Good morning, ladies and gentlemen, and welcome to 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 that this event is being recorded. I would now like to turn the conference over to Mr. Sam Fisch, Veru Inc's Executive Director, Investor Relations, and Corporate Communications. Please go ahead.
Good morning. 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 of 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.
Good morning. With me on this morning's call are Dr. Gary Barnette, the Chief Scientific Officer, Michele Greco, the Chief Financial Officer and Chief Administrative Officer, Michael Purvis, the EVP, General Counsel, and Corporate Strategy, and Sam Fisch, the Executive Director of Investor Relations and Corporate Communications. Thank you for joining our call. We have successfully navigated through one of the most challenging years in the history of the biotech sector, coupled with the waning of the COVID-19 pandemic threat, resulting in the loss of regulatory urgency. Veru did so by cutting costs and by prioritizing clinical programs to pivot and to transform Veru into a late clinical stage biopharmaceutical company, focusing on the development of novel medicines for the treatment of obesity and oncology. Why did we pivot into obesity?
Glucagon-like peptide-1 receptor agonists, and I'll refer to them as GLP-1 receptor agonists, like Ozempic, which is semaglutide, Wegovy, which is semaglutide, Zepbound, and Mounjaro, which is tirzepatide, are very effective drugs that result in significant weight loss. Unfortunately, up to 50% of total weight loss comes from muscle, which is problematic, as muscle is necessary for metabolism, strength, and physical function. 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, which means patients are overweight or obese and also have age-related low muscle mass.
Sarcopenic obese patients are potentially at the greatest risk for developing critically low amounts of muscle mass when taking a GLP-1 receptor agonist medication for the treatment of obesity. Patients with critically low muscle mass may experience muscle weakness, leading to poor balance, decreased gait speed, mobility, disability, loss of independence, falls, bone fractures, and increased mortality. We believe there is an urgent, unmet medical need for a drug when given in combination with GLP-1 receptor agonist that could prevent the loss of muscle while preferentially reducing fat in not only overweight or obese patients, but especially for sarcopenic obese or overweight elderly patients who are at risk for developing muscle atrophy and muscle weakness, leading to frailty. We pivoted because we believe that enobosarm, our novel small molecule, our oral selective androgen receptor modulator, may be the best drug candidate to address this unmet medical need.
Enobosarm has been studied in five clinical studies involving 968 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 loss or wasting of both muscle and fat mass, similar to what is observed with a GLP-1 receptor agonist treatment. These clinical trials include two phase II clinical trials in 168 healthy, older, or sarcopenic subjects, and one phase II-B clinical trial and two phase III clinical trials in 800 subjects who have lost muscle loss caused by cancer. The totality of the clinical data from these five clinical trials demonstrates that enobosarm treatment leads to dose-dependent increases in muscle mass, with improvements in physical function, as well as significant dose-dependent reduction in fat mass.
Although these five clinical trials were not specifically conducted in an obese population, an ad hoc subset analysis was performed on obese patients who had a BMI of greater than 30, who were enrolled in the phase III placebo-controlled 505 clinical study, which is the one that evaluated enobosarm 3 mg treatment in metastatic lung cancer patients on chemotherapy. Even though a small sample size of 29 subjects, notable differences consistent with an obesity drug that preserves muscle and decreases in fat were observed. At 12 weeks, enobosarm 3 mg treated subjects had a 4.96% increase in total lean body mass, that's muscle, compared to placebo, and a 5.77% reduction in fat mass compared to placebo.
By 21 weeks, enobosarm 3 mg treatment resulted in a 14.4% loss in total fat mass and a 4.51% loss of total DEXA body weight compared to placebo, while maintaining total lean body mass. It should be noted that that these results were from the short-term treatment of enobosarm alone. The expectation is that enobosarm, in combination with a glucagon receptor agonist, would potentially augment the fat reduction and 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 a duration of treatment in some patients for up to three years. In this large safety database, enobosarm is generally well-tolerated, with no increase in gastrointestinal side effects. This is important as there are already significant and frequent gastrointestinal side effects with a glucagon receptor agonist treatment alone.
Although these studies were previously conducted by GTx or Merck, Veru owns all of this clinical data as well, as part of our enobosarm exclusive global in-license agreement. Because of these of these key clinical attributes, we believe that enobosarm may address this unmet medical need. The patient data that were generated from these five enobosarm clinical trials, in both elderly patients and in patients with cancer-induced starvation-like state, provides strong clinical rationale for enobosarm to address two possible populations. First population, enobosarm, like glucagon receptor agonist combination treatment, will initially be studied in an at-risk, sarcopenic obese, or overweight elderly patient subpopulation. The enobosarm glucagon receptor agonist combination therapy has the potential to augment weight loss by preferentially increasing fat loss while preventing muscle loss and improving physical function.
