Thank you very much for joining our healthcare conference today. I'm Miyabi Yamakita, a Jefferies analyst covering Japan biotech companies. In this fireside chat session, we have Nxera CEO Chris Cargill, CFO Hironoshin Nomura, and partner in R&D division, Raj Dattani. Thank you very much for your time today. Thank you for having us. As you may already know, Nxera Pharma is a Japanese biotech company that engages in drug discovery and development, as well as commercialization in Japan. Nxera develops some programs in-house and also partners with other firms through licensing agreements. Let us start with your in-house programs. There are a lot of things happening right now. You have initiated a phase II trial for your EP4 agonist, and I believe the phase I data readout for GPR52 is coming soon. Could you share an update on the progress of your in-house pipelines first? Yeah, yeah, sure. Thank you very much. I think thanks for the Jefferies team too for having us. Before I dive straight into the clinical programs, I might just set the scene a little bit for how our company is structured, and then Raj will assist me to talk through the clinical program. As Yamakita-san said, we are a Japanese biotech company. Essentially, we do all of our discovery and early clinical work in the United Kingdom. We have a large operation up in Cambridge, U.K. Actually, we have approximately 170 scientists on site, and we do all of our discovery and early clinical work here. We have a commercial pharmaceutical business in Japan where we now have two products on the market. The most recent one launched at the end of last year. We are building towards having an international commercial pharmaceutical company. What we do is, in the U.K., when it comes to the clinic, we develop our assets through to phase I, I- B typically, and then we seek the assistance of global pharmaceutical or biotech companies to work with us to develop those molecules for global patients. That is sort of how we are structured. In terms of our in-house programs, thank you, Miyabi. Yes, we're really excited. We have got a program that has recently moved into a phase II expansion study. This is our EP4 antagonist program. It is a program for multiple types of solid tumor. This is something we are really excited about. Recently, a competitor company, Ono Pharmaceutical, released some data that effectively achieved proof of concept with the mechanism in combination with the checkpoint. We are doing something very similar. We've gone into four tumor types recently. Raj, would you like to talk perhaps a little bit about the program, its progress, and how it's shaping up? Thank you, Chris. As you mentioned, we are highly excited about this program. The EP4 antagonist program has been in a basket trial with CR UK. We recently presented data at the ESMO conference, ESMO 2025, demonstrating responses in colorectal cancer. This is a highly challenging to treat patient population, which has traditionally been non-responsive to immunotherapy and is characterized as an immunologically cold tumor. You referenced also our competitor, Ono Pharmaceutical. They recently press released top-line stat-sig data in gastric cancer. Comparatively, gastric cancer is a tumor type in which PD-1 agents are approved in the first-line setting. As such, we are obviously highly interested in their progress in gastric cancer, but also very encouraged by our own data as presented at ESMO. The drug is now in phase II trials, and we will look forward to presenting further data on this asset as and when appropriate. We are very, very encouraged by where we are currently with that asset today. Thank you very much. Could you share a little bit more about GPR52? Yeah, certainly. GPR52 is a first-in-class mechanism that we've been working on for a number of years. We actually have a partner for this program, Boehringer Ingelheim. We're working together very closely with them. We're super excited. The teamwork has been fantastic. This is a program that is indicated for schizophrenia. Traditionally, an area where our company has been quite strong, we have, we'll talk about it a little bit later, but we have a very large suite of muscarinic agonists for neuropsychiatry partnered with a company called Neurocrine. This particular area of neurology has been a bit of a hot area for us. This particular project has been going well. It's actually very close to completing phase I studies, which means a decision is actually rather imminent on whether or not our partner, Boehringer Ingelheim, will choose to license this project and take it into their portfolio going forward. We are very excited. We are almost there. Raj, do you want to make a couple of comments on the mechanism and the program? Indeed. The mechanism is highly attractive and differentiated. If you look at the schizophrenia market overall, there has been a paucity of new mechanisms, and that is why there's been significant interest in those new mechanisms when they've arisen, as we have seen with Karuna and Cerevel with M4, and of course our own program, which is partnered with Neurocrine, also against M4. Given that differentiation, we are keen to see this asset progress. We have a very strong relationship with Boehringer. As you can see on the slide, we have some early PK data presented there. What we're trying to illustrate with that is the predictability of our platform. We have a leading platform in generating chemistry assets