Nxera Pharma Co., Ltd. (4565) Earnings Call Transcript & Summary

Welcome. So we will now begin the Financial Results Briefing of Nxera Pharma for FY 2024. Thank you for taking time over 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 Heptares and Head of U.K. R&D; and Dr. Makoto Sugita, Chief Medical Officer and President and CEO of Nxera Pharma Japan. Simultaneous interpretation is provided. Please click on the Earth icon in the lower right corner of the screen or click the Details button and then the Globe icon and select either Japanese or English. If you choose off, you'll 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 our website by selecting IR News from the Shareholders and Investors tab in the upper right corner of the website. For the Q&A session in the second half, 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 any time during the webinar and will be answered as time permits during the Q&A session later. So we will start the briefing. I will first explain the full year financial results, followed by an operational update from Chris; Japan and APAC commercial business by Sugita; and are R&D progress, mainly in the U.K. by Matt. Finally, Chris will explain our FY 2025 goals and medium to long-term objectives. Please turn to Page 5 of the presentation. This is Page 5. This is the summary of the financial results for the fiscal year-ending December 2024 divided into 3 parts: Revenue, profit, and cash. First, revenue increased 126% to JPY 28.8 billion, compared to JPY 12.8 billion in the prior year. Details will be explained later, but this is thanks to the fact that sales of PIVLAZ were strong and that it contributed for the full year in 2024, while it only contributed for 5 months after the acquisition in 2023. And also thanks to an increase in milestone due to the progress of many partnered programs. Next regarding profit, core operating profit increased by JPY 3.6 billion, compared to a loss of JPY 3.1 billion last year. This is thanks to the sales growth mentioned earlier, as well as the fact that R&D and SG&A expenses were both lower than the revised estimates as the integration progressed well. Also operating profit on accounting basis was a loss of JPY 5.4 billion, which is calculated by subtracting non-core expenses of JPY 9 billion. Of these non-core expenses, most of the M&A related non-recurring expenses in 2023, mainly additional cost of sales charge and integration costs were completed in 2024 and will not be carried over to 2025. Finally, cash decreased to JPY 36.2 billion, compared to JPY 49 billion in the prior year. This was mainly due to the advanced purchase of API of QUVIVIQ to ensure the stable supply in line with the launch. Moving on to Slide 6. The summary is explained in a bit more detail, showing the trends in revenue and its breakdown, operating profit, and core operating profit on the left, and the factors behind the increase or decrease from the same period last year on the right. One thing I should add from the summary is that, as you can see from the breakdown of milestone on the upper right, 2 milestone payments from Neurocrine in line with the development progress of M4, the success of the long-term toxicity study and the Phase II study of M4 contributed greatly. Next is Slide 7. Slide 7 shows the breakdown by business domain, as well as by core operating profit and accounting operating profit. As mentioned in the summary, the non-recurring costs associated with the acquisition of Idorsia Japan in 2023 specifically, A, the inventory adjustments, and C, integration costs shown in pink on the right side, ended in 2024 and will not be carried over to 2025. Including these non-core expenses for 2024 amounted to approximately JPY 9 billion, putting pressure on accounting profits, but the core operating profit for the entire group was JPY 3.6 billion. Next Slide 8. This slide shows our forecast for R&D and SG&A expenses for the fiscal year. R&D expenses are expected to be between JPY 12 billion and JPY 14 billion, a slight increase from the JPY 11.8 billion forecast for this year. The main factors behind the increase are the costs associated with the progress of development of our 3 in-house developed products that have entered clinical trials, EP4 antagonist, EP4 agonist and GPR52 agonist, as they move from Phase Ib to Phase II and the expected development costs in Japan and APAC through in-licensing. Regarding SG&A expenses, as the integration process has settled down and we have made progress in streamlining our expense usage, this will offset the increase in amortization of intangible assets due to the launch of QUVIVIQ and the increase in IT investment costs aimed at further efficiency. And we are aiming for a flat to slightly decreased level overall from 2024. That concludes my brief summary for the full year financial results. Chris will now update you on the business. Chris, please.

