Greg Young: Hello and welcome to the Life 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.
David Bautz: Hey, HH. Hey, Marshall. How are you guys doing this morning?
Marshall Woodworth: David, good, thank you.
DB: Excellent. All right, let’s jump right into it. MetaVia is obviously pursuing both obesity and MASH simultaneously. You could argue that these are two of the hottest areas in biotech. I was wondering if you could start with the overarching strategic vision for the company at this point with those two assets.
HH Kim: Let’s start this way. Obesity, MASH, the liver side, everything is a very hot area right now, and we’re lucky to be one of the companies that’s developing a therapeutic alternative or an option for the patients out there. But at the end of the day, when you look at the competition, when our drugs are going to market like 2030, 2031, and ’32, somewhere around there, the competition will be very fierce, and we fully acknowledge that. And 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 very promising datasets, and 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. So at the end of the day, we are considering that at one point we will have to partner with bigger companies.
DB: Okay, let’s dive into DA-1726, which you’re targeting for obesity, and of course, that drug targets both GLP-1 and glucagon. I wanted to dig into that a bit. Specifically, what physiological advantages do you think that glucagon agonism has beyond what we’re seeing with, say, GLP-1s or GLP-1 and GIP co-agonists?
HK: Everyone knows about GLP-1s, right? A great glycemic control coming from the drug, plus appetite control, which results in great weight loss. Now you add glucagon to it. What does it do? Glucagon has direct hepatic effects, it has energy expenditure, increased energy expenditures and that will add additional benefit than just GLP-1 alone. But in a bigger picture, let’s think of other duals as well, like tirzepatide, which has a 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. And tirzepatide, Mounjaro, and Zepbound are great drugs. Now, the hype of these days, amylin, what does it do? It has glycemic control, and it has a bit of the appetite control. So it’s mostly similar to what GLP-1s do. So 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 will have better glycemic control as well. But at the end of the day, that sounds pretty similar to what GLP-1s do. So, enhancing the GLP-1, that’s what amylins do.
HK: So when we look at the landscape right now, glucagon is the one that has a unique benefit than a GLP-1 standalone. And that’s why everyone is pursuing GLP-1/glucagon dual agonists. And of course there’s Triple G, which is GLP-1, GIP, and glucagon, and 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, so we’ll have to see how the results come out on the liver side of the Triple G.
DB: Okay, how do you think about the ideal balance between, say, GLP-1 activity and glucagon activity?
HK: On the ratio side, our drug is 3:1, three on GLP-1 and one on glucagon. And let’s look at the whole table of drugs. There is pemvidutide, Altimmune’s GLP-1/glucagon, which is a 1:1 balance. It’s perfectly balanced. So GLP-1 lowers blood glucose while glucagon actually increases it. So if you have a perfect 1:1 balance, it just knocks out both of the effects. So Altimmune’s pemvidutide will not be able to be used in type 2 diabetes patients, which consists of about 70 to 80% of the obese population. Now we have our drug, which is a 3:1 balance. In our study, although a small sample size and early in phase one, the last dataset we have released in the 48 milligram non-titrated cohort, we were lucky to have one patient who had HbA1c of 6, which is pre-diabetic, and after eight weeks of treatment, his HbA1c went down to 5.5, normalizing in just two months. So we believe the 3:1 balance can work great on glycemic control. Then you have mazdutide, which is Eli Lilly’s drug, 5:1 balance. They haven’t released it, but our research center analyzed it and came up with the 5:1 balance.
HK: And it’s a great drug. It’s approved in China. Eli Lilly is trying to push it up another level on the dose level to 12 milligrams, which isn’t approved in China. China, I believe, is approved up to 9 milligrams, and it’s doing great. 12 milligrams of mazdutide lost about 21%, 22% of weight in their phase two. It’s just that they had to go through a lot of titration to go up that high. Then you have survodutide, Boehringer Ingelheim’s drug, which had the data released at the ADA early this month, showing great direct hepatic effects in the liver. It’s just that discontinuation was about 24%, it had a lot of GI side effects, and had almost six to seven titration steps. So 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 and not just because you have a lower balance like 1:1 with pemvidutide 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. It’s the balancing act between it which is more important.
HK: And we believe that 3:1 is the right balance because we haven’t seen any severe side effects up to now. We haven’t had any discontinuation due to the drug, which is very different compared to any other GLP-1 plus glucagon out there.
DB: Okay. As you look at the wider field and speaking of the glucagon agents, do you see any signs that glucagon agonism could become a required component of next-gen obesity therapies?
