Good day, ladies and gentlemen, and welcome to the virtual KOL event highlighting unmet needs in postpartum depression and the clinical profile of LPCN 1154. LPCN 1154 is targeted as short-duration potential rapid relief treatment option for PPD. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session. Instructions will follow the presentation at that time. As a reminder, this conference call is being recorded. Leading the call today is Lipocine's President and CEO, Dr. Mahesh Patel. In addition, Drs. Deligiannidis and Jain, Lipocine's Vice President of Clinical Development, Dr. Benjamin Bruno will be presenting. Dr. Patel is joined by Dr. Deligiannidis, professor and director of Women's Behavioral Health, Zucker Hillside Hospital, Northwell Health, N.Y., and Dr. Rakesh Jain, clinical professor at the Department of Psychiatry at the Texas Tech University School of Medicine, Permian Basin in Midland, Texas. Dr. Anthony DelConte, Lipocine's medical director, Dr. Nachiappan Chidambaram, the President's Vice President of Research and Product Development, and Ms. Krista Fogarty, Lipocine's Principal Accounting Officer, are also on the line and will be available during the Q&A session. The presentation to accompany today's call will be released by Lipocine later today and available on the corporate website at www.lipocine.com, and will be filed on Form 8-K with the SEC. An archive of this webcast will be made available on the website later today as well. I will now turn the call over to Dr. Mahesh Patel. Mahesh, please go ahead. Thanks, Tara. Good morning, everyone, thanks for joining us today. I'm Mahesh Patel, President, CEO, and co-founder of Lipocine. We're pleased to host this event highlighting unmet needs in postpartum depression, also known as PPD, and the clinical profile of LPCN 1154, our innovative oral brexanolone candidate. Today, we'll discuss a potential paradigm-shifting 48-hour treatment option with clinically meaningfully improved tolerability for treatment of PPD, a serious condition in need of rapid relief. Currently, in the U.S. alone, about a quarter of a million women are diagnosed with PPD annually, and about 144,000 women are actively seeking interaction. Next slide, please. First, I would like to go over today's agenda. Following opening remarks, Dr. Deligiannidis will discuss the clinical burden, treatment landscape, and remaining unmet needs in treating PPD. Dr. Deligiannidis will be followed by Dr. Ben Bruno, Lipocine's Vice President of Clinical Development today, who will review clinical outcome highlights, including safety and efficacy findings from our most recent phase III study. Dr. Bruno will be followed by Dr. Jain, who will discuss our clinical findings and offer his clinical interpretation and the relevance to clinical practice, followed by Dr. Deligiannidis, who will offer her views. I'll return to discuss why LPCN 1154 matters now, review next steps in the development program, provide concluding remarks, and open the call for Q&A. Next slide. Before we begin, I need to remind you that certain statements we'll be making in this presentation are forward-looking statements within the meaning of Private Securities Litigation Reform Act. Also, note, no material non-public information about any publicly traded issuer or security will be discussed during the webcast. No solicitation for the purpose of any security is or will be made during the webcast, and the meeting participants and any materials shared during the meeting have been authorized by the company. Let's begin. Before we dive into today's discussion, I would like to briefly mention that in addition to an approved commercialized product, Lipocine has a robust pipeline comprising differentiated product candidates at various stages of development based on our proprietary technology. The pipeline includes our most advanced candidate, 1154, for postpartum depression, and is the topic of today's discussion. Antidepressant activity of neurosteroids have been validated through approval of IV brexanolone, also known as brexanolone, previously sold under brand name Zulresso, and more recently, the approval of oral zuranolone, marketed as Zurzuvae. Brexanolone is best known as a positive allosteric modulator of GABA-A receptors. Brexanolone is three alpha, five beta neuroactive steroid that preferentially targets extrasynaptic GABA-A receptors, and specifically delta subunits. Brexanolone is a well-studied molecule that has known antidepressant effects and is thought to be mediated by numerous mechanisms, including GABA modulation, neuroimmune regulation, HPA axis modulation, and increasing level of brain-derived neurotrophic factors. It's also noteworthy that reportedly brexanolone is likely to work as a neuroplasticity modulating agent that restores dysfunctional brain networks in depression. Brexanolone, due to its poor water solubility and poor oral bioavailability, was only administered via injectable IV. Our proprietary oral technology enables attractive oral absorption of brexanolone. With this introduction, it'll be my pleasure to introduce to you Dr. Deligiannidis, a nationally recognized leader in the field of perinatal depression and novel therapeutics research. Her research program includes a focus on neurosteroids and hormones. Over the past decade, she has served as a principal investigator on a series of clinical trials that led to FDA approval of two rapid-acting neuroactive steroids for postpartum depression. I'll pass it on to Dr. Deligiannidis, who will discuss the clinical burden, treatment landscape, and remaining unmet needs in PPD. Dr. Deligiannidis, please go ahead. Thank you, Dr. Patel. It's a pleasure to be with you today. Good day. I wanted just to start off with a background of perinatal mental health disorders and their impact in women. They're among the most common complications of pregnancy in the year after delivery, and the global prevalence rate is over one in four