Veru - Q1 2024

Transcript

Operator (participant)

Good morning, ladies and gentlemen, and welcome to the Veru Inc's Investors Conference Call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After this morning's discussion, there will be an opportunity to ask questions. Please note this event is being recorded. I would now like to turn the conference over to Mr. Michael Purvis, Veru Inc.'s Executive Vice President, General Counsel and Corporate Strategy. Please go ahead.

Michael Purvis (EVP of General Counsel and Corporate Strategy)

The statements made on this conference call may be forward-looking statements. Forward-looking statements may include, but are not necessarily limited to, statements of the company's plans, objectives, expectations, or intentions regarding its business operations, regulatory interactions, finances, and development and product portfolio. Such forward-looking statements are subject to known and unknown risks and uncertainties, and our actual results may differ significantly from those projected, suggested, or included in any forward-looking statements. Risks that may cause actual results or developments to differ materially are contained in our 10-Q and 10-K SEC filings, as well as in our press releases from time to time. I would now like to turn the conference call over to Dr. Mitchell Steiner, Veru Inc.'s Chairman, CEO, and President.

Mitchell Steiner (Chairman, CEO, and President)

Good morning. With me on this morning's call are Dr. Gary Barnette, the Chief Scientific Officer, Michele Greco, the CFO and Chief Administrative Officer, Michael Purvis, the Executive Vice President, General Counsel and Corporate Strategy, and Samuel Fisch, Executive Director of Investor Relations and Corporate Communications. Thank you for joining our Q1 fiscal year 2024 earnings call. Veru is a late clinical stage biopharmaceutical company focused on developing innovative medicines for high quality weight loss, oncology, and ARDS. The company's drug development program includes two late-stage, novel, orally administered small molecules, Enobosarm and Sabizabulin. A weight loss pipeline leads off with Enobosarm, also known as ostarine, MK-2866, GTx-024, S-22, and VERU-024. These are all the identical same molecule, Enobosarm, which is an oral selective androgen receptor modulator.

Enobosarm is being developed as a treatment in combination with weight loss drugs to augment fat loss and to avoid muscle loss in overweight or obese patients for chronic weight management. In our oncology pipeline, we're developing Enobosarm as a treatment for androgen receptor-positive, estrogen receptor-positive, and human epidermal growth factor receptor two negative metastatic breast cancer in the second-line setting. In our infectious disease pipeline, which is pending additional external funding or pharma partnership, is Sabizabulin, a microtubule disruptor, which is being developed as a phase III, in a phase III clinical trial for the treatment of hospitalized patients with viral-induced ARDS. The company also has an FDA-approved commercial product, the FC2 Female Condom, internal condom, for the dual protection against unplanned pregnancy and sexually transmitted infections.

This morning, we'll provide an update on our company's primary focus, the development of Enobosarm, an oral SARM, in combination with weight loss drugs like glucagon-like peptide-1 receptor agonist, which we're going to refer to as GLP-1 receptor agonist. These are being used to avoid Enobosarm in combination is used to avoid muscle loss and physical function loss to augment fat loss and potentially result in higher quality weight loss. We'll also provide financial highlights for our first quarter fiscal year of 2024. Now, GLP-1 receptor agonists like Ozempic, Wegovy, Zepbound, and Mounjaro are very effective weight loss drugs. Unfortunately, clinical studies have shown that up to 50% of the total weight loss comes from muscle, which is problematic, as muscle is necessary for metabolism, strength, and physical function.

Loss of muscle may be also one of the reasons why patients on GLP-1 drugs reach a weight loss plateau, meaning they cannot lose any more weight while taking a GLP-1 receptor agonist drug. According to the CDC, 41.5% of older adults have obesity in the United States and could benefit from a weight loss medication. Up to 34.4% of these obese patients over the age of 60 have sarcopenic obesity. This large subpopulation of sarcopenic obese patients is especially at risk when taking a GLP-1 receptor agonist drugs for weight loss, as they already have critically low amounts of muscle due to age-related muscle loss. Further loss of muscle mass when taking a GLP-1 receptor agonist medication may lead to muscle weakness, leading to poor balance, decreased gait speed, mobility, disability, loss of independence, falls, bone fractures, and increased mortality.

