Good morning, everyone. Thank you very much for joining our Global Healthcare Conference. I'm Miyabi Yamakita, Japan biotech analyst at Jefferies in Tokyo. In this presentation session, we have Healios represented by CFO Richard Kincaid. We will start with presentation. Richard, over to you. Great. Thank you so much, Miyabi. Good morning, everyone. I'm Richard Kincaid. I'm the CFO of Healios. I want to start by thanking Jefferies for this opportunity. I'm not sure how many years this has been. It's really an honor to be able to be here once again. Yamakita-san, thank you for coming in from Tokyo again. This is one of our great pleasures to be able to show up here in New York with you and be able to do this again, at a time when the Knicks are playing in the championship. It's a very special time to be able to do this. I'm here to tell you a story about Healios. Healios is a Japanese cell therapy company. We're listed there. We've been a leader in Japan for about 15 years. We have a really special opportunity to Sorry. Sorry. Excuse me for one second. Let me go Sorry. Yeah. What's going on? That's okay. I'm good. Okay. A very special opportunity, not just because we're a Japanese biotech company, but because how we combine our Japanese opportunity set and the things that we get by being a Japanese-listed biotech company with how we're developing our firm globally. That's a really unique and distinctive thing that Healios K.K. has going, and we're building a global leader in allogeneic cell therapy. Today I want that to be the takeaway for why is Healios K.K. special. Again, we've been at this for 15 years, and we started off by developing iPS cell-derived RPE cells for age-related macular degeneration. That product still exists. That product is in a clinical trial right now, and it is partnered now with Sumitomo Pharma, and that's the original drug that we had. We have a huge opportunity around ARDS. It's a global opportunity. We are preparing for conditional approval for invimestrocel for ARDS. This is our drug that we've been developing in Japan and now globally, and we have an upcoming product launch in Japan. We've been a clinical company, and we're almost here imminently going to be a commercial company. We have an imminent launch of REVIVE-ARDS, our global phase III pivotal trial. This is starting in Japan, and we have a very near-term first patient in to be expected around REVIVE-ARDS. We have, in addition to ARDS, a trauma study going on in Texas. This is funded by Department of Defense. It's called the MATRICS-1 study. It's a phase II study. It's 156 patients. We're in the critical care space, and we're combining ARDS and trauma right now, and the focus very much for the firm is on critical care. We're supporting this with what's 15 years of build around cell therapy manufacturing, and for those of you who know cell therapy development, this is a really critical piece of the puzzle, and we have a huge advantage. This is our team, and our founder is Hardy Kagimoto. He's an ophthalmologist, and that's how we got into this when he started to build iPS cell-derived therapies for eye disease. He's a very dynamic leader and entrepreneur in Japan, and what he and I and the rest of the team have done is we've built a global team. Japanese biotech leaders, global biotech leaders building up a global business focused on succeeding globally from Japan. This is our pipeline. Our pipeline is, again, focused on ARDS right now and critical care, but we have other things in the firm. We have a stroke program as well. It's not in the clinic. That's using invimestrocel. We have our RPE cells, as I mentioned, and we also have gene-modified iPS cells for iPS cell-derived NK cells for solid tumors. That'll be in the clinic next year. We have a drug in invimestrocel that's a cell therapy that's very drug-like, and it's, as it says here, simple to prepare and administer. We have an advantage in cell therapy because of how drug-like this is. It's a frozen, off-the-shelf product. We thaw it. We put it into the patient through an IV bag over the course of about an hour. There is no surgery required. That's straightforward logistically, which will help with uptake as we commercialize. We have a multimodal mechanism of action. Sometimes this gets people confused, but we think it's an advantage in a syndrome like ARDS, where there's not just one button to press. We have cells that are highly immunomodulatory and anti-inflammatory. We have reparative properties with these cells. They work through multiple immune cells, convert what, in the case of ARDS, is a highly inflammatory environment into one that's neutral or anti-inflammatory. The other advantage to the cells, which is really important, is the expansion profile. We have, innately in our MAPCs, multipotent adult progenitor cells compared to MSCs, we can get far more doublings