women that are affected by perinatal depression. That's depression either with onset in pregnancy or after delivery. A recent economic analysis of the impact, the functional impact and economic impact of this untreated disease in U.S. births, this was taken from a data analysis in 2017, concluded that the cost was $14.2 billion, with the average cost per mother-infant pair through age five being $31,800. There are numerous factors that led to this increased cost. Some of them are listed here with reduced economic productivity, increased risk of medical complication and obstetric complications, including preterm births and others, but also myriad other health expenditures. Next slide. The good thing is that numerous professional organizations are increasingly recommending screening. I would say most notably, the American College of Obstetricians and Gynecologists, or ACOG, have really made a vast transformation of their recommendations in 2023 to the OBGYNs. They have increased the number of screenings that are recommended to 3x per pregnancy, which is a big change from prior recommendations and from other organizations. In addition to that, a critical piece was that screening must lead to diagnosis, it must lead to treatment. Now there's increased recommendation and urgency for OBGYNs to initiate treatment, not just refer to behavioral health treatment in the community. We also know that we're seeing increased rates of postpartum women initiating treatment. Unfortunately, far fewer are getting adequate treatment. I can answer more about this in the Q&A because it's a complication that we see as a gap of care that's happening with SSRIs being used as the mainstay of treatment still in postpartum depression and the challenges that OBGYNs have working with their patients and vice versa to use this treatment at an adequate dose and duration in this population. The reality is that many women drop treatment because of side effects and also just having to titrate the medication to take it for long times. Up to 75% of women will discontinue their treatment at least once in the first postpartum year since diagnosis, and almost 40% discontinue it just within two months. Even though we're picking it up and starting treatment, the current treatment regimens are just ineffective. They're not reaching the women that need it. Next slide. I could give a two-hour presentation on the outcomes. Untreated depression has been studied for decades on the adverse outcomes for both the mom, for obstetrical outcomes, infant and child developmental outcomes. Depression is known to worsen every other medical condition that a woman has in the peripartum period. Also including increased rates of poorly managed diabetes, hypertensive disorders of pregnancy, preterm birth, and C-section rates. Also, there's significant data showing that untreated perinatal depression significantly impacts the next generation. Offspring have higher rates of depression and substance use disorders, other developmental disorders because of their exposure to perinatal depression. Next slide. I just want to give a brief vignette. This is not the baby blues, right? This is a DSM diagnosis. It's a major depressive episode with peripartum onset. Onset and pregnancy are within the soon after delivery. It does not resolve typically without treatment. Sorry. The disease itself can last up to three years if it's untreated. I'll briefly describe Abby, 34-year-old married female in the past psychiatric history of recurrent depression and anxiety. She presented about eight weeks after her second child. She was fine during pregnancy, but she developed severe depressive symptoms days after giving birth. She had constant crying and sadness, feelings of hopelessness and worthlessness. Her hopelessness is that she just was never going to get better, that she had had depression before, but she said, "Dr. Dee, this is the deepest depression I've ever felt, I just can't climb out of this. I'm at rock bottom." She felt severe guilt that her entire family, she was letting them down because she just couldn't contribute, and all the responsibilities were being picked up by her husband and her mom, who had moved in with them. She told me, "I can't take care of my children. I can't prepare meals. I can't clean." She said, "My toddler," she had two at the time, "My toddler knows that Mommy's feeling sad." It was apparent to her two-year-old. "I have no connection with my baby," she said, and that she just kept saying, "I failed my family. I failed my family." It would take her hours to fall asleep. She couldn't wake up. If she woke up with the baby, it took her hours to fall back asleep. She was 10 pounds less than her pre-pregnancy weight because she had lost any drive to eat food. She was so exhausted and fatigued that she just said, "It's just exhausting to live like this. I don't know how much longer I can fight this." Next slide The mainstays of treatments have been psychotherapies and serotonergic antidepressants. We have good data for psychotherapies, for monotherapy and moderate, but access to psychotherapy is sometimes complicated for many women. Serotonergics may be beneficial in the RCTs that have looked at that in the postpartum period. But because the pooled risk ratio confidence intervals included one, there was no statistical difference between SSRIs and placebo in this Cochrane review. Next slide. Dr. Patel went over a little bit of neurosteroids. I'm going to just add that allopregnanolone and other neurosteroids rise tremendously during the pregnancy and then precipitously decline in the postpartum period. During this period, you see on this slide the pre-pregnancy, pregnancy, and postpartum GABAergic, pre- and postsynaptic figure there. What's happening is that allopregnanolone is really driving a neuroplasticity of these GABA-A receptors, neurosteroid-sensitive GABA-A receptors, during this peripartum period. There has to be this neuroplasticity