[audio distortion] disorders. Dr. Patel, Dr. Bruno, very good to have you with us. Please go ahead with your presentation. Thanks, Thomas. Thanks for the invitation. Good afternoon to all. I'm Mahesh Patel. I'm the President, CEO, and Co-founder of the company. I'm here to introduce you to the company and give you an update on our pipeline. Then I'll be passing over to Dr. Ben Bruno, who is our Director of Clinical Development, and he will cue you in on the details of our liver asset programs in our pipeline. Before we do that, some disclaimers on the forward-looking statement. I'll give you a few seconds to go over, and dive straight into our pipeline. Lipocine is a clinical-stage biopharmaceutical company with a focus on developing innovative products for metabolic and endocrine disorders. Very recently, we have branched and looked into opportunities in the neuroendocrine arena. I'll be sharing a little bit of that with our new asset that we added to the pipeline, LPCN 1154. All of our pipeline [audio distortion] update on our proprietary drug delivery technology that is to effectively deliver highly water-soluble molecules to get appreciable and relevant blood levels. Our lead asset is TLANDO. It's twice a day oral pill for testosterone replacement therapy. We're very excited that we have received a tentative approval and are closing in on getting a final approval for which we can apply in January, a couple of months after the expiration, which is on March 27, 2020, when the exclusivity of our competing product expires. We'll be eligible for a final approval. It's a convenient dosage form and option that's badly needed in the marketplace that's dominated by non-convenient, non-oral products that require titration. We are actively in discussions with business for commercialization partner. All I can say is the talks are progressing very well and converging. As soon as the deal is consummated, if and when it happens, we'll announce to the street. Our next one on our [audio distortion] for TRT is TLANDO XR. It's a differentiated program, different molecule than the lead asset. It's once a day oral pill to be advanced all the way to pretty much phase III ready status, but we do have to do a food effect study prior to starting the pivotal trial. Again, with TLANDO and TLANDO XR, we believe we can gain and regain market leadership in the testosterone replacement therapy area, which is a huge opportunity. Roughly 7 to 8 million scripts were written last year for TRT. Diving into liver disease programs, Dr. Bruno will talk a little bit more on that, but on LPCN 1144, just a little while ago, we released our top-line data for biopsy-confirmed NASH patients. The data is really striking. The next step there would be to meet with the FDA and get clarity on design for the phase III trial and what would be required for the pivotal study. On the next asset, we have LPCN 1148. That's oral testosterone for cirrhosis management. We're not trying to reverse cirrhosis but helping patients who have a better quality of life or decrease decompensation events while they're waiting for a liver. Also, one of the objectives would be to improve their post-transplant survival outcomes or rehab outcomes. 1144 and 1148 are programs that Dr. Bruno will be talking in details. Next on the docket is women's health assets, LPCN 1154. That's our new exploratory into neuropsychiatric disorders. Here we have an active that's an oral neurosteroid for depression disorder, in particular for postpartum depression. It's a serious unmet need, there's only one approved drug that's an in-hospital IV infusion. We believe that an oral, which is a huge unmet need, would be a significant advancement for women badly in need of in-home treatment option. We are currently conducting a key test study. We have completed the study. We are analyzing the data, and we'll decide on the next step thereafter. The last one on the docket is LPCN 1107. That's the oral hydroxyprogesterone for prevention of preterm birth. There's only one product approved for prevention of preterm birth. That's an intramuscular injection. We're going after the same indication with the same molecule, but through a oral route. We are the first ones to enable an oral delivery of that highly water-soluble molecule. We have advanced that asset all the way to close to pivotal study status. We're currently doing a food effect study. That will help us to define the dosing regimen in the pivotal study. Stay tuned for the results from that study, as well as our interaction with the FDA on the PERLE study. This particular asset has an orphan drug designation, and has the potential to be the standard of care should Makena be withdrawn from the market, that injectable product. In all, we have a robust pipeline, and we are diligently advancing our R&D assets as well as engaged in advanced business development discussion on our lead asset, TLANDO. With this, I will pass it on to Dr. Ben Bruno. He will talk more about our NASH program as well as the candidate for cirrhosis management. Ben? Thanks, Mahesh. I'm really excited today to share with you some of the results from our recently completed phase II study in men with NASH. First, top line take-home messages. We did meet the primary endpoint change in liver fat measured by MRI-PDFF at week 12, as well as a key secondary endpoint, NASH resolution with no worsening of fibrosis, which is a FDA approvable endpoint for accelerated approval subcategories in the past. The magnitude of the treatment effect was really striking if you compare the results of our study in terms of NASH resolution as well as fat reduction compared to other oral agents that are being developed. While we observe positive trends in fibrosis improvement in two of the