Thank you. Welcome, everyone, back to another session here at Oppenheimer's 35th Annual Life Sciences Healthcare Conference. I'm Leland Gershell, one of the analysts on the biotech research team, and very pleased to have with us is our next company, Veru. We have, on behalf of the company, Dr. Mitchell Steiner, who is the company's founder and CEO. Veru is working in the very important and increasingly important area of increasing the quality of weight loss as the GLP-1 agents have been rising in their popularity. We recently saw very good data out of the company's phase II study with enobosarm, and we look forward to hearing more on that from Dr. Steiner, to whom I'll turn the podium over to now. We'll have some questions at the end, so please feel free to submit through the internet. Thanks, and handing it over to Mitch.
Great. Thank you, Leland. I appreciate it. First of all, I'm going to be making some forward-looking comments, and so I refer you to the 10-K and filing that goes through the risk of our company. The focus is going to be primarily based on the concept that about a year and a half ago, it became clear that the GLP-1s, one of the major side effects, is loss of muscle. In fact, this paper showed that at the end of 68 weeks, 40% of the weight loss was muscle, lean mass, and I'll be using those interchangeably. That raised the whole question of, is there a problem? Is it maladaptive? You know, is it adaptive? You know, what's going on? Now, we've taken a different position. Our position was that it really depends on the patient population.
If you're talking about younger patients, like a linebacker that wants to lose weight, that's very, very different than a 65-year-old that has lost so much muscle that they're at risk. It is really focused on older patients because older patients are affected most by the non-selective weight loss that occurs with GLP-1. To be very clear, what GLP-1 does tells the brain to stop eating and tells the gut to stop digesting. You end up moving food, and you end up in a situation where you have a very low-calorie state. That low-calorie state leads to your body losing fat and muscle non-selectively. As again, 40% of the lean mass is lean mass, 60% is fat. It is a problem if you start with low mass. That is where we came in at Veru.
It's a big population, and these are the patients most at risk. Interestingly, in any article you read, they'll always end up by saying, "We're not sure what's happening with lean mass and whether lean mass matters." However, in this patient population, it matters. This is the patient population that we sought to develop an enobosarm. We know it matters because it turns out the recovery label had to be updated for safety because they showed a four- or five-fold increase in hip fractures and pelvic fractures, which, you know, tend to happen because of falls. This is objective evidence that lean mass matters. You know, the real question is what happens to physical function and other things that we're focused on. The other part about lean mass that's important, it's also the lean mass of muscles and metabolic tissue.
For example, everybody's well aware of the plateau. As you can see in this slide to the left, this is from the SELECT trial. This is about 17,000 patients. And what you see in the 4.25 years is that the patients lose about 10% of their weight at about 39 weeks. For the next three and a half years, they're at 10%. That's a plateau. How can you be at a plateau? The plateau can only happen if your brain is being told by the drug, the GLP-1, to stop eating. Something else is telling you to eat because the only way you can do that is have calories. One of those something else is muscle. If you lose muscle and it's depleted, it puts out myokines that tell the brain to eat.
You have this push-me-pull-you where the brain is saying, your brain is being told by GLP-1s not to eat, and muscle's telling the body to eat. Our working hypothesis is if you can break that cycle by leaving muscle alone and taking one of those signals away, that you should get a better weight reduction over a longer period of time. In comes enobosarm. Enobosarm, also known as ostarine and MK-2866, is a new generation of weight- loss drugs that could make the weight reduction by GLP-1 receptor agonists more tissue- selective for fat loss and preserve muscle. I'll say that again. New generation of weight- loss drugs that could make the weight reduction by a GLP-1 receptor agonist more tissue- selective, meaning more fat loss and preserve muscle. As I mentioned, you're in a low-calorie state.
How you can affect what muscle does and fat does can be done at that level. Enobosarm has data from many clinical trials and preclinical studies that support a once-a-day oral dosing. It works with the androgen receptor, which is well established. It's tissue- selective, meaning that it improves muscle mass, lean mass, and function. Independent of that, it has direct effects on fat. There's an androgen receptor that's on fat that stimulates lipolysis, which is fat breakdown, inhibits lipogenesis, which means buildup of fat. You actually decrease fat mass and also has benefits on bone. Because it's non-steroidal, it's not converted to estrogen or dihydrotestosterone. Those kinds of side effects, including masculinizing side effects, have not been seen in women, for example.