of the GABA-A receptors in the neurocircuits during this time. Animal models suggest that the reason why postpartum depression or perinatal depression results is that this flexible plasticity of the GABAergic system is lost. Next slide. There was the breakthrough FDA approval of brexanolone or allopregnanolone IV in 2019, followed by zuranolone, which is a synthetic derivative of pregnenolone, a very closely related neuroactive steroid, in 2023. That is dosed orally 14 days, and I'll tell you a little bit more about that on the next slide. What we have today, and then I'll hand it to Dr. Bruno, I think, is going to follow me, is that this is where we are today. IV brexanolone was withdrawn from the market because having an IV solution 60-hour infusion was very challenging to get for patient access. We have zuranolone, a 14-day course, but there are high rates of sedation with that medication and a box warning. Then I can speak in the Q&A of some of the challenges we have with the serotonergic antidepressant options. With that, I will pass along to the next presenter, Dr. Bruno. Thanks, Dr. Dee. I'm going to discuss the clinical outcome highlights for the recently completed study and also the program in general. As Mahesh shared, LPCN 1154 is an orally bioavailable formulation of brexanolone. IV-administered brexanolone was previously approved for the treatment of postpartum depression. It was highly effective at rapidly treating PPD, although the 60-hour continuous IV infusion limited clinical utility. We have completed numerous pharmacokinetic studies with LPCN 1154, some of which included administration of IV brexanolone as a comparator arm. Our formulation not only enabled oral absorption of brexanolone, but our selected dose and regimen was bioequivalent to the approved IV product in a head-to-head clinical study. The bioequivalence enables a streamlined 505(b)(2) regulatory strategy that leverages Zulresso's established efficacy and preclinical data. Today, I'm going to discuss the results of our recently completed phase III trial of LPCN 1154 in women with postpartum depression. This study utilized the same dose and regimen that was shown to be bioequivalent to the IV formulation. The study was a two-arm, outpatient, randomized, blinded, placebo-controlled trial in women with severe postpartum depression. 90 participants were randomized one-to-one to a 48-hour at-home treatment course of either LPCN 1154 or placebo. The primary efficacy endpoint was changed from baseline in 17-item HAM-D score at hour 60, and participants were followed out to day 30 for both safety and efficacy. Baseline demographics are shown on this slide. A couple of points I'd like to call your attention to. First, about 9% of participants were using an antidepressant at baseline, mostly SSRIs. This is lower than the rate of other trials in women with severe PPD, where rates range from about 15%-30%. Second, only about 60% of participants had some other psychiatric diagnosis. We utilized the MINI to confirm the diagnosis of major depressive episode for inclusion into the study. Looking at the results of the MINI, we noted about 40% of the participants had no other current or prior psychiatric diagnosis. This is a bit unusual for a PPD study. Based on the literature in previous PPD trials, it is estimated that about 80% of women with PPD have either a comorbid psychiatric condition or historical diagnosis. Still, the baseline HAM-D was about 28 and in line with other trials that enrolled women with severe PPD. Moving on to the results. The primary endpoint, placebo-adjusted HAM-D change from baseline at hour 60 was not statistically significant, with a placebo-adjusted difference of 1.3 points. While LPCN 1154 was numerically superior at all time points, nominal statistical significance was only seen at hour 12. Moving on to the safety results. LPCN 1154 was very well-tolerated. All participants completed dosing with only one dose reduction, which was due to a rash. Eight participants in each arm had a treatment-emergent adverse event. The site staff performed multiple check-in calls with the participants throughout the dosing period to strengthen the accuracy and completeness of the AE data. There were no treatment-related serious or severe AEs. The two severe AEs, one of which was also an SAE, were worsening of periorbital cellulitis and worsening of suicidal ideation, which occurred approximately three months after the completion of dosing. Dizziness, somnolence, and nausea all occurred in two participants in the LPCN 1154 arm and no participants in the placebo arm. All cases were mild to moderate in severity and resolved without intervention. As you can imagine, we were quite surprised when we saw these results, especially given the bioequivalence data. We soon noticed that there were numerous anomalies at one high-enrolling site, which raised substantive questions about the validity of their data. First, about 40% of the participants at the site had no evidence of study drug in their blood sample collected at hour 60. Second, there were high rates of de novo PPD. That is, PPD being the participant's first and only psychiatric diagnosis as per the MINI. Finally, placebo participants at this site had extremely high response and remission rates, about 90% and 80%, respectively. Exclusion of the data from this outlier site signals LPCN1154's true treatment effect, a rapid, sustained, and clinically meaningful improvement in depression symptoms. Not only based on HAM-D findings, but also other scales such as MADRS and HAM-A. The results we see align with the known antidepressant profile of IV brexanolone. I'm going to share some more data on the participant phenotype and placebo response at the outlier site. In the next two slides, the blue bars represent the outlier site, and the gray bars, the rest of the sites. At the outlier site, only 23% of participants had any prior or current psychiatric