This can lead to a condition similar to age-related frailty. Because of the magnitude and speed of muscle loss while on a GLP-1 receptor agonist therapy for weight loss, GLP-1 receptor agonist drugs may accelerate the development of frailty in obese or overweight elderly patients. We believe there's an urgent unmet medical need for a drug when given in combination with a GLP-1 receptor agonist that can prevent loss of muscle while preferentially reducing fat in not only all overweight or obese patients, but especially for the large subpopulation of sarcopenic or overweight elderly patients who are at risk for developing muscle atrophy and muscle weakness leading to frailty. We believe that Enobosarm, a novel oral selective androgen receptor modulator, may be the best drug candidate to address this unmet medical need....

Enobosarm has been previously studied in five clinical studies involving 960 older men and postmenopausal women, as well as older patients who have muscle wasting because of advanced cancer. Advanced cancer simulates a starvation state where there's significant unintentional loss or wasting of both muscle and fat mass, like what is observed with the GLP-1 receptor agonist treatment. The totality of the clinical data from these five clinical trials demonstrates that an Enobosarm treatment leads to dose-dependent increases in muscle mass, with improvements in physical function, as well as significant dose-dependent reductions in fat mass. The patient data that were generated from these five Enobosarm clinical trials in both elderly patients and in patients with a cancer-induced starvation-like state, provides strong clinical rationale for Enobosarm.

Our hypothesis is that Enobosarm, in combination with a GLP-1 receptor agonist, will potentially augment the fat reduction and total weight loss while avoiding muscle loss. In addition, Enobosarm has a large safety database, which includes 27 clinical trials involving 1,581 men and women dosed with Enobosarm, with a duration of treatment in some patients for up to three years. In this large safety database, Enobosarm was generally well-tolerated and no increase in gastrointestinal side effects. This is important, as there's already significant and frequent gastrointestinal side effects with the GLP-1 receptor agonist treatment alone.

As for our Enobosarm clinical program for high-quality weight loss, this week, I'm happy to report that FDA has cleared our investigational new drug application for our phase II-B, multicenter, double-blind, placebo-controlled, randomized dose-finding clinical trial, designed to evaluate the safety and efficacy of Enobosarm, 3 mg, 6 mg of placebo, as a treatment to augment fat loss and prevent muscle loss in approximately 90 randomized sarcopenic, obese, or overweight elderly patients receiving semaglutide, who are at risk for developing muscle atrophy and muscle weakness. The purpose of the phase II-B trial is to select the optimal dose of Enobosarm in combination with a GLP-1 receptor agonist that best preserves muscle and reduces fat after 16 weeks of treatment to advance into a phase III obesity or overweight clinical trial.

The primary endpoint to the phase II-B clinical trial will be the change in lean body mass from baseline to 16 weeks. Key secondary endpoints will be the change in baseline to 16 weeks in total fat mass, insulin resistance, total body weight, and physical function, as measured by stair climb tests. We plan to initiate the phase II-B clinical study in April 2024, and the clinical study will be conducted in approximately 15 clinical sites in the United States. The top-line clinical results for the phase II-B clinical trial are expected at the end of calendar year 2024. We believe that assessing the effect of Enobosarm on lean body mass and fat mass at 16 weeks should be adequate to demonstrate significant loss of muscle in the semaglutide plus placebo cohort. Support comes from the step one study, reported by Wilding et al.

In the New England Journal of Medicine publication. In the step one study, it evaluated semaglutide for weight loss in overweight and obese patients and showed that 49% of the total weight loss in the 68-week study actually occurred by week 16, and 40% of the total weight loss was attributable to muscle loss. After completing the 16-week efficacy dose-finding portion of the phase II-B clinical trial, it is planned that participants will then continue into an open label extension trial, where all patients will receive 6 mg of Enobosarm monotherapy for 12 weeks, to determine the ability of Enobosarm to rescue or to reverse the muscle loss and prevent fat and weight rebound after stopping a GLP-1 receptor agonist. The results of this separate phase II-B open label extension study are expected in calendar Q2 2025.

