy, please access the website by selecting IR News from the Investors tab in the upper right corner of the website. Institutional investors, analysts, and members of the media are welcome to raise your hands and ask questions during the Q&A session. For all others, please submit your questions via the Q&A button. Questions can be submitted at any time during the webinar and will be answered as time permits during the Q&A session later in the day. We will now move on to the explanation. First, Chris will explain the overall business strategy, followed by an update on the Japan and APAC business from Sugita, the progress of R&D mainly in the U.K. from Matt, and finally, I will give a brief overview of the most recently announced Q3 results. S o Chris, the floor is yours. Fantastic. Thank you, Nomura-san. Good afternoon, everyone, and welcome to today's R&D event. So, we're broadcasting from our Head Office in Tokyo, and as Nomura-san said, our Head of Research and Early Development, Dr. Matt Barnes, is joining us from our Innovation Centre in Cambridge, U.K. So, Nxera is a truly a big team, drawing talent from the best biotech hubs around the world. With last year's acquisition of its Japanese and Korean businesses, Nxera is now a fully integrated biopharma. And this year, with a new global technical operations hub in Switzerland, our newest location, to support our CMC supply chain and quality management. And this small but critical team bridges discovery, development, and commercial, creating a seamless pathway for innovation to Japan and the world. So, our focus is on driving meaningful innovation for patients and acting swiftly to make a difference. That's why today's theme is Be Bold, Move Fast. This annual R&D event is an opportunity to take a deep dive into our strategic plans, giving you insights into our pipeline and the team building the next era of medicine in Japan. Please turn to slide two. So before we begin, I just want to remind everyone of the customary disclaimers, particularly regarding forward-looking statements, which are subject to change. Today's presentation is for informational purposes only and does not constitute an offer or solicitation for any securities. Please turn to slide five. We want to lead the next era of medicine and become one of Japan's top pharmaceutical companies by 2030. We are determined to drive growth in innovative specialty medicines, particularly neurology, metabolism, immunology, and rare diseases. By 2030, we aim to have at least five products launched in Japan, and we're actively exploring new opportunities to expand our portfolio. Our revenue goal is JPY 50 billion by 2030, which represents 26% compound annual growth from last year's result in FY 2023. Accelerating medicine is at the heart of our mission. This commitment to speed requires that our approach, operations, and mindset support scalability. So, as we work towards our 2030 goals, you'll see continued evolution in our leadership team, including our recent addition of Chief Medical Officer Dr. Sugita Makoto. You'll see investments in talent, business process improvements, and data-driven insights through the implementation of new technologies across our business. Please turn to slide six. So last year, I shared our ambition to create Japan's next-generation pharma company with a focus on patient outcomes, medicines by design, and cutting-edge science. A year later, I'm pleased to report that we're on track and we're moving fast. Over the following slides, I'll detail our progress across four growth pillars. One, growing our core products in Japan, including PIVLAZ and the soon-to-launch QUVIVIQ. Two, designing transformative medicines in key therapeutic areas. Three, building the most advanced drug discovery platform for GPCRs to sustain a robust pipeline. And four, pursuing strategic expansions to bring innovative solutions to patients in Japan. Please turn to slide seven. Our midterm expansion is driven by the success of our flagship product, PIVLAZ, which launched in April 2022 for preventing cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Following its inclusion in Japan's stroke management guidelines, awareness and usage of PIVLAZ is increasing. Over 15,000 Japanese patients have benefited from PIVLAZ, and we're excited to expand its reach to Korea from 2025 to 2026. We anticipate peak sales in Japan to range from JPY 16 billion- 20 billion. Please turn to slide eight. Our second major product, QUVIVIQ, was recently approved in Japan for treating insomnia and will soon launch. Now, given the highly competitive primary care market, we partnered with Shionogi to optimize QUVIVIQ's reach and impact. This partnership allows us to earn product supply revenues and net sales royalties while ensuring QUVIVIQ reaches patients globally and efficiently. Broadly and efficiently, rather. We expect peak sales in Japan for QUVIVIQ to reach more than JPY 20 billion, generating potential net sales royalties of more than JPY 4 billion, plus profit from product supply for Nxera. Furthermore, we're excited to explore indication expansion opportunities with KOLs, in addition to territory expansion across the APAC ex-China territories. Please turn to slide nine. Our long-term growth comes from designing medicines that redefine treatments for significant diseases. In the past year, we've made strong progress in neuroscience with the following advancements. NBI-568 is moving to phase III for schizophrenia in early 2025 after achieving positive results in a phase II proof of concept study. ORX750 is heading into a phase II proof of concept study for narcolepsy following positive interim results. And NXE'149 has been optioned to Boehringer Ingelheim as a potential first-in-class drug treating schizophrenia. Each of these programs is aimed at creating life-changing therapies for patients. Please turn to slide 10. In addition to neuroscience, we're advancing treatments in metabolic and immunology, two critical areas of need. PF'522, a selective GLP-1 receptor agonist, is in phase I-B studies. PF'894 and our own program, NXE-744, are both advancing as first-in-class treatments for IBD. Across all of these programs, we aim to positively impact over 500 million patients worldwide. Please turn to slide 11. Our NxWave platform is one of the most comprehensive drug discovery engines for GPCRs, and it's been built over 15 years and fully integrated within our biopharma operations. This platform powers a continuous pipeline of new opportunities, allowing us to partner with external innovators to expand our capabilities and reach. Please turn to slide 12. Molecules remain central to our approach due to their safety, efficacy, and ease of manufacturing. The latter point is increasingly important as reducing the economic burden on healthcare systems becomes very relevant. As seen with the GLP-1 class, there is increasingly limited large-scale global manufacturing capacity for peptide drugs, and therefore small molecules provide a cost-effective and scalable alternative in the biggest areas of disease. While our primary focus remains on small molecules, we're also exploring new modalities, including antibody and peptide technologies, to address unmet needs that small molecules tackle. Dr. Matt Barnes will discuss this further in his presentation. Please turn to slide 13. GPCRs are the most productive target class in drug discovery, yet 75% of GPCR drug targets remain unexplored. This is why we have seen a portfolio and proliferation of GPCR companies being founded and listed on NASDAQ, and we welcome this new competition as it highlights the importance of GPCRs as a target class. Our long-standing expertise in this area gives us a significant head start, allowing us to lead in structure-based drug design for GPCRs. Across all metrics, we believe we have the world's most comprehensive and valuable drug discovery platform for GPCRs, and this unique positioning allows us to meet a substantial global need. Please turn to slide 14. Leading pharma companies continue to choose NxWave to tackle GPCR targets, generating hundreds of millions of dollars in revenue for us through partnerships with billions of dollars in revenue to come, and when priorities shift for partners, we often reclaim those programs, which allow