Second, is enobosarm monotherapy for treatment of at-risk, sarcopenic, obese, or overweight elderly patients who discontinue the GLP-1 receptor agonist therapy. In this case, enobosarm may rescue the patient by increasing muscle mass, improving physical function, while preventing the rebound weight and fat gain that typically occurs when the GLP-1 receptor agonist is stopped. Now, how about the enobosarm clinical program for obesity? Our current phase II clinical program is designed to provide clinical data to support the development of enobosarm for these two possible patient populations. The IND for enobosarm for obesity is expected to be submitted to the FDA today.
Subject to receiving clearance of our IND, we plan to conduct a phase II-B, multicenter, double-blind, placebo-controlled, randomized dose-finding clinical trial, designed to evaluate the safety and efficacy of enobosarm 3 mg, enobosarm 6 mg, or placebo, as a treatment to augment fat loss and prevent muscle loss in approximately 90 randomized sarcopenic, obese, or overweight elderly patients, receiving a glucagon receptor agonist, who are at risk for developing muscle atrophy and muscle weakness. The primary endpoint of the phase II-B clinical trial will be the change in lean muscle mass from baseline to three months. Key secondary endpoints will be the change from baseline in three months in total fat mass, insulin resistance, total body weight, physical function that's measured by stair climb tests. The primary three-month clinical data from the phase II-B clinical trial is currently expected in calendar year Q4 2024.
The purpose of the phase II-B clinical trial is to select the optimal dose of enobosarm, in combination with a glucagon receptor agonist, that best preserves muscle and reduces fat after three months of treatment, to advance into the phase III obesity or overweight clinical trial. After completing the three-month efficacy dose-finding portion of the phase II-B clinical trial, participants will then be allowed to continue into an open-label extension trial, where all patients will receive 6 mg of enobosarm for three months, to determine the ability of enobosarm to rescue or reverse muscle loss and prevent fat and weight rebound after stopping a glucagon receptor agonist. Now, about the intellectual property. Enobosarm is one of the most well-studied SARM, having been evaluated in over 27 clinical studies. For the overweight or obesity indication, we believe enobosarm has strong intellectual property in addition to potential regulatory protection.
Enobosarm is a novel small molecule that has not been approved for any indication anywhere in the world. We hold an exclusive worldwide license to 16 issued U.S. patents, six pending U.S. patent applications, 74 patents and patent applications in countries outside the U.S., and one pending PCT application, including issued molecule and polymorph composition of matter and method of use patents in the U.S., E.U., and Japan, relating to our Enobosarm drug candidate and related compounds, the use in breast cancer and patents related to enobosarm and related compounds, having statutory expiration dates from 2024- 2034.
In addition, we are prosecuting a method of use patent application related to the use of enobosarm in combination with or following a GLP-1 receptor agonist in obese or overweight adult patients, to increase or preserve muscle or bone, as well as the use of SARMs in general for treatment of obesity and chronic weight management. If issued, this patent will be expected to expire in 2044. In connection with this patent application, we've engaged an independent third-party search firm to perform a prior art search, and this independent firm identified no prior art likely to prevent the issuance of the claims of this patent application. Next, for regulatory protection. We expect that enobosarm, as a new chemical entity, would qualify for patent term extensions that could result in later expiration dates with a maximum five-year patent term extension in the U.S.
Enobosarm would qualify for 10 years of regulatory market exclusivity, exclusivity in the European Union countries and 7.5 years of regulatory market exclusivity in Japan. Finally, to further solidify these intellectual property and regulatory protections, we plan to develop a new modified release enobosarm tablet with a novel release pharmacokinetic profile that utilizes patented technology. We expect to file a patent application for this new formulation, and if such patent issues, it would likely serve to provide additional formulation composition and matter patent exclusivity until 2044. How do we stack up? What's the competitive landscape? Although the competitive landscape for GLP-1 receptor agonist containing weight loss drugs has been rapidly expanding, it has only been recently that the significance and desire to avoid the adverse effect of significant muscle loss caused by GLP-1 receptor agonist has been appreciated.
All GLP-1 receptor agonists work by creating a starvation state that non-selectively reduces both muscle and fat tissues to cause the weight loss. Using a muscle-preserving drug in combination with a GLP-1 receptor agonist would be a new indication. There are no human clinical data currently available with any potential muscle-preserving drugs in combination with any GLP-1 receptor agonist. Consequently, no drugs are approved by the FDA for the indication of chronic weight management with preservation of muscle, either alone or in combination with a GLP-1 receptor agonist. There are at least two classes of drugs that have at least phase II muscle data in other conditions that are being developed as a combination therapy with a GLP-1 receptor agonist to address the muscle loss and provide incremental higher loss of fat.
