Good morning, and welcome to the Lipocine's KOL event to discuss the obesity landscape and LPCN2401 clinical results. At this time, all attendees are in a listen-only mode. A question-and-answer session will follow the formal presentations. If you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player or by emailing your questions to questions@lifesciadvisors.com. As a reminder, this event is being recorded, and a replay will be made available on the Lipocine's website following the conclusion of the event. Leading the call today is Lipocine's President and CEO, Dr. Mahesh Patel. Dr. Patel is joined by Dr. Frank Greenway from Pennington Biomedical Research Center and Lipocine's Vice President of Clinical Development, Dr. Benjamin Bruno. In addition, Lipocine's Chief Medical Director, Dr. Anthony Delconte, and Dr. Chidu Chidambaram, Lipocine's Senior Vice President of Research and Product Development, is also on the line and will be available during the Q&A session. I'd now like to turn the call over to Dr. Mahesh Patel, President and Chief Executive Officer of Lipocine. Please go ahead, Mahesh. Okay. Thanks, Tara. Good morning, everyone, and thanks for joining us today. I'm Mahesh Patel, President, CEO, and Co-founder of Lipocine. Let me first go over today's agenda. So following my introduction, Dr. Greenway will discuss the obesity treatment landscape. Dr. Greenway's presentation will be followed by a presentation of data from our phase II study by Dr. Ben Bruno, our VP of Clinical Development. After Ben's presentation, I'll offer some concluding remarks and open up for Q&A. Before we begin, I need to remind you that certain statements we will make in this presentation are forward-looking statements with the meaning of the Private Securities Litigation Reform Act. Also note that no material public information about a publicly traded issuer or security will be discussed at this meeting. No solicitation for the purchase of any security will be made at the meeting, and the meeting participants and materials shared during the meeting are authorized by the company. So prior to diving into today's topic, I would like to briefly review Lipocine's development pipeline at a high level. In addition to our approved product, we have a robust pipeline, which includes an advanced asset, LPCN1154, with anticipated NDA filing this quarter for treating postpartum depression. If approved, eleven fifty-four could be a differentiated therapy option for postpartum depression, a potentially life-threatening condition. Our pipeline also includes several candidates with positive phase II results, which we are actively exploring partnering slash monetization and NDA submission for eleven fifty-four, in addition to advancing LPCN2401, the subject of today's call. There remains an unmet need for a product, for chronic weight management with a convenient dosage form, preferably oral, with favorable benefit to risk profile, especially with respect to improved efficacy, better tolerability, and improved body composition. So what is twenty four oh one? Twenty four oh one comprises a proprietary androgen receptor agonist, aka testosterone esters, targeted for once-daily oral treatment. We have also tested LPCN2401 with vitamin E that has shown some additional benefits. Of note, there is no testosterone product approved for juvenile patients or women, and not all esters enable once-daily dosing. Testosterone undecanoate enabling QD dosing is unique and proprietary to Lipocine, with strong patent protection. So let me review possible mechanisms of action that inform the design of our product candidate. So in addition to its anti-inflammatory effects, LPCN2401 has the potential to improve body composition through actions on all three critical tissue types, namely fat, muscle, and bone. With respect to fat, ARA, androgen receptor agonist, could induce lipolysis of fat breakdown, lower lipogenesis of fat production, and also inhibit expression of adipocytokines such as TNF-alpha, IL-one. With respect to muscle tissue, LPCN2401 is expected to stimulate muscle satellite activator, fibroblast growth factor, and modulate muscle growth suppressors such as myostatin and skeletal muscles. And with respect to bone, it could act directly on osteoblasts and consequently promote bone formation and increase androgen receptor expression in the osteoblasts. To remind, what is obesity? In individuals with obesity, the excess adipose tissue stimulates release of inflammatory mediators, predisposing them to pro-inflammatory state and oxidative stress. We have observed some additional benefits, potential amplification of the androgen receptor agonist when LPCN2401 was co-formulated and co-administered with vitamin E, a powerful antioxidant. Alpha-tocopherol, being a free radical scavenger, protects tissues against oxidative stress, helps maintain membrane fluidity, and pending confirmation in a larger trial, inclusion of vitamin E may be justified. Just a reminder that testosterone esters in our LPCN2401 are extremely lipophilic and highly water-insoluble and present oral absorption challenges. Let me briefly review how we are enabling effective oral delivery. We utilize our best-in-class, validated through an approved product, effective oral technology, delivery technology platform. That is to achieve effective levels of the lipophilic actives. Testosterone undecanoate and testosterone tridecanoate, the components of LPCN2401, are extremely water-insoluble and need effective delivery for efficient oral absorption. Interestingly, vitamin E, that has also shown some additional benefits, and some of the next generation non-peptide GLP-1s that are under development are also lipophilic and need oral effective delivery. So our platform, as needed, can enable multiple actives needing efficient oral absorption to be co-formulated in a single one-unit dosage form and potentially improve compliance. With