NASDAQ: MTVA
Lili Elston: Hello, and welcome to the Life Sciences Investor Forum. On behalf of OTC Markets and our co-host, Zacks Small Cap Research, we're very pleased you've joined us. The next presentation of the day is from MetaVia. Their session will be moderated by David Bautz, Senior Equity Analyst with Zacks Small Cap Research. Please note that you may submit questions for the presenter. You can also view a company's availability for one-on-one meetings by clicking Book a Meeting. At this point, I am very pleased to welcome H.H. Kim, Chief Executive Officer and President of MetaVia (NASDAQ: MTVA). Welcome, H.H., and David.
David Bautz: Thanks, Lili. Hi, H.H., how are you doing?
H.H. Kim: Hey, David. Good, good. How are you?
DB: Very good, thank you. Glad you could join us today. I'm excited to dig into what you guys have been up to. I think we'll mostly be focused on the obesity market today. I thought we'd have a nice discussion about your lead asset there, DA-1726. So, if you're ready, let's get into it.
HK: Yeah, I'm happy to be here.
DB: So, as you know, most of the currently approved obesity drugs are GLP-1-based, the GLP-1 or GLP-1/GIP combos. Now, your program is a little bit different as it has a GLP-1 and a glucagon receptor agonism. So, can you walk us through the scientific rationale for targeting both GLP-1 and glucagon, and maybe what advantages your molecule has in terms of weight loss and metabolic outcomes?
HK: The approved drugs are GLP-1 or GLP-1 plus GIP. I think everyone now knows what GLP-1 does. Now, for a drug like tirzepatide, what GIP does is it enhances the GLP-1's efficacy and provides added support for the side effects. That's why we're seeing tirzepatide being a lot more tolerable than just a standalone GLP-1. Now, all of these drugs, when they started, started off targeting type 2 diabetes. And as they've seen side effects of loss of appetite and weight loss, it turned into an obesity drug. Back in those days, there were other companies, and there are still companies pushing forward, but trying to develop a GLP-1 and glucagon dual agonist in type 2. So, both of our assets in clinical, when we first started the programs, were targeting type 2 diabetes. Now, GLP-1 lowers blood glucose level, but actually, glucagon increases it. Then why did we have this combination targeting type 2? It's because glucagon actually has increased energy expenditure and has direct hepatic effects as well, compared to GLP-1. If the balance between the GLP-1 and glucagon is well balanced to cross out, don't cross out the glucose control, then we may be seeing added benefits better than a standalone GLP-1, of course, and even GLP-1 and GIP. So that was the journey that we started. We went with type 2 diabetes first, made sure that our drug has a glucose-lowering effect and glycemic control. Then everyone found out that GLP-1s actually work as an obesity drug, so we're focused on obesity.
DB: I want to dive in a little bit to what you said. You're talking about the ratio of glucagon versus GLP-1 receptor activation. So, your company has stated that you're at a three-to-one ratio of GLP-1 to glucagon. How did you arrive at that balance, basically? And what do you think that does in terms of optimizing the efficacy and tolerability?
HK: When we first started the journey, there were other GLP-1/glucagons in clinical, and what we noticed was that the balance is very important. If you have a perfectly well-balanced one-to-one ratio, there is a chance that the lowering of glucose and upping of glucose all cancel out and there is no glycemic effect. Just because we have the higher GLP-1 side in the ratio, it doesn't mean that at the end it shows better glycemic control either. So, the balance was really important for us, and the focus was to make sure that we have a drug that has great glycemic control to be a type 2 diabetes agent. Now, with that three-to-one balance, we have witnessed through our animal models while we're developing the drug that the mice actually ate a lot more compared to other drugs. For example, when we looked at the tirzepatide comparison with the obese mice model, our drug, with the three-to-one balance, ate about 25% more food while losing the same amount of weight. So that was something different that we started to see, and we believe that this balance may be the key to tolerability and safety, since, as you know, animals, if they feel sick, they don't eat.
HK: It's not like humans, right? If the mice ate 25%, 30% more food and still lost that much weight, then it has to be something different. And we've seen through our early-stage Phase 1 that that could actually be true, because we went up to 48 milligrams. And yes, at 48, we started to see moderate side effects, but below that, we only had mild GI side effects.