The first class are the myostatin inhibitors, which has a novel mechanism of action, and there are no approved drugs that utilize this mechanism. Currently, myostatin inhibitors under development are administered intravenously, and gastrointestinal adverse effect events appear to be common, especially diarrhea. The second class of drugs are the selective androgen receptor modulators, of which enobosarm is a first-in-class small molecule that has tissue selective and well-established mechanism of action, which is using the androgen receptor to change body composition. Activation of the androgen receptor increases muscle mass, improves physical function, decreases fat mass. We know that. Enobosarm has been generally well tolerated without masculinizing effects in women and has similar frequency of gastrointestinal side effects as observed in the placebo-treated subjects. Again, this is important as there are significant and frequent gastrointestinal side effects with a GLP-1 receptor treatment for obesity alone.
I want to emphasize, 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 potentially be combined with any one of the many GLP-1 receptor weight loss drugs to avoid muscle loss and augment fat loss. Again, at this time, there are no clinical development, no clinical data with either myostatin inhibitors or SARMs in combination with any of the GLP-1 receptor agonists. This is truly a new indication, enobosarm has the potential to have the ideal product profile in combination with a GLP-1 receptor agonist.
That is an oral once-a-day dosing, potential to maintain improved muscle mass, physical function, potential to directly reduce fat and decrease total weight, and the potential to improve insulin resistance with a favorable side effect, without adding to the gastrointestinal side effects that are observed in GLP-1 receptor agonist treatment alone. Market. The market, the global market for obesity and overweight drugs is projected to be $100 billion by 2030, and this is from Barclays analyst in 2023. Drugs used for weight loss, such as Ozempic, Wegovy, Zepbound, Mounjaro, and other GLP-1 receptor agonists, cause a significant loss of both fat and muscle.
Again, in the United States, 42% of older adults, that is greater than the age of 60, have obesity, and 34% of these patients also have sarcopenia, a low muscle reserve. Accordingly, enobosarm is targeting the at-risk, older, obese, or overweight patients who may already have low muscle mass, and are at risk for further drop in muscle mass of these all-important muscles, which will increase the risk of muscle weight, weakness, functional limitations, mobility, disability, falls, higher hospitalizations, greater mortality. It should be emphasized that enobosarm may potentially be combined with any one of the many GLP-1 receptor agonist weight loss drugs, not only for older, overweight risk patients, but all overweight or obese patients who want to avoid muscle loss when taking a GLP-1 receptor agonist for weight loss.
The combination of enobosarm with a GLP-1 receptor agonist potentially represents a multi-billion-dollar global opportunity. We're very excited about the prospects of enobosarm to address this new and important unmet medical need. Now, to update you on the oncology program, our oncology drug pipeline is focused on the clinical development of enobosarm in AR positive metastatic breast cancer. The design of our phase III clinical trial, evaluating enobosarm alone or in combination with abemaciclib, which is a CDK4/6 inhibitor in patients with AR -positive, ER -positive, HER2 -negative metastatic breast cancer, we have tumor progression while receiving palbociclib, which is a CDK4/6 inhibitor, plus an estrogen blocking agent.
Primary endpoint for the stage one portion of the phase III trial was objective tumor response rates. As of August 2023, we have completed the target enrollment of three patients in Stage 1A portion of the phase III clinical trial to assess the safety and pharmacokinetics of the combination of abemaciclib and enobosarm. There are no reported drug-to-drug interactions with abemaciclib and enobosarm or new safety findings in three patients as of the data cutoff. Further, the early preliminary clinical results showed two partial responses and one stable disease in these first three patients, based on local assessments. Also as of the cutoff date, these patients were on study at nine, 11, and 12 months from the first day of dosing to the disease progression that was determined by a blinded central assessment.
In January of 2022, we entered into a clinical trial collaboration and supply agreement with Eli Lilly, a company that supplies abemaciclib for the ENABLER II study. As we have prioritized our clinical programs to focus on enobosarm for obesity, the continued clinical development of enobosarm for treatment of metastatic breast cancer is subject to availability of sufficient funding. In an infectious disease program, we are developing sabizabulin 9 mg, which has both host-targeted antiviral and broad anti-inflammatory properties, as a two-pronged approach to the treatment of hospitalized patients with viral lung infection and high risk for ARDS and death. We have completed a positive phase II and a positive phase III COVID-19 clinical trials, which demonstrated sabizabulin treatment resulted in significant mortality benefit in hospitalized moderate severe patients with COVID-19 viral infection, and high risk for ARDS and death.
Although in September of 2023, we received positive feedback from the FDA on the design of a phase III clinical trial, broadly evaluating sabizabulin in any of the viral-induced ARDS, we will continue to seek external funding through government grants, pharmaceutical partnerships, and similar sources to fund the clinical development program. To be clear, without such external funding, we do not plan to advance the development of sabizabulin as a treatment for viral-induced ARDS, and will not commence our phase III clinical trial to evaluate sabizabulin in viral-induced ARDS until we have such external funding. Now, let's turn to our financial position. As of September 30th, 2023, we had $9.6 million in cash and $4.5 million in accounts receivable.