diagnosis. Per the MINI, the only diagnosed condition was a current episode of PPD. At the other 14 sites, almost 80% of participants had a historical or current diagnosis in addition to their current postpartum depression episode. The story is similar for history of PPD, 0% versus 23%, and major depression, 7% versus 60%. History of depression is the top risk factor for developing PPD, and anxiety disorders are the most common psychiatric comorbidity in women with PPD. Based on the HAM-A, about one-third of the participants at the outlier site had moderate to severe anxiety, compared to about 80% of the participants at the other sites. The participants at the outlier site had significantly lower rates of psychiatric diagnoses, not only compared to all other sites in the study, but also compared to the rates reported for other PPD studies and what is known about the real-world prevalence in women with PPD. Moving on to the placebo effect. This slide shows HAM-D data for participants randomized to placebo only. This is only placebo data. Hour 60 on the left, day 30 data on the right. You can see that as early as hour 60, the placebo-treated participants at the outlier site had markedly larger improvements compared to the placebo-treated participants at all other sites by about two to threefold. The data for day 30 is even more striking. Response is defined as at least a 50% reduction in HAM-D score, and remission as a HAM-D score less than eight. At the outlier site, 92% of placebo-treated participants had a response and 83% remission. The change from baseline of these participants was -23 points. This is in contrast with the placebo-treated participants at all other sites whose data are in line with other severe depression trials. Not surprising that this site was identified as an outlier by treatment by site interaction analysis. I'm going to shift into sharing the results with the data from this outlier site removed. Overall baseline demographics for the subgroup are aligned with the overall study population. However, with removal of this outlier site, the rate of de novo PPD is consistent with what we expected, about 20%. On to the efficacy results. In our post hoc subgroup analysis, LPCN 1154 treatment demonstrated rapid, durable, and meaningful improvements in depressive symptoms across all time points, starting at hour 12 and persisting through day 30. As you can see in the table on the right, the placebo-adjusted differences were at least five points at all time points, and Cohen's d ranged from 0.5-1.1. The HAM-D response and remitter results corroborate the strong treatment effect. Cumulatively, about 75% of LPCN 1154 treated participants had a HAM-D response, and about 50% were remitters. From a baseline of about 28 points, that is a large improvement. LPCN 1154 demonstrated rapid effects seen at the earliest time point measured, 12 hours post first dose across scales and subscales. For the HAM-D17, HAM-A, a measure of anxiety symptoms, HAM-D response, and HAM-D6, a subset of the HAM-D questions that measure core depressive symptoms, statistically significant and clinically meaningful improvements were observed with LPCN 1154 at hour 12. The rapidity of efficacy is supported by EEG data collected in a previous clinical trial of LPCN 1154. Beta band QEEG activity is a validated objective biomarker of GABA-A receptor modulation. Significant increases in beta band amplitude were seen at the earliest post-dose time point where it was measured, two hours, and sustained through 12 hours after the single dose was administered. Compared to IV brexanolone with its up titration dosing regimen, LPCN 1154 reaches significantly higher brexanolone levels much earlier in the treatment course, which may help explain LPCN 1154's rapid efficacy. Earlier, I shared how the minority of patients with PPD have de novo PPD, about 20% or less. Women with a history of depression or anxiety may have impaired compensatory mechanisms and are unable to adapt to the large fluctuations in peripartum neuroactive steroid levels, resulting in PPD. In these participants with underlying dysregulation of the GABA system provide some evidence that LPCN 1154 has potential for treating major depressive disorders beyond PPD. Here I'm sharing the results of the subgroup, which excludes those with de novo PPD. Only those with a history of psychiatric diagnoses are included. Again, you can see that LPCN 1154 demonstrated a rapid, durable, and statistically significant improvement in symptoms across multiple time points in this subgroup analysis. With placebo-adjusted differences greater than four at all time points, and Cohen's d ranging from about 0.5- 1.1. In summary, the results of the two subgroup analyses support LPCN 1154 as an effective, rapid-acting antidepressant with durable efficacy. When the outlier site data is excluded, when we look at just those with a history of a psychiatric condition, LPCN 1154 treatment results in rapid and clinically meaningful effects as early as 12 hours after the first dose, with a HAM-D absolute change from baseline of -11 points. The median time to response, the time at which 50% of participants had a response, was about 2.5 days with LPCN 1154 compared to about 30 days with placebo. While today I mostly shared HAM-D efficacy data, we saw consistent outcomes across scales, including MADRS and HAM-A. LPCN 1154 was at least numerically superior, if not statistically significant, across all scales and all time points in these subgroup analyses. LPCN 1154 was very well tolerated, with low rates of mild to moderate AEs and no drug-related severe or serious AEs. About 5% of participants reported a CNS adverse event. Taken together, LPCN 1154 has the potential for a differentiated treatment profile and could deliver rapid and sustained relief with a short at-home treatment. I'll hand it over to Dr. Jain, Professor of Psychiatry and seasoned expert in CNS drug development, to share his thoughts on the study results and the potential implications for LPCN 1154 as a treatment for depressive disorders. Dr. Jain? Thank you, Dr. Bruno. I love the choice of your words, "seasoned," which I think is code for old. I'm pretty smart. I think I figured that out. Folks, it's so nice to be with all of you to talk about this important topic. I got into a reflective mood a little bit because today is two weeks shy of 40 years ago when I did an NIMH fellowship in research psychiatry. 