this background, let me introduce to you today's speaker. You know, it is my pleasure to introduce to you Dr. Greenway, Professor and Chief Medical Officer at Pennington Biomedical Research Center, a globally recognized institution for metabolic health research. Dr. Greenway is actively involved in numerous clinical trials, many of which have led to advancement in obesity management, and he was a recipient of Distinguished Leader Award from the American Board of Obesity Medicine in 2018. Now I'll turn over to Dr. Greenway. Dr. Greenway? You're on mute. Okay, I will try to give a little overview of the treatment landscape for obesity in preparation for Dr. Bruno's talk. Obesity is a global public health crisis. It is a physiologically controlled problem of excess body fat, which is more than just an increase in body weight. It carries a number of disabilities complications that you can see on the right-hand side of the slide, including cardiometabolic health. By 2030, it is thought that 15 billion people in the world will have obesity, and among those, there will be 50% of American adults between the ages of 40 and 85. And so there is still a critical unmet need medically for better obesity treatments. There has been improvements in the pipeline of drugs that have been used to treat obesity recently. The long-term treatment for obesity was approved, the orlistat back in nineteen ninety-nine, which gave around a 5% weight loss. The combination medications and short-acting GLP-1 agonists increased that to around 10%. But more recently, semaglutide, tirzepatide, and other things in the developmental pipeline have increased the weight loss to 15%-25%, and perhaps even more effective treatments are on the horizon and competing with the obesity surgery, like gastric bypass, which give in a range of 25%-30% weight loss. But the GLP-1 agonists, these, especially these long-acting ones, are associated with an excess loss of fat-free mass. In dietary treatments, it's always been assumed that you shouldn't have a loss of fat-free mass in excess of 25%. The fat-free mass loss with one of these semaglutide studies was 40%, and that is on top of the fact that with aging, one loses about 3%-8% of their muscle mass per decade after the age of 30. There are important medical benefits from having muscles, more than just power. It's muscles use insulin, and so loss of muscle induces an insulin resistance, which is a precursor to diabetes. The muscles put stress on the bones, which stimulate increasing their density, and it contributes to cognitive function. In a meta-analysis of 16 studies, the low muscle mass index has been associated with a 50% increase in all-cause mortality. In addition to muscle loss, the GLP-1 agonists have been associated with accelerated bone loss. They both-... Losses been seen in the hips and spine and in decreased tibial cortex thickness, and it's been suggested that reoperation for lumbar fusions have been affected by this as well. Muscle loss is associated with bone loss, and they're both associated with aging. Accelerated bone losses end up with developing sarcopenia, which leads to frailty and falls and pathologic fractures. Then the three- to four-year cardiovascular outcome study of semaglutide. It was found that there was an increase in hip and pelvic fractures compared to the placebo group. In women over the age of 75, that increase was 4-5% greater, 4-5 times greater than the placebo group. These complications of low bone density can be expensive and a major cause of morbidity and mortality. And the first approach that has been taken to try and address that is by using myostatin inhibitors. And myostatin is a hormone that reduces muscle mass and also tends to increase the bone resorption and to inhibit bone formation. In addition to the effects on muscle and bone, discontinuation of the GLP-1 agonist, which happens in two-thirds of the people who take these drugs in the first year of treatment, because in large measure due to the nausea and vomiting that associated with these drugs. But when one stops these medications, as you can see on the right-hand side of the slide, there's a rapid increase in weight gain, and that weight gain is primarily fat, which also includes the visceral fat, which has a higher incidence and of increasing cardiovascular risk. Although it's not a common problem, the slowing of the gastrointestinal tract does double the rate of rupture of the intestines due to some of the constipation that can occur from that. From that background, I think it's obvious that since obesity is a disease of increased fat and not just weight, it's important to determine what the composition of the weight loss is, when one evaluates these treatments. The DEXA is thought to be the sort of gold standard of how to measure body fat. It's quite accurate at doing that. It also measures bone mineral content, and what's left over is called fat-free mass. It's not all muscle. It contains water and organs as well. Muscle is usually, or on average, about 50%, but that's quite variable depending upon how muscular the person is. And you can see in the middle panel on the bottom of the slide how the muscle is about, represented as about 50% of the lean body mass. So that brings up the issue of: How does one evaluate weight loss now in a clinical situation? The usual way has been for people to step on the scale when they come to the physician's office, and that's... The BMI is based upon height and weight, but the correlation with the body fat and its medical liabilities is only about 60%-70%. And the Body Roundness Index takes into consideration the waist circumference, which is a surrogate measure for the visceral fat, which has a higher prevalence of cardiovascular risk, and that increases the correlation to 80%. Bioelectrical impedance, which is a way of non-invasively measuring electrical activity, can increase that to between 