In December of 2023, Veru announced an underwritten public offering led by Raymond James & Associates and Oppenheimer & Co. Inc., 52.7 million common shares, with the net proceeds to Veru from the offering of $35.2 million. The offering was oversubscribed, and the underwriters fully exercised their over-allotment option. Equally as important, through the offering, the company has brought into our stock many highly regarded biotech institutional investors who are attracted to the potential of enobosarm for the weight loss indication.
Although some of the net proceeds from our recent successful financing may be used for working capital purposes, including existing debt obligations and general corporate purposes, we will prioritize the use of the net proceeds for the development of enobosarm, with a primary near-term focus on funding the proposed phase II-B clinical trial to evaluate the safety and efficacy of enobosarm as a treatment to augment fat loss and to prevent muscle loss in sarcopenic obese or overweight elderly patients receiving GLP-1 receptor agonist, who are at risk for developing muscle atrophy and muscle weakness. We anticipate the phase II-B primary clinical trial data in calendar Q4 2024, and the results of the phase II-B extension study in calendar first half of 2025. We believe we have sufficient resources on hand to reach these important milestones.
If successful, we'll use the primary clinical data from the phase II-B that we expect to receive in calendar Q4 2024 to plan the next clinical study. Although we had to make hard choices in 2023, we believe we are now in a great position with the resources to advance enobosarm as an important drug to be used in combination with any glucagon receptor agonist. The overweight and obesity market opportunity is expected to be $100 billion by the end of the decade, and with the potential addition of enobosarm, treatment with the glucagon receptor agonist drugs may be able to avoid loss of muscle and preferentially reduce fat for high quality and safe weight loss. We are looking forward to a very successful 2024. With that, I now would like to open the call to questions. Operator?
Thank you. 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 are using a speakerphone, we ask that you please 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, it is star, then one to rejoin the question queue. We will pause momentarily to assemble our roster. The first question comes from Dennis Ding with Jefferies. Please go ahead.
Good morning, and thanks for taking our question. Maybe on enobosarm and its safety profile, how do you think about the safety data that you guys have to date? And how do you think that would translate in obesity, and how the FDA would think about these SARMs and enobosarm, given the risk-benefit profile is much different in obesity versus in cancer? Thanks.
Thank you for your question. First of all, to answer that question, the safety profile in our large safety database shows enobosarm to be, again, well-tolerated and actually really across the board. And we don't see masculinization in women. We don't see. It's neutral on prostate. And so from a safety standpoint, it's extremely well-tolerated. With that said, you know, the FDA did allow GTx to use enobosarm to treat in a phase II-B setting, women with stress urinary incontinence. And as you know, women with stress urinary incontinence, that's not a lethal indication. Stress urinary incontinence means when they cough or sneeze, they lose urine.
So in that post menopausal, premenopausal population, they, you know, allowed to use the, the enobosarm specifically. So, so the benefit-risk ratio in that setting could be very similar to an obesity patient. And, and so I think the FDA's already kind of voted on that, so I think it can be easily translated. We are looking at a subpopulation of patients that are, that have, you know, low muscle reserve, and that's the patient population we're most worried about. So we do have a spectrum of clinical benefit versus risk that we can go after, not just the obese patient who's 22 years old and, wants to try to avoid muscle loss, but also the greater than 60-year-old patient that with potentially accelerated frailty.
To be clear, what I mean by that is that what the reason why there is a concern, and this is, again, the risk-benefit ratio, is the issue that patients over the age of 60, you know, typically it will take them to go from age 60 to age 80 to get something called frailty. Frailty means you lose muscle, and you lose enough muscle that you end up having functional limitations, which is worrisome. And when you give a GLP-1 receptor agonist, you're typically taking you can typically take a 60-year-old patient, and you're basically putting them through an accelerated frailty process because they're losing so much muscle in such a short period of time.
So I think there's a lot of room when you look at risk-benefit with a SARM from stress urinary incontinence to patients with frailty. And the reason we used it in cancer is because it worked. You know, in the clinical trials, it showed that going after the androgen receptor could be very interesting. But equally, you know, the data that we have in otherwise healthy patients, postmenopausal patients, sarcopenic patients, you know, again support the clinical benefit-risk ratio.
Got it. Thank you.
Thank you.
The next question comes from Leland Gershell with Oppenheimer. Please go ahead.
Hi, Mitch. Thanks for the update. A couple questions from us. First, with respect to the modified release formulation that you mentioned you're working on. Enobosarm is a once-daily. Just wondering, beyond basis for a new IP, what might be the clinical advantages of the modified release that you're going after? And secondly, would you expect to take that into a pivotal program in sarcopenia? And also, would the primary endpoint of the phase II-B be applicable to the phase III? How do you see any differences in what's required for registration for enobosarm in sarcopenia? Thank you.