40 years. 40 years ago, the first conversation I had with my supervisor, he told me, "Keep your eyes on two neurotransmitters because you'll be thinking about it half-century from now." The first neurotransmitter was acetylcholine, which at that time was not cool at all. Today, I'm happy to tell you acetylcholine has become a very prominent player in the world of schizophrenia. The other neurotransmitter that wasn't cool back in 1986 was GABA. He said, "Keep your eyes on GABA because it's going to play a big role in depression." Today, and he's passed since, I sit across from you telling you that he was right. I'm a child psychiatrist in addition to being an adult psychiatrist. I want to add a couple of words to what Dr. D said about the impact that postpartum depression has on the lives of women. I'm sadly going to report that in addition, the ripples of postpartum can not just affect children, but children as they grow up. This is not just a severe disorder. It's almost a metastatic disease. It seems to spread into the family. That's why effective and quick treatment is really important. Just one other quick comment. In addition to being an expert on postpartum and on major depression, I have real expertise in postpartum depression because both my mother and my sister, my only sister, have suffered from it in past years. Someday when we have more time, I'll tell you about what it's like to live at the other end of postpartum depression. It's zero fun. Let's move on to the next slide. I really appreciated, Dr. Bruno, that you did not shortchange our colleagues in the investor community about the importance of understanding adverse events. Adverse events are a potential barrier with all medications, but could be with GABAergic medications. I was pleased to see a couple of things that are relevant. The first, of course, is the relatively low numbers. That's impressive to me. As an outsider, and remember, my interaction with Lipocine is really as a consultant. As an independent-minded, independent-thinking consultant, I look at things with a jaundiced eye. That's my job. My job is to look for problems. That's what researchers have to also do. I'm happy to report to you, I'm not seeing a lot of challenges. The fact that none of your serious adverse events were treatment-related, as deemed by the investigators, is important. I was particularly pleased to see that dizziness, somnolence, and nausea, which can be real challenges, actually resolved for the most part without any specific intervention. I'm giving this particular formulation, 1154, from a safety perspective, a pretty strong thumbs up. I've had experience both with brexanolone and zuranolone. This actually stacks up quite nicely. Let's move on to the next slide. This is where I think the fireworks begin. The fireworks, thank you, Dr. Bruno, for highlighting why that particular site's data was worrisome. You were actually too mild. It's very worrisome. To a consultant, as someone who runs national-level trials with multiple sites, that's not just a red flag, that's a red flag with blaring horns. There's a problem with site recruitment. I don't need to go into the details of what challenges I think, but it's enough that to exclude that data is. Mahesh, it looks like we lost Dr. Jain. Rakesh, you're on mute. Perhaps we can pick up with I think he's frozen for a minute. See if he comes back, and maybe we can move on. Should I just jump ahead to? Yeah Dr. D's section? Dr. D, yeah. Okay. We will hope that Dr. Jain comes back to finish his review of the data as an outside consultant. I will tell you a little bit about what I think about the data, too. Next slide. I see the data as well. I was site PI on all of the brexanolone trials and the lead PI on the zuranolone trial. I have been working with these compounds for many, many years in addition to my federal funded work in neurosteroids and GABAergic neuroplasticity in the neural circuit. I do brain imaging and steroidomics as my main role in my research institute. I'm very familiar with the data and to try to understand the pluses and minuses and how these things differentiate. I will piggyback off of what Dr. Jain said about tolerability, which is not on this slide, because I think this is really key. It was a challenge in the brexanolone IV study, I think mainly because it was an IV and there were some pump issues that drove some of those tolerability issues. With zuranolone, we do see high rates of sedation, and that has been, again, I can speak more in the Q&A, a challenge for both patients wanting to take the medication. Even though it's a 14-day course, there's concern that they're going to sleep through the night and not wake up for their baby to get up in the middle of the night. There's concern around side effect profile. For me, as a perinatal psychiatrist for the past 18 years, it's really important that we have options that have different side effect profiles, different onset of rapidity, that we have something for everyone, and to do better each time we move forward. For here, what I'm really seeing is that, and obviously there are challenges with we don't have head-to-head trials. The trials were designed a bit differently with different time points. The patient populations were a little bit different. Again, that outlier site was the biggest outlier I've seen, and we've all seen it. We were at a conference presenting this data, and the audience just said, "Yep, we've seen an outlier