80% and 90%. These three modalities are potentially things that can be used in the office. DEXA, however, requires sophisticated equipment that's expensive and is not practical for clinic use. So there's still a lot that can be done to improve the quality of care for people that are living with obesity, because it hasn't really been. There hasn't been concern about the composition of the weight loss in the past, and as I mentioned, the first sort of attempt to try and address this has been through myostatin inhibition, which does increase muscle size, but doesn't increase muscle strength. Bimagrumab has a publication that describes that approach, and bimagrumab gave a fat loss of over 20%, whereas the fat loss with semaglutide, one of the GLP-1 agonists, was 19%. But with bimagrumab, the lean body mass or fat-free mass was increased by 3% to 4%, where in semaglutide, it was reduced by almost 10%, and that, of course, was reflected in changes in total body weight loss. The bimagrumab, with a 6.5% weight loss, has equivalency from fat loss of the 15% lost with semaglutide. There has been, over the last decade, an injectable testosterone ester that's very lipid-soluble and is absorbed through the lymphatics and doesn't cause the liver problems that older testosterone esters had. And this injectable testosterone was used to help replace testosterone for those people who had low testosterone initially, but then has also been used in people with normal testosterones. As you can see from the graph on the right, there's a gradual weight loss that ended up being a total of about 20% over the course of a decade. Lipocine has found a way to make that kind of testosterone ester available orally and has combined it with tocopherol. And the graph on the left shows that the dark bars are the testosterone ester alone, and the green bars are the combination. And so, as you can see, the fat mass loss was greater with the combination. The fat-free mass increase was about the same, but slightly better with the combination. The combination seems to be better in addressing the abdominal fat that's associated with cardiovascular risk, and unlike the testosterone ester alone, it caused an increase in bone mineral content, so in summary, obesity is an excess of abnormal fat tissue. It's not just a matter of too much weight. The GLP-1 agonists and other associated incretins that have been combined with it have shown an ability to increase the total weight loss to levels that rival bariatric surgery, but despite that, the GLP-1 agonists are associated with a loss of excess lean body mass, a loss of bone density, and rapid weight regain with dosing interruptions, which is common, and we do need better methodologies in the clinic to try and accurately look at body composition rather than just weight. And agents that reduce body fat, improve metabolic health, and mitigate against muscle loss, and increase muscle strength, and decrease bone loss would certainly be ideal. And, I'm going to turn this over to Dr. Bruno, who's gonna describe such a treatment. Great. Thank you, Dr. Greenway. And before I dive into our phase II results, I wanted to share some literature data regarding the benefits of androgen therapy on weight loss and diabetes. First is the study Dr. Greenway just discussed that followed a cohort of men for up to eleven years, about two-thirds of whom received androgen therapy and one-third who did not. As he shared, those that received T therapy experienced sustained weight loss, and the loss did not plateau even after eleven years. But there are a few more details about this study I want to share. First, the study did not require overt hypogonadism, that is, testosterone less than three hundred nanograms per deciliter, for study eligibility, and about half of the study's participants were diabetic. Beyond weight loss, there were improvements in other cardiometabolic markers, such as hemoglobin A1C, blood pressure, and cholesterol. Importantly, there were significantly fewer deaths and major adverse cardiac events with T therapy in this prospective observational study. Second is a study that investigated T therapy in men with either prediabetes or newly diagnosed type 2 diabetes. This randomized controlled trial found that the rate of new diabetes diagnosis was halved with T therapy and that glucose tolerance was improved at the end of the two-year study. It is important to note that the average baseline testosterone in this study was approximately 400 nanograms per deciliter, meaning the vast majority of participants were not hypogonadal. Also, the improvements noted were independent of baseline testosterone level, together suggesting that these euthenal men can also benefit from androgen, androgenic therapies, and these findings on diabetes and glucose tolerance are not a surprise. The class label for T therapies makes it clear that androgens can decrease blood glucose. This study, T4Diabetes, had a companion study, T4Bone, which investigated bone health in these participants and found that T therapy increased bone mineral density to a similar extent as anti-resorptive drugs such as alendronate. Now, moving on to our phase II study design and results. This was a three-arm, blinded, placebo-controlled study of men with metabolic dysfunction-associated steatohepatitis, MASH, previously known as NASH. In this population, there are high rates of obesity and weight-related comorbidities, including dyslipidemia, hypertension, and diabetes. The 56 participants were randomized to one of three oral treatment arms for 36 weeks. Treatment A was oral LPCN2401, testosterone ester monotherapy with testosterone undecanoate. Treatment B, LPCN2401 plus E, was the same dose of T ester in combination with vitamin E or alpha-tocopherol, and treatment C was matching placebo. While this was a NASH study, we did have pre-specified endpoints related to change in fat and lean