Thank you, Nomura-san, and good afternoon, everyone. Please turn to Slide 10. So it was a fantastic year of progress as we continue to invest to transform the company into one of Japan's leading biopharma companies. We achieved our full year sales target for PIVLAZ, a JPY 15.2 billion, beating our guidance set at the Q3 2024 results for sales greater than JPY 15 billion. We secured the on-time PMDA approval in Japan for daridorexant; brand name QUVIVIQ. And while we did not achieve an in-license of a new product in the financial year 2024, we remain active in multiple discussions with global partners to secure new products for Japan and APAC. We executed 2 new major partnerships. Boehringer Ingelheim paid for an exclusive option-to-license our GPR52 agonist program for schizophrenia. Shionogi became our powerful commercial partner in the successful launch of QUVIVIQ, a potentially best-in-class treatment for adults with insomnia. We initiated a new Phase I study for our wholly owned EP4 agonist program targeting IBD. And we launched a new brand concept for the entire company, Nxera Pharma, which was well received internationally. We've now completed all transitional service agreements with Idorsia and are now fully independent of Idorsia's supply chain, and financial and IT systems following the acquisition of Idorsia's businesses in Japan and Korea. Please turn to Slide 11. So across our core businesses, we remain extremely productive. We're accelerating investments in science and drug development to support our goal to build a high growth, high profit, emerging biopharma company for Japan. In the U.K., we continued to invest in the NxWave drug discovery platform to ensure we're the definitive leader at drugging GPCRs. And we're focused on developing drugs that target GPCRs in the largest areas of unmet need, such as neurology, metabolic disease, and immunology. It's a very exciting time to be at Nxera, as together with partners, we now have multiple programs advancing through the clinic. Of note was the successful Phase II study of NBI-568, by our partner, Neurocrine, which is a potentially best-in-class profile, muscarinic M4 agonist, fast-follower program for patients with schizophrenia. Following its successful end of Phase II meeting with the FDA in January, Neurocrine will move this program into a global Phase III study in the first half of this year. In Japan, PIVLAZ has firmly established itself as the leading product preferred by neurosurgeons for the prevention of cerebral vasospasm associated with aSAH. And furthermore, our second product, QUVIVIQ was successfully launched by our partner, Shionogi, in December 2024. QUVIVIQ rapidly became one of the most detailed products in Japan across December 2024 and January 2025, which validated our strategy to secure a powerful commercial partner to ensure QUVIVIQ is available to as many patients in the USD 1 billion market for dual orexin antagonist treatments in Japan. Please turn to Slide 12. As you can see on this slide, we have a broad and balanced innovative pipeline that's targeting some of the biggest areas of unmet medical need. Nxera Pharma is well advanced in its mission to accelerate innovative medicines to patients and become a leading player in Japanese pharmaceuticals. With 2 recently launched products driving stable top line sales growth plus a pipeline of innovative clinical stage programs, the risk-reward is very attractive. We have the upside potential of a biotech with the diversification and protection of a commercial pharma company. Please turn to Slide 13. So we are delivering on science with significant future commercial potential. In Japan, where our commercial business is now thriving, we prioritize focusing on diseases that truly matter in this region, such as age-related conditions and quality of life diseases. PIVLAZ and QUVIVIQ are both amazing products servicing diseases in this area. We're focused on recruiting the best team in the industry. And collectively, our colleagues have contributed to 9 Japanese NDA approvals in recent history. And we aim to stay lean and agile. We believe we're second only to Chugai in Japan when it comes to sales force efficiency, generating over JPY 400 million per sales representative annually in Japan. In the U.K., the hub of our research activities, we focus on the continued investment in our NxWave drug discovery platform to be the definitive leader in drugging GPCRs. We focus on innovating in areas that matter, especially neurology, metabolic disease, and immunology. And our partnered programs are exposed to some of the fastest-growing areas of healthcare such as muscarinic agonists for neuropsychiatry with Neurocrine, orexin agonist for narcolepsy and sleep disorders with Centessa, and oral small molecule GLP-1 agonist for obesity with Pfizer. In the next sections, my colleagues, Sugita-san and Matt Barnes, will provide more detail regarding the 2 products that we've recently commercialized in Japan and our most advanced programs in the clinic, including both partnered and wholly owned programs. Thank you, and over to you now, Sugita-san.

