Great! Thank you. Thanks for joining us here at Oppenheimer's 36th Annual Healthcare Life Sciences Conference. I'm Leland Gershell, one of the analysts with the Biotech Equity Research team at the firm. We're delighted to have with us as our next presenting company, Veru, which is a public company. That is the ticker V.
We're running through a slide presentation. We may have time at the end for a few questions. Please feel free to put any of your own through the portal. We will do our best to include those. Without further ado, I'll hand the microphone off to Mitch.
Great. Thank you, Leland, I appreciate it. Thank you, everybody, for being on our presentation. We're making forward-looking statements. I refer you to the risks that are summarized in our 10-K and recent 10-Q. Veru had done a hard pivot, taking one of our exciting drugs, enobosarm, and putting it together with a GLP-1.
We had a positive Phase 2b quality study, which I'll briefly talk about. Most of the time, I would like to spend and talk about the study that will start in this quarter, which is the Phase 2b Plateau study, not the Phase 2b quality study. Here's the issue. We've been one of the companies that have been focusing on what we think loss of muscle.
As you know, with GLP-1s, you can lose between 40% and 50% of lean mass. That may be fine for a 32-year-old linebacker, but for a older patient over the age of 60, that can be detrimental, such as causing poor balance, decreasing gait, functional limitations, falls and fractures, higher hospitality rate, higher hospitalization rates, and increased mortality.
We're trying to avoid that. How do you get the benefits, the cardiovascular benefits, without some of the problems? The agent under investigation is enobosarm, previously called ostarine. It's a non-steroidal selective androgen receptor modulator. This has been one that has gone through 27 clinical trials. 6 of the clinical trials had muscle endpoints, and without question, this is a agent that, it can be an agonist, a partial agonist or antagonist, which means it has tissue selectivity.
What we know that's relative to the GLP-1 issue is that it improves muscle mass and physical function, independently breaks down fat, stops fat from forming, and also, again, from the name ostarine increases bone mineral density.
I think that's pretty exciting given that's a problem with the GLP-1s, and it's well-tolerated. The first study we did, again, in a backdrop, put it in context, there were no data in what happens when you combine an anabolic agent like enobosarm with a GLP-1. We need to understand that first.
While we were trying to understand this, the agency also made it very clear, "Please focus on functional endpoints, not just whether you preserve muscle or burn more fat, but, well, you know, how does a patient feel, survives, and functions?" is what they were interested in.
The study was designed as a short study, 16 weeks, looking at the GLP-1, starting for the first time with GLP-1 at 3 mg enobosarm and 6 mg enobosarm, and we did that for 16 weeks. Why 16 weeks? In our previous muscle studies, we showed that we should be able to show a functional benefit, and we did. That was the appropriate time.
Then we stopped the GLP-1, because one of the things we heard is you get this rapid weight regain, and the question, of course, is, can we prevent that rapid regain? We saw with the 3 milligram, we were able to. This was a successful study. Again, I want to spend most of the time on a new study, but suffice it to be, we preserved lean mass, we increased the fat loss.
Body weight change was similar in spite of the retention or preservation of lean mass, and the weight that was lost was 100% adiposity, which is important, because 100% fat is what you want out of a weight loss drug.
As you think about new generation drugs in combination with GLP-1s, you want something that will complement the GLP-1, provide something that GLP-1 is either causing a problem or that it's not addressing, and that's what makes enobosarm a great complement to GLP-1.
With that said, if you look at the patients with BMI greater than 35, which means they had a lot more weight to lose, we did see incremental weight loss, and higher proportion of patients with enobosarm three achieved greater or equal to 5% weight loss, and this was done in the background of preservation of lean mass of 84%. Weight loss is possible if you retain muscle. With that said, also said, function is important, and there's been a lot of con...
not controversy, but understudied, incompletely studied patient populations with the GLP-1. If you focus on the older patients, again, remember, these are the patients who are going to show a problem. If there's a problem, we see a problem. What we saw with semaglutide plus placebo, is you're able to see that if you use a cutoff of greater than 10% physical decline on stair climb, which has implications, because stair climb power portends problems with falls and fractures and mortality.
We picked 10% because that represents about greater than 7 years of power loss with aging. We're asking: Can that happen in 16 weeks? We saw about 44% patients on semaglutide alone had a greater than 10% decline, and we're able, with the enobosarm, to prevent that.
