Good afternoon, everyone, and welcome back to another session here at Oppenheimer's 34th Annual Life Sciences Conference. We are delighted to have as our next presenting company, Veru. With Veru, we have the company's CEO and founder, Dr. Mitch Steiner, who will be walking us through the presentation. The company has recently switched gears and is focusing on the development of its SARM, enobosarm, to mitigate the muscle loss that occurs with GLP-1 weight loss, which, as you may know, has become a really big problem. I think the lay media have really kind of raised the profile of that liability. There is a venue for you to ask questions on the web. Please submit, and I will ask on your behalf.
With that, I will turn the podium over to, to Mitch.
Thank you, Leland, and thank you everybody for being on today's call. First of all, I'm gonna be making some forward-looking statements in safe harbor, so I refer you to our filings in 10-K with the SEC to go through the risks of the company. Now, Veru is focused on enobosarm in combination with a GLP-1 receptor agonist, 'cause we are a muscle drug, and muscle loss has become a key issue. But I want to make it very clear that we do have two other phase II, two other phase III programs. The phase III program for sabizabulin, it, you know, we're trying to find a pharmaceutical partner to help us with this program, but it's, it's gone through FDA clearance from a standpoint of phase III design.
So, you know, once we have a partner, then we'll be able to move this forward. Breast cancer, same story, phase III asset. We're focusing primarily on enobosarm in combination with GLP-1, because it's such a major market with a real opportunity for a drug that's a muscle drug. With that said, as you know, and Leland pointed out very nicely, what we're learning is that everybody wants to get on a GLP-1 receptor agonist that's overweight or obese, because of the weight loss benefits. But what we're recognizing very quickly is it doesn't come without side effects. And the biggest side effect is muscle loss, and the muscle loss is causing pause to patients that want to be on the drug or are on the drug.
This really came from, and it was well characterized in New England Journal of Medicine article by Wilding, that basically showed that of the weight loss that occurs, and this is at 72 weeks, the weight loss that occurs, about 40% of that weight loss is muscle. So another way to think of it, and just round it out to 50/50, for every pound of fat you lose, you lose a pound of muscle. That's what you have to pay. Now, the problem with losing muscle is you need that tissue. It's critical tissue. And so losing fat, you can lose fat right down to, like, less than 5%, but you can't do that with muscle. You'll be dead.
The patient population that's most at risk are patients over the age of 60, which, 42% of patients over the age of 60 could benefit from a weight loss drug. However, a third of these patients already have muscle loss that happens with age, and that's called sarcopenic obesity, where they have muscle loss that's critically low, but they're also obese. So if you look to the right, you'll see, cross-section across the thigh, and, well, and you'll see bone right here, and fat is in white, but that's pretty good, healthy-looking muscle. If you take a patient who's sarcopenic obese, an older patient, the circumference of the leg looks the same, but what you see inside is different.
What you see is a lot of fat, but there's very little muscle, and it's well marbleized, which means that it probably has some poor function. If you take this patient and you start taking a pound of muscle for every pound of fat you lose, you'll see you get into trouble, and they can't get into trouble. They get muscle weakness, which can lead to poor balance, decreased gait, loss of muscle strength, functional limitations, mobility disability, et cetera. Essentially, you're creating frailty. And so you're taking these patients and they're developing accelerated frailty in months instead of years. So that's the problem. But really, if you look at the whole patient population, not only the older patient, but the whole patient population, you'll find some very interesting information that shows you why a muscle drug could be very important. First information, this is the...
straight out of the Wegovy package insert. And you see there were four studies that were there to support the approval. And I'll point your attention to these, some very interesting characteristics of these four studies. So, for example, this first one, which is STEP 1, you'll see that the placebo is here. This is weight loss for placebo, weight loss for the treated. What you see is in the first 16 weeks, half the weight loss is gonna occur, and then at 16 weeks, so one more year later, the additional half will go away. So it takes 50-50% of the weight loss over a year, and that first 16 weeks, you have 50% of the weight loss. So why does it hit a plateau? Why does it slow down? And you see it in every one of these studies.
You know, about 16 to 20 weeks, slows down, slows down, slows down. And so people get complaining that, "It doesn't feel like I'm losing the same amount of weight as I did at the beginning." The reason for that is, because muscle goes down. Again, a pound of muscle for every pound of fat you lose, and the body just does not like that. When you... fat-free mass goes down, when muscle mass goes down, it triggers appetite. And so essentially what you're seeing is a fight between appetite and the GLP-1, in that, you know, beyond 16 weeks. If you're able to keep the muscle from, preserve the muscle, that should lead to a deeper weight loss.
