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 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, which trades on Nasdaq under the symbol MTVA. Welcome, H.H. and David.
Thanks, Lily. Hi, H.H. How are you doing?
Hey, David. Good, good. How are you?
Very good, thank you. Glad you could join us today. 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. If you're ready, let's get into it.
Yeah. Well, happy to be here.
All right. As you know, most of the currently approved obesity drugs are GLP-1 based or GLP-1 GIP combos. Now, your program is a little bit different as it has a GLP-1 and a glucagon receptor agonism. 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?
Yeah. The approved drugs are GLP-1 and 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 plus provides with added support on the side effects. That's why we're seeing tirzepatide being a lot more tolerable than just a standalone GLP-1. Now, all these drugs, they started off with targeting type 2 diabetes. As they've seen side effects of loss of appetite, 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. Our Both of our assets in clinical. When we first started the programs, it was targeting type 2 diabetes. Now, GLP-1 lowers blood glucose level, but actually glucagon increases it. 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-1s.
If the balance between the GLP-1 and glucagon is well-balanced to not 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. That was the journey that we started. We went with type 2 diabetes first, made sure that our drug has a glucose-lowering effect, glycemic control. Everyone found out that GLP-1s actually work as an obesity drug. We're focused on obesity.
All right. I wanna dive in, a little bit to what you said. You're talking about the ratio of, glucagon versus GLP-1 receptor activation. Your company has stated that you're a 3-to-1 ratio of GLP-1 to glucagon. How did you arrive at that balance, basically, and then what do you think that does, in terms of optimizing the efficacy and tolerability?
When we first started the journey, there were other GLP-1 glucagons in clinical. What we noticed that was that the balance is very important. If you have a perfectly well-balanced, 1-to-1 ratio, there is a chance that, lowering of glucose, upping the glucose, all those crosses out and there is no glycemic effect. Just because we have higher GLP-1 side in the ratio, it doesn't mean, at the end it shows better glycemic control either. 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 3-to-1 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. Like if, for example, when we looked at tirzepatide comparison with obese mice model, our drug with the three-to-one balance ate about 25% more food while losing the same amount of weight. That was something different that we'd start to see, and we believe that this balance maybe the key to tolerability and safety since, as you know, animals if they feel sick, they don't eat. It's not like humans, right?
If the mice ate, like, 25-30% more food and still lost that much weight, then it has to be something different. We've seen through our early stage phase I that that could actually be true, because we went up to 48 mg. Yes, at 48 mg we started to see moderate side effects, but below that we only had mild GI side effects.
We'll get into the data in just a second, but I did wanna ask you one more question about the glucagon receptor activity and the ability to increase energy expenditure. Do you think that is gonna be a large component of why this drug causes weight loss?
Yes. I believe 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 your food intake goes down. When you don't eat, you lose weight. One of the KOLs told me that, well, this is long before, but the way to lose weight is eat less and exercise. Exactly. Now, exercise, I don't know, but eating less happens with a GLP-1.
If that is only the case, then you have a huge rebound once you stop the medication. It's not like yourself has changed, it was just the power of the medication that made you lose appetite. Once you're off of it, appetite comes right back, and you lost a lot of weight, and gaining it is much faster. 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 more weight than we even start this journey. That's one of those patients interviews.
Now, for us, because we have the energy expenditure, the way we see it and we're trying to prove 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 be losing the weight, meaning you eat a little more than the other GLP-1s. In that case, the rebound should not be as big as the competition.
Okay. Excellent. Let's dive into your data that you've presented so far for the phase I study. Just a couple of top-line numbers that I've got here. You reported 9.1% decrease in body weight, 3.8 inches decrease in waist circumference, 0.22 decrease in HbA1c, and a 23.7% decrease in liver stiffness. Obviously, when investors are evaluating new obesity therapies, most of it is just, "Okay, who loses the most weight the fastest at this point?" 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 gonna be a combination of both?
It's combination of both. When we started off, some of the investors and shareholders may remember, but in the early stages of our phase I study, we were comparing us to other GLP-1 glucagons. There are like Altimmune's pemvidutide, survodutide from Boehringer Ingelheim, mazdutide from Eli Lilly that are in phase I or going into phase III . We're comparing us to them. Now with this eight week study result, we are definitely faster in losing the weight because -9.1% weight loss.