That is a big step because, one, it shows we have a problem, and second, it shows that we have a solution to the problem. Drug is well-tolerated, as it has been in all the other clinical studies we've done. We do have a unique and selective androgen receptor modulator that continues to show good safety. We go to the FDA, and as you know, the FDA's mindset is evolving, particularly the obesity division.
They came back and said, basically, as you think about your next steps, incremental weight loss could be a primary endpoint for approval. If you hit at least 5% or greater, that alone can serve for approval for efficacy.
Alternatively, if you have less than 5% incremental weight loss with a combination of enobosarm and a GLP-1 versus a GLP-1, then if you show a clinically significant positive benefit, such as preservation of physical function, in combination with GLP-1, that can be approvable. On the basis of that, we're very, very excited because that means the FDA's expanded their thinking in terms of how a body composition drug could be potentially approved through a regulatory pathway with regulatory clarity.
With that said, we also heard in December, and this is a general announcement by the FDA, that the FDA now considers total hip bone mineral density, which you measure by DEXA, as a surrogate endpoint for osteoporosis drug development.
In other words, BMD, bone mineral density, at 24 months, can be used instead of a fracture study, and so if, particularly in post-menopausal women with osteoporosis. This opens up another avenue for us as a body composition drug, 'cause both semaglutide and tirzepatide have been reported to cause bone loss of the lumbar spine and hip.
The Wegovy label has highlighted, based on the SELECT trial, that in women, female patients, there was a 5-fold increase in hip fractures and pelvic fractures. In patients over 75, it was a 4-fold increase. It matters. As I mentioned, enobosarm is a very unique agent. It's anabolic to cortical bone. It's anti-resorptive, so it's got a dual function of both stimulating osteoblasts and inhibiting osteoclasts.
In our published models, it shows it increases bone mineral density. The question is now, where do you go? What are you going to do? The thinking for us is there's still some major problems. The first problem, and this just came out again over the last 18 months to 2 years, is that GLP-1s work until they don't work. Meaning that you take them, and you hit what's called a weight loss plateau, where you're not losing any additional weight. In this slide, this is a select study. At about a year, you hit about 10% weight loss, and for the next 3.25 years, you're still at 10% weight loss.
There is a problem, and we believe that the central reason for that problem is the fact that in addition to losing fat, you can lose all the fat in your body, but you can't lose muscle. If you keep losing too much muscle, the body's going to respond to that by causing you to increase calories. The only way you can keep it the same weight is to increase additional calories.
Is there a way to break through that plateau? The answer is you can break through the plateau if you can hold on to muscle, 'cause muscle burns calories. If you don't get signals from muscle telling your brain to eat because you depleted muscle, that could be interesting. The plateau is not just the problem. The problem is when the plateau happens.
The plateau happens at about a year. At about a year, this is tirzepatide, you'll see about 2/3 of the patients still have what's classified as BMI of 30 or greater, which is they're still obese. In fact, if you look at patients that start with a BMI of 35, almost all those patients, on average, are still obese and now have a drug that won't lose any more weight.
This is a problem. When you look at the, quote, "problems" that we can address with enobosarm in combination with GLP-1 is you can address the non-selective weight loss, you're losing only fat. Muscle in older patients, you want to preserve. The weight loss plateau, almost 90% of patients will hit.
Unfortunately, if your BMI is greater than 35, you will have persistent obesity, in which your GLP-1 will not help, and it becomes an unmet need. You need a therapy that, with a combination of a GLP-1, can preserve muscle and function and cause you to lose only fat. This is the study. This is the Plateau study, clinical study. This will initiate this quarter, as I mentioned.
Is a study that's designed to essentially match a Phase 3 program so that when we're done, at the end of it, we'll be able to understand what path to take forward, which I'll get to in a moment. With that said, the patient population is greater than 35 BMI, so the patients have more weight to lose. They're non-diabetics. Age is greater than 65. This is a big patient population.
About 44 million Americans are on Part D of Medicare over the age of 65, about half of them can benefit from weight loss drugs. This is a massive market. The plan is to randomize these patients to either semaglutide alone or semaglutide 3 milligrams, this is a study to go on for 68 weeks. 16 weeks to titrate up to the maintenance dose and 52 weeks at the maintenance dose. There will be an interim look at 34 weeks, looking at lean body mass, which you always, almost always hit, and fat mass, at 34 weeks. We chose semaglutide because, as you know, semaglutide has an oral form now. Zepbound does not have an oral form.