Thank you Chris. Thank you very much, ladies and gentlemen, for taking time out of your busy schedule to attend today. I'm Makoto Sugita. As of October 1st, last year, I assumed the position of Chief Medical Officer at Nxera Pharma, Inc. and concurrently serve as the President and CEO of Nxera Pharma Japan, Inc. Today I'd like to provide you with an update on the latest developments in our commercial business in the Japanese and Asia-Pacific markets, focusing on the market growth of PIVLAZ and QUVIVIQ as well as our future plan. Now let me begin the presentation. Next slide, please. Let me introduce PIVLAZ, one of our key products. PIVLAZ is an endothelin A receptor antagonist developed to suppress cerebral vasospasm following surgery for subarachnoid hemorrhage caused by cerebral aneurysms. By doing so, it helps prevent secondary complications such as cerebral infarction and ischemic symptoms. Currently, surgical treatments for cerebral aneurysms such as coiling and clipping are widely performed. However, postsurgical complications due to cerebral vasospasm remain a major challenge that significantly impacts treatment outcomes. PIVLAZ was specifically developed to address this issue by reducing the risk of postoperative vasospasm. In doing so, it supports neurosurgeons in their treatment efforts and contributes significantly to improving patient outcome. Market growth and sales performance of PIVLAZ. Since its launch in 2022, PIVLAZ has demonstrated steady growth, last year achieved a market share of 69%, and we expect this to exceed 75% by 2025. Sales have also expanded steadily with a 47% increase from 2022 to '23, and 14% increase from 2023 to '24. With this continued growth in both market share and revenue, we are targeting sales of JPY 13 billion to JPY 14 billion in 2025. Moving forward, we will strive to reach more patients and promote broader adoption in medical institutions. Now the NHI-based revenue will be shown on net basis or revenue basis going forward. So the numbers will be different going forward. So please take note. Now to further accelerate the growth of PIVLAZ, we're implementing 3 key strategic initiatives, enhancing medical information dissemination. We will strengthen educational activities for neurosurgeons by leveraging clinical data, promoting the appropriate use of PIVLAZ, and expanding adoption across more medical institutions. Next is further expanding -- expansion of market share. While PIVLAZ has already secured over 70% market share, we aim to exceed 75% by 2025. To achieve this, we will deepen our collaboration with medical institutions and expand our network to ensure continued market penetration. Lastly, improving profitability and ensuring sustainable growth. By optimizing our sales strategy and maintaining competitiveness, we aim to build a solid foundation that supports long-term market growth. As demonstrated, PIVLAZ is accelerating its market penetration, while maintaining stable revenue growth, establishing itself as a leader in the neurosurgical field. With our 2025 revenue target of JPY 13 billion to JPY 14 billion, we will continue to drive market expansion and strengthen our leadership in this sector. Next slide, please. Next is QUVIVIQ for insomnia. Let me first explain the mechanism of action of QUVIVIQ. QUVIVIQ is an insomnia treatment classified as dual orexin receptor antagonist, DORA. Orexin is a neurotransmitter that plays a crucial role in maintaining wakefulness in the brain, keeping the brain in the state of alertness through its interaction with the orexin receptor types A 1 and 2. DORA works by simultaneously blocking both of these receptors, thereby suppressing the excessive wakefulness system and promoting natural sleep. This makes QUVIVIQ a new type of insomnia treatment. Next is market growth and expansion of QUVIVIQ. QUVIVIQ entered the market as the third DORA insomnia treatment. In recent years, there's been a rapid market shift in Japan from benzodiazepine and Z-class insomnia treatments to DORA medications. The market data clearly shows this growth. The growth trends of DORA-based insomnia treatments in Japan are as follows. Since 2019, the market for the 2 existing DORA drugs have grown by over 10% annually. The prescription rate for DORA drugs has now reached nearly 50% with further increases expected. The domestic market size in Japan is projected to reach approximately USD 10 million. As such, the market share of DORA medication in the insomnia treatment market in Japan is rapidly expanding. And Japan's importance as one of the key markets for DORA globally is growing. Nxera Pharma has formed a strategic partnership with Shionogi & Co., and we are working together to make QUVIVIQ the best-in-class treatment. We're accelerating its market launch with this partnership. By implementing this appropriate marketing strategies and strengthening collaboration with healthcare professionals, we aim to further drive the growth of DORA market and evolve QUVIVIQ into a leading product in this space. Next slide, please. The growth of QUVIVIQ is not limited to the Japanese domestic market. We are currently actively expanding into Asia-Pacific market. In Japan, through our partnership with Shionogi & Co., Ltd. we've built a system that can address over 20 million insomnia patients. Since its market launch, QUVIVIQ has steadily increased its recognition in Japan and along with the growth of the overall DORA market, further market expansion is expected in the future. In South Korea, we are progressing with partnership with local companies, and clinical trials are progressing smoothly, with a market launch targeted for 2027. With more than 6.5 million insomnia patients in South Korea, there is significant market growth potential. Currently, our partnership is in the form of development cooperation, but we will continue to consider strategies for sales and marketing going forward. And we are also in discussion with several potential partners in other Asia-Pacific markets, and we are committed to building optimal strategies tailored to the unique characteristics of each country to ensure steady market expansion. As shown, our company is not only focusing on the Japanese market but is also actively expanding in the Asia-Pacific region, building a system to reliably deliver QUVIVIQ to patients who need it. We will continue to strengthen collaborations with our partner companies and develop market-specific strategies to drive the growth of the DORA market, clearly differentiate QUVIVIQ from our DORA products and achieve sustainable revenue growth. Through these efforts, we will strive to provide sustainable corporate value to our shareholders. This concludes the report on QUVIVIQ's expansion strategy in the Asia-Pacific market. I'll now proceed with an explanation of our 2025 revenue targets and future growth strategies. In my last slide, I will explain the sales growth of our key products, PIVLAZ and QUVIVIQ and 2025 revenue targets. So our target for 2025 fiscal year, PIVLAZ, JPY 13 billion to JPY 14 billion; QUVIVIQ, JPY 4 billion to JPY 5 billion. To achieve these targets, we will focus on 3 pillars. One, expanding market share. Two, optimizing sales strategies. And 3, accelerating growth in the Asia-Pacific market. These initiatives will ensure steady growth toward our revenue goals. PIVLAZ has consistently grown in the market, while QUVIVIQ is now at a crucial stage. We're building a solid foundation for its future growth and expansion is key. PIVLAZ is achieving stable market share expansion and revenue growth. QUVIVIQ expanding from the Japanese market into Asia-Pacific region, achieving the 2025 revenue target of total JPY 17 billion to JPY 19 billion. We are committed to providing innovative treatments that contribute to improving patients' quality of life, while also driving further market growth. We also promised to continue enhancing corporate value for our shareholders. Next, R&D progress will be explained by Dr. Matt Barnes. Matt?