The other thing that happens is if you stop the GLP-1, and this is in this study, you get what's called a rebound, a weight gain. So this rebound weight gain is almost all fat. And again, what's happening there, and this has been shown in starvation studies, is that when you have your muscle mass deficit, so you have low amount of muscle, that triggers appetite. And so when you stop the GLP-1, that appetite is ferocious, and you find that you're overeating, and that leads to the rebound weight gain, which is all fat. If you leave muscle alone, that should dampen the reflex weight gain. So these are areas where muscle, muscle, muscle can be important.
Now, as I mentioned, they're now calling this the Ozempic plateau, where patients are taking the drugs and saying, "Look, everybody hits the weight loss plateau," I'm just reading the quote, "but the race is on for the next generation of drugs to help patients lose even more weight." So in other words, you know, you know, "What do I do about a GLP-1 drug? It stopped working. What do I do about it?" It's not stopping - it didn't stop working. Your muscle mass has gotten to a point, and this is one of the explanations, that your appetite kicks in, and it's a... and you're fighting it, basically. If there's a way to maintain muscle and preserve muscle, get a deeper weight loss, and to preserve muscle in patients at risk, that would be great. In comes enobosarm.
So enobosarm is a non-steroidal agent. This is a drug that we're developing. The phase 3 clinical trials and preclinical studies show it's a once-a-day dosing. It works in the androgen receptor, which is a well-known receptor that we know that testosterone-like products that work with the receptor build muscle, quality muscle that leads to performance. It's tissue selective, and that enobosarm can improve muscle mass, and that translates to function. But independent muscle, it also has the ability to stimulate lipolysis, and which means it stimulates fat breakdown and stops fat from being made, so you see a decrease in fat mass. And because it doesn't get converted to estrogen, as you know, testosterone gets converted to estrogen, that's one of the safety issues, this is non-steroidal.
It does not get converted to estrogen, and it doesn't get converted to dihydrotestosterone, which is, you know, that drug from finasteride, is it's the drug that leads to masculinization and prostate issues, and we just don't get converted to DHT. So these are some of the, some of the attributes that make this selective. enobosarm has had a rich history, being in 27 clinical studies, of which five are depicted here, that shows it's a muscle drug. In these five studies, the first two studies were done in healthy patients, and what I want you to take away, and these are healthy patients over the age of 60. What I want you to take away from this is that in these healthy patients, you see an increase in lean body mass, again, muscle.
That translates to function and decrease in fat mass. In one study that was done in sarcopenic post-menopausal women, they were given 3 milligrams of enobosarm. This was a study that was done by Merck. They took 3 milligrams of enobosarm and no change in diet, no change in exercise, and by the end of 3 months, the patients that took enobosarm had an increase of 1.54 kilograms of muscle, and that translated to an improvement in leg press of 22 pounds. So this drug, you know, generates strength and function. Now, this drug was originally being positioned to go into frailty. Frailty is muscle loss that occurs with aging from the age of 60 and beyond.
Sometimes it takes 20 years to appreciate it, but again, with this drug, with a GLP-1, you can accelerate that. But what we decided to do was to go into muscle wasting related to cancer, because cancer is like a GLP-1. It causes starvation state. The starvation state means you're in a hypocaloric state, meaning that the body doesn't see the calories, and therefore, you lose muscle and fat, just like a GLP-1. And in this setting, we're still able to show increase in muscle, increase in function, decrease in fat at 16 weeks. And then in two lung cancer studies, totaling about 640 patients, again, increase in lean body mass, and one of the studies had improvement in function.
The other one, the patients were too sick for function, but definitely increase in lean body mass. The idea is you have a muscle drug that can maintain muscle, preserve muscle, not trying to make Arnold Schwarzenegger by building up too much muscle, but you want that quality tissue, because that quality of tissue dictates what happens when you're on a GLP-1, meaning you can avoid the plateau, and what happens, potentially avoid the plateau. And what happens when you stop a GLP-1, if you don't have a muscle deficit, a loss of muscle, then your appetite doesn't come back so ferociously. So this could be very, very interesting for enobosarm. And this shows you with enobosarm, it's dose-dependent increase in lean body mass, in stair climb power, and again, as I mentioned, separate effect on fat. Decreases fat in a dose, dose-dependent fashion.
And so yin yang, it increases muscle, decreases fat. But it has metabolic changes. It decreases glucose, decreases insulin, improves insulin resistance, and in fact, at 3 milligrams, the reduction in insulin resistance is similar to potentially giving a patient a metformin. So, we have one study in, you know, in lung cancer patients that we're able to find a subset of patients that were obese in the lung cancer patients. Remember, the lung cancer, metastatic lung cancer is causing the caloric weight loss, and what you see in this study is that in total lean body mass with enobosarm 3 milligrams, that the placebo patients lose muscle just like a GLP-1 over a 12-week period, and then, we're maintaining muscle.