We're using injectable semaglutide here, but the information that we learn from this study can bridge easily to an oral semaglutide in a Phase 3 setting. The primary endpoint is total body weight, but we're going to be heavy on the functional endpoints, which we've de-risked from the previous program, the quality study, and that's stair climb tests, physical function PROs, mobility, disability assessments, and of course, measuring body composition and bone mineral density.
We're very fortunate that Dr. Steven Himmelfarb, who was the PI for the quality study, has agreed to return to the PI for the Plateau study, and he's a very prominent and well-respected individual in the field. This study will start this quarter, and we're on track for that to happen.
you know, what is the evidence that we have that we're going to see incremental weight loss? Let's put that aside. In other words, let's address that directly. Well, first of all, if you look at the BMI greater than 35, as I showed you, we do see incremental weight loss in patients that have the ability to lose more weight. That's why in our study, we're picking patients with great BMI greater than 35. That's number one. Number two, if you look at obese patients taking testosterone, which uses the same receptor that enebosarm uses, you don't see a plateau.
What you see here in obese patients, even with a normal diet or whatever they want to eat, they'll lose weight on something that stimulates the androgen receptor, and almost 5% at year one, 10% at year two. What you notice is a straight line down.
You don't see a plateau. That tells you that if you preserve muscle, that may be the secret to breaking through the plateau so you can actually lose more weight in patients that have more weight to lose, so you have fewer patients who are still obese at the end of a year. We've seen some of this in a phase 2, a Phase 3 that was done in cancer patients. Why are you picking cancer patients? Cancer causes unintentional weight loss, kind of like a GLP-1.
You see in 3 months, lean body mass goes down tremendously in these patients. These are patients that present with obesity. You have to look at obese patients to see what's happening to weight loss, and then the total fat mass goes down.
What's most important is by 5 months, there's about minus 4.5% incremental weight loss. We actually see with the enobosarm monotherapy in obese patients in this population, weight loss. Interestingly, our competitors, Scholar Rock, Regeneron, and Lilly, have also presented their data, and it's very instructive. These are myostatin inhibitors, all injectables. We're an oral, we believe that everything equal, oral will be better.
Put that aside, and what you'll see is that we had 100% lean mass preservation, but if you go long enough, like the Regeneron and Scholar Rock of 6 months, didn't really show significant incremental weight loss. With the Versanis study, Lilly study showed that at 72 weeks, 6.4% greater weight loss. The longer you leave muscle, a metabolically active tissue that burns calories, the more weight you're going to see and lose.
Plus, we saw with our own study, and this is the second part of the quality study, that if you stop the GLP-1 and you treat with an enobosarm monotherapy, what we saw is, the first thing we saw is that it stopped the regain by about 46%.
If the patients lose about 11.88 pounds in the placebo, the GLP-1, and they stopped the GLP-1 for 12 weeks, that they gained 5 pounds, so they got 43% regain. Enobosarm was able to stop that by 46%. The weight that was gained in enobosarm was muscle, and it continued to burn fat.
In fact, it burned so much fat that when you look at the 28 weeks, which is the end of the study, you'll see that about 6.28 pounds was totally lost by placebo and 8.8 pounds by enobosarm 3 and 10 pounds by enobosarm 6. You do see incremental fat loss over time. What does this all mean for this study, and why am I excited about the study that we're doing?
I think the study that we're doing is going to be incredibly informative because there's multiple ways to go forward. We're starting out in the Plateau study with obese patients with greater than equal to BMI of 35, and they're non-diabetics, and their age is greater than 65, and they're starting a GLP-1 for the first time, this time it's semaglutide.
If you follow the regulatory discussions, publicly and privately, you'll see that if your incremental weight loss is greater than 5%, the Phase 3 study that we would do, it would be a primary endpoint, total body weight, probably in all patients, with a secondary endpoint, pre-specified in the older patients, the physical function and sarcopenic obesity, mobility, disability, in other words, function, and then BMI.
If the incremental weight loss is less than 5% in the Phase 2b study, then we have two options. The first option is to do a primary endpoint of physical function. Just like the FDA said, physical function is a primary endpoint if it's clinically meaningful in the patient population, and we show that in sarcopenic obese patients greater than the age of 65, with a mobility disability. They can benefit from a muscle preservation drug.