In summary, our phase II-B clinical program is designed to provide clinical data to support the development of Enobosarm for high-quality weight loss for two possible patient populations. The first population, Enobosarm dose-finding, will be evaluated in a large, at-risk subpopulation of obese or overweight patients who are the sarcopenic, obese, or overweight elderly patients receiving GLP-1 receptor agonists for weight loss. The Enobosarm GLP-1 receptor agonist combination therapy has the potential to augment weight loss by preferentially increasing fat loss while preventing muscle loss and improving physical function, potentially leading to higher quality weight loss. Second, Enobosarm monotherapy treatment for the at-risk sarcopenic, obese, or overweight elderly patients who discontinue a GLP-1 receptor agonist.

In this case, Enobosarm may rescue the patient by increasing muscle mass and improving physical function while preventing the rebound weight and fat gain that typically occurs when the GLP-1 receptor agonist is stopped. We believe we have sufficient financial resources on hand, which includes the recent financing of net proceeds of $35.2 million, to complete and provide results from both the phase II-B clinical trial and the open label extension clinical trial. I will now turn the call over to Michele Greco, CFO, CAO, to discuss the financial highlights. Michele?

Michele Greco (CFO and Chief Administrative Officer)

Thank you, Dr. Steiner. Overall, net revenues were $2.1 million, compared to $2.5 million in the prior year's first quarter. The U.S. prescription channel net revenues increased to $634,000 from $163,000 in the prior year's first quarter, as a result of increasing sales through our telehealth portal. Global public sector net revenues decreased to $1.5 million, compared to $2.3 million in the prior year's first quarter, due to the timing of orders and shipments. Gross profit was $1.2 million, or 54% of net revenues, compared to $702,000 or 28% of net revenues in the prior year's first quarter.

The increase in gross profit and gross margin is driven primarily by the change in the sales mix, with our U.S. FC2 prescription channel representing 30% of net revenues in the current period, compared to 7% in the prior period. Sales in our U.S. prescription channel have a higher profit margin. On December eighteenth, 2023, we completed an underwritten public offering of our common stock, which included the exercise in full of the underwriter's option to purchase additional shares. Net proceeds to the company from this offering were approximately $35.2 million, after deducting underwriting discounts and commissions and costs incurred by the company. All the shares sold in the offering were offered by the company. As of December 31st, 2023, our cash balance was $40.6 million, compared to $9.6 million on September 30th, 2023.

We believe our current cash balance will be adequate to fund the planned operations of the company as we continue to focus on developing Enobosarm for high quality weight loss. Now I'd like to turn the call back to Dr. Steiner.

Mitchell Steiner (Chairman, CEO, and President)

Thank you, Michele. It has only been recently that the significance and clinical need to avoid adverse effects of significant muscle loss caused by GLP-1 receptor agonist has been appreciated. All the GLP-1 receptor agonists work by creating a starvation state that nonselectively reduces both muscle and fat tissues to cause weight loss. Using a muscle-preserving drug in combination with a GLP-1 receptor agonist would potentially allow for a higher quality weight loss. I want to emphasize that Enobosarm is not competing with GLP-1 receptor agonist drugs that are already on the market or under development for weight loss. The expectation is that Enobosarm may be potentially combined with any one of the many GLP-1 receptor agonist drugs to avoid muscle loss and to augment fat loss. This is truly a new indication.

We believe Enobosarm is the best investigational drug candidate to address the muscle loss caused by GLP-1 receptor drugs for weight loss. Enobosarm is a first-in-class, has oral once-a-day dosing, has demonstrated tissue selectivity, and utilizes a well-established known mechanism of action, the androgen receptor. Favorably changed body composition. Activation of the androgen receptor increases muscle mass, improves physical function, and decreases fat mass to potentially achieve a higher quality weight loss. Enobosarm has favorable safety profile and would not add to the gastrointestinal side effects that are already observed with the GLP-1 receptor agonist treatment. Global obesity and overweight drug market is projected to be $100 billion by 2030.

It should be emphasized that Enobosarm may potentially be combined with any one of the GLP-1 receptor agonist weight loss drugs, not only for older or overweight at-risk patients, but also all overweight or obese patients who want to avoid muscle loss while taking a GLP-1 receptor agonist for weight loss. The combination of Enobosarm and the GLP-1 receptor agonist potentially represents a multibillion-dollar global opportunity. We are very excited about the prospects of Enobosarm to address this new and important unmet medical need. With the FDA go-ahead, we're looking forward to the initiation of this important and timely phase II-B clinical study. With that, I'll now open the call to questions. Operator?