out of our cells than in the case of an MSC. That's one of the key advantages. When we combine that with our manufacturing technology, we can make hundreds of thousands of doses from a single donor. Again, in cell therapy, manufacturing is really key. We can make a commercial product, we can make it at scale, we can make it with a low cost of goods, and we don't have to worry about donor-to-donor variability when we are generating lots of doses of the product. The cells are also smaller in size. That's important in the context of ARDS because the ARDS indication, we put the cells in the patient, and we'll show a slide here shortly. The cells will go to the lungs. They deeply penetrate lung tissue, and that's also an advantage. We can do that without safety risks around pulmonary embolism or otherwise. This is our manufacturing progression, if you will. We used to be in 2D manufacturing. Most cell therapy companies still are there. We are in 3D. We're making this product in 50-liter bioreactors. We're close to being in commercial and production now. We have a commercial suite. It's at Minaris in Yokohama. We've tech transferred it there very successfully. We're just on the cusp of producing our first commercial product there, as we prepare for commercialization in Japan, which is near. That's happening in a 50-liter reactor, but we have a 500-liter reactor process too that's being put up in a commercial suite now in Kobe. This is, I believe, one of our biggest advantages to be in this format. Going back to what I was saying about Japanese opportunity, there's an industrial policy push in Japan that's ongoing in relation to cell therapy, and it's affecting us in multiple ways. One of the key ways is with respect to this manufacturing platform. We got a JPY 45 million grant from the Ministry of Economy in Japan to create these 500-liter commercial suites. invimestrocel in our 50-liter process is expected to be the first bioreactor-produced product for an allogeneic cell therapy product approved anywhere in the world, right? Between that and having this 500-liter production capacity, which will put us in a position to make 40,000 doses a year, while we're commercializing in Japan, again, it's one of the key reasons why when you think about, okay, what's interesting about Healios, we have a commercial program or budding commercial program in Japan. We'll be selling, we'll be making a lot of the product ready to commercialize in the U.S. when data reads out, and that is hard to do. We wouldn't be able to do this 500-liter commercial suite without this government funding. We're starting with ARDS, right? You have to start somewhere, and we want to get a win in our first indication. Ultimately, this platform is applicable rather broadly beyond that. ARDS is an unmet medical need, and there are about 400,000 patients in the U.S., Europe, and Japan each year. About half these patients die, and so it's a lethal condition. In Japan, it's about 28,000 patients per year. Like I said, that's where we're starting in terms of commercialization, right? We have, again, a confirmed path to approval in Japan. We're getting ready to file our application for approval. It's a big opportunity for us to commercialize there, but a huge opportunity for us to commercialize in the United States. When we take this drug, invimestrocel, and we put it into patients, again, the cells go to the lungs on the first pass and they deeply penetrate lung tissue, and that's the site of the inflammation. When we think about mechanism here, right? Broadly speaking, these cells are highly immunomodulatory, anti-inflammatory, they're reparative. In ARDS, they're at the site of the inflammation, physically go there. If you're going to win in an indication, well, mechanism being real direct is helpful. What happens? The patient's lungs are filled with fluid. After that inflammatory cascade that's ongoing, that assault, well, our cells end up there and they convert the environment back to one of homeostasis. The alveolar edema will subside. You can remove the ventilator faster than otherwise, and then the patient's morbidity and mortality odds improve greatly. That's what we're trying to achieve in ARDS. That's what we achieved in our phase II studies, and it's of potential great benefit to these patients. When we look at preclinical data, and this has been going on for a long time, and this is over 10 years ago in these published preclinical studies. These slides at the top, you can see on the left-hand side, this is ARDS lung tissue. It's human lung tissue with ARDS, with inflammatory infiltrates. On the right-hand side, you can see those just cleared away when you have endovascular cell infused in the lung tissue too. You can see at the bottom right, a chart or a graph of showing the types of immune cells that were there, and then what happens in the presence