Yes. Thank you, Sugita-san. Good afternoon, everybody. My name is Matt Barnes. I'm the President of Nxera Pharma U.K. and Head of R&D. 2024 has been a year of significant achievements with substantial progress across our portfolio and the achievement of significant milestone payments from key partnerships. So let's begin with an overview of our accomplishments. Please turn to the next slide. So as I mentioned, 2024 has been a transformational year for Nxera Pharma U.K., marked by major milestones across all aspects of our R&D portfolio. In the clinical phase from our partner pipeline, we were extremely pleased to see 3 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. We were also excited to see the progress of Centessa made with ORX750, a selective OX2 receptor agonist for narcolepsy as it entered Phase I trials in May this year, and on the back of encouraging data subsequently into a Phase II study in November. From our in-house pipeline, we initiated a Phase I study with NXE-744 for inflammatory bowel disease in March. And also at the end of the first quarter, we were proud to announce our collaboration with Boehringer Ingelheim to progress our first-in-class novel GPR52 agonist for the treatment of schizophrenia. I will talk more about these important programs on subsequent slides. In the early phases of research, we have strengthened our AI-driven approaches through strategic partnerships with PrecisionLife to identify novel autoimmune disease targets and with Antiverse to design novel GPCR-targeted antibody therapeutics using generative AI. We also achieved a milestone payment in our collaboration with AbbVie in the neurology area, transitioned 2 new projects into our internal discovery phase and completed the reversion of our GPR35 agonist preclinical candidate from GSK. So these milestones underscore the success of our strategic approach, progressing high-value programs at pace, while leveraging partnerships to maximize innovation. Please turn to the next slide. So our collaboration with Neurocrine Biosciences has enabled the development of one of the most comprehensive muscarinic receptor agonist portfolios in the whole industry. The lead program, NBI-568, an M4 selective agonist, has now completed Phase II trials in schizophrenia, demonstrating promising efficacy and safety. This success paves the way for Phase III initiation in the first half of 2025 as well as exploring an additional indication, bipolar mania in Phase II in second half of 2025. Beyond NBI-568, the broader muscarinic agonist portfolio is progressing well. NBI-570, a dual M1/M4 agonist is advancing to Phase II trials in schizophrenia in the second half of 2025, while NBI-567, the M1 agonist, is currently in Phase I development with further data expected later this year. So with multiple assets advancing in this space, we believe Neurocrine are enabled to deliver innovative therapies that redefine the treatment landscape for neurological and psychiatric disorders. Please turn to the next slide. So 2 additional exciting partnerships we have are also with Centessa and Pfizer. Centessa's ORX750, an orexin-2 agonist discovered using our NxWave platform, has now entered Phase II trials for narcolepsy and idiopathic hypersomnia with data expected across all these indications in 2025. This compound is positioned as a potential best-in-class therapy addressing critical unmet need in sleep disorders. Similarly, we were encouraged to hear Pfizer commenting at JPMorgan Healthcare Conference that they were all in on oral small molecules for metabolic disease. Pfizer's PF-522, an oral GLP-1 receptor agonist for Type 2 diabetes and obesity, and discovered by Pfizer using the NxWave platform, continues to advance in Phase I, further reinforcing the versatility of our structure-based drug discovery approach to generate high-value assets that translate into the clinic. These partnerships are key to our strategy, leveraging our cutting-edge platform while maximizing value through collaborations with industry leaders. Please turn to the next slide. So now focusing on our in-house programs, which continue to make significant progress with a growing impact on global healthcare. Our pipeline spans multiple therapeutic areas, including neuroscience, immunology, and oncology, positioning us as a key player in the development of next-generation treatments. We are focused on pioneering breakthrough therapies that address substantial unmet medical needs. Our internal assets, including NXE-149, 732, and 744 target a range of critical diseases from schizophrenia to inflammatory bowel disease and cancer. And over the next few slides, I'll provide a detailed update on these key programs currently advancing through clinical development that have made significant progress since the last update at our R&D Day in October. So our innovative GPCR-targeted therapies combined with our structure-based drug discovery platform continue to drive scientific and commercial success. Please turn to the next slide. So for GPR52, NXE-149 is a first-in-class GPR52 agonist, that's designed to address the full spectrum of schizophrenic symptoms including positive, negative, and cognitive impairments. And this program represents a novel non-dopaminergic approach to treatment. As previously mentioned, neuropsychiatry is attracting a lot of attention, and we're pleased to have a clinical stage asset in this space. The unique feature of GPR52 is based on its receptor's co-expression profile. GPR52 receptor is located on D2 dopamine neurons in the brain and its activation may provide a similar effect to D2 antagonist, which is the target of atypical antipsychotics, offering a pathway to manage positive symptoms like hallucinations. In addition, GPR52 is also co-expressed with D1 dopamine receptor in the prefrontal cortex suggesting that it could positively impact cognitive symptoms such as attention deficits. So we have now completed initial Phase I studies and confirmed an excellent pharmacokinetic profile in line with preclinical predictions with low variability, dose linearity, which is all consistent with a once-daily dosing profile. We are really encouraged by this data, and so we're now conducting Phase Ib studies to determine proof of mechanism by utilizing a pharmacodynamic endpoint to confirm GPR52 activation in the brain. So given the persistent need for safer and more effective treatments beyond traditional dopamine targeting antipsychotics, we anticipate significant market interest in this program as it approaches Phase II. Next slide, please. So now turning to NXE-732, which is a selective EP4 antagonist designed to enhance immune checkpoint inhibition in oncology. With checkpoint inhibitors benefiting only a subset of patients, there is a pressing need for combination strategies that improve response rates. Prostaglandin E2, PGE2, often found in the tumor microenvironment binds to EP4 receptors to suppress immune responses, allowing tumor progression. So 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 this type of treatment. The Phase I/IIa clinical trial is being carried out by Cancer Research U.K. Both monotherapy and combination with checkpoint inhibitor arms are near completed with no dose-limiting toxicities, good pharmacokinetic profile, and early data suggesting positive target engagement. These data all support a recommended Phase II dose decision in March, and the initiation of the actual Phase II study in the second quarter of 2025, positioning NXE-732 as a potential best-in-class immuno-oncology therapy. As the Phase I study is directly in cancer patients, the data we can expect in the second half of 2025 will likely include pharmacokinetic data, safety data plus biomarker data in the blood as well as in the tumor by way of T-cell infiltration, which is an important marker of stimulating the immune system to attack the tumor, which will be very useful in correlating with any reports of stable or partial responses in terms of efficacy. Please turn to the next slide. So in my final slide, I would like to provide an update on our GI-targeted EP4 agonist program for IBD, which is particularly exciting as it aims to address the unmet need for therapies that go beyond immune modulation to promote mucosal healing. In inflammatory bowel disease, current therapies have a treatment ceiling where only about 40% of patients achieved satisfactory outcomes and no current treatments directly repair the mucosal barrier. We were extremely pleased to announce in March last year that NXE-744, which was identified through our NxWave platform, commenced the first-in-human Phase I study in healthy volunteers. Our Phase I trials progressed well with the 5th multiple ascending dose cohort now complete with no concerning adverse events noted to date. So next steps in the clinical protocol will be focused on demonstrating target engagement and supporting the generation of a Phase II enabled data package, which is on track for the second half of 2025. So given the significant unmet need in inflammatory bowel disease, NXE-744 has the potential to establish a new standard of care. So that concludes my R&D update from both our partnered and in-house programs from Nxera Pharma U.K. I'll now hand over to Chris to finish with our high-level view for 2025. Over to you, Chris.