Operator (participant)

Ladies and gentlemen, at this time, we will begin the question-and-answer session. To ask a question, you may press star, then one on your telephone keypad. If you're using a speakerphone, we ask that you pick up your handset before pressing the keys to ensure the best sound quality. To withdraw your question, please press star then two. Please limit yourself to one question and one follow-up. If you have further questions, you may reenter the question queue. Once again, that is star one to rejoin the question queue. Our first question comes from Dennis Ding with Jefferies. Please go ahead.

Dennis Ding (VP and Equity Research Analyst)

Hi, good morning. Thanks for taking our question, and congratulations on all the progress. Just one for me around the obesity program. Given various GLP-1s have, you know, different levels of weight loss as well as muscle wasting, what, you know, what's clinically meaningful level of muscle preservation, and what's clinically meaningful additional weight loss that you guys are looking for in your phase II-B, and how do you define success from that trial? Thank you.

Mitchell Steiner (Chairman, CEO, and President)

Thank you. Good question. So the first question relates to how we're going to view muscle loss, and particularly in the context of our phase II. So you're absolutely right, all the GLP-1s have muscle loss associated with them because the mechanism is hypocaloric calorie, in other words, low-calorie amounts, and that's why muscle waste and fat waste; it just doesn't. It's not specific for one tissue type. They all do it, but the range is about 20%-50%. And a lot of it depends on the potency of the GLP-1 receptor agonist. The more potent it is, the more muscle you lose.

With that said, success for us at 16 weeks is to show that we can basically maintain muscle because we know we're going to be losing about 40% of muscle with semaglutide. We picked in our phase II-B study only one GLP-1 receptor agonist, so that we don't have the confounding concern that each GLP-1 receptor agonist may have a different muscle loss amount. So we're using semaglutide, which is Wegovy. So the expectation based on the STEP 1 study is about 40% of the muscle loss of the half of the 50% of weight loss that occurs in the first 16 weeks will be at that point. We will just define success as you stopping the decline. So the delta is going to be the difference between what we've maintained and what is lost.

If we can maintain and stop the decline in function and maintain function, that's, that's considered a success. The other success, and this is important, is fat loss. Total body fat loss correlates with weight loss, ultimately, week 48. We chose to go to 16 weeks because we're using this, the DEXA scan, think of it as sort of a biomarker. We know if we maintain muscle at 16 weeks, if we maintain the muscle at 48 weeks. If you lose fat and preferentially lose more fat at 16 weeks, you expect to see a deeper fat loss at 48 weeks. So the idea is, don't spend the 48 weeks now in the phase 2.

You know, get the information you need, which could be, there's examples of other drugs in which, you know, they showed the maintenance of muscle and showed the reduction of fat at 16 weeks, and it was fine. Now, fine, meaning at 48 weeks, you saw, you know, a further decline in fat and further decline in weight loss. With that said, you know, success for us is, again, focusing on lean body mass being maintained, fat loss, you know, greater fat loss, at the 16-week time point.

Now, in terms of total weight loss, you know, if we had a situation where we had a weight loss comparable in both arms, that would be great because what you're basically saying is in one arm, you lost all fat, and that would be the semaglutide, where you lose fat and you lose muscle. And in the treated arm, with the Enobosarm, you maintain the muscle, you lose fat, but you have the same weight loss. That's a high quality of weight loss. But the expectation is, if you leave the muscle alone, you can get a deeper weight loss.

As I mentioned in my comments, the concern is that, and you can look at any one of these 48-week to 70+-week studies and, in the lay press, that people will tell you that after about 16-20 weeks on a GLP-1 receptor agonist, they hit a plateau. They just can't lose any more weight. What's happening there is they've lost enough muscle that it kicks back in their appetite. And that's why people are saying, do resistant exercise, take protein. It... All these studies have that same plateau. How do you get beyond that plateau? And the answer is, if you can maintain muscle, you can have a much deeper weight loss. The fat compartment in an obese patient is so much larger than the muscle compartment.