DB: We'll get into the data in just a second, but I did want to ask you one more question about the glucagon receptor activity and the ability to increase energy expenditure. Do you think that is going to be a large component of why this drug causes weight loss?
HK: Yes, I believe that that is where we're trying to get to. When you have the GLP-1 side, and this is pretty well known now, the appetite control is the key to losing weight. When you start on the GLP-1 journey, all of the patients lose appetite, they don't want to eat, they feel nauseous, they feel continuously full, and their food intake goes down. When you don't eat, you lose weight. One of the KOLs told me this is long before, but the way to lose weight is to eat less and exercise. Exactly. Now, exercise, I don't know, but eating less happens with a GLP-1. But if that is only the case, then you have a huge rebound once you stop the medication. It's not like you have changed. It was just the power of the medication that made you lose your appetite. And once you're off of it, appetite comes right back; you lost a lot of weight, and gaining it back happens much faster. So that is one of those rebounds that people are worried about. Even before starting the GLP-1 journey, they're worried that once you stop, you're gonna rebound back or even gain more weight. Why do we even start this journey? That's one of those patients' interviews.
HK: Now, for us, because we have the energy expenditure, the way we see it, and we're trying to prove it, is that, yes, appetite control needs to be there, as the KOL mentioned, but energy expenditure can help with the speed of the weight loss. Plus, you may not be heavily dependent on the appetite loss to lose the weight, meaning you'd be eating a little more than the other GLP-1s. In that case, the rebound should not be as big as the competition.
DB: Excellent. Let's dive into the data that you've presented so far for the Phase 1 study. Just a couple of top-line numbers that I've got here. You reported a 9.1% decrease in body weight, a 3.8-inch decrease in waist circumference, a 0.22 decrease in HbA1c, and a 23.7% decrease in liver stiffness. So obviously, when investors are evaluating new obesity therapies, most of it is just, okay, who loses the most weight the fastest at this point? But based on these numbers that you've generated, where do you see your drug differentiating? Is it in terms of weight loss, maybe the metabolic parameters, or do you think it's going to be a combination of both?
HK: It's a combination of both. When we started off, we found out, and some of the investors and shareholders might remember, but in the early stages of our Phase 1 study, we were comparing ourselves to other GLP-1 glucagons. There are like Altimmune's pemvidutide, survodutide from Boehringer Ingelheim, or mazdutide from Eli Lilly, that are in Phase 3 or going into Phase 3. We're comparing ourselves to them. But now, with this eight-week study result, we are definitely faster in losing the weight because of the minus 9.1% weight loss. The other drugs hit it around 16 weeks or 12 weeks, somewhere around there. Now, the most important thing here is the glycemic control. As I mentioned, we targeted that when we started this program. We've seen a -0.2% HbA1c reduction in just eight weeks. But these were obese but otherwise healthy subjects. So we're not talking about HbA1c of higher than 8 or higher than 7. It was normal for people losing or reducing -0.2%. We were lucky to have one pre-diabetic patient in our active arm, and he started the trial with a baseline of 6% HbA1c. Eight weeks later, normalized to 5.5. That's a pretty good result compared to any other GLP-1 glucagons.
HK: But one of the highlights is the waist. When you ask anyone, "Where do you want to lose weight?", people won't be that focused on your face or your arms, right? It's the waist. That's what everyone wants. With the waist almost four inches down after eight weeks, you basically have to buy a new pair of pants, and that will motivate the subjects or patients to stay on the drug because it makes you happy. So that's where, we believe, compared to other GLP-1 glucagons or any other GLP-1, this is one of the highest waist reductions seen up to now. I believe this is coming from our glucagon side of it. It attacks the white adipose tissues, the fat, and it breaks it down, and that's how you lose this much waist in just eight weeks.
DB: As you mentioned, the weight loss number, the -9.1% over eight weeks, is pretty impressive. And I think one of the things that people see when you get to later, longer time frames is a plateau. So what are your thoughts about or expectations for a plateauing effect for your drug?
HK: We haven't seen any plateauing with the eight-week study. I don't believe we will plateau anytime soon. But the thing is, -9.1%, this is pretty much close to the triple-G that everyone believes will go beyond 30% weight loss. Now, I do understand that a lot of people are frustrated. I agree with everyone because I'm frustrated too. After all, we're still on the Phase 1 study. We're increasing the dose level to 64 because we believe, looking at the side effect profile, we can go higher. Now, 48 milligrams is close to triple-G at week 8, and of course, the side effects are much better than triple-G. If we go up to 64 with our just two-step titration, and if we can see higher results at the 16-week mark and we're right there with triple-G, then we could be one of the best weight loss drugs in the GLP-1 space.