Thank you, Matt. Please turn to Slide 28. So looking ahead for the next 12 months, these are our priority objectives. So we aim to achieve combined sales of more than JPY 17 billion from the 2 recently launched products in Japan. We will strengthen the late-stage pipeline in Japan by securing at least one new late-stage medicine. We're going to execute at least one new major partnership and initiate at least one new wholly owned Phase II program. We'll be continuing investment in systems and applications for efficiency and scalability. And for example, we've initiated an enterprise collaboration with OpenAI to deploy generative AI on top of our foundational technology systems. And lastly, if we are successful with GPR52 and our partner, Boehringer Ingelheim, triggers its exclusive license, we expect to achieve robust IFRS operating profits. Please turn to Slide 29. As I detailed earlier, we have an exciting pipeline that is poised to move forward across multiple programs this year. So over the next 12 to 18 months, across the wholly owned and partnered portfolio, we expect to see up to 6 programs moving to Phase II and 1 program moving to Phase III. There is no other emerging biopharma in Japan demonstrating this much progress and potential. Please turn to Slide 30. So we are very strategically positioned in some of the fastest-growing areas of healthcare; neurology, neuropsychiatry, metabolic disease, and immunology-GI. There is huge unmet medical need in these areas. So our approach harnesses major GPCR target classes, the muscarinics, the orexins, the incretin hormones. And we do this via 2 waves of clinical development and potential launch timings. Our Wave 1 programs are moving from now through to the end of 2030. These are programs that could launch commercially by the end of this decade, 2030. And Wave 2, these are the programs that are expected to launch in the 2030 to 2035 time frame or window. Now the value to Nxera Pharma in the form of royalties and milestones could be transformational if only 1 or 2 of these products successfully makes it to market. Please turn to Slide 31. And so, a slightly different view here. By 2030, we aim to lead the Nxera in medicine in Japan, and we're going to build a high-growth, high-profit company that consistently invests in the best innovations for patients. Specifically, we're on track to grow our top line to over JPY 50 billion by 2029 to 2030, which is an anticipated 25% plus compound annual growth rate. We aim to achieve sustainable profitability in the long-term, and we can unlock significant upside if only 1 or 2 of the Wave 1 product launches is successful, and with the Wave 2 launches to drive further growth into 2035 and beyond. Please turn to Slide 32. This slide details that we have a very big year ahead, loaded with possible catalysts across the partnered and wholly owned portfolio. We aim to hit every catalyst on time, and we're confident that together with our partners, we will. So thank you for your time this afternoon. The management team and I are now available for your questions. Thank you.