three methods to investigate the changes in fibrosis, the treatment effects observed on fibrosis need confirmation in a larger study. Changes in key liver enzymes and body composition both support beneficial treatment effects of LPCN 1144. Most importantly, LPCN 1144 was well-tolerated with an overall safety profile comparable to placebo. Changes in cardiovascular markers, androgenic markers, and GI adverse events were comparable between the two arms. These positive top-line results strongly support LPCN 1144 development for regulatory approval. [audio distortion] a little bit about the study design and endpoints. The LiFT study, short for Liver Fat Intervention with Oral Testosterone, was a phase II paired biopsy study in men with NASH. Men were eligible for the study with NASH and F1 to F3 fibrosis. Subjects were randomly assigned one-to-one-to-one to three treatment arms. Treatment A was oral testosterone twice daily. Treatment B was oral testosterone plus d-alpha-tocopherol twice daily. The third arm was matching placebo twice daily. Subjects were treated for a duration of 36 weeks. The primary endpoint in the study was change in hepatic fat fraction measured by MRI-PDFF at week 12. The key secondary endpoints that we'll be discussing today were change in NASH activity and fibrosis measured on liver biopsy, and change in body composition and liver injury markers. I'd like to talk a bit about the baseline characteristics of this study. In general, the baseline characteristics were comparable to other phase II studies. I'd like to just draw your attention to a few notable differences. The mean ALP and AST values are on the slightly lower end compared to some of the other NASH studies. While mean NAFLD activity score was well-balanced between the three groups, the subjects in the placebo arm did have a higher stage of fibrosis compared to the two treatment arms. Here we present data that was released in January of this year on the MRI-PDFF measured reductions in liver fat at week 12. We see that both treatment arms met with statistical significance absolute liver fat reduction. Both treatment arms had about an 8%-9% liver fat reduction, compared to 1.5% in the placebo arm. Now for the key secondary endpoint, NASH resolution with no worsening of fibrosis on liver biopsy, we see that we have a set here that I haven't described yet, which is the NASH resolution subset. We had 44 subjects complete the end of study biopsy. However, not all of these 44 met the FDA's phase III definition of NASH at baseline. In order to be eligible to be analyzed for NASH resolution, you must have had NASH at baseline. This subset includes 37 total subjects at baseline and end of study biopsy data. In the placebo arm, none of the subjects, 0%, had NASH resolution with no worsening of fibrosis. In treatment A, six subjects, 46%, and in treatment B, nine subjects, 59%, met the FDA endpoint of NASH resolution with no worsening of fibrosis. Given that this is a subset of our overall data, we did a sensitivity analysis where we categorized anybody who had either missing biopsy data or who did not meet the FDA's definition of NASH at baseline as non-responders. In here, the safety set, the placebo group still had zero subjects, who had NASH resolution with no worsening of fibrosis. Treatment A had 33% of subjects, and treatment B had 47% of subjects. Even in this conservative analysis, nearly half of the subjects in treatment B met the endpoint of NASH resolution with no worsening of fibrosis. This chart shows a breakdown of the individual components of the NAS and the changes from baseline. In the pie charts, a color of red indicates that the score worsened by at least one grade. Yellow means that there was no change between the baseline and end of study biopsy, and green means that there was an improvement, a decrease of at least one grade from baseline to end of study. We see that both treatment arms led to significant improvement across all of the NASH components. Moving on to some other markers. For two remaining markers, ALT and AST, we saw early, sustained, and significant reductions in both treatments, starting at week four and continuing through the end of the study. For ALT, the mean group absolute reduction in treatment B was as large as 23.4 units at the end of the study, and AST reduction was 13.3 units at the end of the study. We also saw positive effects in terms of changes in body composition. Both treatment A and treatment B increased after [audio distortion] mass and decreased whole body fat mass. In terms of fat and lean mass, the increase was about 2%-3%, and the whole body fat mass reduced about 4%-7%. Given the high overlapping comorbidities of metabolic disease and NASH, these body composition changes could be clinically meaningful. Here we show a side-by-side comparison of our list of study results from other oral drugs under development for NASH. On the top, we see the endpoint of NASH resolution with no worsening of fibrosis. In the bottom, we see absolute changes of liver fat from baseline. By comparing these, we can get a better idea of how remarkable the changes were with both of our treatment arms in terms of liver fat reduction and rates of NASH resolution. Please note, these data are derived from published reports from different clinical trials at different points in time. These trials had differences in design, size, and patient population. No head-to-head trial has been completed. Moving on to the changes in fibrosis. We had pre-specified in this study three different analytical techniques to investigate the change in fibrosis on liver biopsy. All three of these techniques read the same slide sets. As we see here, we have two of the paired reads and the digital reads. Both of those