Because of the DHT not being made, because enobosarm can't get converted into a substrate of 5-alpha reductase, that's one of the reasons why it has the ability to be given to women and to men without those kinds of side effects. It relates to liver. No DILI, drug-induced liver toxicity, has been observed in 27 clinical trials. People say that, you know, there's SARM. Yes, we're a SARM, but SARMs are all very different molecules. They all have to be empirically tested in patients. After 27 clinical trials, we feel pretty good. We have a good handle on what the drug can and cannot do. We also have a lot of data. Enobosarm improves lean mass and physical function of other conditions. When you talk about lean mass, that's muscle. The component of that, you have muscle strength.
With muscle strength, you have physical function and quality of life. You can see that we have several studies that show that we can have an effect on lean body mass. That is why we are not surprised that the phase II-B results that came back show that we hit on lean body mass. We showed an increase in stair climb power in older patients as well. In all these studies, we use a 3 milligram dose because in our multiple ascending dose studies, where you actually look at which dose does the best for which tissue, 3 milligram was the best dose. That was in 600 subjects where we showed increase in lean mass and improved physical function in the net net of the data.
In the multiple ascending dose study, which helped inform what dose we go into for the condition of trying to preserve lean mass and augment fat loss, this is a separate study. This is a multiple ascending dose study done in 18-24-year-old aged males. The non-obese, this is a 402 study. When we looked at this study, and this shows you why we picked the 3 milligram. Three milligram dose is the best dose. The 10 milligram was not as good as the 3. However, when you look at fat mass, the 10 milligram and one of the 3, I mean, there's a dose-dependent complete response. I think the reason for that is the muscle compartment is not as big as the fat compartment. You can overload the androgen receptor and not get additional benefit.
That is why you do these dose responses. Now, we did the dose responses, and we used what we learned to design the phase II-B. The phase II-B is a phase II double-blind placebo-controlled randomized dose finding study to show that enobosarm can selectively prevent muscle loss, increase fat loss in patients receiving GLP-1 for weight reduction. We reported the top line results at the end of January. The sample size is 168 patients. This is a blinded study, randomized, done by an independent CRO. Patients are obese or overweight, greater than the age of 60. They are starting a GLP-1 receptor agonist for the first time. We picked semaglutide because it had the best information on muscle. We have three groups.
We have a placebo group with a semaglutide, which is expected to lose lean mass and lose approximately 50% of the body weight that you would lose at 68 weeks. You would lose at 16 weeks. Enobosarm three was added because that's what we bridged to all the other data we had that showed that we should hit on lean mass. The six milligram was added to the third arm because with the six milligram, we're not expecting additional muscle benefit. What we were hoping for is to show more fat loss. At 16 weeks, we see the data. The patients roll in a blinded fashion into the maintenance part of this study. The maintenance part of this study is what happens when you stop at GLP-1. That's the other big topic.
If somebody wants to discontinue GLP-1, the problem is you get this rebound weight gain, and it's mostly fat and very little muscle. The working hypothesis is that it's a depleted muscle because of GLP-1 that causes patients to overeat. It takes more time to get the muscle back. Fat comes back. Patients are very disappointed that they've gained the weight back. It's all fat. In some cases, it made them worse. Primary endpoint was lean body mass for the phase II-B. Change in total body fat. We were trying to show more reduction in fat. Change in total body weight. We were trying to show that we could hold weight in spite of holding on to the lean mass, that we can have the same weight loss. Stair climb physical function tests. I'll talk more about that in a few moments. What do we learn?
Phase II-B quality study demonstrates enobosarm selectively preserved muscle and physical function and augmented loss of fat in older patients receiving semaglutide for weight reduction. It is an add-on to semaglutide to make semaglutide, in this case, a better drug. Demographics was 69% females, 31% males. You can see the rest of the information on the slide. The dropout rate was low at 13%. What do we see? Study met its pre-specified primary endpoint with its preservation of total lean mass at 16 weeks. There was a 71% relative reduction in the loss of lean mass in patients receiving enobosarm, all patients receiving enobosarm plus semaglutide versus placebo. That p-value is 0.002. Three milligram did best with a mean of no loss of lean mass, 0.21% versus placebo semaglutide alone, which is almost 4% at 16 weeks with p-value of less than 0.001.