HK: Glucagon’s best benefit is that it has receptors in the liver. 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, matching up with a GLP-1. But if you’re looking at the type 2 diabetes population, I think amylin is a great dual. But if you look at the liver side of things, glucagon will be the most important dual agonist. So it’s just like, how do we look at this whole obesity field? You have type 2 diabetes patients, which is about 70 to 80%, and you have MASH or liver disease, which is quite similar to that. Then you have obese, otherwise very healthy people, which I am still a little puzzled about how you could be over 30 BMI and not have any comorbidities. But it’s all segmented, and I believe the next-generation GLP-1 drugs, which will have to be a dual or a triple or quadruple…
HK: Will have their own unique set of patient pool that people will be targeting.
DB: So let’s talk about the part three of your phase one 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 hoping to answer from this study before you get into, say, later-stage development for the drug?
HK: So when we ran the 48 milligram without titration, in eight weeks we had 9.1% weight loss, we had glycemic control at the glucose levels, we had VCTE, which is liver stiffness. We’ve seen everything that was very positive. But what was different between the 48 milligram non-titration and the previous lower dose levels was that we started to see moderate side effects increase, a little bit of an increase in vomiting. So 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 taking the drug and staying on it. And that is one of our top priorities for this drug. And we are doing the titration because we want to get rid of that moderate side effects. So we’re doing a one-step titration and a two-step titration, which is much shorter than any other drug out there. One-step titration will be 16 milligrams for four weeks. Then we bump it up to 48 milligrams for 12 weeks. So we’ll have a 16-week data on that. Then we have the two-step titration, which is 16 milligrams for four weeks, then we double that to 32 milligrams for four weeks.
HK: Then we double that again to 64 milligrams for eight weeks. And that 16-week result with the one-step titration will be available before the end of this year. And the goal is to make sure that we have fewer side effects coming from a higher dose. And let’s look at early signals of efficacy. And we had the first patient in April and we are literally cruising through the study. So it’s double-blinded, and I’m blinded as well, so I don’t know what’s going on over there. But up to now, what I’ve seen is that we are looking at something that is much more safer than the other studies that has been released.
DB: Okay, and when do you expect top-line data?
HK: Before the end of this year.
DB: Okay, sounds good.
HK: All right. And safety is one of the priorities for a phase one anyway. Another aspect that we’re focused on is titration is one, second would be the waist circumference. So, in our 48 milligrams, we had almost a 10-centimeter reduction in the waist in just eight weeks. That’s about three inches. And you can’t just lose outside fat, the belly fat, for that much. I don’t believe that’s possible. So this must be coming from the visceral fat and…
HK: Notably, Boehringer Ingelheim, with their survodutide, the GLP-1 glucagon, released the data in the ADA that 34% of visceral fat was reduced in their phase two study, which lasted more than a year and a half. So when we look at their waist circumference reduction, much slower than our 1726. So we’re doing a full-body MRI in this phase one part three to see where that waist reduction is coming from. Why is it happening? Is it visceral fat? And if we can prove that it is the visceral fat reduction so fast and in 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, tirzepatide, or anything else about how the inside fat has gone away. But that’s what people want, a reduction in the waist and to get rid of that inside fat.
DB: All right, I want to switch gears for a second and talk about danuglipron, your MASH drug, which targets GPR119. For those who aren’t familiar with that target, maybe talk a little bit about the mechanism there, and then explain why it’s a good target for metabolic disease.
HK: So GPR119, simply put, produces natural GLP-1s in the gut, and that’s how you have the glycemic control coming out. And plus there are GPR119 receptors in the liver, which result in a direct hepatic effect. Typically, GPR119 was targeting type 2 diabetes, but a lot of drugs that were targeting GPR119 failed. So we were very cautious in moving the program forward to make sure that we had the efficacy. And in our phase 2a, which was in MASH, we did show great glycemic control in the type 2 diabetes subpopulation. And plus we showed the ALT lowering effect, which was the primary endpoint. We met that and the secondary endpoints as well. Now, with that mechanism of action and the fact that we are probably the only ones in the GPR119 agonist field, we have a potential best-in-class drug.
DB: Right. So you recently showed preclinical data at ADA and combination data of danuglipron and resmetirom. What do you think those findings suggest for the future of MASH drug development?