mass, and to that end, DEXA scans were performed at baseline, week 20, and week 36. All participants had access to LPCN2401 in a 36-week open-label extension trial that followed completion of the placebo-controlled trial. It is important to note that low testosterone was not required for study eligibility. We did measure baseline testosterone, but individuals were eligible regardless of baseline T level. This study enrolled both hypogonadal and euthenal men. However, there was a high prevalence of low testosterone in this study population, which is expected as T levels have been found to be inversely correlated with BMI, and the vast majority of severely obese men have low testosterone. Moving on to baseline characteristics. These are the characteristics for the body composition analysis set, which includes all participants who had a baseline and at least one post-baseline DEXA scan. That is, this set includes every participant whose DEXA data we could analyze for change from baseline. The characteristics of this population were in line with other weight therapeutic studies. Participants were middle-aged and had a BMI in the mid-thirties. Importantly, all participants met criteria for a weight loss therapeutic. They either had a BMI of at least thirty or at least twenty-seven, with one weight-related comorbidity. Moving on to the results. Sorry. Moving on to the results and starting with the fat mass to lean mass ratio. LPCN2401 therapy has resulted in improved body composition, with about 6% to 8% improvement in the fat-to-lean ratio compared to a worsening seen with placebo. Overall, both LPCN2401 therapies were mostly weight neutral, with the loss in fat offset by a gain in lean mass. However, there was a trend towards weight reduction noted in the open label extension trial, in line with literature evidence that suggests a longer treatment duration, such as 72 weeks, may result in significant weight loss. The improvement in the fat-to-lean ratio was driven by both a reduction in fat mass and an increase in lean mass. For the LPCN2401 plus E formulation, improvements were noted not only for total fat but also trunk fat. As the muscle-building effects are driven by the anabolic, anabolic properties of the testosterone ester, it is not surprising that both LPCN2401 formulations resulted in similar increases in total and appendicular lean mass. Participants on the LPCN2401 therapies gained about 1.8 kilograms of lean mass. Given some of the benefits seen with the 2401 formulation, I wanted to share some results of a study that looked at the impact of vitamin E alone on body composition. The results of this study, known as the PIVEN study, clearly demonstrated that vitamin E alone does not reduce fat mass. The daily vitamin E dose administered in the PIVEN study was the same as the daily dose delivered with the LPCN2401 plus vitamin E formulation. Therefore, it is likely that the androgenic agent, the testosterone ester, is driving the improvement in body composition, both decrease in fat mass and increase in lean mass. However, based on our data, it is possible that the addition of vitamin E increases either the rate or extent of body composition improvement over the androgen receptor agonist monotherapy. Note that the vitamin E alone data comes from a separate study. No head-to-head studies comparing LPCN2401 to vitamin E alone have been performed. One final piece of body composition data for today relates to bone health. There is a trend towards increased bone mass and density in participants who received LPCN2401 therapy, and those who received the combination with vitamin E saw significant increases in overall bone mineral content, as well as hip and femur T-scores. We also collected some functional test data as exploratory endpoints. There have been concerns that some therapies that increase muscle mass may not result in the increase in functionality we would like to see. However, with LPCN2401 therapies, we did see a trend towards improvements in two tests: hand grip strength, as well as ten-meter walk time, and the T ester therapy significantly improved liver health. As this was a NASH study, we were closely monitoring the liver, and both formulations significantly improved liver injury markers, reduced liver fat by 40%-50%, and even resulted in NASH resolution on liver biopsies in over half of the treated participants. In terms of safety, both formulations were well-tolerated in this relevant obese and overweight population, with no safety signals through the 36-week placebo-controlled study. While four participants from the placebo arm discontinued study drug due to adverse events, only one total subject in the combined LPCN2401 arms discontinued due to an AE. The rates and severities of gastrointestinal effects were similar to placebo, which is promising for LPCN2401 use with therapies having GI tolerability issues, such as incretin mimetics. Androgen, androgenic adverse events such as edema, BPH, prostate-specific antigen increase, and hypertension with the T ester therapies were similar to those observed with placebo. In fact, there were declines in blood pressure seen with the vitamin E-containing formulation. There are also no muscle spasm adverse events. When we consider the open-label extension study, LPCN2401 was well-tolerated with up to 72 weeks of exposure. Overall, these therapies were safe and well-tolerated, reduced fat mass, increased lean mass, improved bone health, and improved liver health, making it a promising option for use in obesity management. And we have reason to believe that the combination of LPCN2401 with an incretin mimetic may lead to additive or synergistic effects on weight loss and fat loss, and potentially increased insulin sensitivity. Androgen receptor agonists have been shown to increase GLP-1 receptor expression in both diabetic and non-diabetic mice. This may be particularly important, given lower