Yeah, great question. So, I'm gonna answer some of that question, and I'm going to ask Dr. Gary Barnette, our Chief Scientific Officer, to answer some of that question as well. I'll work backwards. The plan is that the only formulation that will be in the phase III pivotal study will be the new formulation. There'll be no data in the phase III setting with the formulation that we'll be using in the phase II-B. And so the expectation is that, yes, it's once-a-day dosing, but we're changing the pharmacokinetics to decrease and change the Cmax and keep the exposure the same.
If the exposure is the same, then you can directly relate exposure to the phase II-B formulation to the new formulation, but making it more difficult for generics to come in, because they, as you know, have to match the Cmax and the AUC. I'll have Gary give you some additional comments and some insight in terms of where we are with the development. Gary?
Yeah, we've done some preliminary development work with the molecule, physical chemical property work and some preliminary work with it. We do anticipate that there will be a, you know, in FDA vernacular, lower or the minimal effective dose, lower AUC, lower Cmax, but effective continues to be the target. So while we do believe that the safety profile of enobosarm is very good, we will be optimizing that through this formulation with a specialized release profile.
Thanks. Just curious, in terms of the phase III design, would you expect that to be replicative of the phase II-B or any significant differences required for registration?
You mean for the phase III?
Yes.
So, for the phase III, for the pivotal, do I think the phase II-B? No, I would say the way I would look at it, I jumped ahead. Let me just come back to the question. The question is, do I think that the phase III design is going to look like the phase II-B design? And the answer is no. I think the way to think of the phase II-B design is, how much information can we get so we can better understand what is the right design of the phase III? So that's the reason why we're asking a lot of questions. The first question is, use a biomarker. The biomarker is lean body mass. Lean body mass is not your endpoint. It's not a regulatory endpoint.
However, we know that if you can pick a drug that has the best effect on lean body mass, which is muscle, and the best effect in reducing fat, and the reduction of fat is going to translate to weight loss, you don't have to wait 45, 48 weeks to get that information. You can get that information in 12 weeks. And so the idea is, do your dose finding. Remember, there's no drugs, muscle drugs currently, that in combination with a glucagon receptor agonist, we have information. So we want to get that information, get the combination information of the glucagon receptor agonist by itself versus the enobosarm 3 mg and versus the enobosarm 6 mg.
And we're expecting to see is the 3 mg would, you know, maintain or improve muscle and decrease fat, and that the 6 mg would maintain or improve muscle and decrease fat even further. So the idea is we would have the best opportunity to directly decrease fat, augment the fat loss, if you see with a glucagon receptor agonist. The problem with the glucagon receptor agonist, because you lose muscle and fat, that you'll see a plateau in your weight loss. And the plateau is because your body's telling you, you can't keep losing 40% of your muscle. And if every pound you lose, you're losing 40% of that as muscle, at some point, your appetite kicks in, and you get a plateau.
But yet there's plenty of fat that you can melt away and burn, but you can't do that because you're burning muscle at the same time. So if you can maintain muscle, you may be able to get a deeper and more pronounced fat loss. So that's the reason why I want to hold muscle constant or higher and decrease fat deeper. And you can get that information at 12 weeks in the design of the study that we have now. Second part of this study, and then by the way, then that dose would then be moved into a clinical study that either is going to include all patients, depending on, you know, how we're thinking about it and resources, or focus on the sarcopenic obese patient.
If you do all patients, we still would do a subpopulation of sarcopenic-obese patients in a phase III setting. And then that kind of study would go on for 48 weeks because that's what's required by the FDA guidance for weight loss. The second part of the study, which is the extension study, which is a rollover study, if you will. The concept there is the other problem that you have with the glucagon receptor agonist is that if a patient stops the medicine, for whatever reason, they get this rebound fat gain and weight gain, and the muscle doesn't come back. So you can actually make a patient with low muscle worse in that setting.
So, you know, so if you're dealing with a sarcopenic obese patient or an older patient that actually gets in trouble with a glucagon receptor agonist, it would be nice to have a medicine that we can have in the endocrinologist tool chest, that they can say, "Okay, I have a drug I can give you now that will restore that muscle," and not... And, you know, and minimize the fat rebound and the weight gain rebound, because you're actually making them worse. So we're going to learn that information in this study as well. But probably, if that becomes a phase III that'll be a separate study. It's just asking a different question.
So the primary question is still the same one: Can we augment fat weight loss, maintain muscle, get a deeper weight loss because you're losing fat, and you're losing fat because you're directly reducing fat, and by maintaining muscle, you can get deeper fat loss? That would be the goal. So think of the phase II-B as trying to answer those questions in a short period of time because you want to spend your time in the phase III program, not in the phase II program.
Understood. All right, thanks very much.
Thank you.
Again, if you have a question, please press Star, then one. To withdraw your question, press Star, then two. The next question comes from Yi Chen with H.C. Wainwright. Please go ahead.
Thank you for taking my question. Just to clarify, so you expect the top-line results of the phase II-B trial to show that the muscle mass to remain roughly the same, correct? So clinically speaking, what percentage, in terms of percentage range, what would be considered roughly the same for the muscle mass?