did show that our two treatments had a beneficial effect over a placebo. The standard NASH CRN scoring had a placebo improvement rate of 40%, six subjects in the placebo, and in the treatment A, four subjects, 27%. Treatment B, two subjects, 14%. We're still looking into what is responsible for the disparity between these reading methodologies as well as this high placebo rate. One explanation is the fibrosis severity was unequally weighted in the study. That is, the placebo group had more F2, F3 subjects, which are more prone to show improvement even without study drug treatment. In terms of the safety overview, LPCN 1144 was well-tolerated with an overall safety profile comparable to placebo. The frequency and severity of treatment-emergent adverse events in both treatment arms are comparable. In terms of discontinuance of study drug due to TEAEs, four subjects in the placebo arm and one subject in the combined treatment arms discontinued the study drug. Cardiovascular events were balanced among the groups. There were no reports of hepatocellular carcinoma or drug-induced liver injury. [audio distortion] was comparable among all groups, as were changes in lipids. Here we show the rates of some AEs of special interest. In terms of interest, we mean either the androgenic effects known of testosterone as well as AEs that are common of drugs under development for NASH. Here we see that the rates are again comparable to placebo and low throughout all study treatment arms. In summary, we did see significantly reduced liver fat compared to placebo. We met the significance, the pre-specified histology-based regulatory endpoint of NASH resolution with no worsening of fibrosis. The key changes in liver enzymes and body composition support beneficial treatment effects. We had a well-tolerated safety profile comparable to placebo. Now I'd like to shift gears and talk about our LPCN 1148 project, oral testosterone for the management of liver cirrhosis, the end-stage liver disease. Some information about cirrhosis. There are over 2 million cases in the United States and NASH is the most rapidly increasing indication for liver transplants in the U.S. There are over 500,000 people in the United States living with decompensated cirrhosis, and 62% of all those on the liver transplant wait list are males. There is an extremely high economic cost to liver transplant at about $800,000 per transplant. 40%-70% of all men on the liver transplant list have sarcopenia. Sarcopenia is pretty much another word for muscle wasting and low muscle mass. What's the importance of sarcopenia in cirrhosis? Well, first, a progressive drop in testosterone worsens sarcopenia throughout the progression of cirrhosis. The presence of cirrhosis in men on the liver transplant list is associated with a twofold increase in waitlist mortality, and that association is stronger with men than it is with women. Men and women with sarcopenia have increased risks of hospitalization and prolonged hospitalization. They report poorer quality of life. They have higher medical costs at transplant, prolonged hospitalizations at the transplant, as well as requiring more time spent in the intensive care unit, and have poor post-transplant outcomes, including lower survival rates and higher infection rates. Finally, having sarcopenia increases your risk of decompensation. Having either an initial first decompensation event, a core initial decompensation event, or even your risk of acute-on-chronic liver failure. About our proof-of-concept study. It is a phase II multi-center, double-blind, placebo-controlled study of male subjects with cirrhosis of the liver and sarcopenia on the liver transplant list. This is really a two-phase study. It really has a built-in open label extension. Phase I is weeks 1 to 24. There are two arms, placebo-controlled. It's oral LPCN 1148 or placebo. 1148 is actually testosterone undecanoate. It is a different testosterone ester than has been studied in NASH or in any of our testosterone replacement therapy indications. After that phase I is complete, we will move into phase II, which is an open label extension where all subjects are going to have access to 1148. All subjects in the placebo arm will be switched to the active drug, LPCN 1148. The primary endpoint for this study is change in skeletal muscle index at week 24. Key secondary endpoints include change from baseline in Liver Frailty Index. That is a functional outcome. The skeletal muscle index is really an imaging-based outcome looking for changes in muscle mass. The Liver Frailty Index is looking at functional capacity. We're also looking at change in number of wait list events, so hard clinical outcomes including all-cause mortality, hospitalizations, as well as further decompensation events, and rate of breakthrough hepatic encephalopathy. This is really our first foray into these end-stage diseases. In this study, while it is designed to look for improvement in muscle mass, and we believe that will have beneficial effects not only on the patient-reported outcomes, but also the clinical outcomes. Really, we're going to gain a lot of information about the role in testosterone and its effects in these end-stage patients. Some of the clinical outcomes we're looking at are, of course, overall compensation, overall survival, and decompensation events, including hepatic encephalopathy and ascites. Survival to and through transplant. There's a good number of subjects and patients who die either at the liver transplant or shortly after the liver transplant. Low muscle mass really puts you at increased risk for poor outcomes surrounding the transplant. Finally, rates of hospitalizations and infections. In terms of the sarcopenia and cachexia endpoints, we are looking