us to further develop these assets for their strategic value. This year alone, we proactively reverted multiple programs from Takeda, GSK, and AbbVie, securing additional valuable programs for us to advance and to potentially partner these programs again in the future. Please turn to slide 15. Our strategic expansion includes focused licensing and acquisitions, particularly in Japan and APAC. Our acquisition of Idorsia's Japan and Korea businesses has rounded out our biopharma capabilities, and we now have $300 million in capital and are actively evaluating phase II and phase III opportunities in these regions to support our JPY 50 billion revenue target by 2030. Please turn to slide 16. We are taking a rigorous approach to business development. We've identified over 20 potential product opportunities, each with peak sales potential between JPY 15 billion and JPY 50 billion, with a subset of these product opportunities advancing in contract discussion. We maintain very strict investment criteria but remain confident in securing new product opportunities in the midterm. Please turn to slide 17. We've evolved a discovery-focused company into a fully integrated biopharma, building a business that is not only growing in Japan and APAC, but that will also expand globally with our NxWave discovered products. Please turn to slide 18. In summary, our vision is bold, and our mission is simple. Be bold, act fast, and accelerate medicine. We've made exceptional progress this year, but we're not finished yet. Thank you very much for your time today. I'll now hand over to Dr. Sugita Makoto, our new Chief Medical Officer, to discuss our programs in Japan. Thank you. All right. Chris, a lot of thanks. Thank you, Chris. I joined this October 1st. My name is Makoto Sugita. I am Chief Medical Officer of Nxera Pharma, and I also serve as the President of Nxera Pharma Japan. Today, I would like to explain why we consider the Japanese market as critical, and I would like to talk about the growth up to now about PIVLAZ, which is already launched. And also, lastly, I would like to talk about QUVIVIQ immediately before launch after approval. Please move on to the next page. First of all, the Japanese market is a huge and attractive pharmaceutical market. Not only that, it serves as the base to expand across APAC. In terms of the market size, excluding China, it is the second largest market after the U.S. Japan is not the only large in market size, but it has established regulatory structure comparable to FDA and EMEA, and Japan's phase I drug clinical trials are no longer needed for global clinical trials. Expansion framework for rare disease designation, and furthermore, NDA submission in English began. Tailwinds from the near-term regulatory changes are expected. Japanese government's measure toward resolution of drug lag and the recent drug laws continue, but furthermore, this July, the Japanese government, in the Drug Discovery Ecosystem Summit, said Japan will be a hub of drug discovery, contributing to people in the world. The government is committed to that and declared. It is known that Japan has conducted high-quality clinical trials, not to mention about high-quality commitment by medical institutions, ACPs, and on top of that, access by ACPs to evaluate new drugs is considered, and the speed of new drug penetration to patients is faster. After approval, within 60-90 days, a drug price is listed, and we have the wonderful system of UHC. If you take a look at the Asia-Pacific region, it has extremely diverse economies, cultures, and regulations, but it is the second highest-growth pharmaceutical market. Please move on to the next page. Let me talk about PIVLAZ, which was launched in 2022. This product's efficacy is basically to prevent ischemic symptoms and cerebral infarction and post-aSAH surgery cerebral vasospasm as a result of brain aneurysm. For aSAH caused by brain aneurysm, we used the method of coiling and clipping, but post-operative vasospasm was the complication and the challenge, so with PIVLAZ, lowering of the onset of vasospasm is possible, supporting the high level of operation by the Japanese neurosurgeons, and we are able to contribute to the patients. After one year from launch, we were able to surpass 50% of the market and have a steady trend. In 2024, in the market share, it reached 66%. On NHI-based sales, we are targeting for JPY 15-16 billion in revenue. Between 2022 to 2023, the revenue increased by 47% and 60% from 2023 and 2024. As you can see from the slide, PIVLAZ is rapidly penetrated, and it is becoming the de facto standard for post-operative cerebral vasospasm prevention. In terms of the forecast for revenue, we have slightly revised it downward from JPY 16 billion at the beginning of the year, but for the individual factors, Nomura will explain later on. Please move on to the next page. Next is the explanation on QUVIVIQ. This September, as a treatment for insomnia, MAH was obtained. First of all, before I talk about QUVIVIQ, I would like to talk about DORA. This drug is DORA, and this is the acronym for dual orexin receptor antagonist. To maintain awakening in the brain, orexin neurotransmitter plays a pivotal role. This orexin acts on type 1 and type 2 of orexin receptor. DORA inhibits both type 1 and type 2. It excessively inhibits excessively functioning arousal system and transitions the brain from arousal to sleep. This orexin was discovered by Japanese researcher Dr. Yanagisawa, and the Japanese researcher has played an important role. This originated from Japan. QUVIVIQ is the third insomnia treatment and participated in the market. Recently, this DORA in insomnia treatment rapidly established its position with existing DORA drugs. According to the NHI drug basis from 2019, it has been increasing over 10% every year. In the prescription frequency, it is increasing to close to 50%. As I explained, in the insomnia market, the DORA market is dramatically expanding. Japan, from the global point of view, it is evident that it is a main market for DORA. Please move on to the next page. Why QUVIVIQ is being the third DORA, yet best in class, and how can it contribute to the market needs? First of all, optimization is possible, and I would like to talk about the change of the business scheme of QUVIVIQ. According to the previous scheme, licensing was Idorsia, domestic MAH, sales and distribution was our company, Nxera, Mochida, Shionogi. Three companies were in charge and needed to cultivate part of the market as the company's own cost. Now the scheme is changed. MAH is Nxera, our company. Sales and distribution will be covered by Shionogi Pharmaceutical, and we will be receiving royalty from Shionogi. With that, three companies' two-channel scheme shifted to one exclusive company and one channel. Shionogi has the exclusive sales rights and is responsible for sales and distribution by a single company. With that, clearer strategy can be compiled and to deploy seamless strategy and tactics, deliver faster and appropriately to more patients. Please move on to the next page. Our QUVIVIQ, not only in the area of DORA, we will target for best-in-class in insomnia treatment. We have seen the launch of many insomnia treatments, but the unmet needs at the moment include nocturnal awakening and rapid sleep onset carry-over effects to the next day. Going forward, the improvement of quality of sleep, easy onset of sleep, no carry-over effects to the next day, and daytime function recovery will be critical. QUVIVIQ for a neuropeptide-inducing awakening orexin receptor type 1 and type 2, it does suppress and bond is selectively inhibited. That is kind of DORA is QUVIVIQ. According to European insomnia guidelines, in short- and mid-term insomnia treatment, it is recommended as the only usable drug as ORA. So, from PK perspective, after administration, Tmax, peak blood concentration is 0.5-1.4 hours, and the drug half-life time for blood concentration to have is 6-9 hours. From immediate sleep and carry-over effects to the next day, it has the desirable profile as insomnia treatment. Dr. Teshirogi of Shionogi says that it's the most favorable orexin, and balance between safety and efficacy is extremely good. And he did mention that in the financial results meeting last month on the 