like this before." This does happen. That's why looking at the data, excluding the outlier site, is just so striking to me. The signal's there. That was my first impression, and remains how I see the data. Given the data we have, with what we've published with zuranolone, there's a potentially faster onset here. This is probably because they are not the same thing, right? brexanolone is not zuranolone. They're different molecules. Again, brexanolone is a naturally occurring. It's made in the brain. It's made in the testes, in the ovaries, the placenta, the adrenal glands. It's a naturally occurring neurosteroid with numerous beneficial effects for the CNS. This is a shorter treatment duration, so we run into issues with longer and longer. I told you that women stop the medications when they have to titrate them or take them for long times or have side effects. We'll have women start treatment, but that's not good enough. We've got to get them to remission. The signal that we're seeing here is that this is not only a shorter treatment duration, but a potentially faster onset of action compared to what we have on the market today. What we're also seeing here is that both medications, both investigational and zuranolone, the FDA-approved product, are showing sustained effects after stopping treatment, which is really critical for what we need to care for women. Next slide. I'd say really, the differentiators are here is that the LPCN 1154 is, for me, the rapid onset is critical. The field, I believe, is not going to tolerate antidepressant development that doesn't have rapid onset, that meets the criteria for rapid onset of action. The fewer doses, just a 48-hour course for me is a key differentiator as we develop more rapid acting acute treatments for postpartum depression. The tolerability. The side effect profile, which you can see in the figure on the right, is just again, a differentiator. We're just not seeing that signal with the bioidentical oral brexanolone product. The SSRIs have their own challenges, and again, I'm happy to answer those in the Q&A. We've been using them for decades. We have really high rates of discontinuation with those. Also, weaving those into OBGYN practices where many of these women are detected is challenging because they're just not set up to care for women in a longitudinal, longer-term way to uptitrate those medications, get them to efficacy, and then treat for four to nine months for the acute course. To do all that piece as they're getting connected to behavioral healthcare in the community. With that, those are just a few of my thoughts, impressions about the data as I've worked in this field for the past 18 years. Thanks. I'm back, folks. We had rolling thunderstorms in Texas, so the transformer blew. Apologies for dropping off for a minute. Great. Can we go back to the slides, the financial forecast- Yeah. Maybe just a couple more minutes. Yeah. Thank you. The attention I wanted to draw everyone's attention was the hour 12. The rate of descent is really important to a researcher. It's not just the magnitude of change, but the rate of change that matters. The fact that we saw changes statistically, very significant changes at every time point really matters. Maybe we can try and remember this, that GABA-A receptor is an ionotropic receptor. If you touch that receptor the right way, if you act as a positive allosteric modulator, you should anticipate not just quick effects, but sustained effects. The other point I really think is worthy of note is on the extreme right of the slide, which is Cohen's d. I, in fact, recommended to Lipocine some months ago that we really do need to look at effect sizes because that's how psychiatry now measures the power of an intervention. These are impressive numbers. During Q&A, you can perhaps, if you have further questions, you can ask me about that. Next slide. I think this is worthy of our thought. As Dr. D said, things are moving in the field. The field is no longer tolerant of low remission rates. The field is no longer tolerant of slower onset. We want reliability, and we want it now. That's a legitimate need we have. Perhaps we should be quickly reminded that of all the receptors we have in the human cortex, of all, there is not one single receptor that is found more frequently than the GABA-A receptor. Of all the neurons in the human brain, of all the neurons, the number one most common neuron in the human brain is the interneuron. Over 95% of them are GABAergic. GABA is a major player in depression. There's a reason why for 50 years we have had the GABAergic hypothesis of depression. While we're very interested in talking about LPCN 1154 in postpartum depression, I can't help but then start thinking, what about the non-postpartum depression in women? What about, obviously, depression in men? Could this product have a role to play there? I would say the answer is most likely yes. Let's look at the next slide. This is my final slide that I will cover before I turn it back to you, Mahesh. This is a big deal because majority of patients who have postpartum, in my experience and the data shows, have either a concurrent or a previous history of psychiatric disorders, most likely one of two or both of them, depression, anxiety. Here, we are actually looking at that group of individuals, which is the majority, who had a psychiatric diagnosis in this trial, in addition to the postpartum. May I encourage you to look at the fact that one more time, the curves of response replicate, but go to the extreme right. Effect size matters, and the effect size at hour 12 of 1.1 is a really big deal. Benjamin Bruno presented something else to you folks that was such a gem that I wanted to make sure it didn't pass your attention. He presented HAM-D6 data, not just HAM-D17, not just other HAM-Ds. The reason why it caught my attention, because HAM-D6 are the core symptoms of depression. Not sleep, not appetite. Those are important. The core symptoms of depression, and the fact that 1154 on the core symptoms of magnitude, I have to call it a real antidepressant. Okay. Thank you, Mahesh Patel. I think I get to pass it back to you now. Thanks, Dr. Jain. Before I review the importance of 1154 in targeting unmet medical needs, let me briefly review the commercial opportunity. Next slide. PPD is expanding market opportunity. Approximately 10%-12% of births could result in PPD, and the market opportunity is poised to grow with increased diagnosis and raised awareness. Our recently launched Zurzuvae in late 2023, has experienced a significant uptake in the initial post-launch years. Given the limitations of available options, there remains significant unmet needs, as described by Dr. Jain and Dr. D for the treatment of PPD, especially for rapid relief of symptoms with superior tolerability. Next slide, please. 