DB: Okay, yeah. You mentioned the next part of your Phase 1 studies. Why don't we talk about that a little bit? Why don't you give us the details of that? And then you do have a titration in this part of the study, actually two different titrations. What are you looking to gain? What info are you looking to see from each of those different titrations?
HK: Now, we are aware of the other GLP-1 glucagons that are quite notorious for GI-related side effects. Plus, when you look beyond the GLP-1 glucagon, if you look at the triple-G controlling the tolerability and side effects is going to be one of the key elements to differentiating. At 48 milligrams, we started seeing moderate side effects in vomiting. And part 3A, the new clinical trial we're starting, will start with 16 milligrams for four weeks, then 12 weeks of 48. The design is to make sure that we try to control those moderate side effects. If we go into a bigger study, we don't want our drug to look like other GLP-1 glucagons or glucagon drugs. So that's the key for part 3A. Then for B, since we haven't really seen other moderate side effects or an amazing amount of other nausea or other GI side effects, we believe we can go higher. So, 64 milligrams is the target. Two-step titration: 16 milligrams for four weeks, then we bump it up to 32 milligrams for four weeks, then we double that to 64 for the rest of the 16-week trial. Now, with that, we believe we'll be able to control the GI side effects. The target will be eliminating any moderate side effects, but trying to see where we can get to with the 64 milligrams.
DB: What do you think you're going to have to show in terms of efficacy, be it weight loss or metabolic parameters, in these Phase 1 studies to really start to differentiate your drug from what else is out there?
HK: Now it's a Phase 1, 16-week. The target will be weight loss of anywhere between 12 to 15%. That's in the elite level. And 9.1% in eight weeks, that's elite level as well. So, the 16-week result, anywhere between 12% to 15% will be a winner on the weight loss side. I'm quite confident that we'll see a lot of waist reduction. Plus, although obese, they’re otherwise healthy, and we would like to see how the glycemic control works. At -0.2% at eight weeks, it probably won't go lower than that because that's HbA1c of 5.5, so we'd want to maintain that throughout the whole 16 weeks. But the most important part of it is, how do we understand the drug? And this is a longer study. We're implementing a full-body MRI and MRI-PDFF on the liver. We'll be able to see what is going on with this waist reduction. I think my focus is not on the overall, but just on the waist. How do you lose four inches in eight weeks? How much are the subjects in the new study going to lose in 16, and is it the outside fat? Is it really? The main concern of the waist is the internal fat that's stuck on your organs and the gut. If we can remove those effectively, I think we'll see something very different than what other GLP-1s have been looking at. The full body MRI, I think, is going to be the key to our 16-week study that will differentiate us from the other GLP-1s.
DB: A lot of people are concerned now with the body composition, as you said, fat loss versus lean loss. Is that something that's going to be incorporated as well with this MRI scan that you're doing?
HK: Yeah.
DB: And then do you think the glucagon component of your drug is having an effect there?
HK: Yes, definitely. Definitely. You just don't lose like four inches off your waist, this is the mean, right? This isn't the max waist loss. It's a mean waist loss of almost four inches in eight weeks. There is something happening in the waist, and we would like to find out what it is. I don't know if it’s the fat loss, lean mass... That's very important, but if this drug can show that it is attacking the internal fat that is the most dangerous for metabolic disease, then it could be something different. Quality of fat loss, I guess that could be the phrase.
DB: And when do you expect the results from the study to be announced?
HK: Before the end of this year.
DB: Excellent. All right. So, another concern with obesity treatments is obviously tolerability. One of the knocks on them is that people can't stay on them for very long. From where you're standing, how are you thinking about the durability of response and the ability for patients on your drug to stay on it long term?