Six milligram dose, as I showed you before, was not better than the three milligram dose. The explanation is probably we've oversaturated the androgen receptor. If you look to the graph to the right, you can see the far right just holding on to lean body mass. We look at the three milligram versus semaglutide. The placebo plus semaglutide, where semaglutide alone essentially is where you see the lean mass loss. We hit splendidly lean mass. We would have three milligram data for 600 patients. It shows that three milligram works, not a surprise. Now, how about fat? Could we put six milligrams in to show there's an increase in fat loss? If we can show an increase in fat loss, that would be very interesting because of the concept of changing the selectivity of the GLP-1.
For all patients, a 27% relative greater loss of fat mass, and all patients receiving enobosarm plus semaglutide, it's 10.5% versus 8.36%. At 16 weeks, the p-value is 0.096. The 6 mg dose, as expected, was the best dose with a 46% relative greater loss of fat. That's minus 12.2% versus minus 8.36%. Again, 46% relative greater loss. That p-value is highly statistically significant. It's 0.014. No surprises at this point. Retained lean body mass, increased fat mass. This is very, very interesting. What happened to weight? This is the period of time where you see the precipitous weight reduction, and then you hit the plateau after 16 weeks.
I'm happy to report that even holding on to lean body mass, the enobosarm was able to stimulate enough fat loss so that the weight loss at the end of 16 weeks was essentially the same. We showed that several ways. One is means and medians. You see there's not much minor differences. If you look to the far right, you'll see there's a response analysis that shows that patients greater than 5% weight loss was not different in any of the arms, and greater than 10% were not different, meaning that there's essentially no different weight. Although enobosarm semaglutide significantly preserved lean mass, the additional loss of fat mass caused by enobosarm treatment was able to replace the lean mass preserved to allow for a similar net mean weight loss by placebo plus semaglutide alone at 16 weeks.
What's interesting is now what is the tissue composition of the weight that was lost? Adding enobosarm to semaglutide therapy retained lean mass, and total weight loss shifted to a selective greater loss of adiposity or fat. Remember, the definition of obesity is excess adiposity. Definition of a weight reduction drug is a drug that reduces fat adiposity, not muscle. What you see to your left is very similar to what we saw with the STEP 1 study, which showed 40% of the total weight loss was muscle with lean mass, and 60% was fat mass. In our study, it was 32% was lean mass, and 68% is fat mass. Enobosarm all, 9.4% was lean mass, which means that 91% or so of the weight loss was fat mass.
The three milligram group, which is even more fascinating, showed that 0.9% was lean mass that you lost. 99.1% of the weight that was lost is fat. That's what you want out of a fat drug. If you have a new generation drug that can make the weight you lose almost all fat, that's a big step forward. Enobosarm and semaglutide improved body composition during weight reduction, which resulted in more selective and greater loss of adiposity than subjects receiving semaglutide alone. The composition of the total weight loss looks pretty interesting. Now, here's some really fascinating stuff. As you know, the myostatin inhibitors have a hard time showing function. If you're going to show function, you have to show the right kind of function. In older patients, I'll tell you what matters.
What matters is in older patients, you lose what's called the explosive type 2 muscle fibers. That's the muscle fibers responsible for explosive force, like getting out of a chair, getting out of a tub, going upstairs. It's not endurance. It's not how far you can walk. It's those other activities of daily living. Stair climb in those muscles are the quadriceps, for example. Stair climb is an activity of daily living. Stair climb test measures functional muscle strength, balance, and agility. Actually, it's associated with or correlates with mobility disability, physical limitations, hospitalizations, falls together. There is a connection. If you have a decline in stair climb and you're older, that predicts outcomes. In fact, older patients lose about 1.38% of stair climb power each year with aging. Enobosarm increases satellite cells and type 2 fibers.