GLP-1 receptor expression is thought to be one possible reason for the reduced weight loss seen in diabetic patients treated with incretin mimetics. The increased receptor expression resulted in increased insulin release in both diabetic and non-diabetic mice, indicating the increase in receptor expression resulted in increased receptor activity. Androgen receptor agonists have also been shown to increase insulin sensitivity throughout the body and increase the number of insulin-secreting beta cells. The combination of androgen receptor agonist and incretin mimetic has been shown to increase the activity of GLP-1 receptors, again, measured by the increased insulin release. That is, when an ARA is present at the same time as the incretin mimetic, there is more GLP-1 receptor activity. So not only is the ARA increasing the amount of GLP-1 receptors, but it also non-genomically increases the activity of the GLP-1 receptors. Taken together, the combination of incretin mimetic and ARA may increase weight loss, particularly in diabetics, through both increased expression and activity of GLP-1 receptors. While the results discussed today focus on our previous results from studies in men, we do believe LPCN2401 is a potentially safe and effective intervention to improve body composition in women. It is well known that women have much lower testosterone levels than men. However, less well known is that women have much higher levels of testosterone than estrogen. Testosterone is an important hormone for female health, playing a role in reproductive health, bone density, mood, energy, libido, muscle mass, and fat distribution. And numerous studies lasting up to one year have found that administration of testosterone resulting in normal T levels increases muscle mass in both pre- and post-menopausal women. These physiologic levels of testosterone achieved in these studies importantly avoided the so-called masculinizing effects of androgens, such as acne or unwanted hair growth. The safety of testosterone therapy in females has been demonstrated across numerous interventional trials in both pre- and postmenopausal women, including products AndroFeme, LibiGel, and Intrinsa, and the data generated do not indicate increased risk of breast cancer or cardiovascular events in women receiving testosterone. Therefore, we plan to develop LPCN2401 for both men and women, although different doses of the testosterone esters will be required for the sexes. In terms of next steps in our clinical development, our plan is to investigate the combination of incretin mimetic and LPCN2401 with and without vitamin E in a proof of concept study to determine if there is additional fat or weight loss or less lean mass loss with a combination compared to any of the monotherapies. This study design optionally allows us to collect data on the impact of LPCN2401 use after discontinuation of incretin mimetic therapy, including the impact on rebound in fat or weight, hemoglobin A1C, and other markers of cardiometabolic health. Now I'll turn it back over to Dr. Patel for concluding remarks. Mahesh? Yeah. Thanks, Ben. In summary, GLP agonists have demonstrated the ability to reduce total body weight and positive therapeutic effects and aesthetically appealing results. Chronic weight management agents, preferably oral, that reduce body fat and improve metabolic health while preserving lean mass, would be ideal. The positive results with twenty-four oh one treatment with an androgen receptor agonist suggest paradigm-shifting potential as an adjunct to GLP-1 agonist for quality weight loss, while preserving lean mass or reducing the loss of lean mass in the first place, amplifying fat loss, and preferentially inducing more of the bad fat, such as visceral or trunk fat loss. Furthermore, post GLP-1 agonist cessation, twenty-four oh one may be able to minimize weight/fat regain, increase lean mass, and sustain metabolic health, you know, of cardiometabolic markers such as blood pressure and HbA1c. There are numerous approaches under exploration to address the unmet need in obesity management. What makes 2401 unique? LPCN 2401 is an oral therapy, unlike some of the other therapies that are being pursued, myostatin and activin modulators, and it's targeted for once-daily dosing. And it's a product of bioidentical androgen receptor agonist testosterone. 2401 comprises a novel diester, that's testosterone tridecanoate, unique to Lipocine, enabling once-daily dosing. Just as a reminder, there is no oral testosterone approved product for any indication that's once-daily dosing. We believe 2401, with positive phase II results, has the potential to improve body composition with muscle and bone health improvement. In contrast to, you know, the unclear bone improvement benefits with regards to, you know, the monoclonal antibodies currently in development, where they may also be, you know, targeting activin modulation along with myostatin inhibition. The other thing to note is that, as Ben mentioned, there's more. The potential of GLP-1 amplification via genomic and non-genomic means may indicate twenty-four oh one could address current unmet needs in obesity management with favorable benefit-to-risk profile. Twenty-four oh one has demonstrated good tolerability for chronic use, with minimal GI effects or even sex hormone imbalance, such as FSH and LH imbalance. In addition, twenty-four oh one has beneficial liver effects, in contrast to liver safety concerns with some SARMs, selective androgen receptor modulators, under development, not to mention possible estradiol imbalance via non-natural SARMs that could impact negatively the bone health. So in conclusion, LPCN 2401 presents a convenient and differentiated compelling development opportunity to manage a looming healthcare crisis of lean mass loss in obesity management, while meeting fat and weight loss objectives without overlapping additive adverse