28th, QUVIVIQ is considered to be the solution for the current unmet needs. So please accept for this product. That concludes my presentation. Now, Matt, over to you. Thank you, Sugita-san. And good evening, everyone. My name is Matt Barnes, and I'm the President of Nxera Pharma U.K. and Head of R&D, and I will present our recent progress from the U.K. Please turn to the next slide. So, this slide is a summary of our key milestones to date in 2024, which range broadly across all aspects of the R&D pipeline. In the early phases of research, we have entered a new partnership with PrecisionLife to identify new drug targets in autoimmune disorders, which I will talk about later. We've achieved a milestone payment in our collaboration with AbbVie in the neurology area. We've transitioned two programs into our internal discovery phase and completed the reversion of our GPR35 agonist preclinical candidate from GSK. In the clinical phase from our in-house pipeline, we've initiated a phase I study with NXE-744 for IBD in March and also signed an option to license agreement with Boehringer Ingelheim for our GPR52 program in schizophrenia. From our partner pipeline, we are extremely pleased to see three significant milestones in our highly successful partnership with Neurocrine around a suite of muscarinic agonist programs for schizophrenia and other neuropsychiatric disorders. These included the completion of a successful long-term toxicology assessment and phase II study in schizophrenia with NBI-568, an oral selective M4 agonist. In addition, we were also pleased to see NBI-567, an M1 oral preferring agonist discovered by Nxera, enter into phase I trials in May. And finally, on this slide, we were also encouraged to see the progress Centessa have made with ORX750, a selective OX2 agonist for narcolepsy, as it entered phase I trials in May this year. So, in summary, we've made excellent progress on both our internal and partner pipeline broadly across all phases of R&D. Please turn to the next slide. So, this slide is just to remind you that our focus centers on GPCR targets, the largest family of drug targets. GPCR-based drugs account for a significant proportion of all FDA-approved therapies, underscoring their importance. GPCRs have applications across many diseases, providing a powerful basis for developing first or best-in-class medicines. The opportunity here to deliver substantial therapeutic advances remains compelling. Please turn to the next slide. So as Chris mentioned previously, our approach to developing GPCR-targeted medicines utilizes our NxWave platform, which involves a five-step process aimed at optimizing every stage of drug development. Firstly, in order to identify the right target, we spend significant time in the early phases of drug discovery to ensure there is a convincing mechanistic link between target and disease, that the target is tractable, that the target is commercially attractive in our therapeutic areas of interest, and can be experimentally validated. When we use our world-leading platform to generate NxStaR proteins, NxHits, and employ NxDesign to support our structure-based drug discovery approach to identify high-quality candidate molecules, which when combined with our translational medicine capabilities ensures the right drug and clinical trial design. This approach has been extremely productive over the years, leading to the identification of 26 preclinical and 17 clinical candidates to date. Please turn to the next slide. Our pipeline is designed to bring innovative therapies to market across several therapeutic areas, and you've already heard from Sugita-san how we are doing this with PIVLAZ and QUVIVIQ. In-house, we have over 10 programs in the discovery and preclinical stages, with three promising programs, two first-in-class GPR52 agonist, EP4 agonist, and one best-in-class EP4 antagonist progressing through phase I. Additionally, we have multiple active partnerships, including nine clinical stage programs, bringing the total number of clinical programs we have ongoing to 12. These partnerships, such as with Neurocrine and Centessa, enable us to accelerate our drug discovery and expand our reach in the therapeutic landscape. I will discuss these collaborations in more detail on the next slide. So firstly, on Neurocrine, let's look briefly at the historical development of muscarinic M4 receptors. Research into muscarinic receptors dates back to 2008, with initial clinical evidence of xanomeline supporting M4 agonist efficacy in treating schizophrenia. Since then, M4 receptor agonist projects have advanced considerably, reaching important milestones. Phase two positive data from KarXT in 2019 and subsequent phase III results and FDA approval underscore the potential of M4 agonists in treating schizophrenia, alongside phase I-B positive data from Emraclidine and M4 PAM. Nxera Pharma's interest in M4 began in 2012, and what was to become NBI-568 was then partnered with Neurocrine in 2021, alongside a suite of muscarinic receptor agonist programs. Neurocrine has published the most recent phase II positive data supporting the role of M4 in schizophrenia on NBI-568, and I will highlight some of the key outputs from this study in the next few slides. Please turn to the next slide. So highly selective M4 agonists represent a novel approach to treating dopamine-related disorders. This is possible because M4 receptors are thought to modulate dopamine activity without involving the D2 receptor, which is a common target in traditional antipsychotics and also associated with common adverse events. This selectivity is thought to allow M4 agonists to control dopamine synthesis and release while potentially reducing side effects seen in D2 targeting drugs such as motor and metabolic complications. However, this selectivity also presents a challenge as some compounds like KarXT show activity at M2 and M3 receptors, leading to additional cholinergic side effects. An additional challenge is to ensure broad utility across a range of neurological indications, including those where acetylcholine levels are diminished and where PAMs would be predicted to be less efficacious. To address this challenge, Nxera focused on developing highly selective orthosteric M4 agonists using structure-based drug discovery, which offers a pathway to precision targeted therapies, resulting in what we see today as NBI-568, which was progressed into phase II clinical trials in schizophrenia by Neurocrine. Please turn to the next slide. So this slide outlines the design of this phase II clinical study, which set out as a dose range finding and early efficacy study in schizophrenia. Prior to this study, there were already a number of data points supporting a predicted human efficacious dose of 20 milligrams, including preclinical data and phase I clinical data with EEG and CSF exposure, providing confidence in the predicted human efficacious dose. The phase II study was a six-week dose range finding study in schizophrenia patients with the objective to explore different doses and different dosing regimens with and without titration based on a once or twice-a-day administration. The excellent drug-like properties of NBI-568 really supported exploring a broader range of doses above that predicted efficacious 20 milligram dose that previous M4 competitor molecules was difficult to do. Please turn to the next slide. Please turn to that. Thank you. The results demonstrated a clinically meaningful and statistically significant efficacy at 20 milligram once daily dose with significant reduction in the PANSS score, which is widely used to assess schizophrenia symptoms from as early as week three, and a PANSS total effect size comparable to other known muscarinic programs and antipsychotics. Differences when adjusting for placebo are reflective of the placebo effect size for this study, which is similar to those anticipated in phase III studies. Please turn to the next slide. Importantly, with respect to safety and adverse events, NBI-568 was generally safe and well tolerated at all of the doses tested, with treatment emergent adverse events occurring in around 5% of patients, which was similar to placebo. Some of the adverse events associated with this class of receptor have been clinically associated