at a handful of functional capacity endpoints, including Liver Frailty Index, which I mentioned on the previous slide. A six minute walk test, so how far the subjects can walk in six minutes. Timed up and go, time it takes them to get out of a chair and walk a little bit. Besides the functional capacity, we are looking at the muscle mass and quality. Sarcopenia, which is really just muscle mass. We're just going to look and see how much muscle they have in a specific region of their body. The L3 region, lumbar vertebra three, correlates well with the overall muscle mass throughout the body. Muscle mass isn't the only thing that is of interest to us. You can have high muscle mass, but it can be loaded with fat. That's called myosteatosis. You can have regular muscle mass, but your muscle quality is much lower because of all this fat in your muscle. Myosteatosis, along with sarcopenia, correlates with poor clinical outcomes. We'll be measuring whole body composition by DEXA, and also a handful of patient-reported outcomes regarding quality of life and sexual health. Finally, in terms of biochemical measurements, we're going to be looking at anemia status in these patients. There's a possibility that testosterone may aid in production of red blood cells and clotting factors. We may increase albumin levels in these subjects, and albumin is extremely important in these cirrhotic patients in terms of their overall health and really robustness, and low albumin is associated with higher infection rates. Ammonia levels will be measured and that correlates with hepatic encephalopathy. Possibly, if we're increasing muscle mass, there's at least a mechanistic reason why we believe that ammonia levels may drop and we may see improvements in hepatic encephalopathy. The MELD and Child-Pugh scores, those are used to clinically stage patients in order to get them on the transplant list and also decide where they are in terms of priority on the liver transplant list. Finally, we'll be looking at creatinine and calculating kidney function, as that is a common comorbidity in this disease. In terms of next steps, first for our LPCN 1144 for NASH. Our next step is really meeting with the FDA to find a path forward for our phase III study, discussing primary endpoints. We're thinking, of course, NASH resolution with no worsening of fibrosis. We're going to be seeking recommendations on key elements of the phase III design, including treatment arm size and the duration of treatment. We want to understand the FDA's current stance regarding digital imaging analyses of biopsy slides and understand FDA's expectation on exposure requirements as it relates to cardiovascular risk for a serious condition with no approved therapy. For LPCN 1148 in cirrhosis, we do expect our first subject in that trial to be dosed in the first quarter of 2021. That is our presentation for today. I appreciate your attention and look forward to your questions. Thank you very much, Dr. Patel and Dr. Bruno, for the presentation. Perhaps a couple of quick questions from me. As we can see here, 1 144, and as you outlined earlier, 1144 left you improvements in multiple aspects in NASH patients. It definitely has a unique mechanism of action relative to other NASH therapeutics in development. Have you considered any potential in 1144 in perhaps [audio distortion] patients and perhaps other patient populations that are closely correlated with NASH? Ben, do you want to take that? That's a great thought, and it's really getting at our underlying theory here that NASH is a metabolic disease. There's a lot of inputs here. Our treatment is really pleiotropic in attacking many of these different inputs into what eventually leads to liver disease. There have been a handful of studies looking at the effects of testosterone in hypogonadal men with diabetes, and they show improvement in insulin sensitivity. However, those are always interesting questions to look at down the line in terms of other possible indications. For the time being, for this 1144 asset, we are going to be focusing on NASH and liver disease. Perhaps one question for 1148. You mentioned survival endpoint. Obviously, that's a primary endpoint. You also have the Liver Frailty Index as a key secondary endpoint. What are your expectations for this endpoint, and can you outline why it's a significant secondary endpoint? I'll just correct you on one thing. The primary endpoint for this proof of concept study is actually change in muscle mass. The key secondary was overall survival. As you said, another key secondary is this Liver Frailty Index, which is made up of three functional tests. One for example, is the hand grip strength. We'll be tracking the subject's hand grip strength from the beginning, week one through week 52 of the study and looking for changes in hand grip strength and the other two metrics as well, to see if we're seeing an improvement in their functional status. Dr. Lai out of UCSF has done some really interesting work looking at what is really the best predictor in terms of clinical outcomes. Is it the muscle mass measured by imaging, or is it the functional capacity of the patients, of the subjects? With the imaging by CT scan, we're going to be looking directly at muscle mass. We're also looking at a number of these functional outcomes to see if the muscle mass increase or muscle mass change correlates to changes in functional capacity. Sounds good. Thank you again, Dr. Patel and Dr. Bruno, for your presentations today. We look forward to 1144, as you can see here, phase III design to be finalized with the FDA as the next really key endpoint, and then 1148 trial progress throughout next year. Thank you again. Thanks, Thomas. Appreciate it. I want to thank our audience.