events. This concludes our remarks for today. At this point, we'll turn over to Tara and Peter for question and answer session. Great. Thanks, Mahesh. So at this time, we'll be conducting a question and answer session with our speakers. To the audience, as a reminder, if you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player. Please hold for a brief moment while we poll for questions. So the first question comes from Matt Kaplan at Ladenburg. Please go ahead, Matt. Hi, good morning, and thanks for hosting this session. I guess a question for the doctors, following the presentation: I guess, given the strength of the data that we've seen for twenty-four oh one so far, what are... what are your thoughts in terms of how you would incorporate this therapy into the continuum of treatment for patients with obesity if it's approved? Thanks, Matt. Thanks for the question. I'll let Dr. Greenway, you know, take a shot at it, and Ben can jump in later. This is, I think, a way to address not only the problems of, the deficiencies of the GLP-1 agonist, but it, something that improves muscle even over what diet does and, in addition, you know, has a, a beneficial effect on fat that, should be, equivalent to some of these GLP-1 agonists without, the, you know, separately. So I think, what I think you're driving at is, would you combine it with a GLP-1 agonist, or would you use it alone? And I think that would probably have to do with, how fast you wanted to have the weight loss. I think that weight loss with the GLP-1 agonist now is very rapid, and I think that's part of the reason why we're seeing this excess loss of fat-free mass. I think that this could well be a very effective treatment on its own. Although certainly if one was to turn to a GLP-1 agonist, I think this is something important to include along with it so that you don't have the detrimental effects of the GLP-1. Thank you, Doctor. That's very helpful. Ben, do you have anything to add if, well? Not much. I am not a physician treating patients- Yeah Struggling with their weight. But what we have heard is that there's a particular concern potentially in the elderly. There's a large number of elderly people with obesity, and they are at increased risk for sarcopenia or functionality issues after weight loss. Especially if they're losing much of the limited lean mass that they had to begin with. So there may be some specific subpopulations that may particularly benefit from this therapy. But as Dr. Greenway was sharing, given the sustained weight loss that was seen over years, as well as the lean mass preservation that we have seen, that this really could be a preferred therapy option, either on its own or in combination with incretin mimetic- Mm-hmm For a large majority of patients. Okay, thanks. Great. Thank you for the questions, Matt. Our next question comes from Scott Henry at Alliance Global Partners. Please go ahead, Scott. Thank you, and I think this is mostly for Dr. Greenway, but, welcome comments from Dr. Bruno as well. Your GLP-1 treatments seem to have these apparent blind spots of bone loss and lean muscle mass, which seem very clear. And my question is, when you talk to the GLP-1 companies in development, you know, how do they react to these issues? And as well, in practice, you know, how are patients reacting? Are they seeking supplemental therapies, or are most people just focusing on the weight loss and ignoring these kind of blind spots? Thank you. I think they're primarily ignoring the blind spots and using the therapy. It gives dramatic weight loss. People are very excited about it. The degree of weight loss is not what was available when the guidelines, the guidances to industry, were promulgated at the FDA. And so with a 5%-10% weight loss, this wasn't really an issue. So now we have drugs that were approved based upon the weight loss criteria that the FDA has as their guidances, and I think that we are noticing now that we need to concentrate on what obesity really is, and that is an excess of body fat because the quality of the weight loss is important. Okay. And our patients, are they supplementing therapies? Or, again, it sounds like they're just looking at the weight loss, and they- I'm sure they're thrilled with that, but these other problems, they may surface longer term, I imagine. Yeah, I think that's right. I don't think we're gonna see them short term, and we don't have anything at this point that's approved for to address that problem. And I think that's why drugs like the Lipocine is developing are important. And I think that as time goes on, this is gonna become more apparent, and the need for these treatments that look at body composition in regards to the weight loss are gonna be important. And, you know, even the companies you were asking what their attitude towards this was, I think that they're recognizing that. Lilly bought Versanis, that made bimagrumab, and there are other of the companies that have these drugs that are looking for solutions as well. Okay. Great. Thank you for taking that question. If I could just sneak one in for Dr. Bruno. With regards to testosterone ester, it seems very safe in the near term, in the medium term. You did mention about in women. What are the long-term, you know, risks with that treatment, and what should we be kind of on the lookout for? Thank you. Sure. Yeah, a good question. There was, I guess about a year ago now, a kind of a relatively definitive study on the long-term, at least cardiovascular risks of testosterone that was published. It's a fairly good study, about five-year duration, 5,000 people, showing that men with low testosterone who were treated with testosterone did not have an increased risk of cardiovascular events. There have been other long-term studies, like we talked about. This T4DM study was two years, but some of these cohort studies go out to 8 to 11 years. You know, so there are