with really attractive profiles. This is another example here whereby we were able to preclinically design a molecule, and it has translated very elegantly in terms of that pharmacokinetic data. We are, as I say, pleased with where we are and looking forward to Boehringer Ingelheim's imminent decision. There is a huge unmet need in this patient population. The reason these new mechanisms are so sort of indexed upon is actually the patients cycle through therapy. They are on a therapy for one to two years, and they cycle through. We are motivated by that unmet need and would love to bring this new mechanism towards patients. Thank you very much. It sounds very interesting. I'm looking forward to that data readout. Thank you. You also have EP4 agonist in IBD. In IBD area, the competitive environment is pretty fierce. What kind of positioning do you expect for your EP4 agonist in IBD? Certainly. Let me just start by referencing, we actually made a press release this morning regarding strategic prioritization of our pipeline. This is a program that has actually been going very well. It's extremely interesting. In fact, Raji has led this one from start to finish, so he'll touch on it in a moment. As you referenced, Miyabi, IBD is a very competitive space. There are seven or eight major pharmaceutical companies that are trialing lots of different combinations and mechanisms. What we have decided as a company is actually it's a very, very complex and expensive area to be developing an asset going forward. Probably from our perspective, we're probably not the best company to be advancing this program further ourselves. What we are looking to do is round out the phase I package very shortly. In time for a major healthcare conference in January, we will be ready to talk to potential partners about how we move forward with this program. From our perspective as a company, we're going to round out phase I, but we're not going to put any further capital into this program. As I said, Raji has led this program start to finish, so he can talk about how this asset is positioned and why we think it's a very exciting first-in-class opportunity potentially for one of the existing players that has a large franchise in this space. Thank you. It's a great question actually to talk about positioning within IBD. If we look at the mechanism here, the mechanism is highly orthogonal to current approved standard of care treatments. You'll be familiar with the fact that there are five different approved mechanisms of action within IBD. All five of these are some form of immune blockade type approach. What we're attempting to do with this mechanism is to drive epithelial barrier restoration. That is extremely orthogonal to immune blockade. In fact, the bacterial translocation across the epithelial gut has been hypothesized to be a key initiating event within the pathogenesis of IBD. Being able to repair the epithelial barrier is something that has been a long-standing goal of interest to the community within IBD. The positioning therefore we think could be either as an oral prebiologic as a monotherapy, but perhaps more relevant would be the combination play whereby one will leverage that orthogonality in combination with some form of immune blockade. We are likely to see a sixth approach to immune blockade recently coming through, which is the TL1A class. Any of those six mechanisms which are focused on immune blockade would be great partners in combination with this agent. That is why we currently position this as something which we think could be done well in partnership with any of those agents and therefore any of those players who have one of those agents, which as Chris mentioned, is most of the major pharma companies. Thank you very much. As Chris mentioned, they announced a restructuring plan this morning. Could you explain why you decided to do the restructuring and what was your latest situation, cost situation in your latest earnings? Sure. We announced focused restructuring really to enhance the company's path to profitability. As I mentioned earlier, part of our business model is to advance great science, discover differentiated molecules, oral small molecules predominantly. We work on GPCRs exclusively as a target class. We take those molecules into the clinic and we try to complete early signal-seeking studies in phase I- B. At that point, we seek partnerships. As I mentioned, we've got a partner effectively lined up for our GPR52 program, and we've decided to not invest further in the EP4 program because we've earmarked that one for partnership. The EP4 antagonist, which we talked about earlier, is already in partnership with CR UK. Beyond that, most of our programs are in early chemistry. When it comes to this side of our business, it's always a difficult decision to make, but we don't really have a need for a large early clinical team at the moment. We announced a focused restructuring. These decisions are difficult. We're going to have to say goodbye to some fantastic colleagues that have poured a lot of effort into our company over the years. We need to reset our cost base for the future. We also need to have our resources aligned with the programs that we are seeking to deliver. Right now, our pipeline is full of early and very interesting best-in-class targets where we understand the biology and we are seeking to develop molecules, oral small molecules that are differentiated based on profile. These