HK: So once we had the phase 2a results, the whole landscape of MASH changed. When we were starting the clinical trial, resmetirom wasn’t approved. GLP-1s were getting hot, but not in the liver space. But after we got the data, the landscape changed. Resmetirom was conditionally approved, and semaglutide was approved; then we have FGF21s targeting cirrhosis. So it got very crowded very fast. Now 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 the MASH field is looking for a combination. So 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, and in that poster you can see that the combination with danuglipron and metformin did show great glycemic control plus a bit of weight loss as well, which was a little more than what metformin can do. So that was very interesting in the type 2 diabetes field. Then we went ahead and did a combination study on resmetirom. So we used a CRO called Gubra.
HK: They’re very well known in this field. Everyone uses it, like Novo, Madrigal; everyone uses the Gubra model. And it was interesting because the first thing they contacted us about once the study started, I was thinking that we would be getting the MASH results. But they actually contacted us out of surprise that there is a great weight loss happening. So that was interesting. And when you look at the poster, it’s on our website. Compared to the control and the mono arms of danuglipron and resmetirom, the combination lost about 22% of weight in that study. But the most important part is that, 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 and very important in this combination. So what we’re looking at with this combo is that if there are like at least 20% of people out there who try the GLP-1 and can’t tolerate it or aren’t responsive, there are people out there who want to lose weight who just do not respond to GLP-1s. That could be one of the targets of this combo. Plus, it’s an oral drug, and both resmetirom and danuglipron didn’t really show any adverse events, and they don’t require any titration.
HK: So it’s going to be something different if we push this forward as a combination. Very added effects, the benefits to the patients out there.
DB: Okay. How large do you think the eventual treated MASH population could become?
HK: I believe, when you look at just the obesity market, people talk about a 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. And it helps because the FDA does not require biopsies to prescribe the drug, which is the right way to go.
DB: Okay, now company-specific here. As your dataset matures, how are you thinking about the right time to engage larger pharma on partnering versus keeping the economics in-house?
HK: Licensing or company sales or whatever form the transaction takes, it takes time, and we are already engaged with Big Pharma, and we are actively talking, so we’re not just sitting around waiting for the right time; we’re actively moving.
DB: Okay, how at this point are you thinking about balancing the speed of development versus disciplined execution as far as, I guess, as it relates to financing, we’ll say that.
HK: I think that the most important thing is that, 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. And 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. But at the end of the day, it’s about speed and the quality of the data. And 1726, safety, waist circumferences, and last, will be how the weight loss is happening. But we are actively engaged with multiple angles to make sure that we are executing in the right direction.
DB: Okay, as we’re looking out, say a year, year and a half from now, what do you think investors should be focused most on over that time frame as far as data readouts, inflection points, things like that?
HK: So by the end of this year, we’ll have the 1726 titration 16-week data out. With that, we are already preparing for a phase two design, and we’ll be able to hopefully let everyone know where we’re going with the phase two and what kind of design we are focused on. Then for the vando, for 1241, we were actively looking at 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 combine this with resmetirom, which is already an approved drug, which already has a very sizable biopsy dataset, do we still have to do a biopsy? And those are the questions that we’ve been waiting to ask the FDA before we push this combination into a phase two or a phase three. So 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 three with this combo. But we’ll see.
DB: Thinking of MetaVia more as a cardiometabolic company, are there any indications beyond obesity and MASH that you’re excited about?
HK: We did run the AI model on pemvidutide, and it did show different angles. But 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. So 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 out of it.
DB: 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?
HK: We went through a lot- myself, Marshall, everyone’s been through a lot, and I believe this is the year where we break out. I believe that everyone who has been a patient, or anyone who’s coming in for the first time, that 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 MASH. It’s painful to go through all this for years, but we are getting there, and we hope everyone believes in us.
DB: All right, sounds good. Thanks, guys, for the discussion today, and thanks, everyone, for tuning in.
MW: Thanks, David. Appreciate it.
HK: Thank you, David.
SUBSCRIBE TO ZACKS SMALL CAP RESEARCH to receive our articles and reports emailed directly to you each morning. Please visit our website for additional information on Zacks SCR.
DISCLOSURE: Zacks Investment Awareness (ZIA) is a Zacks SCR product. The Zacks SCR analyst conducting this Chat hereby certifies that the views expressed accurately reflect the personal views of the analyst about the subject securities and issuer. Zacks SCR certifies that no part of any analyst’s compensation was, is, or will be, directly or indirectly, related to the recommendations or views expressed in this Chat. Zacks SCR believes the information used for the creation of this Chat has been obtained from sources considered to be reliable, but we can neither guarantee nor represent the completeness or accuracy of the information herewith. Such information and the opinions expressed are subject to change without notice.
This text is not a verbatim transcript. This transcript has been edited and does not reflect the video-recording exactly. You may find the video recording in its entirety here. Full Disclaimer HERE.