a lot of data out there now. You know, this is a known entity. Testosterone is something that's natural in the body, and it's been used for, you know, decades plus, in humans. So that has a very well-defined safety profile, and I'd say some of these more recent trials really, really aimed and answered the question about any potential long-term risks of the therapy. And these studies did not find an increased risk and even potentially benefits for these men who were receiving testosterone therapy. There is a bit of a, you know, population concern here, where we are looking at treating hypogonadal and eugonadal men, so people with and without low testosterone. But that is, you know, what we've done in a number of studies now, and we haven't seen any potential safety risks, given the body's own natural mechanisms. You know, when you're giving testosterone to people, they, they start to reduce their natural production of testosterone. So we haven't seen any of these super physiologic testosterone levels with twenty-four oh one, you know, anything that would be concerning for, for really giving high levels of testosterone. We're giving, you know, more of the natural levels of testosterone. And then for the women question, again, testosterone has been used for decades, if not longer, in, in women. There's a lot of data out there for some sexual dysfunction disorders, and some of these studies go out for years looking at the risks for this product in the populations, and again, there was really nothing concerning in those studies that were found, so you know, people hear testosterone, and you know, their guard may go up, but kind of thinking of it the opposite way, where you know, this is a compound that there is a ton of safety and exposure data on. It's really well-known, you know, metabolism, well-known potential risks of this drug, compared to so many of these others that are looking to treat the same problem using either a new molecule or a new route or even potentially using older molecules that have known safety issues. I do think that long-term, this product really has the inside track in terms of long-term safety, as well as with the efficacy that we have seen to date. Thank you for taking the questions. Tony, you want to add anything more? No, I think Ben covered that pretty well. In addition, you know, one study that Ben mentioned, there were actually a lot of benefits in glycemic control, metabolic effects, even some benefit in reduction of major cardiac events. So I think that whole issue of cardiovascular safety has pretty much been put to rest with those long-term studies. And in terms of women, a lot of data out there, and I think some of the products that weren't approved were done more because of the political climate and maybe theoretical risks. Whereas, you know, a lot of products in men had been approved that had some real risks. So I think there's a lot of data out there, and we have-- we're pretty confident in the long-term safety of these products. Okay, thanks. Thanks for the question, Scott. Our next question comes from Oren Livnat at H.C. Wainwright. Please go ahead, Oren. All right, thanks for taking the questions. Dr. Greenway, and I guess for the company, you mentioned that there are thresholds we're all familiar with with the FDA in terms of development on weight loss, but clearly this drug is not just about weight loss, right? I think you saw pretty neutral results, at least at 36 weeks, right, with lean mass offsetting the fat loss. So how do you think one should approach, and maybe the FDA would look at approaching, development of this kind of drug, either as monotherapy or in combination with the GLP-1, if we're not seeing the headline weight loss that is sort of the minimum threshold as a development hurdle? And when should we hope to get some feedback from the FDA on that front? Presumably, the other companies are dealing with a similar issue, right? Yeah. You know, the FDA has these guidances, and if people that develop drugs follow those guidances, they, you know, realistically should feel that, you know, that's what the FDA would judge them upon. Those guidances, that meeting was held, well over a decade ago, maybe almost two decades ago, and it was a different milieu for developing drugs than it is now, and I just don't think that the, the rules have caught up with things. I would presume, I mean, the FDA is a pretty reasonable agency in my experience, and I would think that if you're getting the fat loss, that it would be equivalent to what a 5% weight loss would be, or greater, and had good safety, that, that they would take that into consideration. But of course, that's my presumption, not... I think what needs to be done, as you probably sort of suggested, is that another guidance committee be assembled, and that committee sort of reevaluate the need for making the criteria around fat loss, since obesity is excess fat, not just excess weight. Chidu, you want to add in your perspective on regulatory? Sure. Thanks, Mahesh. Yeah, just to add to what Dr. Greenway was mentioning, the guidance has also touched on the aspect that weight loss is a surrogate marker for the fat loss. So we are under the assumption that FDA will be more favorably looking the body composition improvement in addition to the weight loss. So that's what we'll be looking forward to discussing with the FDA. Yeah, Ben, do you have any regarding weight loss? Okay. Nothing else for me. I mean, have you had interactions with the agency at all about this issue? And, do you have ambitions to discuss that further with them or is that after the next proof of concept data you hope to generate? Ben, go ahead. Yeah, so we haven't discussed this with the regulatory agencies yet, or FDA yet. We do think it's, you know, a path that needs to be addressed. You know, FDA has said in their guidance that at least 50% of the weight loss should come from fat