It's just you can't get to it, because for every pound of muscle you take, every pound of fat you take, you pay with a pound of muscle, if it's 50%. So success for us would be if we can show comparable weight loss with a different kind of body composition in 16 weeks, the expectation that that would ultimately translate into a greater weight loss at 48 weeks, which is what the phase III would be studying. With that said, the agency has made it clear that what they'll be looking for, if you look at total weight loss as your endpoint in 48 weeks, is an incremental increase in weight loss.

But the incremental increase in weight loss is about 5% of the total weight loss by the control arm. So it's not 5 percentage points, 5 percentage points greater, it's 5% up. So it's a low bar to hit, but if we can do that same low bar or greater and maintain muscle, then, and which means most of that weight loss was fat, that would be success at 48 weeks. So hopefully that answers your question.

Dennis Ding (VP and Equity Research Analyst)

Yeah, yeah. And maybe a quick follow-up.

Mitchell Steiner (Chairman, CEO, and President)

Sure.

Dennis Ding (VP and Equity Research Analyst)

Can you remind us some of the statistical assumptions from the phase II-B and whether the study is powered to show statistic? Thank you.

Mitchell Steiner (Chairman, CEO, and President)

Yeah, I'll be happy to. So what I'm going to do is I have Dr. Gary Barnette answer that question. So, Gary, can you talk about the sample size and power?

Gary Barnette (Chief Scientific Officer)

Yes, this is Gary Barnette. The way we did it is we looked at the step one study. The step one study lost about 6 kilos of lean mass over a 68-week period. That if you just do assume a linear loss of muscle, that would be 0.102 kilos per week. Multiply that by 16 weeks, you get approximately 1.6 kilos of loss of lean mass in the control arm, meaning the GLP-1 plus placebo. And if we look at our data that we have in obese patients with cancer, as Mitch mentioned, cancer has a tendency to create a hypocaloric state, much like a starvation state.

We basically maintain lean mass in that patient population, so it's a 0.3 kilo loss to a 0.4 kilo increase. So what we did is we used an alpha of 0.05, two-sided, 80% power, comparing a 1.6 kilo expected loss in the control arm versus a -3 kilo or -0.3 kilo loss in the treated group, and that's approximately 26 subjects per arm. We powered it three- at 30. Now, let me also say this, as Mitch mentioned, 49% of the loss of weight occurs in the first 16 weeks of GLP-1 treatment. So what happens if you use that number and say that 49% of the muscle also is lost.

That's three, over 3 kilos of lean mass that we're expected to lose. But we're being conservative in our sample size calculation, using 0.3, -0.3 versus -1.6.

Mitchell Steiner (Chairman, CEO, and President)

Right. The expectation is you're going to have a much greater muscle loss than we've put into the numbers to be conservative in the arm that's getting the semaglutide without Enobosarm.

Dennis Ding (VP and Equity Research Analyst)

Got it. Thank you. That was very helpful. Thank you.

Mitchell Steiner (Chairman, CEO, and President)

Thank you. Thank you for the question.

Operator (participant)

The next question comes from Leland Gershell with Oppenheimer. Please go ahead.

Leland Gershell (Managing Director and Senior Biotechnology Analyst)

Hey, good morning, Mitch. Thanks for taking our questions. If you could just review with us how you're going to define the eligibility in terms of what it means to be sarcopenic for entry into the trial. Thanks.

Mitchell Steiner (Chairman, CEO, and President)

Yeah. So what we're doing to make sure we get the biggest patient population as possible is restricting it to age. So if you look at it, we say greater than the age of 60. Greater than the age of 60 puts you in that population of 42% of patients that could potentially use a obesity drug because they're obese, overweight. So that gets you a wide net. We also know, and this comes from our previous experience in frailty, and let me pause for a moment. I mean, Dr. Gary Barnette and myself and Domingo Rodriguez and Gary Bird, these are all people here. We worked on-- we've been working on the space of frailty for, you know, for, you know, at least 15 years with Enobosarm in these patient populations that we have find...