of endovascular cell. That big bar is macrophages. That's what seems to have been most present, and it gets pretty much wiped out with our drug. When we look at the data that we had in our human studies, in the phase II studies that we ran, we had a phase I, II, and then we had a phase II, MUST-ARDS and ONE-BRIDGE. MUST-ARDS was U.S., U.K. ONE-BRIDGE was in Japan. These similar studies, 20 by 10, treated versus control. In our U.S., U.K. study, we had a 12-day median ventilator-free day difference out of 28 days for treated versus placebo. All right. That's a lot. In other words, in 28 days, patients got off a ventilator 12 days faster. There was 38% reduction in mortality. Then we did our Japanese study. The Japanese study showed nine days of median ventilator-free day difference and a 38% reduction in mortality. Basically replicated the data more or less. When we combined the data and looked at 40 versus 20, we had a 10 and a half median ventilator-free days difference out of 28 days, and we had a very robust change. Would be like next coming of penicillin if this is what we got. It's in our phase III. It's really remarkable to be able to get patients off a vent that much faster. When we looked under the hood, we saw something very interesting and not to be unexpected. It was related to time to treatment. If you look on the left-hand side here, this chart shows the top line is treated group and the bottom line is control. The treated group, that gap, that spread is basically effect size. This is ventilator-free days. That middle point is roughly two days. If you cut it off into two different time frames, like up to two days, and then after two days, you get a much larger effect size in the first two days. These patients are on a mechanical ventilator. They're under this inflammatory insult, or assault, and they're getting worse by the day. There's damage being incurred in their lung tissue. Intervening faster is better. Sort of an obvious thing to propose. We've made one change in our phase III study, which is to treat patients within 48 hours of meeting diagnostic criteria instead of about three days or four days. That could ultimately cause us to have an uplift in data in the phase III study. We're not betting on that. That's not how we've powered the study, but it's an important thing to point out. This is the one key change we made in moving to phase III. If you look in the bottom right, the categorical data analysis, there's a big lump of responders in the greater than 20 box or column. The treated group had almost 60% of patients be, quote, "responders," patients that got off the vent in a week or less versus 20% in placebo. That's what we would expect to see is a lot of patients responding if we treat the earlier we treat. In terms of what's going on, again, underneath the hood, in a way, biologically, one of the studies we had this good biomarker analysis. We showed with treated patients, the inflammatory biomarkers being much lower as a result of the drug as compared to the placebo group. Our study is a pneumonia-induced ARDS study, right? Our Japan ONE-BRIDGE study was all pneumonia-induced ARDS. Our U.S., U.K. MUST-ARDS study was upwards of like 90% pneumonia-induced ARDS. We're keeping it consistent. In phase III, we're treating pneumonia-induced ARDS patients. We're doing this globally. We're starting in Japan, but we're rolling out to the U.S., Canada, Korea, Taiwan, Australia, Europe here in stages. It's a global study being run by a Japanese-listed biotech company, right? We're doing that with an operation in Japan. We're doing that with an operation in the U.S. We're working with several CROs. It's a very exciting time for us. Again, we're real close to first patient in. This, as I mentioned, we're treating patients within 48 hours of meeting diagnostic criteria. These are moderate to severe ARDS patients, so their P/F ratio is 200 or less. They all have Berlin definition of ARDS. They're all invasively mechanically ventilated. It's a big cell therapy study. It's up to 550 patients. It's I'd say overpowered relative to what we saw in phase II, overpowered by a lot. That's because we're insistent on winning somewhere, and you can get and uncover a degree of effect. At 550 patients, that's still extremely clinically meaningful, even though a lot lower than what we saw in our phase II studies. Clinically meaningful and relevant for a cell therapy like this being commercialized in the U.S. We're powered to win. We can win early at 300 patients. I think the odds of that are not small. We're getting going here soon. Any day now, you're going to see us progressing this and have patients being enrolled, starting in Japan, then moving on to these other markets. This is a very exciting time for us and is a huge endeavor for a Japanese-listed company. We're preparing our application for our conditional