Sciences Investor Forum. On behalf of OTC Markets and our co-host, Zacks Small-Cap Research, we are very pleased you have joined us. The first presentation of the day is from MetaVia. Their session will be moderated by David Bautz, senior equity analyst of Zacks Small-Cap Research. Please note you may submit questions for the presenter at any time. You can also view a company's availability for a one-on-one meeting by clicking Book a Meeting. At this point, I'm very pleased to welcome HH Kim, Chief Executive Officer and President, and Marshall Woodworth, Chief Financial Officer of MetaVia, which trades on the NASDAQ under the symbol MTVA. Welcome back, HH and Marshall. Hey, HH and Marshall. How are you guys doing this morning? David, good. Thank you. Excellent. All right, let's get right into it. MetaVia is obviously pursuing both obesity and MASH simultaneously. You could argue that these are two hottest areas in biotech. I was wondering if we could start with maybe kind of the overarching strategic vision that you have for the company at this point with these two assets. I think the office internet went out. I just came back. Could you repeat the question? Yeah, sure. I was saying that MetaVia is pursuing both obesity and MASH, which are hot areas in biotech, wanted you to start with kind of the overarching strategic vision for the company at this point. Yeah, sure. Well, let's start this way. Obesity, MASH, the liver side, everything is a very hot area right now, we're lucky to be one of the companies that's developing a therapeutic alternative or an option for the patients out there. At the end of the day, the competition, when our drugs go into market like 2030, 2031 and 2032, somewhere around there, the competition will be very fierce we fully acknowledge that. In order to be competitive and try to give these great drugs, I think we are still in the early clinical stage, but unlike other drugs that fail clinical trials in efficacy or in safety, we have been showing a very promising data sets. With that, we will have to have a partner who is much bigger than us, to give the full potential to these drugs and put it into the market. At the end of the day, we are considering that, at one point, we will have to partner with a bigger company. Okay. All right. Let's dive into DA-1726, which we're targeting for obesity, and of course, that drug targets both GLP-1 and glucagon. I kind of wanted to dig into that a bit. Specifically, what specific physiological advantages do you think that glucagon agonism has beyond what we're seeing with, say, a GLP-1s or GLP-1 co-agonists? Well, everyone knows about GLP-1s, right? A great glycemic control coming from the drug, plus appetite control, which results into a great weight loss. You add glucagon to it, what does it do? Glucagon has direct hepatic effects. It has increased energy expenditures, and it will add additional benefit than just GLP-1 alone. In a bigger picture, let's think of other duos as well, like tirzepatide, which has the GIP with the GLP-1. What does it do? It doesn't really have its own unique benefit, but it helps out with the safety side and enhances the GLP-1's efficacy, which is great. tirzepatide, MOUNJARO, Zepbound, is a great drug. The hype of these days, amylin, what does it do? Has glycemic control, it has a bit of the appetite control. It's mostly similar to what GLP-1s do. You add it together, you have an enhanced appetite control, which probably will result in a bigger weight loss, just like Novo Nordisk's CagriSema, and plus will have better glycemic control as well. At the end of the day, that sounds pretty similar to what GLP-1s do. Enhancing the GLP-1, that's what amylin does. When we look at the landscape right now, glucagon is the one that has a unique benefit than a GLP-1 standalone. That's why everyone is pursuing a GLP-1 glucagon dual actions. Of course there's triple G, which is GLP-1, GIP, and glucagon. It showed great weight loss effect, and that could be one of the best drugs in this field. It's just that it's very heavily biased on the GIP side. We'll have to see how the results come out on the liver side of the triple G. Okay. How do you think about the ideal balance between, say, GLP-1 activity and glucagon activity? Well, on the ratio side, our drug is 3:1, three on GLP-1 and one on glucagon. Let's look at the whole table of drugs. There is pemvidutide, Altimmune, GLP-1 glucagon, which is 1:1 balance. It's perfectly balanced. GLP-1 lowers blood glucose, while glucagon actually increases it. If you have a perfect 1:1 balance, it just knocks out both of the effects. Altimmune, pemvidutide will not be able to be used in type 2 diabetes patients, which consists about 70%-80% of the obese population. We have our drug, which is 3:1 balance. Although a small sample size and early in phase I, the last data set we have released in the 48 mg non-titrated cohort, we were lucky to have one patient who had HbA1c of six, which is pre-diabetic. After eight weeks of treatment, his HbA1c went down to 5.5, normalized in just two months. We believe the 3:1 balance can work great on glycemic control. You have tirzepatide, which is Eli Lilly's drug, 5:1 balance. They haven't released it, our research center analyzed it and came up with the 5:1 balance. It's a great drug. It's approved in China. Eli Lilly is trying to push it up another on the dose level to 12 mg, which isn't approved in China. China, I believe, is approved up to 9 mg. It's doing great. It's 12 mg of tirzepatide lost about 21%-22% of weight in their phase II. It's just that they had to go through a lot of titration to go up that high. You have survodutide, Boehringer Ingelheim's drug, had the data release at the ADA early this month. Showed great direct hepatic effects in the liver. It's just that discontinuation was about 24%, had a lot of GI side effects, and had almost six to seven titration stacks. To me, it feels like in this dual agonist of glucagon, it's pretty well known that the companies are having issues with GI side effects. Not just because you have a lower balance like 1:1 with semaglutide or a higher balance of 8:1 with survodutide, it doesn't mean that you have more increase of side effects or you have more