So I'm going to have Dr. Barnette answer that question. So Gary?
Yeah. Can you hear me, Mitch?
Yes, now we can.
Okay, good. All right, so roughly the same. So what you are expecting in this study is for the treated arm with the the placebo arm to have a reduction in lean mass. If you look at the STEP 1 study with semaglutide, they showed a 6.92 kg reduction in lean mass over 68 weeks. This is reported by Wilding et al. in New England Journal of Medicine. If you assume that that's a linear reduction, that's 0.102 kg per week. Over a 12-week period, you would expect that the lean mass to reduce by 1.2 kg in the placebo plus GLP-1 arm. What we're talking about in the, so you have a reducing baseline with the GLP-1 of lean mass. What we're talking about in the treated arm, when Mitch talks about no change, we're talking about preservation of that.
So essentially zero change, or we don't necessarily expect the lean mass to increase from baseline in this population, but basically stay the same, so don't lose that valuable muscle so that the weight loss becomes more valuable or optimal than just losing weight, where you lose muscle and fat together. Does that make sense?
Yeah. Yep. Okay, thanks. So, once you start recruitment, patient recruitment for this trial, shall we expect the top-line results to become available before the end of 2024?
That's our objective. To be clear.
Mm-hmm.
Go ahead. I was just going to say, to be clear, there's a second portion of the study, which is the extension study, that is, again, provides phase II proof of concept information, but it's the data that we get in the fourth quarter of 2024, calendar fourth quarter of 2024, that we will move forward with the design of the next study.
Got it. And currently the company is funded to complete the entire phase II-B trial?
That is correct.
Okay, got it. Just one last question. Do you think enobosarm monotherapy would be good enough for the sarcopenic overweight patient population?
It can be. It's a great question. It is, because if you go back and look at some of the data from the, you know, one thing we don't have with enobosarm , but we do have with testosterone, because it, we use the same receptor, the androgen receptor. If you look at the testosterone studies, you do see significant weight loss. If you have to get above 5% at one year, I mean, testosterone does that, and so enobosarm should be able to do that as well or better. If you look at, you know, some of the competitors, myostatin inhibitors that have made it to 48 months as monotherapy, you know, they hit about 5%-7% weight loss at a year.
So that's, that's what you're getting, you can expect with the monotherapy, with a drug like this. But if you're doing that and you're not losing muscle, then you have to build in the weight that stays behind because you didn't take the muscle, and the weight that you're losing is mostly fat, then that becomes, you know, that's the quality. So I do think, you know, there is a, there. And by the way, the longer, interestingly, in the testosterone data, and again, the reason I bring it up, because we're an androgen receptor target, the longer you treat, the more fat loss.
Thank you very much.
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.
Thank you, operator. Actually, what I'd like to do at this point is I've received over the last two weeks since we've done our financing and stated kind of our, you know, reset and the position of the company to pivot. I received several questions from investors that I promised we would try to address. And so I have a few questions I'll go through to address some of the comments that came up so that this would be, you know, a forum that I could do that publicly. So first question that came was: What's the main driver for prioritizing the clinical programs? Is it money? You know, what happened? Is it lack of efficacy?
So the answer is, the reason for it was, as you know, after we got the Emergency Use Authorization declined, and given the state where the markets were in, you know, like most biotech companies, we had no choice. We had to prioritize because of resources. We didn't prioritize because of efficacy. In fact, one of the studies that we did pause is the ARTEST phase III study in breast cancer, and we even, you know, with the thirty-nine to forty patients that were enrolled in that study, we did release the data to show you that it has very good efficacy in that patient population. So it wasn't because of efficacy.
Of course, with the sabizabulin program, the whole world saw our data, and the FDA made it very clear that we gave them a positive study. The question is whether they want another study, given the lack of urgency for COVID. “What’s the rush?” quote, unquote, one of the panel members said at the FDA advisory committee. So, we have, you know, so that's not efficacy. That was a very positive study, but, you know, the urgency changed. Now, the reason we did what we did is because resources.
And second, you know, this is a brand-new indication. This indication really came out of nowhere, in a sense that the glucagon receptor agonist took the whole space by surprise because of the effectiveness and then the light was shone on, you know, how can you make it better? Can you have an oral agent instead of a subcutaneous IV agent? You know, can you avoid muscle loss There's a lot of things you can do to tweak the weight management programs that are going on now through drugs.
And so we were actually alerted to this opportunity by an investor that told us that, "You know, if you're thinking about preserving muscle, improving muscle and physical function in women that are taking the drug for breast cancer, you know, would it have an opportunity in this real important problem that's happening in this rapidly growing large market?" And we had the data. We have, you know, five clinical studies and 1,000 patients that, you know, from patients, it shows, you know, very much so that we improve muscle. The totality of data, as I mentioned in my comments, we improve muscle, improve physical function, decrease fat. And this is not just in healthy patients, but in patients that have cancer, and the cancer acts like a glucagon receptor agonist.