approval filing. If we can just treat the first part as a column, where are we? We're running 50-liter process GMP runs right now in Minaris, in Yokohama. We did a tech transfer into that facility, again, successfully. It's going extremely well. We just are now really on the cusp of making our first commercial product, it's been a long time coming, in these three reactors to sell in Japan. We're assembling our commercial team. You'll see, if you're trying to read tea leaves out there for us, we added about 15 people over the last year. We'll probably add another 15 over the next six months or so. It's been mostly manufacturing at first, commercial operations, sales and marketing, clinical development. Just fits with what I've been saying. We're getting ready to commercialize in Japan. We're getting ready to run with REVIVE-ARDS, a global phase III study that's up to 550 patients in a cell therapy. That build is happening right now. Once we file for approval in Japan, it'll be nine months to get approval. This has all been confirmed already with Ministry of Health and PMDA. We have a launch to do thereafter. We're selling this product by ourselves in Japan. Again, it's important to point out maybe on the timeline, 50-liter reactor production now. By 2028, we'll have 500-liter commercial suites up because we're funded by the Japanese government. I want to bring this back to what I'm saying. Building a biotech company in Japan is advantageous to an extent. You need to commercialize in the U.S. You need to clinically develop elsewhere, too. By building in Japan, we have a relaxed regulatory path to be able to get off of phase II data, this commercialization going early. That's really important. We have a JPY 45 million grant helping us create a 500-liter reactor facility to make tens of thousands of doses of product per year. We've got a low-cost environment, there hasn't been a lot of inflation there for decades, with highly skilled scientists and engineers who do really great work. We're combining that with global operations to run a clinical study and ultimately win in the U.S., too. Speaking of that, this is our some U.S. market study or kind of access and affordability studied output that we have. I don't have a slide here for Japanese commercialization. It's a bit of a sensitive thing right now because we're right in front of it. In Japan, again, 28,000-patient market, we think we can sell thousands of doses once we're commercialized per year. In the States, it's like a 250,000-patient market. When we boil it down to moderate to severe ARDS and then below that, we get to 20,000 patients of expected sales in the U.S. Ignoring Europe, ignoring the rest of the world. That's a lot, and as I mentioned, the manufacturing's going to be set up ready to go to be able to deal with tens of thousands of patients. In pricing terms, we didn't see any pushback up to JPY 200,000 a dose. We see this in the U.S. as like a JPY 3 billion to JPY 4 billion opportunity. Let's say JPY 150,000 to JPY 200,000 a dose, 20,000 patients, and again, that's a huge opportunity for a Japanese biotech company. Back in Japan, I just want to say one thing, and maybe we can talk about this in Q&A with Yamakita-san, there's a pricing regime in Japan that I think has evolved. Five years ago, it looked more like JPY 100,000 a dose was how these things got priced in Japan for cell therapies under conditional approval. You had a couple recently in the kind of JPY 300,000 to JPY 500,000 range from our peers. I'd say if you're trying to do the math about what this can be for Healios under a conditional approval in Japan, it's important to pay attention to those recent price points. Note that we have a drug that is drug-like, that just thaws and goes into an IV bag, doesn't require surgery, and is an unmet medical need where patients die. We are excited about the commercial opportunity in Japan that we have right in front of us. What are we doing? We are specifically very focused on going for our conditional approval in Japan, getting it done and launching the product, and launching and running this study really well, the REVIVE-ARDS study. Those are our two focuses, and the trauma study's there and going, and that is important, and it is going to read out before ARDS, and it will be a read-through for ARDS, we think. But we are really focused right now. It is very much execution mode. We are excited to get these things done for patients. I will just wrap up by saying, again, Healios is a Japanese-listed biotech company. We have some great advantages going for us there. We are pairing that up with global operations, global development, and a global strategy, and that puts us in a different bucket, I think, than the typical Japanese BioVenture. I think we are a company that is worth paying attention to, and we are a global leader in allogeneic cell therapy. Thank