efficacy in weight loss. I think it's the balancing act between it, which is more important, and we believe that 3:1 is the right balance because we haven't seen really any severe side effects up to now. We haven't had any discontinuation due to drug, which is very different compared to any other GLP-1 plus glucagon out there. Okay. As you look at the wider field and the glucagon agents, do you see any signs that glucagon agonism become kind of required component of next-gen obesity therapies? Glucagon's best benefit is it has receptors in the liver, and that is one of the biggest advantages. If we can control the side effects, it will be one of the best next generation GLP-1 drugs. I do believe that amylin is a great component to it with matching up with a GLP-1. But if you're looking at type 2 diabetes population, I think amylin is a great duo. But if you look at the liver side of things, glucagon will be different. It will be the most important dual agonist. It's just like how do we look at this whole obesity field? You have type 2 diabetes patients, which is about 70%-80%. You have MASH or liver disease, which is about quite similar to that. You have obese, otherwise very healthy people, which I still am a little puzzled in how you could be over a 30 BMI and don't have any comorbidities. It's all segmented, and I believe the next generation GLP-1 drugs, which will have to be a dual or triple or quadruple, will have their own unique set of patient pool that people will be targeting. Let's talk about the part three of your phase I study that's going on right now. You're looking at higher dose exposure, titration also. Why don't you tell us what the key questions are that you're really hoping to answer from this study before you get into, say, later stage development for the drug? When we ran the 48 mg without titration, in eight weeks, we had 9.1% weight loss. We had glycemic control of the glucose levels. We had VCTE, which is liver stiffness. We've seen everything that was very positive. What was different between the 48 mg non-titration and the previous lower dose levels was that we started to see moderate side effects, a little bit of an increase in vomiting. Our goal is to make sure that we have a drug that has efficacy, meaning weight loss and other benefits, but the patients will be much more comfortable in taking the drug and staying on it, and that is one of our top priorities in this drug. We are doing the titration because we want to get rid of that moderate side effects. We're doing a one-step titration and two-step titration, which is much shorter than any other drug out there. One-step titration will be 16 mg for four weeks, then we pump it up to 48 mg for 12 weeks. We'll have a 16-week data on that. Then we have the two-step titration, which is 16 mg for four weeks. Then we double that to 32 mg for four weeks. Then we double that again to 64 mg for eight weeks. That 16-week result with the one-step titration will be available before end of this year. The goal is to make sure that we have much lesser side effects coming from a higher dose. Plus, let's look at early signals of efficacy. We had the first patient in in April, and we are literally cruising through the study. It's double-blinded, and I don't know. I'm blinded as well, so I don't know what's going on over there. Up to now, what I've seen that we are looking at something that is much more safer than the other studies that has been released. When do you expect to have data? Before end of this year. Okay. Sounds good. All right. The safety is one of the priorities for a phase I. Another aspect that we're really focused on is titration is one, second would be the waist circumferences. In our 48-mg, we had almost a 10 cm reduction in the waist in just eight weeks. That's about three inches. You can't just lose outside fat, the belly fat for that much. I don't believe that's possible. This must be coming from the visceral fat. Notably, Boehringer Ingelheim with their survodutide, the GLP-1 group, they released the data in the ADA. 34% of visceral fat was reduced in their phase III study, which was more than a year and a half. When we look at their waist circumferences reduction, much slower than our 17.6. We're doing a full body MRI in this phase I, part three to see where is that waist reduction going. Why is it happening? Is it visceral fat? If we can prove that it is the visceral fat reduction so fast and in a great depth, then we're looking at a data point that we haven't seen with any other GLP-1s. Nobody heard anything about semaglutide or tirzepatide or anything else about how the inside fat has gone away. That's what people want, reduction in the waist and get rid of that inside fat. Yep. All right. I want to switch gears for a second and talk about the DA-1241, your MASH drug, which targets GPR119. For those who aren't familiar with that target, maybe a little bit about the mechanism and then explain why it's a good target for metabolic disease. Well, GPR119, simply put, it produces natural GLP-1s in the gut. That's how you have the glycemic control coming out. Plus, there are GPR119 receptors in the liver, which it results in hepatic lipogenesis. Typically, GPR119 before was targeted in type 2 diabetes. A lot of drugs who were targeting GPR119 failed. We were very cautious in moving the program forward, so make sure that we have the efficacy. In our phase IIa, which was in MASH, we did show great glycemic control in the type 2 diabetes subpopulation. Plus, we show the ALT lowering effect, which was the primary endpoint. We met that and the secondary endpoints as well. With that mechanism of action, and the fact that we probably are the only ones in GPR119 agonist field, we have a potential best-in-class in this drug. Right. You recently showed preclinical data at APASL and the combination data, vanoglipel and resmetirom. What do you think those findings suggest for the future of MASH drug development? Once we had the phase IIa results, the whole landscape of MASH changed. When we were starting off with the clinical trial, resmetirom wasn't approved. GLP-1s were getting hot, but not in the liver space. After we got the data, the landscape changed. Resmetirom, conditionally