Some people find out they have cancer because they have this unintentional weight loss, and they're losing fat and muscle. We were able to show that we have activity there as well. So the proof of concept data is very strong to move enobosarm forward, and being oral really puts it in a very interesting spot. So no, it's not lack of efficacy, it's not. It's resources, and it's, and the commercial opportunity, it's such a large commercial opportunity with a drug that has a lot of clinical efficacy and safety data, for moving it forward towards a GLP-1 receptor agonist [inaudible].
Another question is, "I see that you're focusing the phase II-B in older, overweight or obese patients to avoid muscle loss when receiving a glucagon receptor agonist. Can Enobosarm be indicated in all obese or overweight patients receiving a glucagon receptor?" So I did try to address that as well. The answer is yes, absolutely. If you regulatorily go after all patients with muscle weight with obesity or overweight on a glucagon receptor agonist, the primary endpoint there would be incremental increase in weight loss at year, basically at a year. And you know, somebody mentioned on the call, you know, how about the clinical benefit versus risk ratio? And you know, again, this drug was being developed for stress urinary incontinence, which is a patient population that wearing pads, it's a pretty pretty pretty interesting population, cancer population. It's not a frail population.
And so, yeah, I think enobosarm has an opportunity to be used in the bigger picture. That's why I'm saying, let us get past the phase II-B, and the phase II-B will allow us to think, you know, more, more broadly in terms of what's the right patient population. And not to forget, 'cause the investor made it very clear, that you still have a real opportunity in the patient population that is losing muscle, have to stop the drug. Older patients, some endocrinologists are telling me, afraid to go on the drug because of the muscle loss. So we have to keep that in mind 'cause we're a solution for that patient population, but we could be a solution. "Are you, are you in discussions with any pharmaceutical partners now for Enobosarm obesity?" The answer is yes. We are in discussions.
Again, you would expect that, and that's all, that's all I can say at this point publicly. And another question is:
"What's the projected size of the muscle loss market for weight loss now and in 2030?" So I've seen numbers between $100 billion-$130 billion for the end of the decade for the glucagon, well, called the weight loss drug market. It's massive. And I will tell you that, you know, now it looks like for 2024, it may be more in the order of about $20 billion-$24 billion or something of that number. So if you're giving a drug in combination with a GLP-1 receptor agonist, I mean, and that's such a big number, that this is clearly a multi-billion dollar opportunity.
It's another reason that's driving us to take this drug, that we know has muscle activity, and we know has direct effects on fat, independent of increase fat. We know as a class, it can decrease, and maintain bone. It could be the right drug for the right time, and so we think there's a big opportunity. Now, somebody brought up the point, it looks like enobosarm failed in a phase III study in lung cancer. You know, you know, what happened, and what does it mean for the obesity indication? So, so let's be very clear, enobosarm , in every clinical study, has shown an improvement in maintenance in muscle. So it's a muscle drug, and it's shown a improvement in function in almost all studies and so it does matter what patient population.
So the studies this is referring to is we ran two studies in lung cancer, advanced lung cancer, stage 4. One population, POWER 1, was healthier patients by virtue of the kind of chemo they got, and the other one was sicker patients by virtue of the chemo they got. In the sicker patients, we were able to improve muscle, but function did not improve. In the same patients, lung cancer patients, but more healthy, meaning less sick, we were able to show muscle and function. So it does matter on the patient population. As a result, the obesity population is more likely to mimic the healthy volunteers and the sarcopenic patients, older patients.
And so in older patients, we do show an increase in lean body mass improvement, a decrease in fat, and improvement in physical function. So the expectation is that we'll see that in the obese. The other important point is you see much more weight loss, the bigger the patient. So another way of saying it is normal patients, overweight patients, obese patients, severely obese patients. As you go up that spectrum, you lose more weight, the more patient has weight to lose. And so that, again, it depends on the patient population. So if we go after an obesity population, we expect to see much more weight loss than the otherwise healthy population.
And here's another interesting question: enobosarm is being abused now for performance enhancement. Where are people getting it? The FDA says SARMs are not safe. What does that mean for enobosarm? Well, I'm going to answer part of that question, and I'm going to ask Dr. Gary Barnette to address some of the question as well. So for real-world data, you know, enobosarm is being illegally used as a performance drug. So from a positive standpoint, that means nobody's gonna abuse a drug if it doesn't work. So clearly they're seeing an increase in muscle, decrease in fat. They're getting shred, which means they're losing fat, and they're having a physical performance. And so that's good news. The bad news is we have no clue, and again, this is coming from bootleggers in India, bootleggers in China.