Thank you very much. So we would like to move on to Q&A session. To institutional investors and analysts and media people. please use their raise hand function. I'll call out your name and please unmute yourselves and state your question. We have simultaneous interpreters. We would appreciate if you can speak slowly and succinctly. The other people, please submit your questions from the Q&A button. We would like to respond to your questions as long as the time allows. We would like to move on to the first person, Mr. Hashiguchi-san from Daiwa Securities. Please unmute yourself and ask your question.

Hashiguchi from Daiwa Securities. My first question is about your in-house products and the outlook for the development in the future. As I listen to your explanation, EP4 antagonist is in -- has the possibility of implementing Phase II. And EP4 agonist still requires to have more evaluation, but am I correct in my understanding? And for these items, for internal development, do you have the possibility of continuing internal development? Or is there a possibility for licensing out to other companies? Can you talk about both cases, respectively?

Thank you. So development schedule will be covered by Matt and the strategy will be covered by Chris.

Yes. Thank you so much for the question and your interest in our in-house program. So starting with EP4 antagonist. So yes, you are correct. So we are ending the Phase I part of the study with our partner, Cancer Research U.K. And we will intend to start the Phase II study in the second quarter of 2025, which will basically be an expansion study in a smaller number of tumor types. So we are on track for that. So the data we've generated so far looks very promising and informative with respect to selecting the doses that we will use in Phase II. And so yes, that is all on track for EP4 agonist. So you are correct in that. We've passed some of the initial hurdles, I think, that you come across in Phase I. So understanding the pharmacokinetic profile, understanding the safety profile, we've now identified some doses that we think are relevant. And now, we wish to test those in a more target engagement or pharmacodynamic fashion to get some understanding of an early sign of efficacy. And that will really inform how we think about Phase II. And we mentioned in the slides that we are gearing up to Phase II. So we are generating all the toxicology data that needs to be provided. We are scaling up material to help support that as well. So we're really, really on track with that at the moment. So Chris, maybe you can add something about the strategy with licensing or taking it forward on our own.

Sure. Thank you, Matt. With regard to the EP4 antagonist, this is currently partnered with Cancer Research U.K. However, they are assisting us both financially and with execution of the clinical trials, but we own all the intellectual property. So if this program is successful in Phase II, we have the ability to execute a large partnership or collaboration with a global company that specializes in oncology. Nxera Pharma is not a company that specializes in solid tumors. So you can imagine that if we do achieve very good results in Phase II, that in the future, in order to take this program forward and maximize its potential, we will likely partner with one of the major global oncology companies. With regard to the EP4 agonist, as Matt said, we are funded and prepared and planning to take this program all the way to Phase II. However, there is always the possibility that in a highly competitive space like IBD, where this program would be positioned potentially as an adjunctive therapy on top of biologics, that this may find its way in the future to a partner that specializes in the IBD space, a global pharma company, for example. However, for now, we have all the funding in place, all the planning, and all the capability to move this forward to Phase II ready position, and we plan to do so. Thank you. That concludes my response.

I have another question, which is on QUVIVIQ and it's about your revenue target. It's between JPY 4 billion to JPY 5 billion, you mentioned. And I think you talked about the sourcing of API and also for the supply of the products, you will be slightly accumulating the inventory. And the sales or the revenues seem to be slightly higher by frontloading. Am I correct in my understanding? Or after next fiscal year, are we able to expect the same level of revenue of sales? Do you have such outlook for the next fiscal year?

Thank you very much for the question. I would like to briefly respond to this question. Speaking from the conclusion, as Mr. Hashiguchi mentioned, the latter is correct. Since we are a pharmaceutical company, the initial year or the second year will accelerate, as we mentioned. So we try not to empty the inventory. That is what we are incorporating. But on the other hand, based on our plan, this figure is not expected to decline. We are expecting to see the increase to a certain extent by having the momentum. Am I responding to your question?