are largely in the areas of obesity, chronic weight management, metabolic disease, and endocrine disorders. The reason we are choosing to focus in those areas is what we are really trying to do is enhance our probability of success and our speed to signal early on in the clinic. That was really what our announcement this morning was all about. In addition to some cost resetting in the U.K. business, we're doing the same in Japan as well. In Japan, I'm sure we'll touch on it shortly, but a few years ago, we made a pretty sizable acquisition for our company. We acquired two pharmaceutical products from a Swiss company called Idorsia Pharmaceuticals. Since acquiring those products, the business has been going really, really well. Beyond our initial expectations, we've been able to grow revenue extremely quickly, and we've been able to cut costs. This is just a further step in enhancing the prospects of our company achieving profitability next year by getting the cost base down to a sensible level so that next year when we expect there to be multiple milestone events for us on our partnered programs, there is a very strong possibility that we'll be able to swing to profitability. That was really the crux of what we've done and announced this morning. That makes sense. Thank you very much. Now let's move on to the next topic, which is partnering pipelines. I think this area is going very well because Neurocrine initiated phase III schizophrenia trial with your muscarinic agonist. Also, Centessa recently announced impressive two-week data in sleep disorders. Could you share your view on the partnering program overall? Yeah, sure. Look, and I'll just caveat that obviously once we license a product or a suite of products to a pharmaceutical partner, it's really no longer our place to talk too much in detail about those programs, but I can certainly give you a high-level understanding of where we are. You mentioned we have two major partners or collaborators right now, and we're very proud of what those partners have been able to do with the molecules that we discovered. Neurocrine, a very large proportion of Neurocrine's neuropsychiatry portfolio are molecules that were discovered by our team of scientists in Cambridge, and those are now progressing very well through the late clinic. We have a muscarinic M4 agonist, which is indicated for patients with schizophrenia. That's in registrational trials now in the U.S. That same molecule will go into a study in the near term in bipolar mania. There is a suite of muscarinic agonists that have both M1 and M4 selectivity, so dual or M1 selectivity that will be moving forward in phase II as well very shortly. There is a lot of activity ongoing in that space, and we are very excited at the progress Neurocrine are making. They've done a fantastic job. They've clearly got the world's most kind of comprehensive portfolio of muscarinic agonists, as you can see up there on the slide. We are really looking forward to 2027 when we actually expect to see the first phase III readout of a molecule that was discovered by our scientists in Cambridge. That's something we're looking forward to. When it comes to Centessa, I mean, that's been a fantastic and wonderful story. Centessa are advancing an OX2R agonist, and they actually released some data not too long ago, it was about a week or a week and a half ago that demonstrated that the molecule ORX750 is really shaping up as a potential best-in-class product in narcolepsy. We are very excited about that. Centessa, again, what a great partner. The origins of that molecule were a joint venture effectively between ourselves and Medici. The team at Medici and then subsequently Centessa have done a fantastic job to raise a wonderful amount of capital so that they can really take that asset forward and other molecules. They are obviously right now focused on narcolepsy, but there is a lot of potential for that molecule to indication expand as well. It's very pleasing for us to see that we've chosen the right partners for our portfolio and that these assets are rapidly moving through the mid to late clinic, which is something that we would not be able to do ourselves as a company just from a capital perspective. The partners are really doing a fantastic job of it, and it's great to see them moving forward. I mean, I don't know, Raj, if you wanted to make any other comments on either of the programs. I guess I'd only remark to emphasize that Centessa's remarks around best-in-class were probably highlighted further by the recent alchemies data where I think they struggled to show exactly what they were looking to show. I think there is definitely some open space in that narcolepsy universe. Actually, broader than that, as sleep-wake disorders have an important role in neuropsychiatry more broadly, I think there will be a lot of indication expansion space. I think just highlighting that competitive positioning of the Centessa molecule in light of recent data is something I would draw your attention to. Yeah. I think the company said that its full phase II-A data will be relatively imminent and that they expect it to support a move towards registrational studies towards the end of Q1 next year. Yeah, it's a very exciting time for us as a company as we watch our partners move forward with those assets. Thank you very much. As Raji mentioned, there are some competitors, particularly in narcolepsy type one field. For example, Takeda