More importantly, and much more importantly, they're at the highest risk of having trouble with absolute muscle loss. The secondary endpoint, which would be a pre-specified subgroup, would be BMD in postmenopausal women. We, an endpoint that has now become available with the FDA validating BMD as an endpoint, that's very interesting.
If we see significant BMD changes in our Phase 2b study, one option is obesity and osteoporosis, where the primary endpoint is bone mineral density. Not a fracture study, which are large, but it will potentially be a much smaller study looking at BMD as a new path forward for approval. Essentially, there's different ways to chip at this patient population to get a body composition drug forward.
Where do we stand as on our balance sheet? With cash, we just announced we have $33 million of cash as of December 31, 2025. And in terms of a timeline, you know, we're right on track. For the obesity program, the Plateau study is set to start in the first quarter, so this quarter of 2026.
We expect enrollment to be completed by 3rd quarter of 2026. The interim look will be in 1st quarter of 2027, now I'm guiding that our Phase 2b Plateau study top line data will be available Q4 2027. A busy year and a half coming up with the news flow, and which puts us well ahead of our competitors in answering the critical questions on how a drug in combination with a GLP-1, such as enobosarm, has multiple paths forward from a regulatory standpoint. This concludes my prepared comments, and I'll be more than happy to answer any questions.
Yeah, that's great. Thank you. Thank you so much, Mitch, for the for the update and and the overview. You know, interesting, one thing I caught during your prepared remarks was that kind of, you know, any of these muscle-sparing agents will eventually lead to weight loss. As a corollary to that, should we take that enobosarm itself has it's a separate weight loss promoting effect, and therefore should be advantageous over the others in that domain?
Yeah.
Is that a fair statement or? Yeah.
Statement. I think it makes sense that we're going to see incremental weight loss. The reason it makes sense is because we're holding on to the muscle. People say, "Oh, muscle," that, you know, muscle weighs more than fat.
By the way, muscle's only 12%, and fat's 10 different than fat. So it's a 2% difference, so it's not a lot. They're very comparable. With that said, in this setting, with 84% preservation of lean, you have the incremental weight loss, and you have 47% of your placebo semaglutide group hitting a greater than 5% weight loss at 16 weeks, and you see 65% with enobosarm.
Point being is, you hang on to muscle, and you're still burning more fat and losing more weight, and that makes sense. If you think of muscle as being that pivotal tissue that's going to determine not only how you feel and function, but also could play a role in the weight loss, and maybe it can play, and should play a role in stopping the mixed messages that the brain is getting that cause the weight loss plateau. You got a GLP-1's, very effective to shut down appetite, but that's getting overridden by what they call the metabolic set point.
I think one of those things that contribute to the metabolic set point are myokines, things that are made by the muscles, that, "I'm not going to let you starve me to death, so you have to eat." Take care of the muscle problem, one less signal, and potentially you can see multiple ways where incremental weight loss could happen.
With that said, the combination with incremental weight loss just allows us to also bring in the physical function. That's why we're spending a lot of time on physical function in BMD, because then what you can envision is your primary endpoint being incremental weight loss, but your secondary endpoints being very, very important, because you can't claim muscle preservation without showing what they mean.
We have a function endpoint or a function limitation benefit and then a bone benefit. This could be very interesting.
Got it. Okay, that's very helpful. If you wouldn't mind skipping back down to one of the more recent last slides, which had the kind of the tripartite kind of options, you know, kind of ±5% weight loss. You entered, like, the BMD boxes and the. There we go. Yeah. Is there anything just to be clear, have you finalized your primary endpoint analysis for the Plateau study, right?
That's right. We've also finalized the analysis and analysis for these other endpoints as well. These endpoints are all going to be measured.
Right.
The whole idea is to again be able to use these to help us understand what fit patient population. Let me pause a moment, because this is a very important point. I'm going to let you in a little secret. We went to the FDA, they told us, I fit in this category, being over 60 years of age is not a disease. 60 or older, it's not a disease.
The point being is that you can't pick an older patient population and say that's your population. Your population will be older patients with obesity, and muscle loss, and functional loss, bone loss. If you look at how we're laying out our program, is we're trying to pre-specify...