you so much for your time. Thank you. Thank you. Excuse me. Thank you very much, Richard, for the great presentation. Back in last October, you had disclosed the subgroup analysis data on acute kidney injury, which I think is very exciting. I understand that you are developing in trauma, of course, and which is somehow related to kidney failure. But given that great data, do you consider developing in AKI as well? Yamakita-san. Thank you so much. We are running a trauma study right now. It is a 156-patient study. It is happening at University of Texas, Houston, and it is nominally in trauma, which is severe injury-induced trauma with hemorrhagic shock. The patients are getting stabilized and getting blood transfusions, and then they are getting treated with our drug, right, in 24 hours from the injury. The primary endpoint is degree of acute kidney injury. All right? Our drug is going in, and it is just like in ARDS, it is halting the inflammatory cascade, and it is doing so in a way that we believe is protective to multiple organs. These patients suffer from multiple organ failure, but we are measuring through AKI. We have blinded data there, where we see it being very promising with respect to that study. We see the same thing in our other past studies. These cells are very protective of the kidneys. It is a potential opportunity for us. We're intent on getting this trauma study to read out as fast as possible, there's some things we're doing right now working on accelerating that. If you think about our timeline, we're starting the ARDS study now, the global phase III study, that's going to get going. That's a multi-year thing. Starting in Japan, adding the U.S., Canada, Korea, Taiwan, Australia, Europe, and it's going to be, like, 80 sites. While that's going, again, in this march to 300 patients where we can get this big win in ARDS globally, somewhere along the way, that trauma study's going to come out, and it's going to be a readout that is going to say, "These patients did this well in terms of degree of acute kidney injury." That's a big indication. That's a leading cause of death in people 45 years and younger in the United States. If we're treating acute kidney injury that's trauma-induced, there are other things that induce AKI, too, logically, it would make sense to kind of expand out from there. We have ideas of what we can do with that in Japan. There's not a lot of trauma in Japan. Japanese people are too nice and gentle and careful and we don't have any guns and all these things. There's a version of AKI we can treat in Japan, too, and potential conditional approval pathways, there's a lot to do with AKI. It's actually very exciting for us. We get excited and we're like, "Okay, all the things that this platform can be," we got to stay focused right now. The focus is, again, it's ARDS approval in Japan, it's ARDS global clinical study, this phase III study. These are big efforts for us. It's really all hands on deck right now. It's crazy execution mode. In the background, we have this trauma study going, we keep looking at the blinded data, we're like, "Oh, wow, that looks really good" when we compare it to contemporary reference data. Great. Thank you. I'd like to ask about the eNK cells as well. I saw you published a study on the efficacy about the lung cancer the other day in preclinical data on lung cancer. Any update on the eNK cell development, and when can we expect the clinical trial entering? That's another great question. Again, at the risk of repeating myself, we're very focused on ARDS right now, but we have other things. Healios has been at this for a while, and we've got a lot of assets and technology and know-how and capability. We've built this really amazing gene-modified iPS cell-derived NK cell platform. We've got a version that doesn't have any CARs attached to it but has a lot of enhanced functionality, and we have some dual CAR versions. You know that we've optioned the base version out to Akatsuki Therapeutics in Japan. They've been funding the development. We're getting close to being able to be in the clinic. There's a plan to take it into the clinic next year in mesothelioma in Japan. As a starting point, and of course, it's a platform with broad applicability across solid tumors. I suspect you'll see it in the clinic next year. Let's get first in human data and then see what we should do with it. Again, as a firm that has limited resources, we're a, I don't know, JPY 400 million market cap company or thereabouts, JPY 300, JPY 400, and it's very much focused on ARDS. We've got a win right in front of us. We're about to be commercial. Well, there's lots we can do with the NK program, maybe starting next year. Okay. Thank you so much. We are running out of time. Thank you very much, Richard, for your time, and thank you very much everyone for joining. Have a nice day.