Yes.

We'll move on to next question, Citigroup Securities, Yamaguchi-san, please unmute yourself and ask your question.

Yamaguchi from Citi. So 2025 forecast, Boehringer Ingelheim, if this is triggered, then on IFRS basis, you can achieve profit. So in other words, if the option is not exercised, you cannot achieve the profit. Is that what it means?

Thank you. So Chris, if you could answer the question, please.

Yes. Thank you for your question. If we are successful with the partner, we are very confident that we are robustly positive on IFRS profits. If the license is not triggered, then it's very much -- it can be a swing factor. As you know, Yamaguchi-san with our business, milestone income is difficult to predict. So we still could have a possibility of achieving IFRS profits, but it is more difficult to forecast is what I would say. So with 52, it's -- we're very, very confident. Without, it's probably much closer to breakeven, and that is where we'll be managing to. Hopefully, that answers your question.

So GPR52 is EUR 60 million trigger, it will be EUR 60 million? Is that million euro?

Yes. Yes. euro.

Okay. Euro. I see. And other milestones, is it JPY 11.1 billion milestone came in this year? Other ones, I think you were referring to it. Is there a list of other milestones, it will help me.

Okay. So let me briefly explain that. So milestone -- I'm sorry, we do not know when it happens. It's difficult to forecast. But we have the list of catalysts here, events. Usually, if partners start new study, I would not say all of them, but usually milestone comes in. So if you could take a look at this list and, yes, I would appreciate it. That is all we can do from our side.

So it's not so much the individual milestone, the platform deal, you mentioned that you want to do platform deals in '25. So including all that, and with Boehringer Ingelheim, all inclusive, you can achieve operating profit. Is that your forecast?

Yes. Allow me to answer that question. So Boehringer, if we have the -- from Boehringer, there are unforeseeable factors. Even without the deal, this portion will be secure. That is what is mentioned on #5. But as you can see and as you probably know, we want to forecast, but there are swing factors, variables. So we cannot say anything for certain so that we do not be misleading. But with GPR52, regardless of other swing factors, we can achieve this #5. And I think you have the same agreement, same view. So that's why we mentioned this.

So let us move on to the next question. So I will mute Mr. Yamaguchi, excuse me for that. Pathology Associates, Dion. Please unmute yourself and ask your question.

I just want to follow-up on Yamaguchi-san's question regarding GPR52. And I was wondering that at JPMorgan, Boehringer announced failure of Phase III schizophrenia program, I think CONNEX program. Do you expect that to make them more likely to exercise their option? And can they do so at any time? Or do you expect them to wait until the Phase Ib results are available? And except for Boehringer, do you have -- and are you able to currently also look at -- are you receiving other interest on this program should Boehringer not exercise their option?

Do you want to go first, Matt, and then I'll...

Yes, yes. I can answer.

Sure.

Yes. Thank you for the question, Dion. Very insightful question. So yes, of course, we were aware of the Boehringer announcements around the GlyT1 inhibitor. And I should just point out that mechanistically, that is very different from GPR52. Whether that stimulates their interest in this, you would have to ask them, of course. I think they will be very focused on treating individual assets based on their own qualities or individual qualities, right? So I think that they will still want to see a very positive solid data package before they exercise the license. Although I would say that any changes in your pipeline may influence the companies from a strategic perspective for sure. And then just to your point around if they -- if they can exercise, of course, they can exercise the option when they want to. And so they have that flexibility in there to do that if they so wish. So that's to answer that question. And then to answer your point about other interest, I mean, as I mentioned in my presentation, this is such a hot area right now in neuropsychiatry. And we have been asked about this program by other companies, that's for sure. But I won't say any more than that, but we have been. But of course, we do have an agreement with Boehringer Ingelheim at the moment, but there are other companies that we've spoken to about it. Chris, anything to add?

I mean all I would say is they're committed to this area. And if they are looking to take control of a novel asset in this space, Dion, it's a lot easier to take control of one you've already got an exclusive option-to-license over. You're in the box seat rather than going out and having to find another one. So certainly, it's within their control. They obviously are overseeing the work that our teams are doing. They can trigger at any time, as Matt said, and they get the first look. So they're in the box seat to bring this into their portfolio should they choose to do so.

May I just ask a quick second question regarding NBI-568. So you'll be moving into -- or Neurocrine will be moving into Phase III. And I wonder if it's possible to make any comments on the design of that Phase III study. And I guess I realize that is with Neurocrine. But will that be a fairly complex design? Or how do you -- how should we think about the design of the Phase III?