with a range of dose-limiting adverse events, which has made drug development challenging as these are typically associated with peripheral cholinergic activity at the M2 and M3 receptors. So this low adverse event profile of NBI-568 is highly consistent with an improved muscarinic M4 selectivity versus xanomeline with respect to these GI adverse events, and there was also no weight gain relative to placebo observed in this study. Please turn to the next slide. So in summary, NBI-568 is well positioned for a phase III clinical study in the first half of 2025, which would be the first asset from Nxera Pharma U.K. to progress to phase III. It was shown to be highly effective after a 20-milligram dose comparable to competitor molecules, has the improved convenience of being dosed once daily with or without food, has good tolerability across all the doses tested, supporting good future compliance, and has the advantage of a broader potential therapeutic utility across multiple indications where selective M4 agonists may be effective. Please turn to the next slide. I would also like to take the opportunity to acknowledge the progress of ORX750 and orexin-2 selective agonists from Centessa into phase I clinical development in May this year. ORX750 was developed using our NxWave structure-based drug discovery platform. Furthermore, in September 2024, Centessa shared positive interim phase I data showing ORX750 as effective and well tolerated in acutely wake-promoting sleep-deprived volunteers. This was followed by promising preclinical findings on a second orexin 2 selective agonist, ORX142, which was presented at Sleep Europe in 2024 this year, which highlighted the compound's impact on sleep/wake regulation patterns. ORX750 is well positioned in the competitive OX2 narcolepsy landscape with a total potential market size of $5 billion in the medium term. Please turn to the next slide. Having provided a brief summary on our partner programs, I would now like to switch to some highlights from our internal portfolio. Firstly, I would like to start with our novel first-in-class clinical stage GPR52 agonist program to address positive, negative, and cognitive symptoms of schizophrenia. As previously mentioned, neuropsychiatry is attracting a lot of attention, and we are pleased to have a clinical stage asset in this space. The unique feature of GPR52 is based on the receptor's co-expression profile. GPR52 receptor is located on D2 dopamine neurons in areas of the brain, and its activation may provide a similar effect to D2 antagonists, offering a pathway to manage positive symptoms like hallucinations. In addition, GPR52 is also co-expressed with the D1 dopamine receptor in the prefrontal cortex area of the brain, suggesting that it could positively impact cognitive symptoms such as attention deficits. NXE'149 was developed using our NxWave platform, with the phase I study proceeding as planned. Human pharmacokinetic data is excellent and in line with our preclinical predictions. It has low variability, is approximately dose linear, and consistent with a once daily dosing profile. So we're really encouraged by this data. The multiple ascending dose parts of this study, including pharmacodynamic measures, are now ongoing. Please turn to the next slide. I would also like to provide an update on our GI targeted EP4 agonist program for inflammatory bowel disease, which is particularly exciting as it aims to address the unmet need for therapies that go beyond immune modulation to promote mucosal healing. In IBD, current therapies have a treatment ceiling where only about 40% of patients achieve satisfactory outcomes, and no current treatments directly repair the mucosal barrier. We are extremely pleased to announce in March this year that NXE-744, which was identified through our NxWave platform, commenced the first in-human phase I study in healthy volunteers. Dosing in the phase I study is progressing as planned, with the seventh SAD cohort underway and the third MAD cohort currently being dosed, with no concerning adverse events noted to date. Further activities to support phase Ib, phase II studies start are underway, including additional cohorts under this first-in-human umbrella. Please turn to the next slide. So our third program turning to our EP4 antagonist program, this is another promising area, especially in treating solid tumors, either alone or in combination with checkpoint inhibitors. Prostaglandin E2 or PGE2 is often found in the tumor microenvironment and binds to EP4 receptors to suppress immune responses, allowing tumor progression. By blocking EP4, we aim to restore immune function and potentially boost the effectiveness of checkpoint inhibitors, addressing the needs of patients who don't currently respond to checkpoint inhibitor treatment. With only about 20% of eligible patients benefiting from current checkpoint inhibitor therapies, there is a clear unmet need. By combining our EP4 antagonists with these checkpoint inhibitors, we expect to enhance the immune response, providing new hope for cancer patients through a more robust and lasting treatment. Please turn to the next slide. So based on this hypothesis, we set out to use our NxWave structure-based drug discovery platform to generate a selective EP4 receptor antagonist and identified NXE-732 as our clinical candidate. This candidate emerged from a rigorous discovery process, starting with an extensive big data pattern and literature analysis, followed by computational homology modeling to guide hybrid scaffold hopping, which resulted in a high-quality initial lead compound, NXE'309, which had good potency and ADME properties but required some refinement on selectivity. Through further use of structure-based drug discovery, our team was able to further optimize and enhance the selectivity of this lead series, with supporting structural biology confirming the binding mode was differentiated from competitor molecules, and this resulted in the clinical candidate NXE-732, as shown in the slide. Please turn to the next slide. NXE-732 shows an excellent profile with high potency against its primary target EP4, with more than 5,000-fold selectivity over other EP4 family receptors. It has a clean in vitro safety profile, potential for low-dose once daily administration, and its pharmacokinetic profile has been robust across multiple species, demonstrating low clearance and long half-life, features that improve patient convenience and adherence. Our simulations predict that a low dose, less than 100 milligrams, once daily administration should be sufficient to achieve effective trough levels and improvement over previous treatments like Eisai's E7046, which required significantly higher doses. These characteristics position NXE-732 as a potentially best-in-class treatment with a lower dose burden for patients. Please turn to the next slide. In preclinical models, NXE-732 has shown a strong synergistic effect with the PD-1 checkpoint inhibitors in reducing tumor growth. In the CT26 syngeneic model of colorectal carcinoma, combining EP4 antagonists with an anti-PD-1 antibody produced a durable anti-tumor response and even longer-lasting immunological memory against tumor recurrence. This combination approach offers a promising path forward in immuno-oncology with the potential to enhance checkpoint inhibitor efficacy and provide durable responses even after treatment completion. This strong synergy highlights EP4 antagonist potential in future cancer treatments, especially for patients who are checkpoint inhibitor resistant. Please turn to the next slide. And so this is the last slide on EP4 antagonists. So following a collaboration with Cancer Research U.K., NXE-732 was progressed into phase I/II- A clinical trials in 2023, and this is currently ongoing across cancer centers in the U.K. The initial phase of the trial involves a monotherapy escalation arm, which has been completed without any dose-limiting toxicity, and a combination escalation arm with atezolizumab, a PD-L1 checkpoint inhibitor, which is also just recently completed. Further details of the trial design were presented by CR U.K. at the European Society for Medical Oncology in September. Pharmacokinetics observed to date are in line with our predictions and exhibit general