The other drugs hit it around 16 weeks or 12 weeks, somewhere around there. Now, the most important here is that, yes, glycemic control, we as I mentioned, we targeted that when we started this program, so we've seen -0.2% HbA1c reduction in just eight weeks. These were obese otherwise healthy subjects. We're not talking about HbA1c of higher than eight or higher than seven. It was normal 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 baseline of 6% HbA1c. eight weeks later, normalized 5.5. That's a pretty good result compared to any other GLP-1 glucagons. One of the highlights is the waist. When you ask anyone, "Where do you wanna lose your weight?" People won't focus on your face or your arms, right? It's the waist. That's what everyone wants with the waist. Almost 4 inches down after eight weeks, you basically have to buy a new pair of pants.
That will motivate the subjects or patients to be on the drug because it makes you happy. That's where we believe compared to other GLP-1 glucagons or any other GLP products, this is one of the highest waist reduction I have 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. It browns it, and that's where all people, how you lose this much weight in that much, like, in just eight weeks.
Right. Yeah. Okay. As you mentioned, the weight loss number, the -9.1% over eight weeks is pretty impressive. I think one of the things that people see when you get to later or longer time frames is a plateau. What are your thoughts about or expectations for, you know, plateauing effect for your drug?
We haven't seen any plateauing with the eight week study. I don't believe we will plateau anytime soon. The thing is, -9.1%, this is pretty much close to the Triple G that everyone believe 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 because we're still on phase I study. We're increasing the dose level to 64 because we believe looking at the side effect profile, we can go higher.
Now 48 mg is close to Triple G at eight week. 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 in the 16-week, and we're right there with Triple G, then we could be one of the best weight loss drugs in the GLP-1 space.
Great. Okay. Yeah. You mentioned the next part of your phase I studies. Why don't we talk about that a little bit? Why don't you give us the details of that? You do have a titration in this part of the study or sorry, two different titrations. What are you looking to gain? What info are you looking to see from each of those different titrations?
Now we are aware of the other GLP-1 glucagons. They're quite notorious in side effects, GI related. When you look at even beyond the GLP-1 glucagon, if you look at the Triple G, the side effects are controlling the tolerability and side effects. This is gonna be one of the key elements to differentiating. 48 mg, we did start seeing moderate side effects in vomiting. The phase III-A , the new clinical trial we're starting, will start with the 16 mg for four weeks, then 12 weeks of 48. The design is to make sure that we try to control that moderate side effects.
If we go into a bigger study, we don't want our drug to be looking like other GLP-1 glucagons or glucagon drugs. That's the key for that phase III-A . Since we haven't really seen other like moderate side effects or amazing amount of other nausea, other GI side effects, we believe we can go higher. 64 mg is the target. Two-step titration, 16 mg for four weeks, then we bump it up to 32 mg 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. Target will be eliminating any moderate side effects, but trying to see where we can get to with the 64 mg.
Okay. What do you think you're gonna have to show in terms of efficacy, be it weight loss or metabolic parameters in these phase I studies to really start to differentiate your drug from what else is out there?
Now it's a phase I, 16-week. The target will be weight loss of anywhere between 12%-15%. That's an elite level. Nine point one percent in 8 weeks, that's an elite level as well. Sixteen-week result, anywhere between 12%-15%, will be a winner on the weight loss side. I'm quite confident that we'll see a lot of waist reduction. Although this is obese otherwise healthy, we would like to see how the glycemic control works and minus 0.2% at 8 weeks. Probably won't go lower than that because it's like HbA1c of 5.5. But maintain that throughout the whole 16 weeks.
The most important part of that is how do we understand the drug. This is a longer study, so 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 that. Not 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 gonna lose in 16 weeks? 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 the other GLP-1s I've been looking at. The full body MRI, I think, is gonna be the key to our system study that will differentiate us from the other GLP-1s.
Yeah. A lot of people are concerned now with the body composition, as you said, more fat loss versus lean loss. Is that something that's gonna be incorporated as well with this MRI?
Yes
Scan that you're doing? Yeah.
Yeah.
Do you think the glucagon component of your drug is having an effect there?
Yes. Definitely. You just don't lose your waist like four inches. This is me, right? This isn't the max, waist loss. It's a mean weight 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. Like if, say if, the fat loss, lean mass, that's very important, but if this drug can show that it is attacking the internal fat, that's the most dangerous for, metabolic disease, then we, it could be something different.
Yeah. When will you?