announced very impressive data in sleep, oral sleep, back in September. In the future, what kind of factor is important to focus the positioning in narcolepsy type one? I think it's obviously going to turn on the risk-benefit profile, right? People have been talking about what numbers of MWT numbers. I think there's been a lot of index into that. I'd also highlight actually the safety profile. The safety profile of these agents has some on-target effects, as I'm sure you're aware of. I think there will be differentiation both along the axes of safety and tolerability to define the final positioning. Really, I think it's very early in the data right now to be able to actually draw any definitive conclusions about which of the assets will sit where on those two axes. Okay, thank you very much. Moving on to the next topic, Japan and APAC commercial business. Could you provide a recent trend of your products, PIVLAZ and QUVIVIQ? Yep, certainly. As I mentioned earlier, in 2023, in July, we acquired the Japanese business, which consisted of two products and a team from Switzerland's Idorsia Pharmaceuticals. This has been a really fantastic acquisition for us. As I mentioned earlier, the products have performed far beyond our expectation, which was wonderful. That is obviously a huge positive. We have been able to sort of size that business more appropriately such that we've been able to not only do it with a leaner team, but we've also been able to take quite a bit of cost out of the supply chain as well. We are responsible for the supply chain of those products. They're doing really well. I mean, on the slide here, you can see PIVLAZ, which is a drug for aneurysmal subarachnoid hemorrhage, really is the standard of care in Japan. It is growing double digits every year. This year, we're slowing down. We've almost reached peak. We're sort of at about a 75% penetration now. It is more likely to be a high single-digits kind of growth trajectory going forward. It is a fantastic product. It has the full support of the neurosurgeon community in this space in Japan, and we've been really pleased with it. It's saving lives every day. It's a wonderful product. The second product, QUVIVIQ, which we launched in December last year with our partner, Shionogi. Shionogi is currently in the first 12 months of this. It is a primary care drug. What we are really excited about is actually in the first 12 months of a launch in Japan on these products, there's a two-week prescription limitation. There is a somewhat limited amount that you can push the product. Shionogi have that will come off on December the 19th, and the product will hopefully thereafter grow. Shionogi has a very broad plan in Japan to expand their franchise in this space. They have an upcoming medicine in the depression space that they're looking to launch. These two products will go very well together in their commercial portfolio. This is a dual orexin antagonist too, by the way. It is part of the DORA class of drugs. It is a very big class in Japan. We are third to market, but we do believe we have the best profile. Shionogi was the right partner to support us in launching that product. We are very excited to see a much more upward trajectory once that two-week prescription limitation rolls off in December of this year. Thank you very much. Sounds great. Thank you very much. Last question, I'm looking forward to your R&D meeting tomorrow. What's going to be the major topics there? Sure. We will be touching, I guess first and foremost, we'll be touching a little bit on the announcement that we made this morning. A focused restructuring, positioning the business to enhance its path to profitability, a pivot away from novel first-in-class products, and a much more rigid and exclusive focus on best-in-class drugs, GPCRs specifically. We'll talk about that. We also announced this morning a new Chief Scientific Officer who's going to lead that effort. It will be the first opportunity for Patrick Forge to introduce himself. We are very excited to have him on board. He will be absolutely leading the charge in helping us push that pipeline that I referenced earlier. We have got an abundance of targets that we are working on in obesity, chronic weight management, metabolic disease, endocrine disorders. There are a lot of programs for him to focus on. We are going to talk about how we have positioned the business to operate with discipline and with speed so that we can move these programs forward to development candidate stage as fast as possible. We will also use the opportunity tomorrow to touch again on some of the things we've mentioned today. There is real clinical momentum in the company right now. We have talked about all of the programs that are being advanced by Neurocrine Biosciences, Centessa, but the EP4 antagonist, we're really excited by that one as well. CR UK have done a fantastic job to operationalize that trial. We will talk a little bit more about that. Yeah, I think it's mostly reminding everyone that we have a fantastic business that with this cost-based reset and all of these imminent clinical milestones that will come next year, we are really positioning ourselves to have a very strong possibility that we can turn to profitability quite quickly. Great. Thank you very much. We are running out of time, so we will conclude this session here. Thank you very much and have a nice day. Excellent. Thank you very much. Thanks for having us.