dose proportionality across all doses tested. We have observed target engagement at all dose levels tested, and additionally, an additional pharmacodynamic analysis is underway, and preparation for the phase II study is now ongoing. So lastly, in this section, I would also like to provide a short update on our platform innovation growth. So we are focused on employing two parallel and scalable approaches, namely in silico and phenotypic screening, to enable us to systematically identify next-generation GPCR drug targets across various diseases. For the in silico approach, we use machine learning and big data to analyze molecular disease signatures and discover potential drug targets in stratified patients by specific biomarkers. This approach supports broad disease applications and enhances scalability. Our partnerships with PrecisionLife and Intelligent Omics enable us to harness this data-driven method across multiple indications. For phenotypic screening approach, we use disease-specific functional assays to screen a curated compound library targeting approximately 270 GPCRs. This method identifies functional responses directly related to disease, an approach already successful in IBD with Kallyope as a partner and under exploration in neurological conditions. So together, these methodologies allow us to identify new tractable drug targets effectively and efficiently. Please turn to the next slide. So to provide some more context on PrecisionLife, our partnership brings advanced genetics to our discovery platform, focusing on autoimmune disorders initially with plans to expand into additional complex diseases. This collaboration is designed to uncover novel GPCR drug targets and patient biomarkers in heterogeneous populations, such as those with rheumatoid arthritis. PrecisionLife's combinatorial analytics identify non-linear gene interactions, giving us unique insights into disease biology and allowing us to create biomarker tools for refined clinical trial design. This mechanism-driven approach enables us to tackle complex multi-gene diseases like rheumatoid arthritis and CNS disorders and other autoimmune conditions, and it's a highly scalable strategy with potential applications across over 50 diseases. Please turn to the next slide. So in addition to GPCRs, I also wanted to update on our progress utilizing our structure-based drug discovery approach to other integral membrane protein target classes, such as ion channels and transporters, which I have mentioned previously. So by producing high-quality protein reagents for structural studies, we've successfully generated multiple high-resolution Cryo-EM structures of ion channels and transporter proteins, which has allowed our NxWave platform to deliver atomic resolution structures where we can identify unique binding modes of small molecules at all of these drug targets as depicted in this slide. This really sets us up to start thinking about these other integral membrane proteins as new drug targets in the future. And then next, please turn to the next slide. So this is the final slide. So lastly, I just wanted to highlight a collaboration that we have just announced with Antiverse, which Chris mentioned earlier, to design the next generation of antibody therapeutics against GPCRs. Antibodies present an exciting opportunity targeting GPCRs by offering potentially high specificity and sustained target occupancy than other modalities, and our NxWave platform has been previously utilized in successful discovery of therapeutic antibodies. In this particular collaboration, we are going to use our NxWave platform combined with Antiverse's AI de novo Antibody Design Platform, which enables the rapid design of antibodies with tailored properties at scale. This is a potentially multi-target partnership and licensing agreement to target diseases of high unmet need, and the first project is aimed at designing agonist antibodies against a challenging GPCR target, so in summary, we've seen significant progress across all aspects of the in-house and partnered R&D pipeline, and that concludes my section from Nxera Pharma U.K. Research and Development in 2024 to date. I will now pass over to Nomura-san. Thank you. ありがとうございます。それでは。 Thank you, Matt. それでは最後に3級決算について簡単にご説明をいたします。 I will now conclude with a brief overview of Q3 financial results. This slide, 52, shows a summary of the cumulative financial results from Q1 to Q3 FY 2024. The green area on the upper half shows changes in revenue and its breakdown, and the orange area on the lower half shows changes in operating profit and loss. Revenue grew significantly to JPY 21.9 billion compared to JPY 5.4 billion in the same period last year. This is mainly due to the fact that the product sales shown in dark green sales increased and also contributed for the full year, whereas last year it only contributed for about six months after the acquisition, and milestone grew significantly as a result of R&D progress. In terms of operating profit and loss, orange part, both core operating profit and IFRS-based operating profit and loss have improved year on year, which is due to sales growth as well as cost efficiencies, which will be explained later. Next slide, please. This slide shows the profit and loss for each business unit and the difference between the core operating profit and IFRS-based operating profit and loss. In the first nine months year to date, we were able to turn profitable on the core operating profit basis for both the U.K. R&D business shown in blue on the left and the Japanese commercial business shown in red to the right. Core operating profit shown in dark green totaled JPY 4.4 billion. From there to the IFRS-based profit are the one-off or non-cash, non-core costs shown in the right half, which are divided into four categories from A to D. I will not explain these in detail today, but the pink part, A through C, are related to last year's acquisitions, and in particular, A, PIVLAZ's inventory adjustment, is an expense that will not be incurred from Q4 this year onwards. C is also expected to decrease significantly next year, and a total of about JPY 3 billion will naturally decrease from next year onwards without any action. Next slide, please. Let me explain the updated guidance for SG&A and R&D expenses for the fiscal year. As a separate discussion from the non-core expenses on the previous slide, we have reduced the guidance for R&D expenses shown in green by JPY one billion from a median of JPY 13 billion to JPY 12 billion, and reduced the guidance for SG&A expenses shown in orange by JPY four billion from a median of JPY 19 billion to JPY 15 billion. As a result, the total cost guidance has been reduced by JPY 5 billion. Next slide. This breakdown shows the reason for the decrease. Both R&D and SG&A expenses are beginning to show significant effects of the cost efficiencies associated with the PMI that we promised at the beginning of the year. We are consolidating two offices and separate investments into one and reducing investments that are not in line with our future strategy. In terms of SG&A expenses, costs have been reduced by switching the sales strategy of QUVIVIQ from in-house sales to outsourcing to Shionogi. In addition, PMI-related cost efficiencies are ongoing, so we expect the downward trend in SG&A to continue in 2025. Next slide, please. Finally, PIVLAZ's sales guidance was updated from the previous JPY 16 billion or more to between JPY 15 billion and JPY 16 billion, down by approximately JPY 1 billion. Although it is difficult to accurately forecast PIVLAZ's sales at this time due to the large Q4 sales, as noted on the right side, we expect a decrease of approximately JPY 800 million due to a 5% decrease in the actual aSAH occurrence in 2024 compared to previous years, and a decrease of approximately JPY 200 million due to the effect of optimizing year-end inventory for distributors. As explained by President Sugita, PIVLAZ is rapidly gaining market share of 66% and is establishing a firm position as a standard treatment in the provision of post-operative cerebral vasospasm, and we expect it to continue to grow. That concludes my presentation. Thank you very much for your attention. それではこのまま引き続きましてここから質疑応答に移らせていただきます。 