Yes. Thanks, Dion. Maybe I'll comment and then maybe Sugita-san or Chris can also make some comments. So I don't think Neurocrine have publicly disclosed detailed information around the Phase III design. However, they were asked in the year-end results around the end Phase II meeting they had with the agency in the U.S. And they actually gave some quite encouraging signs, I think. So they were saying they had alignment from the agency about their thoughts around Phase III. They were saying that they had complete support for moving forward with that 20-milligram dose into Phase III, and they also had alignment on endpoints around the nature of the whole registration plan. These were kind of comments they were making. I would suspect they will be going for some more simple type of design in this study. I think they are very mindful about the placebo in these studies based on their own experience, but also the experience of other companies in this space. And so, I would imagine they will be focusing on something that's a more simple based design, but we will look to get more details from them in due course. Sugita-san or Chris, do you want to or have anything to add?

Then Sugita would like to comment a little.

Especially for the schizophrenia area, placebo effect has a higher probability of getting larger. And especially recently, Karuna's KarXT approval, M42 agonist attention is getting much higher. So the effect to placebo is getting higher as well. That kind of tendency exists. So under such circumstances, sites should be selected prudently. And then as much as possibly -- as much as possible, objectively, the effect or the benefit that should be tracked. And with respect to that, Neurocrine is highly aware about that. And within their clinical study, we also need to be conscious and the study design should be formulated and implemented. So I believe that they understand in this manner. So we are assured to monitor the situation. That is all from me.

Thank you very much. We will take the next question. So, Jefferies Securities, Yamakita-san. Yamakita-san from Jefferies Securities, please.

This is Yamakita from Jefferies. So earlier, Yamaguchi-san asked a question, this is a follow-up to his question, Boehringer Ingelheim. Even without the exercise of the option, you can possibly -- there's a possibility you can achieve profit. Now here, how is milestone incorporated there? So what the things you have visibility in the first half are baked in, I think. But for the second half, once you are not so sure, are they already incorporated, factored in? Or are you including some proportion weighted basis?

So Chris, could you answer that question?

Yes, sure. Basically, it's very similar to every other year. We have good visibility over milestones that would come from existing programs. What we don't have great visibility over is upfront income from new partnering deals. So every year, there's always a potential that we will do new collaborations. It's just very difficult for us to know prior to negotiating what the size of those upfronts might be. So as we have discussed on today's call, we have more programs that are moving into Phase II or towards Phase II. And if there is any interest from partners around those programs, Phase II upfronts are usually quite significant. And there's always the possibility that a company will approach us to do a discovery collaboration against GPCR targets that they want to work on. And at this point in time, we just can't accurately predict what the size of those upfronts may be. It's just that almost every year, we manage to achieve 1 or 2. So that's -- that's the thing that makes forecasting quite difficult for our company. I think you all understand though.

So my second question is Idorsia. So this exclusive option right. So this year, you have planned for a few of them this year.

Yes. So Chris, if you could answer that question as well.

Certainly. Thank you for the question. So those exclusive options remain. I think it's fair to say that at the moment, there is some difficulties that our partner, Idorsia, are suffering from financial difficulties. We, therefore, are waiting cautiously before we move forward with a decision on those programs. As it stands today, and I mentioned this earlier on my presentation slides, we no longer have any reliance on Idorsia. Our supply chain operations are completely separate. All transitional service agreements have been completed. We have our own independent financial and IT systems now. So we have no longer any reliance on Idorsia. However, if we were to enter into a new business relationship with them, it could be a little bit difficult at this time, but the option remains, and we plan to move forward as soon as there is clarity regarding the financial future of Idorsia as a company. Thank you. Thank you for the question.

Thank you, Mr. Yamakita. There are many people first raising hands, but the time has come. So lastly, for all the pre-received questions in Q&A, I would like to briefly respond to those questions. First of all, this is related to what Mr. Yamakita said, and it's about Cenerimod and Lucerastat and the options are not exercised. We are not trying to be slow. But as Chris explained, Idorsia's financial situation, and there are several other factors. And as soon as those factors become clear, we already are almost fixed with what kind of actions to take. And I'm sorry that we cannot explain the details, but we're in such situations. We are not just waiting and see. So that is something what I wanted to explain. When the things become -- have a progress, we can take actions. Amongst the questions we received, Neurocrine M4 Japan right. Is there right in Japan or not? We are receiving that question. And after looking at the disclosure from Neurocrine, I believe you asked this question. And in principle, as we explained, we have the right according to this slide amongst Neurocrine, the one with [ J ]. In other words, [ MN ] agonist, we have the right, but including M4 agonist, they are globally licensed out. So there is disclosure from your client side, but this is what we have confirmed, that we hope you would understand the situation. So in the form of Q&A, I just responded to some of the pre-received questions. We just exceeded the scheduled time, but we would like to conclude the Q&A session now. We received many questions in the text. Although it may take time, we would like to respond to your questions in one way or another. As for today's session, you will be able to see through our website as well. If you're interested, please look at the website. Thank you very much for taking your time to join us. And with this, we would like to conclude 2024 financial results meeting. Thank you very much. [Statements in English on this transcript were spoken by an interpreter present on the live call.]