HK: I think it's two ways here. Yes, a lot, like 70 to 80% of the obese population, are pre-diabetic or diabetic. Now, diabetic patients will probably have to be on the drug forever, maybe, as the prescribers are saying. But if we're just looking at obese patients, obese but otherwise healthy, it's an interesting concept, isn't it? Obese but otherwise healthy. But we found out that there are people who are obese but otherwise healthy, not even pre-diabetic, as you can see in our Phase 1 trials. Now, those people, do we really have to have them on the drug forever? I don't believe so. I think it's a matter of how you change their lifestyle, which is one thing, but making them able to start a healthy life, I think that's the focus on that population. Like, over 40 or near 40 BMI, they're too big to be exercising because they're going to have a lot of joint issues and everything. So, what if our drug, on just obese but otherwise healthy patients, can lose 10% in eight weeks or even 15% in just four months? They'll be able to move, they'll be able to exercise, and they'll be able to change their lifestyle.
HK: That could be one of the goals that, for me, for 1726, could be a little different than others. Like, think about semaglutide and tirzepatide, it takes about six months to go to the highest dose level because they do like three, four, five-step titrations. When you look at other GLP-1s, they have to titrate because of the side effects, and people can't tolerate that. But for us, up to 48, it was good. Now, one-step, two-step titration is fast enough so that people will be motivated. But to me, it's the waist. I am confident that people will stay on it. But it depends on the obese but otherwise healthy, obese type 2, how long do we have to have the subjects or patients on the drug? It depends.
DB: Okay, kind of a big picture question here. Obviously, the obesity market is rapidly evolving. It seems almost every day different classes and different combinations. How do you see your drug fitting into that landscape? Is this going to be where you're going to try to compete head-to-head? Are you going to look for maybe a particular segment of patients that you want to target? How do you see it working out?
HK: Right now, I think with glucagon in it, obese with MASH and type 2 diabetes, that patient pool would be one of the perfect matches. You can see a -23.7% liver stiffness resolution in just eight weeks. Liver takes time, but that's quite an amazing result. To me, it feels like our drug's main focus is liver plus obese that would be one of the main focuses, with great glycemic control added to it.
DB: In terms of safety, one of the knocks on targeting the glucagon receptor in the past has been its effect on or potential effect on cardiovascular parameters. What have you learned so far about the safety and tolerability of the drug and any potential risks that there might be?
HK: We're planning to release that during one of the medical conferences this year, because we haven't really shared on the QTcF or the heart side, but what I can tell you is we have not seen any signals.
DB: Excellent. All right. And financing; obviously, it takes some money to run these trials. Can you talk about your cash runway and how far that's going to take you right now?
HK: We did a financing in January this year, and we'll be releasing our 10-K with more details. But what I can tell you is that we have enough cash to run the new parts 3A and B on the obesity program.
DB: Sounds good. As far as just general milestones, obviously, we're going to have the data coming out for Part 3 later this year. But are there any other milestones that investors should be looking for over the next, say, 12 to 24 months?
HK: Vanoglip is one of our other drugs. We finished the Phase 2a. It's a small molecule with a great safety profile, showed direct hepatic effects, and met the primary endpoints. We have been testing a lot of different combinations with it because MASH is changing into a combination market with FGF21s and GLP-1s. But the benefit of our drug is that it's a small molecule, it's cheaper, and it's oral. And because of the safety profile, it's much easier to make a combination therapy. We have not just been in the MASH field, but we've been looking into other indications as well, like type 2 diabetes, because we've shown great HbA1c-lowering effects in 16 weeks. We're hoping to release some of this combination data and preclinical data at the upcoming medical conference, and I believe a lot of people will be surprised. It will be a big surprise about where we're going to take this drug in the next steps. Is it going to be something that we pursue to compete in a much bigger market, like obesity? Really, really excited to show this.
DB: All right, looking forward to seeing that. So, in the final bit that we have left here, what are you most excited about coming up? And why do you think MetaVia is a good investment opportunity right now?
HK: Compared to other obesity drug companies, our valuation is very low. Our stock is low. I have to be honest with everyone out there that I hate doing reverse stock splits, but at one point, if we had to do it, we had to do it, and that's what the result was. After that, we did the financing, and the result was that the stock did go down. But this year, I'm hoping it's going to be the last year where we have to go through these things. I'm quite positive that the data sets you'll be seeing throughout the year on our Vanoglip, and before the end of the year, the obesity drug, this could be the time that people invest, because this will be the lowest valuation you'll see before the end of the year. We have real drugs; we have real results coming up.
DB: Excellent. Sounds good. Well, H.H., thank you for joining us. Really appreciate the overview.
HK: Thank you, David, for having me, and I hope to present again next time.
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.