We would like to move on to the Q&A session. Institutional investors, analysts, and the media, please use the raise hand function, and I will call out your name. Please unmute yourself when your name is called. We have simultaneous interpretation. We hope that your questions will be as succinct as possible. The other people, please use the Q&A button to submit your questions. We would like to respond as long as the time permits. Starting with the first person, Hashiguchi-san from Daiwa Securities, please unmute yourself and ask your question. Hashiguchi from Daiwa Securities, I have two questions. The first question is on page 16. License, and in order to obtain products, you are aggressively negotiating, and already seven have already at the term sheets or contracting stage. In contrast to your experiences, seven are in term sheet status. So, within one year from now, how many will ultimately result in the conclusion of the contracts or agreements? So that's the first question. Thank you very much. So first of all, we would like to ask Chris to respond to this question. Chris, please. Sure. Thank you, Hashiguchi-san, and thank you, Nomura-san. It's a very difficult question to ask because we're not specifically targeting to have a set number by the end of next year. It would depend on where we are successful. So for example, some of the assets that we are looking at are in the rare disease area, so therefore clinical development timelines shorter and the cost associated with development smaller. We can probably take on a few programs like that, but some of the opportunities that we're looking at are much larger and would require larger capital commitment, more clinical development timelines and costs, et cetera. And so we would have to balance out the requirements for resource against other potential product opportunities. So I'm not going to put a number on it. It's very much dependent on where we are successful. As I'm sure you are aware, when it comes to acquisitions or licensing, you can negotiate right up until the final point, and there's still no guarantee that you'll be able to successfully complete a transaction. So what I'm saying is I feel confident that we will be able to bring some new products in, but I'm not going to commit to a number, a certain number, because it depends on the type of program that we're able to license. Thank you. That completes my response. 私から一点だけ、ハシグサ様、ご報告をさせてください。 Chris, please allow me to elaborate one more point. This was mentioned by Chris, but for example, if we make compromise and if we try to sign, there are several out of these seven, but the Shionogi is one good example. From the beginning of the year, we were looking for a good distribution channel for QUVIVIQ, and the announcement took long until October 1st. I think that is your impression, but making compromise is very negative to the future of our company. So we feel that this is our growth driver. So I'm sorry that we cannot give our particular number, but I hope you understand that point. I just wanted to elaborate on that point. Yes, that's clear. Thank you very much. And moving on to the second question, EP4 antagonist competitive advantage. There are clinical stage compounds from other competitors, especially Ono Pharmaceutical product is making progress in cancer types, and they have a relatively large-scale phase II study. I think they have some in some of the cancer types. Against such advanced product, how are you planning to differentiate yourself? I would like to know that point. Thank you very much. I would like to ask Matt to respond to that question. Matt, can you respond to the question? Yes. Thank you very much for the question. So you're correct. So Ono BMS has a molecule which is slightly further ahead than us in phase II. So there is an ongoing study, I think, in gastric cancer and some plans for phase II in pancreatic and colorectal and non-small cell lung. In terms of differentiation, so I mentioned in one of my slides, we do have some understanding of the differences in the way that these compounds bind to the receptor. So we believe that ONO-4578 compared to NXE- 732. 732. So NXE- 732, we believe, binds deeper into the pocket of EP4 receptor. So that's actually more similar to the natural ligand PGE2. We also know that the Ono compound is more hydrophobic and has a higher molecular weight. And ultimately, we believe it's probably more difficult from a synthetic feasibility point of view. And so if you think about the bigger picture in terms of the developability of these compounds, we believe that NXE- 732 is more efficient. ONO-4578, really the structure of that molecule has only fairly recently been realized. And so actually comparing the molecules head to head is something that we could consider doing, but we've not really had a chance to do that because the structure has only recently become available. Thank you. Thank you very much. That responds to your question. Thank you very much. So we'll move on to the next questioner. UBS Securities, Sakai-san, please unmute yourself. Thank you. Yes. This is Sakai from UBS. I have two questions. First, NBI-568. Looking at phase II result, the market response, our response looking at the result was slightly disappointing. And what you showed today, there were some new data today. I understand this, but with this data, what kind of character in the market? 競合品と比較して。それは多分、ニューロクラインのフェーズ3のプロトコル. Neurocrine Phase III Protocol. Depending on how we look at that, I think we can make a judgment to a certain extent. Maybe you will say, please ask Neurocrine, but Phase III Protocol. Do you suggest Neurocrine or what kind of protocol you will structure? I would not say a secret trick. I know there's no secret trick in the clinical trial, but if you could give us some hint? When NXE-732 enters phase III at the early part of next year, we may be able to revisit our evaluation. So what do you think? Thank you very much. That is my first question. Thank you very much. So Matt, if you could answer that question, please. Yeah. Thank you for the question. So actually, you're probably right. So you should ask Neurocrine some of these questions. I mean, they were asked some of these questions in their financial results call around the phase III design. And quite rightly, they commented that they really need to have the end of phase II discussion with the regulators in the U.S. first. That's the first step. And then subsequently, depending on what the feedback they get from that will influence how they do their phase III design. These products are licensed to Neurocrine. Neurocrine are sponsoring the clinical studies. The clinical design will be their responsibility. It may be that we at some point might have some intellectual discussions around this particular design, but really this is Neurocrine's decision. And so I think they suggested that more detail on this would come out in February in their Q4 results. I think they said in their financial results call recently. So that's the point on the phase III design. Just to clarify as well, this is not new data that I'm showing here. This is actually data that was disclosed by Neurocrine in their financial results presentation and earlier in the year as well when they presented the phase II output. But I think that the point here, I think that is really, really clear to make is that our view is that NBI-568 is clearly in the same range as some of these competitor molecules in terms of the readout here, in terms of the total PANSS score. And there are some differences that I referred to in my presentation around the placebo-adjusted score. But we've highlighted there that there are differences in the placebo response across this study. So you really need to take that into consideration when you're looking to compare and contrast across these particular outputs. But we remain confident. We remain excited about what Neurocrine plans to do with this asset going forward into early 2025. Thank you for the question, Sakai-san. Yeah. Thank you for your answer. I mean, I said new data just to refresh my memory. So that's what I meant. I think. Sorry. It was the interpretation. Yeah. Thank you. Okay. So next question. Second question is GPR52. This is the dual agonist. And as you clearly stated here, it's a first-in-class mechanism and novel