You look at the regs, the obesity regs, you're allowed to, you know, treat everybody. If you want a special claim, the claim has to be in a patient population that's at risk, and that it has a disease. For example, a patient population that has sarcopenic obesity is a patient population with a mobility disability, meaning they've already demonstrated they're having trouble with function.
A post-menopausal woman with osteoporosis and obese, knowing that they're gonna be taking a medicine that will confound their obesity, and a select trial is showing a fivefold increase in hip and pelvic fractures, that's your patient populations that could come out of this study.
If I had to predict, it's not gonna be one, it's gonna be many of these. As a body composition drug, we affect muscle, we affect fat, we affect bone, affect weight, then, we're gonna be able to, in a Phase 3 setting, pre-specify these patient populations with phase 2 data.
Yeah. Okay. I guess, you know, when you come to the top-line readout from Plateau, right, I guess the market will sort of have to, you know, 'cause one might say that, you know, the market could be disappointed if you don't show 5% weight loss. However, I think people need to keep in mind that you have optionality as to your registration program.
I think that's what you have to look at. In other words, you have to say to yourself, "We're not another incretin. We're just not." I mean, look what happened to CagriSema. CagriSema was 2 incretins, an amylin, and a GLP-1.
They add them together to get incremental weight loss, they're playing the game of quantity, but not a quantity game. This is a quality game. If we hit quantity, I mean, I would argue that if we have another situation where at 25%, Lilly's at 25%, everybody's at 25%, that's not gonna distinguish you in the marketplace. It's gonna distinguish you in the marketplace, "I'm 25%, but I build bone. 25%, I preserve muscle.
I'm 25%, I improve physical limitations that prevent the physical issues. I think when you think of the next generation of drugs, just like in any area of medicine, I like to use the example of hypertension. If you have hypertension, you give somebody a calcium channel blocker, and at the end of a year, the good news is their blood pressure is down, but the bad news is they still have hypertension.
You don't come back and say, "Okay, I'm gonna give them another calcium channel blocker and make a combination of a calcium channel blocker with a calcium channel blocker." You pick an ACE inhibitor, you pick something with a different mechanism.
Right.
Combination therapy has to be thought through more on the quality side than the quantity side. If you can, because that's why we're spending so much time understanding what could be the secondary claims, because the secondary claims is what's gonna be, you can only claim one primary point, right?
So the primary end point is your obesity product, you're gonna handle obesity. Got it. If you can, if you can preserve function, and you can preserve bone, and address some of the safety issues that happened in this special population, being older patients, that could be interesting.
Yep. All right, good. This should begin enrollment very soon. Are there any gating factors to getting the first patient in?
No, everything's on track.
All right, very good. Just, you know, to review on the IP side, 'cause, you know, people sometimes ask, you know, this compound's been around for some time. If you could remind us of your protections, for exclusivity for enobosarm.
The protection is we have multiple layers of protection. The first one is a new chemical entity, it's never been approved for anything before, so there's not something on the market that you can just grab and substitute. With that saying, you get 5 years of market exclusivity from your approval. We do have... The composition matter runs out in 2029, you can add 5 years of patent protection, as with patent extensions, so that takes you to 2034.
We have about 4 or 5 method of use patents, these methods of use patents will begin to start reading out, meaning we should start hearing from the Patent Office. Once we start hearing the Patent Office with the combination of enobosarm with any of the GLP-1s, that'll take us to 2044.
As you know, we also decided to, for the Phase 3 program and commercial, use a novel formulation of enobosarm, and this novel 3D-printed formulation has a potential protection to 2046. I think we have enough picket fences around this compound, and I think it's a good thing it hasn't been approved for anything else, because now it's a clean way forward for what I think is an indication that didn't even exist when we first started thinking about frailty. Now we have accelerated frailty with the GLP-1s causing accelerated frailty, so it's a perfect indication for a perfect drug.
Yeah. Excellent, good. We look forward to seeing your progress with Plateau, hearing on, you know, how enrollment there moves along. Top line, I think you said the interim is gonna be in Q1 of 2027, is that right?
Q-
Yeah.
2027, Full data set should be available Q4 of 2027.
End of 2027, perfect. Okay, well, thanks again, Mitch, and thank you all for joining us in this session. Please enjoy the rest of the conference.
Thank you.
Thank you.