Quality of fat loss, I guess that could be the phrase.
Yeah. When do you expect the results from the study to be announced?
Before end of this year.
Okay. Excellent. All right, another concern with obesity treatment 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 durability of response, and the ability for patients on your drug to stay on them long term?
I think it's two ways here. Yes, a lot of like 70%-80% of the obese population are pre-diabetic or diabetic. Now, diabetic patients probably will have to be on the drug forever maybe, as the prescribers are saying. If we're just looking at obese patients, obese otherwise healthy, it's an interesting concept, isn't it? Obese otherwise healthy. We found out that there are people who are obese but otherwise healthy, but even pre-diabetic, as you can see in our phase I trials. Now those people, do we really have to have them on the drug forever?
I don't believe so. I think it's matter of how do you change their lifestyle is one, but making them able to start a healthy life. I think that's the focus on those population. Like, you're too big, like over like 40 or near 40 BMI, they're too big to be exercising because they're gonna have a lot of joint issues and everything. What if, like our drug, on just obese otherwise healthy patients can lose like 10% in eight weeks or even like 15% in just four weeks. They'll be able to move. They'll be able to exercise. They'll be able to change their lifestyle.
That could be one of the goals that for me, for just DA-1726 could be a little different than others. Like, you know, 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 titration. When you look at other GLP-1s, they have to titrate because of the side effects, and people can't tolerate that. As up to 48, it was good. Now 1 step, 2 step titration, that's fast enough so that people will be motivated. To me, it's the waist. Again.
Right If you're starting, your pants are getting bigger.
I am confident that people will stay on it. It depends on obese otherwise healthy, obese type 2, how long do we have to have the subjects or patients on the drug? It depends.
Okay. Kind of big picture question here. Obviously the obesity market is rapidly evolving, it seems almost every day, different classes, different combinations. How do you see your drug fitting into that landscape? Is this gonna be where you're gonna be trying to compete head to head? Are you gonna look for maybe a particular segment of patients that you wanna target? You know, how do you see it working out?
Right now, I think with glucagon in it, obese with MASH and type 2 diabetes, that patient pool will be one of the perfect match. You can like minus 23.7% liver stiffness resolution in just eight weeks. It's liver. It takes time, but that's quite an amazing result. To me it feels like our drug main focus liver plus obese. That will be one of the main focuses with a great glycemic control added to it.
All right. In terms of safety, one of the knocks on targeting the glucagon receptor for 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?
We're planning to release that during one of the medical conferences this year because we haven't really shared on the CV or the heart side, but what I can tell you is we have not seen any signals.
Excellent. All right. Financing. Obviously it takes some money to run these trials. Can you talk about your cash runway and how far that's gonna take you right now?
We did a financing in January this year, and we'll be releasing our Form 10-K with more detail, but what I can tell you is that we have enough cash to run the new parts A and B on the obesity trial.
All right. Sounds good. As far as just general milestones, obviously we're gonna have the data coming out for this part three later this year, but are there any other milestones that investors should be looking for over the next say, 12 to 24 months?
Vanoglipel is one of our drug, the other drug. We finished the phase II-A . It's a small molecule. A great safety profile showed direct hepatic effects, met the primary endpoints. We have been testing a lot of different combination with it, because MASH is changing into a combination market. FGF21s, GLP-1s. The benefit of our drug is a small molecule. It's cheaper and it's oral. Because of the safety profile, it's much easier to make a combination therapy.
We have been not just in the MASH field, but we've been looking into other indications as well like type 2 diabetes, because we've shown a great HbA1c lowering effect in 16 weeks. We are hoping to release some of these combination data and preclinical data in upcoming medical conferences, and I believe a lot of people will be surprised. We will be
Great
a big surprise on where we're gonna take this drug into the next steps. Is it gonna be something that we pursue to compete in a much bigger market like obesity? I'm really, really excited to show this.
All right. Well, looking forward to see that. 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?
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 have to do it, we had to do it. That's what the result was. After that, we did the financing and the result of that, we did have the stock go down. This year I'm hoping it's gonna 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 Vanoglipel 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 at the end, before end of the year. We have new drugs. We have new results coming up.
Excellent. Sounds good. Well, Hyung Heon Kim, thank you for joining us. Really appreciate the overview.
Oh, thank you, David, for having me, and hope to present again next time.
All right. Sounds good. Thanks again.
Thank you.