1154's differentiated target attributes offer potential for rapid acting antidepressant, for PPD, with efficacy demonstrated within a week and rapid relief as early as 12 hours. As Benjamin Bruno mentioned, time to response onset of 2.6 days, versus nine d ays reported for Zurzuvae, the recent product on the market. The observed tolerability profile is superior when compared to current available options, with low incidences of CNS depressant effect. This is important as it offers low transference risk to the breastfeeding infant. No observed psychosomatic effects such as hallucinations or dissociation effects as observed with psychedelics, and no observed treatment discontinuation in our experience. Furthermore, there's potential for at-home use with an ultra short 48-hour treatment duration. Just going over the regulatory next steps. Lipocine has multiple regulatory initiatives in play that include pre-NDA meeting to confirm completeness of a reviewable package. For clarification, although we have observed excellent treatment effects in a subgroup of patients with prior history of psychiatric illness, our immediate regulatory strategy is directed to all women experiencing PPD, pretty much identical to approved Zulresso and Zurzuvae label. Based on FDA feedback received to date and given the totality of the available information on hand, NDA filing may be in order. We are seeking clarity through a pre-NDA meeting, which has already been requested. We believe clinical efficacy aspect of NDA filing could be supported by, first, because the underlying efficacy of the molecule is already established via the IV approval. The mechanism of action is validated, therefore. We also know that FDA accepts through IV brexanolone approval the magnitude of the effect, its clinical relevance, as well as the endpoints, that is the MD reduction in HAM-D scores. Second, a pharmacokinetic bioequivalence binding to IV brexanolone enables us to leverage previously established IV brexanolone efficacy. This bridge efficacy expectations from a proven drug to a new formulation can be supported through a 505(b)(2) regulatory pathway. Lastly, while the oral phase III data were compromised by a single problematic site, the subgroup data excluding outlier sites suggests the underlying drug effect appears real and consistent, given its coherency in multiple endpoints. For reason presented earlier by Ben, the results from the outlier sites are likely non-representative of the effects of 1154 for the treatment of PPD. In parallel, based on the observed results, with respect to rapid relief and the importance thereof, as expressed by both of our KOLs, expressed in what we have observed as early as 12 hours post dosing initiation, that the need for rescue/bridging therapy in treating depression. We're also contemplating finalizing our new study protocol plans to confirm the rapid relief findings. Lastly, we're also pursuing expedited designation consistent with our target indication population of women with PPD. In summary, the value proposition offered by LPCN 1154 is compelling because it's targeted to a large patient population with significant market opportunity, with strong pharmacoeconomic justification for attractive pricing and coverage. In addition, it has potentially differentiated product profile addressing unmet needs, rapid and durable response potential with superior tolerability, and of course, the ultra-short at-home self-administration. It has a streamlined pathway to NDA submission. Rapid and effective treatment for PPD is a global unmet need. We have issued impending patents in most major markets. Furthermore, our oral brexanolone platform has potential for expansion, as Dr. Jain mentioned in his presentation, into additional depressive indications such as MDD and TRD, especially in light of the rapid relief observed in patients with prior history of depression. In totality, 1154 could be a possible game changer in the treatment of PPD if approved. In conclusion, our progress represents a major step forward for Lipocine and for women and families affected by postpartum depression. If approved, 1154 has the potential to significantly improve treatment access, due to its oral convenience, and reduce patient burden, as was described earlier. I want to thank our clinical partners, investigators, and women who participated in the study for helping to advance the potential treatment. We look forward to advancing 1154 towards regulatory success and ultimately to helping women with PPD who need better option. This concludes our prepared remarks for the day. At this point, we'll turn over the call to our operator for Q&A. Thanks. Great. Thank you, Mahesh. At this time, we'll be conducting a question and answer session with our speakers. Please hold for a brief moment while we poll for questions. Our first question comes from Scott Henry at Alliance Global Partners. Please go ahead, Scott. Hi. Good, I guess, morning/afternoon. Appreciate everyone's presentation. It was really quite helpful. A couple questions. Just first for either