loss, so you know, we know that they have seen the importance of fat loss for these weight loss therapeutics. In terms of the question itself, you know, yes, it will. It's important for the overall development in terms of what is an approvable endpoint, but at least for this proof of concept study, we may have an answer before then, but still thinking, just looking at this combination study with the incretin mimetics, that it may not be necessary to have that completely figured out before we run a proof of concept study. That makes sense. And to build on the earlier question on safety, and I am sure, Mahesh, you know, I went through with you guys the long and painful ad com process around the oral testosterone Tlando for, I guess, I don't think it was called Low T anymore at that point. But the FDA had, I think, pretty arbitrary bookends and peak exposure issues that they were holding you to. And I'm curious, one, does a once daily formulation that you have here, I guess, comport with those guidelines, as arbitrary as they are? Do you think that like obesity thought at the FDA is evolving and needs to evolve, that those questions would also maybe not apply in the current landscape, and if we look at the overall safety and efficacy, then the FDA would be less concerned about these serum blood levels of testosterone hour to hour and day to day? I think, Oren, you're exactly right. I guess the Tlando product was based on, you know, replacement of testosterone, and so they had a preset pharmacokinetic criteria for efficacy as well as for safety, the bookends you mentioned. I think, you know, our plan is to not to go supraphysiological. It'll be same in a normal range, but I don't think those bookends would apply if you had the full-blown safety and efficacy data in obese patients for obesity management. Ben, Chidu, you want to add anything? I have one thing I might add, and that is that long-term treatment was an observational study with injectable testosterone undecanoate, but the FDA has been very concerned about cardiovascular risk, and that study showed that there was actually an increase in life expectancy, and so you know when you can decrease overall mortality and so forth with the treatment, that's a fairly strong, at least in my viewpoint, in terms of safety. Obviously, you'd like to have a control group, but they did have some people who were in a control group, but it was primarily an observational study. In short, our plan would be, you know, to not exceed, I mean, the levels that are supraphysiological, right? Mm-hmm. Right. I mean, obviously, in the context of weight loss, the cardiovascular risk- You lose weight- Equation is even further differentiated here versus TRT specific- Yeah Development, right? Yeah. In context of newer agents in development, too, very little is known about their long-term safety. So I think we have an advantage over the amounts of data that we actually have, particularly, you know, monoclonal antibodies and those types of agents. All right, thanks. Very interesting stuff. I look forward to the next steps. All right. Thanks for the questions, Oren. So this concludes the verbal portion of our Q&A. I'll now turn it over to PJ Kelleher from LifeSci to read the written questions. Hi, Mahesh, just a couple of questions that have come in through the audience here, and we'll just touch on a few, given the time. But can you just briefly touch on LPCN 2401 again? Sure. I'll have Ben take that question. Go ahead, Ben. Sure. Yeah, so the next step really is this proof of concept study. You know, we're still refining the design of this study, but, you know, we're in talks to get the estimate on the you know, we have estimates on the cost and the time frame and how long the study will take to complete. You know, overall, the timeline does, of course, depend on the design, which is still up for discussion, but the plan is to have the first readout 12 weeks after the last patient starts dosing. So, you know, we could collect data from a number of different time points, but the first readout would be at week 12, and these obesity studies enroll pretty quickly, so we're looking at a total study duration of about 1 year in the current design. However, we are actively exploring creative ways to execute and fund the study, including looking for industry or academic collaborations, and then, in terms of the female question, we do plan to have a discussion with the FDA on that and on our plan, in terms of initial studies, and then followed by a proof of concept study, in women with obesity. Awesome. Thanks, Ben. And then, I guess a question for Dr. Greenway. You know, in your practice, what percentage of your patients on some of these incretin therapies would be candidates for 2401 or any of the other muscle-sparing agents? Well, probably 20%. And I say that because it's mostly women who come for treatment for obesity, and the trials are usually 80% women. I think that represents a real opportunity to fill an unmet need, because I think the idea of getting testosterone and knowing what other kinds of positive side effects they might receive from getting more normal testosterone levels is gonna be attractive to many men, and then the strength aspect of things will be as well. I mean, men have a positive feeling, especially the ones who like to go to the gym. And so I think that there's a whole group of people out there that aren't being reached, that need to be reached, and that this is a treatment that might reach them. Yeah, to add to that, perhaps the prospect of having fat loss with muscle preservation will be attractive, and along with those overall cardiovascular and other benefits of wellbeing with testosterone will be very attractive. Awesome. Thank you both. Mahesh, I'll turn it back over to you, as that concludes our written questions. Yeah, thanks, Peter, and thanks to all of you for participating today. Appreciate it.