dual agonist. How do you come up with this technology, if you like? And this is an exclusive option right to Boehringer, right? Yeah. Yeah. Is that giving you a precious asset if you're giving this asset to Boehringer 100%? So that's my second question in two phases, please. Thank you. Thank you so much for the question. Yeah. So just to clarify, so this is not a dual agonist. So this is just a GPR52 agonist. The reason I refer to the D2 and the D1 dopamine receptors is based on the co-expression of GPR52 receptor in certain parts of the brain with either D1 or D2. We know by the way that the D1 and D2 receptors signal within neurons in the brain. We know that GPR52 can mimic some of the actions of D2 and D1. So what I'm trying to do here is give you some insight into how we think the GPR52 agonist is working relative to the effects of D1 and D2. So just to be clear, it's not a dual agonist. It's a single agonist. I hope that clears that up. And then to address your second point on Boehringer Ingelheim, so yes, we have an option to license agreement. So what that means is that they have paid us an upfront payment for the option to license at a later stage, which is likely to be towards the end of next year or the beginning of the year after. But that's very much dependent on the data that we're generating right now. You make a good point. So you could say that this is giving away a precious asset. But actually, the way that we look at this is that we're guaranteed a partner which has high, high credibility in the neuroscience space. I think our experience with Boehringer right now has been very, very positive. We think they're a really great potential partner to license this asset to as we move into phase II. Of course, at phase II, the costs start rising significantly. I think to have a partner there. I think for us right now is probably an appropriate place to be. The other thing that just to add is that even though we have an option to license agreement, we actually have regular communications with Boehringer Ingelheim. We're actually able to benefit from their experience and insight as we move forward in clinical development. We are gaining some additional intellect or reasoning as we move forward. That is another benefit, I think, to doing this type of arrangement. Thank you for the question, Sakai-san. Thanks for your clarification. Thank you very much. ありがとう。 ご質問ありがとうございました. Mr. Sakai, thank you for your questions. Now, we would like to move on to the next question, Citigroup Securities. Yamaguchi-san, please unmute yourself and ask your questions. Can you hear me? Yes. We can hear you. Thank you. Yamaguchi from Citi Securities. The first question is in the first part about the royalty fee above JPY 4 billion of QUVIVIQ, and that was targeted for 2030. And I'm sorry, I'm not quite sure, but were you disclosing the percentage of royalty? This is a simple question, so I will respond. We don't disclose. But the peak time revenue, was it JPY 30 billion or 40 billion? And from there, if we reverse our calculation, it seems like above 10%, but isn't that the case? Chris, can you respond to that question? Yeah, sure. I mean, I think the easiest way to summarize, we won't give the specific royalty rates, but yeah, we can definitely confirm that it starts in double digits and rises further into the double digits depending on the level of sales that our partner can achieve. If you look back at some of the commentary from Shionogi-san this week, you'll see that they are very much targeting achieving peak sales in line with the competitor molecules that are currently on the market. And if they do that, then it is our expectation that our net royalty will be very much above the JPY 4 billion that I've put there. That is a conservative estimate. And we can also generate, as we are responsible for supplying the finished drug product to Shionogi-san, there is also an opportunity for us to earn revenues from product supply as well. ありがとうございます。もう一つはちょっとごめんなさい。 Understood. And the next question is quite ambiguous. I'm sorry, but DeepMind is a subsidiary of Google, and I think they became the Nobel laureate. And the 3D simulation is now very simple. And the researchers, I believe, did mention that. And you do GPCR 3D, and you are the specialist. And that kind of technology to become common, is that positive for your company, or is it negative for your company? It's very difficult for me to understand. For your company, are you going to increase the efficiency by incorporating that technology, or is there a possibility of becoming a commodity for that technology to become more common? I'm sorry to ask such an ambiguous question. Thank you. So Matt, can you respond to that question? Yes. Please do not apologize for the question. Actually, that's a really, really relevant and important question. So of course, we're aware of DeepMind and the recent Nobel Prize around the AlphaFold technology. So, with AlphaFold, I think that this is a technology that allows you to predict the 3D structure of proteins. Now, of course, our platform is an experimental version of generating 3D structures of proteins. So here, there's a difference between modeling by computer or in silico and actually deriving experimentally. With AlphaFold right now, actually, we use AlphaFold methodology ourselves to complement some of the experimental work that we already do. So we actually feel that it's a useful tool sometimes in helping us determine the experimental structures. So for example, if we're trying to experimentally derive structures, sometimes you might not get quite the resolution in certain parts of the GPCR that you might like. We can use AlphaFold to supplement where there are sort of gaps in that resolution. We think that's a real advantage. If you were to completely rely on in silico predictions, that's actually quite difficult to do with GPCRs or integral membrane proteins in particular because they are dynamic proteins by their very nature. When a ligand binds to a GPCR, the whole GPCR changes shape. We need to really derive experimental structures to take into account some of that flexibility of the protein. I think if you try to predict that with the protein, it will likely come out with just a single or a couple of different conformations. It might not be quite as accurate as doing an experimental version of the structure. It'll be very interesting to see how the AlphaFold technology develops as we move forward. I'm sure it will improve as it goes forward. I hope that answers the question. Yeah. Great. Thank you. Thank you. Thank you very much. Hi, Yamaguchi-san. Thank you. We had similar questions from Zoom. So QUVIVIQ royalty percentage. Let me add some more information. Chris already answered, so I think you have the idea. But this week, Shionogi, JPY 20 billion revenue will be their target. So I think they said they will first aim for JPY 20 billion, and peak is JPY 4 billion or more. So if you could add those two figures together, I think you will get a good picture. So there were many questions on this, so I added some more information. Thank you. So moving on to the next questioner. Pathology Associates, Dion-san. Dion-san, please unmute yourself and ask your question, please. Can you hear me? Yes. Hi, this is Pathology Associates, Dion there. Can I just quickly ask regarding the decline in aSAH regarding PIVLAZ? What is behind that? One would expect the trend to be very constant, and I wonder if you can comment on that. And then this has now really been answered, but I think the market is very much behind the QUVIVIQ opportunity. And given the opportunity previously from Sanofi with Imovane and Sepracor with Lunesta, do you think Shionogi really has the capability? Are they really serious enough about this opportunity to drive this and spending what is needed and putting in place the resources needed to drive this opportunity? Thank you. Hi, Dion-san. A lot of questions. Thank you very much, Dion-san, for your question. So Sugita-san will talk about PIVLAZ, Daridorexant. And Chris, if you could add some more information if necessary. Thank you very much, Sugita-san. Thank you for the question. So aSAH occurrence, number of cases. There are multiple factors that come into play. Of course, in Japan, we