It should be interesting to see what happened in combination with the GLP-1. By the way, the FDA accepts stair climb tests as a regulatory endpoint. What did we find? The lowest eight-step stair climb test was conducted at baseline at 16 weeks. The loss of lean mass matters. 42.6% of patients on the semaglutide alone had at least a 10% decline in stair climb power and physical function. 10%. It was a respondent analysis that was done. The respondent analysis means that you pick a cutoff that everybody agrees is bad, meaning that if you hit that, then it is clinically meaningful. If you lose about 1.38% per year with aging, you know if you pick 10% cutoff, that is like eight years of aging, 16 weeks. That is significant. It turns out 42.6% of the semaglutide-only patients fell in that category.
At 16 weeks, they had a greater than or equal to decline in stair climb power. In comes enobosarm, whether it's a 3 milligram dose, whether it's a 6 milligram dose, whether it's a combination of the dose, meaning all patients, all 100 and some patients, you find there's a 54.4% reduction in the proportion of patients that had a 10% decline in function. The 3 milligram was 62%. The 6 milligram was 46.2%. All of them had a functional benefit. Again, this is the first study to show there's a problem, meaning that in older patients, 16 weeks, you can measure by stair climb a reduction in function. How about the safety data? The safety data remains blinded in the ongoing clinical study. The unblinded safety data set will be available in the phase II-B extension studies done in April of 2025, around that period of time.
However, the aggregate blinded data have not shown significant differences compared to previous studies in enobosarm. I'm also happy to report that yesterday, an independent data monitoring committee met. That was February 10, 2025, to evaluate the unblinded safety data. They made the recommendation to continue the study as planned. As a reminder, we have a large safety database, 27 clinical trials involving almost 1,600 patients, mostly older men and women. Some have been dosed for three years. One of the things we don't see is gastrointestinal side effects. I bring that up because, remember, the gastrointestinal side effects are the biggest problem with GLP-1. Enobosarm does not have that, so you don't want to have an additive problem. In summary, enobosarm represents a new generation of drugs for selective quality reduction.
First human study demonstrated older patients who are overweight or have obesity receiving semaglutide were at higher risk for accelerated frailty and functional decline. Lean mass loss was significant. It's 32% of the total weight loss at 16 weeks, which was lean mass. Loss of lean mass matters. 42.6% of patients on placebo semaglutide had at least a 10% decline in stair climb power function. As I mentioned, that's like eight years of loss of power that you see in aging patients. Pre-specified primary endpoint was met. We definitely have an unambiguous effect on lean body mass and preserving lean body mass. For total secondary endpoints for total fat mass, it was a dose-dependent reduction in total fat. Weight loss, minor difference in total weight, even with preservation of lean mass.
Body composition improved by preserving lean mass, which resulted in more selective and greater loss of fat adiposity in subjects receiving semaglutide. Physical function had statistically significant and clinically meaningful reduction in a portion of subjects that had greater than 10% decline in stair climb power compared to semaglutide alone. Now, interestingly, in the phase III, the expectation is to treat patients longer, 52 weeks plus. The expectation that patients are treated longer with enobosarm plus semaglutide because it's selective, because you're in a low-calorie state, you're holding on to muscle and burning more fat. This should translate to greater quality weight reduction than semaglutide alone when you're looking at a longer time period. As a phase II-B quality study was positive, we're planning to move forward to request another phase II meeting with FDA.
Some investors have asked how we're doing on the development of the novel oral modified release enobosarm formulation. I'm happy to report that it'll be ready for the phase III clinical trial and commercialization. We're using proprietary third-party formulation patents, which could lead to additional formulation and composition amount of patents with additional patent terms. The drug product is currently in animal trials and anticipated it'll be available for phase I bio vailability clinical trial first half of 2025. We'll be clearly ready when we go to the phase III. The interesting thing, if you look to the left, what do we show? This is semaglutide showing the precipitous drop in weight up to about 16 weeks, and then you hit the plateau.
If you can break through the plateau, which means you don't have signals in the muscle saying to eat, and you can potentially reset that plateau to a lower number. This will be very interesting to see. We have clues in the phase II-B, but it will be very interesting to see in the phase III. To remind you that we're also doing a separate study with maintenance. Maintenance means what happens when you stop the GLP-1. Do you get the rebound weight gain? That's mostly fat. If enobosarm can blunt that, then it can create a soft landing for patients that want to come off of GLP-1. There's a reminder. The trial is all patients who stop receiving GLP-1, and they'll continue taking placebo, enobosarm 3, or enobosarm 6 for an additional 12 weeks.