Again, the goal here is not to increase muscle, but to maintain muscle or increase it gently. Fat mass goes way down, so that's, remember, yin yang. Improves muscle in one direction, decreases fat in another direction. When you look at day 147, these patients actually, with maintaining muscle, were still able to lose weight of almost minus 4.51% placebo corrected. So this is a small study, but again, it's showing you that you can change body composition by maintaining muscle and still see the weight loss.
So the study concept, and this is, this was, shared with us by FDA when we had our IND comments come back, that they want us to consider enobosarm not only, not only in an older patient population, but they prefer that in addition, that we try to study enobosarm in the broadest patient population, possible, because younger patients could benefit from a muscle-preserving drug as well. So in that setting, enobosarm can prevent muscle loss. So it's active protein synthesis, even in a hypocaloric state, increases fat loss. And so in combination with a GLP-1, which it decreases, increases fat loss by a different mechanism.
So think of enobosarm as a direct effect on the fat to reduce fat, where a GLP-1 restricts calories, and that's a separate mechanism by which to decrease fat. Can we get a high-quality weight loss, meaning preferential fat loss and leave muscle alone? And the endpoint there is, because it's an obesity study, is an incremental increase in weight loss with enobosarm compared to a GLP-1 receptor alone. Now, do we think we can do that? Well, let's think about that for a moment. The question that keeps coming up: if muscle is preserved, can there still be significant weight loss? Well, let's put this in perspective. First of all, the muscle compartment, as you can see in this diagram, is small compared to the fat compartment. Fat compartment is huge.
So in the situation of a GLP-1, where you take a pound of muscle for a pound of fat, that you don't, you know... At some point, you have to stop because you don't have that much muscle. On the other hand, if you leave muscle alone and you can take just fat, you can get a deeper fat loss. And so by having such a bigger universe of fat that you can go after, that should help with the incremental weight loss by holding on to muscle. The other thing that happens, and this comes from a Dulloo study, in which he summarized that the trigger for appetite is muscle. So if your muscle gets too low, it will trigger appetite and try to override a GLP-1.
And certainly, if you stop a GLP-1, it's gonna be responsible for what they call collateral fattening. What that means is that, you stop the GLP-1, and the body appetite comes back because the muscle mass is so low, and it takes a while before the muscle comes back. In the meantime, you're gaining all that fat, and that's the reason why there's so much more fat when you stop a GLP-1. So the concept here is, if you leave muscle alone, it doesn't trigger the appetite and hopefully gives you, it should give you a bigger compartment of fat for which you can decrease fat by two different mechanisms: GLP-1 and enobosarm directly. Not to forget the older patients, because this is important.
The sarcopenic obese patient is a patient that, from the outside, looks fine, but when you look at their inside, you'll see they have a lot of fat and very little muscle, and these are the patients that can get into trouble with the GLP-1. The idea is, from a clinical development standpoint, is to still focus on quality weight loss. If you can get them to have a deeper weight loss and leave muscle alone, that'd be great. And, and if we can show functional endpoints, as an added benefit, that would be even better. And so that's why in our phase 2, which has been phase 2b, which is this study, this is the study that, the FDA has green-lighted, and, we just announced last week. And the idea, this is not the phase 3 design.
This is a design to allow us to get the critical information of what happens with enobosarm in combination with a GLP-1. No company has data today with a muscle drug in combination with a GLP-1 in humans, so we'd like to be one of the first ones. And since we're a muscle drug, and it's been shown to be a muscle drug in every study that we've done looking at muscle, then that seems to be a reasonable, reasonable endpoint. So the idea is that you have 90 patients, and we randomize 1 to 1 to 1, and they're obese, overweight, over the age of 60, and they're starting a GLP-1. The GLP-1 that we selected is Wegovy. Wegovy is gonna be given by itself with a placebo, or enobosarm 3 milligrams with a GLP-1, or enobosarm 6 milligrams with a GLP-1.
At 16 weeks—remember, 16 weeks in the STEP 1 study, 49% of the total weight that's gonna be lost is lost in the first 16 weeks, and the other 51% of that weight loss is gonna be lost, is lost in the following year. So we think we're in the right window to show that the GLP-1 by itself will have muscle loss and weight loss and a certain amount of fat loss. And what we want to do is look at a DEXA scan, 16 weeks, where muscle is the primary endpoint, and that's acceptable to the FDA.