have an aging society, but on the other hand, the total population is on the decline. And the health level of the aged elderly is improving. So the drinking and smoking situation is improving. So overall, various diseases are on the decline. In the question, there were some global warming that was mentioned. I think all these factors combined led to the decline. But going forward, as shown on this slide, I talked with some neurosurgeons. Among the patients who did not use before, there's still an opportunity that new patients will start using this anew. For example, elderly patients or the post-operative management is difficult. The patients' post-operative management can be improved by starting to use this anew. So from epidemiological factors, there may be some fluctuations, but in this area, we can expect to have a bigger market going forward. But we have to study on the right balance going forward. So that is about PIVLAZ. I hope this answers your question. Next, Daridorexant. QUVIVIQ. I did not talk about this until now, but compared to the previous drugs, half-life is shorter, and Tmax is faster. So the sleep onset is faster, and the carryover is lower. So if you could compare this to the carryover effect to the following day is more appropriate with our drugs. So we will be committed to this. Thank you. I hope this answers your question. Thank you very much, Sugita-san. Thank you. Thank you. Chris, do you have anything to add? Nothing much more. Dion, I think, as Sugita-san said, there is a declining, a flat to slightly declining trend in the total aSAH events. So our focus is really on just driving up the share of usage if we can. And I have absolutely no concerns regarding Shionogi as being the best partner for QUVIVIQ as well. We think that they are a terrific partner, and they've thrown a lot of weight and effort behind preparing for the launch of this product. And having an exclusive relationship with them does just make everything a lot easier. And we know that they're passionate about bringing new innovative medicines to patients in Japan, being a local Japanese company. And yeah, we're really happy with the collaboration so far, and we expect that it will be very successful. We're looking forward to demonstrating those results with them over the course of the next 12-24 months, which is pretty important from a launch perspective. Thank you very much. That completes my answer. Thanks. はい、ありがとうございました。それではちょっと時間も迫ってまいりましたので。 Thank you very much. We are running out of time, so we would like to pick up some of the questions from Q&As. So since the theme is Q and R&D, EP4 antagonists we are receiving many questions. So it has the partnership with CR U.K. for EP4 antagonists. In terms of the economics, what are the situations? Are you in a position to receive money from CR U.K., or are you supposed to pay? Or isn't it possible to do the licensing? Can Matt respond to this question? Yeah, thank you very much for the question. So maybe we can post the original press release with Cancer Research U.K. because there are some details in there which explain this. But in short, or in summary, Cancer Research U.K. are a nonprofit organization, so they are a charity in the U.K. So their aim is to try to help companies bring medicines to cancer patients. So actually, one of the reasons that we partnered with Cancer Research U.K. is because with large cancer studies like this, they can be quite costly and logistically and operationally, they can be challenging. And so partnering with Cancer Research U.K., we're sharing the spend, the investment in the clinical studies. And also, we're benefiting from their network of cancer centers in the U.K. So, there's lots of good reasons to partner with them. The other important thing to point out is that once the clinical study has completed, we actually still retain the rights to the compound. So we don't need to license it necessarily back from them or there's any payment or anything like that. So just to be clear that we'll have the rights to commercialize that product. Hope that's clear. Thank you. はい、ありがとうございます。おそらく大丈夫だと思います。我々が権利を持って。 Thank you very much. I think it's okay. We have the rights, and it is possible to relicense to mega pharmas. So that will be the direct question, direct answer to your question. We just have three more minutes. If possible, we would like to take two questions verbally. The first person is from Wakao-san from J.P. Morgan. Could you unmute yourself and ask your question? I have two quick questions. Muscarinic agonist 568. So, you will wait for the phase III result. So, the profile that you are seeing now, 568, efficacy is my first question. So, for safety. So one is that there is no gastric disorder. In the clinical trial, how big of a challenge could this be? What is your analysis? And in addition, regarding 568, safety. Dizziness was seen. So this is usually seen in the traditional drug. How can we evaluate that? So that is my first point. And second, P ositive Allosteric Modulator, PAM. Responder, non-responder, I understand. Is this a hypothesis or in the past clinical trial, responder, non-responder, is there data that insinuates or suggests responder and non-responder? Thank you very much. So, Matt, could you answer the questions? Matt, thank you. Yeah. So I think based on your question around safety, so just to be clear, so with KarXT, so that's a non-selective muscarinic agonist analogue. And so they're trying to block the peripheral cholinergic adverse events through M2 and M3 with trospium. So they're co-dosing two molecules, and they're doing that twice a day as well. And so inherently, that would suggest that you may expect to see some more variability in how that compound or that compound formulation is tolerated because you're relying on another compound to try and block that effect. And so I think we know now that the KarXT has been approved, and that's fantastic, I think, for schizophrenia patients to have this new mechanism. I believe that really the NBI-568 does offer a best-in-class opportunity here because it's a single molecule, and you can dose it once a day, and you can do it with or without food, and this safety profile that we observed here is an extremely important observation from this phase II study because it reinforces this hypothesis of selectivity of our M4 molecule. I know you touched on dizziness. Sometimes you see dizziness as part of neurological studies with neurological agents, and the fact that it's not really dose-dependent. I'm not sure there's too much concern around that in particular, and then I think to your point around PAM. I wasn't quite sure what you meant about responder and non-responder, but the way PAMs work versus orthosteric agonists is quite different, so PAMs depend on the levels of endogenous acetylcholine. In some particular indications like Alzheimer's disease, for example, you see this degeneration of cholinergic neurons that produce the acetylcholine. So if you think the PAMs are dependent on that acetylcholine to work, so if those neurons are being depleted, the chances of the PAM working become less obvious, I think. You don't have the same challenge with an orthosteric agonist. So that's why we see that broader potential therapeutic utility with an orthosteric agonist versus a PAM potentially. I hope that answers the question. Thank you. So the second half, there's no data in the schizophrenia, but KarXT was originally xanomeline, so it was difficult to be commercialized alone. Therefore, it was difficult to be commercialized alone. Therefore, it is now tested as two drugs and is now approved in the U.S. Our product has high specificity, so I think M4 is high, and so KarXT could not answer all the questions, and we have five more hands, and I feel bad to cut and close the session, but I would like to bring this session to a close for today. At a later date, we'll be answered on our blog. So if you have more questions, please write in the Q&A session. I think you can move to the questionnaire screen after this. So if you could write in your follow-up questions, we'd appreciate it. This will be posted on our IR website, including the presentation and Q&A session. Thank you very much for your attendance. We will now close Nxera Pharma 2024 R&D Day. Thank you.