That we have shared you, shared the data both in frailty patients, post-menopausal women, and also cancer wasting patients that are older. The reason I bring that up is that we had to deal with all the endpoints that the FDA wants for physical function. We had to understand the amount of muscle that somebody loses from the age of 60 to the age of 80, and, you know, what's a critical amount of muscle that gets you to a point that you have problems with functional limitation. You end up with functional limitations, mobility, disability. So we bring all of that history with us as we look at this accelerated development of frailty that occurs in older patients. So the fact that you're 60, you're already beginning to decline in muscle.

And so the idea is, rather than, you know, trying to come up with a sarcopenic population, sarcopenic definition for a population, which there are many, just allow patients over the age of 60, they're going to have reduced muscle mass, follow them along for the 16 weeks, and if you're going to lose, as Dr. Barnette said, you could lose as much as 3 kilos, 3.5 kilos on the semaglutide alone, you're accelerating frailty. You're going to see problems. So we want to have a wide net. So the way to think of it is, we use greater than 60 as the eligibility, if they're overweight or obese, that patient population is enriched for the patients that will get into trouble.

Leland Gershell (Managing Director and Senior Biotechnology Analyst)

All right. That's very helpful. And then just to follow up, you know, being that from what we understand, you know, that to maintain benefit from weight loss from the GLP-1 therapy, one has to stay on that therapy for, you know, long term, effectively for life. How do you view, you know, the ultimate use of Enobosarm, assuming approval, over time? Would it be used as well, kind of the entire time that the GLP-1 is used, or would it be used only during the time that the weight loss is actually occurring, but then once the patient achieves their target weight or their plateau weight, they could go off, since they wouldn't be losing any more mass? How should we think about that?

Mitchell Steiner (Chairman, CEO, and President)

Yeah. So part of the reason we're doing the phase II-B, the way we're doing it, is to get some questions answered, to address that question. So for example, the first part, which is the primary study, is in combination with the GLP-1, you know, how does Enobosarm work? Do we maintain muscle? How much additional fat do we lose? And so that gives you that information, and of course, physical function, and seeing how we can prevent the decline of physical function and that.

Second part, the open-label study, and it's kind of addressing the question you're asking, and that is, if you stop the GLP-1 for the patient that did not take Enobosarm in combination, and they've lost muscle, and the fear is, if you stop the GLP-1, you get the rebound weight gain, which is almost all fat, that you've actually made them worse, because now they have less muscle, and they have the same weight, but it's all fat and weaker. And so it would be nice to see what the effect of Enobosarm is in that situation to rescue and prevent the rebound weight gain, the fat gain. And those pieces of information will allow us to think more globally at a higher level, like you're thinking, and that is how we use it. So here's some examples.

One, could Enobosarm, which by itself has a direct effect on reducing fat and maintaining muscle in combination with a GLP-1 receptor agonist, be used in combination, so you can use less of the GLP-1 receptor agonist? As you know, GLP-1 receptor agonists have GI toxicity, and that's the reason why people have, you know, all kinds of gastrointestinal pain, nausea, vomiting, diarrhea, and bloating, and that kind of stuff. And we can decrease some of those with an agent like Enobosarm that doesn't have any of that. Then you could have a situation where the combination of a GLP-1 with Enobosarm, you can have less of the GLP-1, potentially.

The other way to think of it is the biggest problem that is occurring now is everybody got onto GLP-1, and they're recognizing they hit this plateau. And the plateau, as I mentioned in my former comments, is because, particularly in the sarcopenic obese patient or an elderly patient, where they have very little muscle reserve, happens because when muscle goes down to a critically low level, it kicks off the appetite mechanism. Appetite mechanism is pretty powerful. It won't let you die. And so that happens, then you basically have a push me, pull you, with the GLP-1 is making you lose weight, lose weight, while the appetite is asking you to put the weight back on, all because the muscle has triggered that.

If you maintain muscle, then the question is, could you have a deeper fat loss? If you have a deeper fat loss, then the, again, the combination of our drug plus GLP-1 be a higher quality, but better from the point of view that you mentioned, that is, what is the target weight loss that you want? So if you want a target weight loss that's beyond what your muscle will allow, again, you know, if you do the 50/50 rule, for every pound of fat you lose, you lose a pound of muscle. That's a lot to pay for. If you don't have to make that payment, and you can lose a lot more of the fat, then you can have a better success in getting to your target weight, potentially. And so that could be very interesting in getting rid of the plateau.