What we're gonna look at is to see whether we can stop the muscle loss, preserve, and more importantly, can we show that we have a greater fat loss with enobosarm in combination with GLP-1 than a GLP-1 by itself? That's the main goal. Of course, we'll get functional data to show the muscle that's there is still functional by stair climb. Then that stops the study. Then the patients roll over into a continuation study, blinded still. This is new. And what's different about this is that we have a placebo group. The placebo group is a GLP-1 receptor agonist patient that stops. So we know that's the patient that's gonna have the rebound weight gain without the muscle coming back right away.
We wanna see whether enobosarm monotherapy, because now you've left muscle alone, and that trigger for the rebound has not happened, whether or not we see a dampening of that rebound weight gain, which is fat. So a win here would be to show a reduction in the rebound, so that potentially in the future, enobosarm monotherapy could be given to a patient that wants to stop a GLP-1, because that's the problem right now, is they're on the GLP-1, and what to do next? If you stop it, you get your weight gain back in a rapid fashion. If you continue to take it, you have side effects. What dose do you take? There's so many unknowns.
But to have a drug, a muscle drug, that can help post a GLP-1 to maintain weight, and potentially continue the reduction of weight, that would be very interesting. So this study is slated to begin in April, and we believe that it should recruit pretty quickly. There's a lot of demand for weight loss drugs in this patient population. Safety. Safety, as you know, SARMs have all over the map. SARMs, this is a enobosarm. It's a very specific SARM. This SARM has been in 27 clinical trials, as I mentioned, and in these clinical trials, I'm showing you data from 1,333 subjects.
That's the 5 clinical studies I showed you, the muscle data, plus the phase 1, phase 1s. And what you should focus on is, first of all, liver, which is a safety issue of special interest. You see the liver is – we don't see the bilirubin changes, and you see some mild ALT changes, but again, it's small. But the other thing that's important is an oral drug, you're not seeing a change in diarrhea, vomiting, any of the other GI abdominal pain, that kind of stuff, because that's important because the GLP-1s have those side effects. And what you don't wanna do is add a drug in combination that will add to those side effects.
So we do not see the GI toxicity, that you see with a GLP-1 alone. I think that's important when you think of an agent, adding an agent, that has to be well-defined. You also don't see masculinization and hair loss and that kind of stuff, in these tables, so it appears to be safe. Furthermore, we've done phase 1 studies showing no effects on QT and some of the other things that you would do for the labels. We've also had data in 235 subjects over the age, subjects with greater than 9 milligrams dosing, in some cases as much as 3 years. The effects on the lipids are very similar to what you would see with testosterone.
The reason I say that is we see a reduction in cholesterol, a small reduction in HDL, big reduction in triglycerides, and triglycerides play a big role in fatty liver, for example. So if you see a reduction in triglycerides, that could be important for patients with NASH or MASH. But we also know with the testosterone data that, about 6-8 months, the HDL flips back and starts to go higher again. So that's a known mechanism with the androgen receptor. So how do we stack up with our competition? As you know, the space is becoming quite active. We're the selective androgen receptor to SARM. We're oral. We're entering phase 2b. We expect to see data in the second half of this year, the end of this year.
Other ones, the other, there are five companies are working on some kind of myostatin agent of some sort, of which they're either IV or subQ, entering phase 2, some phase 1. And then, the only other compound is the apelin receptor agonist, which is oral, entering phase 2, and this one is by BioAge Labs. So we think we have a real good chance of staying ahead of the curve with a oral agent without the GI toxicity that can clearly a muscle drug addressing a muscle problem, where muscle is triggering the problems related to not getting the high quality weight loss that people want to get. So in summary, enobosarm is non-steroidal. It works through the androgen receptor, which is an established mechanism.
Our clinical trials and preclinical studies support a once a day dosing. We're trying to avoid muscle loss. We're trying to have a greater reduction in fat. It has metabolic effects. Our safety, we have a large safety database, so we know we, you know, we have good data. They're not converted to estrogen or dihydrotestosterone, so it's even, you know, even better than testosterone alone, because you don't have that, those effects. And the lack of masculinizing effects in women and minimal GI toxicity puts it, puts the potential target profile in a good position. I don't need to tell the group that this is a major market.
Barclays and Goldman Sachs have pegged the obesity medications market to be in the order of about $130 billion by the end of the decade. We're not a GLP-1. We're not seeing ourselves as a therapy that has to compete with a GLP-1. We are a therapy that will be given in combination with a GLP-1 or a GLP-1/GIP. So any one of these GLP-1s could use enobosarm in combination, and our job is to show in our phase 2b the information we need to move forward to the next study. In terms of money, we just did a recent raise, and we just reported cash of $40.6 million.