approved. Semaglutide, got approved. We have FGF21's targeting cirrhosis. It got very crowded very fast. For our drug, a standalone oral drug, to me, it felt like going into that crowded space by itself didn't really make sense, as everyone in MASH field is looking for a combination. From then on, we have been actively doing the non-clinical studies in mice with anything you can imagine, GLP-1s combo. We did metformin, which is a type 2 diabetes agent, first line. In that poster, you can see that the combination with vanoglipel and metformin did show great glycemic control plus a bit of a weight loss as well, which was a little more than what metformin can do. That was very interesting in the type 2 diabetes field. We went ahead and did a combination study on resmetirom. We used a CRO called Gubra. They're very well known in this field. Everyone uses it, like Novo Nordisk, Eli Lilly and Company, everyone uses Gubra model. It was interesting because the first thing they contacted us for, once the study started, I was thinking that we'll be getting the MASH results, but they actually contacted us out of surprise that there is a great weight loss happening. That was interesting. When you look at the poster, it's on our website. Compared to control and the mono arms of vanoglipel and resmetirom, the combination lost about 22% of weight in that study. The most important part is, unlike GLP-1s, where you don't eat to lose weight, the mice actually ate the same amount of food as the mono arms and still lost that much weight, which is very different, very important in this combination. What we're looking at with this combo is that if there are at least 20% of people out there who tried the GLP-1 and couldn't tolerate it or wasn't responsive. There are people out there who wants to lose weight, who just do not respond to GLP-1s. That could be one of the targets of this combo. Plus, it's oral drug, and both resmetirom and vanoglipel didn't really show any adverse events, and they don't do any titration. It's going to be something different if we push this forward as a combination. Very added effects of benefits to the patients out there. Okay. How large do you think the eventual treatment MASH population could become? Wow. When you look at just the obesity market, people talk about $10 billion market, $15 billion market. About 80% of those people have liver issues. Just put it like that, then it's going to be very big. Very, very big. It helps because FDA do not require biopsies to prescribe the drug, which is the right way to go. Okay. Now, company-specific here. As your data set matures, how are you thinking about the right time to engage larger pharma on a partnering versus keeping the economics in-house? Well, in-licensing or company sales or whatever the form the transaction is, it takes time. We are already engaged with the big pharma, and we are actively talking. We're not just sitting around waiting for the right partner. We're actively moving. Okay. How, at this point, are you thinking about balancing the speed of development versus the disciplined execution? As far, I guess, as a real financing, we'll say that. Well, I think the most important is whatever we would like to do with these drugs, we have to generate data. Now, is it the right data? That's the most important. We are very much engaged with the KOLs and the big pharmas, and we make sure that we are putting the resources in the right direction. At the end of the day, it's about speed and the quality of data. DA-1726 safety, waist circumferences, and last will be how the weight loss is happening. We are actively engaged with multiple angles to make sure that we are executing on the right direction. As we're looking out, say, a year and a half from now, what do you think investors should be focused most on over that timeframe, as far as data readouts, inflection points, things like that? By end of this year, we'll have the DA-1726 titration 16-week data out. With that, we are already preparing for a phase II design, and we'll be able to hopefully let everyone know where we're going with the phase II and what kind of design we are focused on. For the vanoglipel 1241, we were actively looking at the combos, as I mentioned, and that is the reason why we haven't had the FDA meeting yet. We will have the FDA meeting in the second half of this year since we have found a combo target, and it's very important because just think of it this way. If we combo this with resmetirom, which is already an approved drug, which already has a very sizable biopsy data, do we still have to do biopsy? Those are the questions that we've been waiting for to ask FDA before we push this combination into a phase II or a phase III. Very much looking forward to that conversation with the agency, and that will be another inflection. My target personally will be no biopsy and go straight into a phase III with this combo, but we'll see. Yeah. Thinking of MetaVia more of as a cardiometabolic company, are there any indications beyond obesity and NASH that you're excited about? We did run the AI model on vanoglipel, it just showed different angles. Right now, our focus will be on the cardiometabolic aspect of these drugs. Going into different angles, I don't believe the big Pharmas are waiting for that data. We're very much focused on what the market is asking for, what they're expecting, and what is the best way to use our investors' investment and get the best results. Excellent. All right. We'll close with this. What's the single most important thing that you want investors to understand about your company right now? We've been through a lot. Myself, Marshall, everyone been through a lot. I believe this is the year where we break out. I believe that everyone who has been patient or anyone who's coming in for the first time, this is the year that we are going to make a big move, we're going to break through, and we're going to be putting ourselves on the map on obesity and NASH. The heart, it's painful to go through all this for years, but we are getting there, and I hope everyone believes in us. All right. Sounds good. Thanks, guys, for the discussion today, thanks everyone for tuning in. Thanks, David. Appreciate it. Thank you, David.