So again, I would see Enobosarm in combination with the GLP-1. It will allow you to manipulate the GLP-1, to reduce dose potentially, and to potentially get to your target weight without hitting the plateau. Now, what happens if we want to stop? As you know, the chronicity of a GLP-1, do you take it for, you know, the rest of your life? And some people wanted to get off of it because of side effects. So if you could have a drug, like Enobosarm, that could be given almost like you're cycling, so you stop the GLP-1, keep the Enobosarm going, then you maintain muscle and Enobosarm has direct effects on fat, so decrease the potential for the rebound of fat.

And then bring back the GLP-1 if you, if you want to, you know, if you want to get back to your target weight again and to keep avoiding that accelerated rebound and just have a more gentler weight loss. And that's when I say high quality. High quality means, you know, weight loss, where your muscle and fat body composition is such that the appetite mechanism it gets you into trouble. Summary, I see us being used in combination with a GLP-1 chronically, potentially changing the GLP-1 dose, potentially using the drug to help you decide how you want to stop the GLP-1 and add it back in.

Then furthermore, for those patients that got into trouble, that did not start with Enobosarm and took a GLP-1 and want to discontinue the drug, then they have an opportunity to build their muscle back if they lost significant muscle, or to potentially stop the fat rebound, weight regain. So there's a lot of information there, but I think the phase II-B, again, it's not meant to be the phase III study, where you say: "Okay, I'm going to look at weight loss at 48 weeks, and am I 5%, you know, greater than, 5% greater than the weight loss of the control arm?" No, this is asking the very critical questions of how ultimately do we want to use Enobosarm?

At the very high level, the two areas are with the GLP-1, and second area is to rescue somebody on a GLP-1.

Leland Gershell (Managing Director and Senior Biotechnology Analyst)

Sorry, thanks for the added information.

Mitchell Steiner (Chairman, CEO, and President)

Thank you.

Operator (participant)

Again, if you have a question, please press star, then one. To withdraw your question, press star, then two. Our next question comes from Yi Chen with H.C. Wainwright. Please go ahead.

Yi Chen (Managing Director and Senior Healthcare Analyst)

Thank you for taking my questions. Just to clarify, because the Enobosarm has the ability to preserve muscle mass, that in the phase II-B trial, it is possible that within the first 16 week of Enobosarm plus GLP-1 drug combo versus GLP-1 drug alone, that for the combo arm, we could see patients lose less total weight versus GLP-1 drug alone arm. Is that right?

Mitchell Steiner (Chairman, CEO, and President)

No, but no, I don't think so. I think what you're going to see in this situation is what's missing in your characterization of Enobosarm: Enobosarm does two things. One, it preserves muscle, and two, it also augments the fat loss. So the GLP-1 receptor agonist by itself, it's muscle and fat. And so if we have a situation where you maintain the muscle... Again, we're not trying to make Arnold Schwarzenegger. We're not trying to pick a dose that you put so much muscle on that that has to counteract the amount of fat that you've lost. Part of it is, can you dial down the muscle part so that you maintain muscle, but you make it up by reducing the fat even more than a GLP-1 by itself?

That's the idea. If it didn't have direct effects on fat, I would say, "Okay, I don't know what's going to happen." But it has direct effects on fat, and so it could be possible that a higher dose of Enobosarm, I mean, you have the same muscle, or similar muscle maintained, but you have a greater fat loss. So we're going to learn that in the phase II-B at 16 weeks. And so again, the key thing here is, can we maintain the muscle, you know, get a deeper fat loss, and the semaglutide is going to take muscle and fat equally, and by 16 weeks, so you're starting to hit the plateau.

Yi Chen (Managing Director and Senior Healthcare Analyst)

Would it be meaningful to have an arm receiving Enobosarm alone in this trial?

Mitchell Steiner (Chairman, CEO, and President)

So we thought of, we thought about that and, because Enobosarm alone would be very, very interesting. But we have, again, not in obese patients, but we have in patients that are normal post-menopausal elderly patients. So we have—we know a lot about Enobosarm in that setting as monotherapy. And we do have data from a 504 study in a subset of patients that were obese in the lung cancer study, that pretty much falls in line with what I just said. And that is, what we saw in that study, where the cancer causes basically a starvation state, that we saw we were able to maintain muscle.