We have no clue what dose, what the quality of the, sometimes we don't even know which SARM it is. It's hard to, in an uncontrolled, you know, wild, wild west fashion, really understand the safety. As the FDA looks at a drug, it determines safety based on controlled studies, for which there are none in this space. Meaning none for, you know, improving muscle in this patient population with, you know, special doses. If you look at our data, again, you see that it is controlled and it's well tolerated and safe. It appears to be safe. But the ultimate data will come from the phase IIIs that we do in obesity, you know, for a year, and that will be how safety is determined for enobosarm, not the safety for enobosarm based on the wild, wild west on the Internet.
But with that said, Gary, do you want to make some comments and tell them a little about your background?
Yeah. I'm a Ph.D. clinical pharmacologist. I'm a former FDA reviewer in three different divisions. Some of what I did at the FDA is I reviewed growth hormones for age-related wasting with Serostim product. I reviewed all the androgen testosterone products. I've spoken at and consulted for the United States Anti-Doping Agency years ago, and I wrote most of the critical studies that Mitch has summarized today. The study report or the study protocols and analyzed the data. When the FDA, any drug that's not approved, the FDA is going to say is not safe and effective, or the safety and effectiveness of the drug has not been determined.
In FDA mind or FDA vernacular, again, the only group in the United States that can determine the efficacy or the effectiveness, or that a drug is effective and safe, is the FDA. So when you see illegal drugs coming into the market or coming into the United States, the FDA is always going to say that. They're going no matter what it is, they're going to say it, it's unsafe, please be cautious, and so on and so forth. The FDA is doing that through part of their initiative to make sure that drugs that come in the United States come in appropriately and are approved and go through the appropriate vetting and review process.
Of course, once enobosarm is, the NDA is submitted and ultimately approved, then the FDA will have deemed it safe and effective. But at that point in time, while they are being aggressive now, they will be more aggressive after some of these more or some of the or all of these illegal drugs that are on the market. That's just FDA speak. You know, we presented our safety data, and it looks very strong, and as Mitch said, we've given doses up to 18 mg for quite some time without significant safety issues. So, we feel pretty confident that the safety profile of enobosarm is supported in this population.
Thank you, Gary. The next question is, "Who are the enobosarm competitors, and how does this enobosarm stack up?" So I did comment, but I think it's worth mentioning it again because there's some confusion. We're not a GLP-1 receptor agonist. So all these new ones coming along, and the big companies are trying to make better ones that are oral. God bless them. They're doing their best to try to get to this huge market, and as you can tell, everybody's getting into it. All of these drugs cause muscle loss because they're doing the same thing, they're causing a starvation state that's non-selective. So the way I see it is that whoever wins, and many could win, we're going to be used in combination.
You know, there is a chance it can be used as monotherapy, but really it's the combination that most of the focus is being used. And so when you look at combination, as I mentioned, it's really only two real classes at this point, and that's myostatin inhibitors, which are, at this point, given IV, and the SARMs. And as I mentioned, the product profile, to be able to take something orally once a day, that, you know, that builds muscle, improves function, decreases fat directly, and augments fat loss be very interesting.
So we think, you know, we think we're in a very good position, particularly with the phase II-B, being able to use a biomarker, lean body mass, as an endpoint, as opposed to having to wait 48 months to see what happens to weight loss. It'll allow us to, you know, to leapfrog our development program because we'll know which dose is the one that's most effective in, and we can see it at 12 weeks, in muscle and, in the reducing fat. So, and then the last, the last. Well, there's two, two more questions, I'm sorry. So one question is, is there any hope for developing sabizabulin for all viral-related ARDS in phase III study? The answer is, yes, definite hope. We just wanna make it very clear to the investment community that we want external funding.
We are talking to companies with potential partnerships. We continue to have dialogue with Department of Defense, et cetera. But until that actually shows up in the bank, or we ink a deal, we're gonna hold. And because this trial will cost $40 million and three years' worth of time at the minimum, and we wanna do it right. And so there is still hope. We do think, I mean, we've got phase III data, phase II data that's positive. But given the size of our company and given the opportunities that we have to increase shareholder value, at this time, it makes all the sense in the world to focus on obesity. If we go forward with the ARDS indication, that'll be a free option, if you will, for our shareholders. Sabizabulin appears to have promising activity against a variety of cancers.
You know, what's limiting further clinical development of sabizabulin in oncology? And that's true. If you look at published data, there's a lot of published data of using sabizabulin, VERU-111, in multiple tumor types. And the reason we got excited about sabizabulin to begin with is because of its oncology benefits. But then, you know, we rolled into ARDS because there was a need to come and get, have some of this antiviral, anti-inflammatory, and it proved out. So the answer is yeah, we'll continue to entertain the potential of developing sabizabulin in oncology, but right now we wanna focus, focus, focus on getting the phase II-B.
You know, hopefully the phase II-B data, from now until the phase II-B data, we'll have a better understanding of what our development programs are gonna look like, potential partnerships, what they're gonna look like. And in the meantime, we can continue to understand, you know, how we wanna develop sabizabulin moving forward. So with that, I appreciate everybody who's joined us on today's call, and we look forward to updating all of you on our progress on our next investors call. Thank you.
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