As of December 31st, 2023, we have the resources to get us beyond the 2025 data readout. The 2024 data readout is the main readout at the end of the year for the first 16 weeks, showing muscle and increased fat loss as the endpoint using DEXA, and then the patients roll over into the enobosarm monotherapy versus placebo, and that data would come in 2025. But we would meet with the FDA with the data that we get at the end of the year. So I appreciate your attention, and if there are any questions, Leland, I'd be happy to take them.
Great. No, thanks for running through the story here. I think, you know, a couple questions. You know, first of all, obviously, you know, this Phase 2b should provide proof of concept to combining enobosarm with the GLP-1 agents and seeing, you know, what could be an extension of weight loss together with, you know, protection of the muscle. As you think about what would be needed for a pivotal study, right, which presumably could get going sometime next year, what that might look like? I think you mentioned there's kind of two ways you can go in recent discussions, and you'll sort of have a large collection of data from the 2b and the 2b extension.
So you may be making decisions about, you know, where to dedicate your resources, with respect to the Phase III plans. I'd love to hear more about that.
Yeah, and so the way we're thinking about it now, particularly the feedback we've gotten from the FDA, is they want this drug to be studied in the broadest patient population possible. So what that means is that the study will be designed to look at weight loss as an endpoint for all comers. And yes, we're gonna look at muscle and body composition and all of that information, but the belief based on the data is that if you leave muscle alone, that allows you to have a gateway to more fat reduction, and that fat reduction ultimately correlates to a greater weight reduction. And so body composition changes translates to greater weight loss. That would be the goal.
We would imagine also embedding within the study a subpopulation of patients over the age of 60, at risk or may already have, limitations related to their low muscle mass. And that population will be nice to show in addition to a greater weight loss. And I imagine if you, if your weight—if your muscle doesn't go away, and you can keep taking the medicine, you'll have a weight loss, a greater weight loss. It would be nice to also show a functional endpoint. You know, stair climb power, stair climb test has been used in the past. The FDA has been comfortable with stair climb, when we spoke with them in the past.
And so to have that functional information, I think will help the totality of the story for why the muscle is important. But by having the weight loss endpoint, you know, that will be the regulatory endpoint. But having the functional endpoint will allow us to, you know, to address what it means to keep the muscle.
Hopefully, the data will show that patients over the age of 60 that are worried now about going on a GLP-1, they'll see, "Hey, look, my muscle didn't go down, and when it got better, and it shows an improvement in function." And so I think that will add to the comfort of a GLP-1 receptor agonist type drug in older patients. But so in summary, it would be a study that would try to get all comers, but an embedded subset that would be analyzed separately, so we can get some important information about how muscle affects patients that are in trouble with the function to begin with.
Okay, that's really helpful. And then with respect to IP, I'm not sure if you had touched on it in the slides, but if you have-
I did not, but I... If you still see the slides?
Yep.
Uh-
Okay, so just wanted to have that in front of people.
Yeah, yeah, so-
Maybe you could just sort of give a summary.
Yeah.
Yeah.
So first thing, enobosarm is a new chemical entity. It's not been approved for any indication, so that means you get all the regulatory protection, if you wanna call it that, opportunities. Enobosarm is a specific polymorph. So because of its specific polymorph, that last patent will run out in 2029 in the U.S. But you get 5 years that you can add patent extension for half of the review time. Excuse me, half of the clinical trial time and all of review time. And so that takes you to 2034 if we choose to use our patent extension for that patent.
In the same time, meanwhile, we have also filed an enobosarm in combination with a GLP-1 method of use patent, and, and that patent, if issued, will go to 2044, and, actually 2045, because you get one year for the provisional, one extra year, so 2045. And we have we've done a third-party independent prior art search, and, and it came up clean, 'cause you're always worried that that may be a problem, so we did the same thing, we've looked at it. So that, that method of use patent will take us to 2044. As I mentioned, in the U.S., you get five additional years for patent term extension, and we can apply it to any patent we want. Japan is 7.5, Europe is 10, 10 years.
We're also working on a composition of matter formulation patent with a new modified release tablet using technology that's patented and it can be further patented once we have the data showing the release pattern. So, and that will go to at least 2045, if issued. So we do have, you know, belt and suspenders for the compound that I think barriers to entry and moat and patent protection.
Great, terrific. Well, thanks again. I think we're at the time here. So thank you, Mitch, and thanks for everybody for joining us for the session.
Thank you, Leland. I appreciate it. Bye now.