Muscle was about 0.3 kilos, where the GLP-1 lost about, I guess, in that study, about 3 kilos or something of that sort. And when you look at total weight at 21 weeks, there was, you know, much greater weight loss in the Enobosarm arm than the placebo arm in that patient population. What we saw, the weight loss was due to the fat loss because you maintain the muscle. So we do have data like that. I think for purposes of this, this study here, we're not trying to make Enobosarm by itself the weight loss drug.

I think where we need to get clarity, and again, no company out there at this point now has clinical data in combination with GLP-1 with their drugs is to get that information, because that's more important. Understanding what is the magnitude of the hypocaloric influence and what is the dose we need to counter that. Then that'll allow us to, you know, ask additional questions later.

Yi Chen (Managing Director and Senior Healthcare Analyst)

Got it. You mentioned that in a future phase III trial the endpoint could be measured at 48 week. Is that correct? And I also wonder how many patients could be required to... for a future phase III trial and whether Veru plans to conduct the trial by itself or potentially with a partner. Thank you.

Mitchell Steiner (Chairman, CEO, and President)

Yeah. So the answer is we're absolutely seeking a partner, but the way we're designing this study is, the way we're thinking about it, is we have a phase III that is potentially an all-comers study, in which case weight loss is your endpoint. And the weight loss endpoint, all you have to show is a 5% incremental increase, which means that would be, again, the standard endpoint of 48 weeks. The FDA wants it to be at least a year. However, embedded in that study are the patients that are in our phase II-B, greater than 60 years of age. And the reason we picked that patient population is because physical function and potentially lean body mass could be interesting endpoints in itself.

So depending on how our discussions go with the FDA, do we focus on a subpopulation in which the clinical benefit risk ratio is different and the endpoints are going to be different, potentially? Or do you go after a weight loss population and in which case you're not worried about muscle, just get the muscle function, because that would be something that you can put in your label, and I think that will be important. But you know get the endpoint of a 5% better decrease in weight at week 48, and you get it. Gary, do you want to add to that?

Gary Barnette (Chief Scientific Officer)

No, I think the outcome of this study, you know, that we're running will dictate that, will dictate where we go and how big that study will be, what the primary endpoint will be, whether the FDA just purely looking at weight loss or whether they're looking at weight loss, as Mitch mentioned, with a component of body composition. Increasing or maintenance of lean mass and increasing fat reduction would be, in my opinion, a very positive outcome for these patients. And that quality, what I'm going to term as quality weight loss, would be very important for overall health benefit.

Mitchell Steiner (Chairman, CEO, and President)

But the fact that we're measuring physical function, we know the FDA likes how, you know, how patient feels, functions, and survives. And so that's why the stair climb test, which is a key component of the phase II-B, is important, because I think that will also influence how we think about endpoints in a phase III. Ultimately, we think, you know, we think Enobosarm is a kind of a programmatic molecule, meaning that you're looking at rescue, you're looking at decreasing doses of GLP-1, you're looking at being used in combination with the whole population, you're used in combination with a at-risk population, potentially be used in combination with a myostatin inhibitor, can potentially be used... So I think this can be pretty interesting.

So, you know, we are active in trying to find a partner that has, you know, the resources to allow us to explore all these possibilities.

Yi Chen (Managing Director and Senior Healthcare Analyst)

Thank you.

Operator (participant)

Ladies and gentlemen, this concludes our question and answer session. I would like to turn the conference back over to Dr. Mitchell Steiner for any closing remarks.

Mitchell Steiner (Chairman, CEO, and President)

Thank you, operator. I appreciate everybody being who joined us on today's call. We're very, very excited about the prospects of Enobosarm. I look forward to updating you on our progress in the next investors call. Thank you.

Operator (participant)

A digital replay of the conference call will be available beginning approximately noon Eastern Time today, February eighth, by dialing 1-877-344-7529 in the U.S. and 1-412-317-0088 internationally. You will be prompted to enter the replay access code, which will be 8260066. Please record your name and company when joining. The conference call has now concluded. Thank you for attending today's discussion.