We're looking for maintenance of weight loss, meaning whether enobosarm can maintain lean mass and prevent the fat weight regain that occurs after discontinuing GLP-1. If successful, this can provide another important obesity-related indication for which enobosarm could be considered. We expect the top-line results for this separate study in the second quarter of 2025. Now, people are saying, well, you've just narrowed your market. It's a big market. Enobosarm is a new generation of drugs that makes weight reduction by GLP-1 receptor agonist drugs more tissue- selective for fat mass. We're focusing on older patients because we've just demonstrated that older patients do have a problem with GLP-1 and that there's an increase in proportion of patients that have greater than 10% reduction in power. There's a decline in stair climb power. Based on Medicare data, there's 22% of the U.S.
Population is older than 60 years of age. That's about 75 million patients. 42% of patients over the age of 60 could benefit from a weight- loss drug. We know that elderly patients get into trouble with sarcopenic obesity. It can lead to muscle weakness, poor balance, loss of strength, functional limitations, falls and fractures, increased mortality. Our competition has also gotten smaller over the last year. We still remain the only selective androgen receptor modulator. We're oral, and we have shown a functional benefit in phase II-B. That really puts us ahead of the pack from a commercialization standpoint as a myostatin inhibitor, so IV or injectable. They still have to show function. Showing just additional weight loss without showing a benefit of what that additional weight loss means is problematic.
In our situation, showing a benefit in function, which falls under the category of how a patient feels, functions, survives, puts us ahead of the pack. A balance sheet as of September 30, 2024 is $25 million in cash. I want to remind you, as of the end of December, we sold our FC2 female condom business for $18 million, of which we netted $12.5 million. Also, when we sold the asset with a change of control, it allowed us to extinguish $9.9 million of debt. We have no debt. We also reduced our workforce from 210 employees to 22 employees. We are a pure form of play at this point. The obesity program, I mean, we said we're going to do what we're going to do, and we did it. We reported the top-line phase II-B data.
It's a positive study to new generation. It's not theoretical anymore. We're anxious to see and excited to move forward. The extension study, which is a maintenance study, we'll have those results in the second quarter. With that, I return the floor back over to Leland to see if there's any questions.
Great. Thanks very much, Mitch. Yeah. It seems like, I mean, given that you have obviously a very promising candidate here in enobosarm to be paired with GLP-1 and maybe even used on its own down the road, it seems like the market is really missing something. Just to reiterate, you said that you had a, the DSMB had a meeting yesterday with a, had the same conclusion they did towards the end of last year where there was really no recommendation based on the observations.
Based on the unblinded safety observation, they see the data and they can report back. That is why you have a DSMB. Between the aggregate data and the bells and whistles, again, we will have the full data set in the second quarter. We will report the maintenance data as well.
Great. I am not sure if I caught in your prepared remarks the IP protections on enobo. I know you are also working on sort of the next gen.
From an IP standpoint, we have market exclusivity as well as patent exclusivity. From a market exclusivity, this would be considered a new chemical entity. No subject has been approved for anything, so you get five years of market exclusivity. You also get five years of additional patent protection as a new chemical entity.
We will have that to add to any patent that we want. We do have a polymorph patent that runs out in 2029. If you add your five years to that, that's 2034. We have about two or three method-of-use patents that are at different stages of evaluation that will take us to 2044. By having a new formulation patent and new formulation, once we file that patent, you get 20 years. We have done, and we're doing the phase III with that new formulation. That would be the formulation that if somebody wanted to do a generic, it would have to match that. We have done a lot to protect enobosarm. In fact, enobosarm is better protected than GLP-1s are. So much better.
I think between the patents, market exclusivity, market regulatory exclusivity, patent protection, and formulation, I think we've done a good job.
Excellent. Good. I think we're just at our time here. I just want to thank you again, Mitch Steiner, for joining us and giving us the update. To everybody who tuned in for this Zoom with our session here at the healthcare conference with Veru, I wish everybody a great day.
Thank you.
Thank you.