Dr. D or Dr. J. In practice, when we think about a new treatment, can you tell me about the 12 hours of non-driving? Obviously, it's a boxed warning. You'd have to take it pretty early at night if you wanted to drive in the morning, whether it's getting someone to school or not. Could you tell me how important is that difference? As well, another difference between the treatments. Obviously, the dosing of two days versus 14 days is a lot easier. In practice, how helpful is that, do you think, for patients? Thank you. I can take that one. Do you want to take it, Rakesh? No, please. Please start. Okay. Yeah. Usually it's dosed around 8:00 P.M., the zuranolone. We recommend our clinicians, our perinatal psychiatry center, and others dose it in the evening to get around the sedation and also the box warning with the driving. They're advised not to drive for at least 12 hours because they may not recognize that their driving's impaired. How big of that is a driver? I think the more important piece is the sedation at night. What we're seeing clinically is this conversation between psychiatrists, psychiatric nurse practitioners, OBGYNs, and other prescribers about the side effect profile of zuranolone. I think that is what's giving significant pause for the use of the medication. Despite that it's rapid acting, that it's a 14-day course, and it's so different than SSRIs, and it's available, that is what is really, I think, prohibiting women from taking the medication. For some prescribers to prescribe the medication, especially that some women are on other medications that are sedating as well that they can't come off of. Having medication that can cause additional sedation like zuranolone becomes challenging when they're on medications that are already CNS depressants or can cause sedation. That nervousness of not being able to get up when their baby needs them, that is striking at a mother's core in a woman who's already feeling like a failure, and that she can't take care of her infant, and that she's impaired. For me, I think that's what I'm seeing clinically. The two-day course versus 14 has a lot of implications. Breastfeeding is, I would say, the biggest one. Adherence, perhaps, but 14 days is not bad for adherence. Very different than taking an SSRI for nine months, 12 months, et cetera. I would want to see breastfeeding data and relative infant dose data. If we can take the data, given the bioequivalence from the IV studies that we did for breastfeeding, the relative infant dose is less than one, and this is a natural neuroactive steroid. Again, different than zuranolone. That is giving, even though it has a low relative infant dose, and we did those breastfeeding studies, there's hesitancy by prescribers and nursing women to take zuranolone. Not by everybody, but by many women, because it's not the natural neuroactive steroid, and that they're taking the medication for 14 days, and that it takes seven more days to get out of their system. That's really how I'm seeing LPCN 1154 differentiate with what we're seeing sort of live with our patients with PPD. Yeah. Well. Dr. Jain, your perspective? Yeah. I'll just underscore everything that Kristina has shared. In fact, I published a paper looking at zuranolone and the sedation worries, because it's a significant worry. Thank you for asking that important question. The difference between two days and two weeks is more than semantic. I think we have to appreciate in postpartum depression, it's no longer a biological disorder, it's a biopsychosocial disorder. For a mother who's struggling to appreciate her motherhood and her parenthood, then have to think about 14 nights, not just 14 days, 14 nights she may or may not be fully available to her child, has been a challenge in me convincing people to try a two-week course of trial. I would say with 1154, in strong support of what Kristina said, one of its greatest assets may be the 48-hour aspect. That's really great insight from both of you. Just one more question for the two of you. When you think about this patient population today, if you saw 100 patients, what kind of market share? Are half of them getting SSRIs and SNRIs? Just trying to get an idea of how people are treating these patients today and how much Zurzuvae has impacted prescribing. Obviously, it's just an estimate. Yeah. Maybe I'll get the ball rolling, Kristina, you can sharpen my commentary. It's distressingly low. There are reasons for it. It's not that it's new. It's not that we clinicians think that Zurzuvae is a bad idea or whatever. It's justice that the challenge of two weeks has been a little bit of a worry. The 12-hour issue has been a little bit of worry. The sedation, the dizziness has been a bit of a worry. You saw the presentation that showed that sadly, the Cochrane Database does not support the use of SSRIs, SNRIs. But I would have to say a lot of them, a lot of my colleagues are turning to them, not because it's logical, but because that's what the professors have done, and they are worried about things. There is clear movement. I cannot tell you how many times I'm seeing patients getting an appropriate trial of zuranolone, but I think the numbers need to be much higher. What do you think, Kristina? I concur. It's much lower than I'd like it to be. Part of it is, there were many things which I learned from, as we follow this from drug approval in 2023. Part of it was the specialty pharmacy piece, there was prior authorizations and insurance pieces that took time. With the insurers, there was initial safeguards, especially with brexanolone IV, because it was an inpatient, that was even more costly. With zuranolone, less costly, but when a new medication comes out, sometimes they want to restrict access a little bit. They had put sort of stringent criteria to get access to the medication. That has all really changed over two years. Now, we have broad insurance coverage for zuranolone. It's still the specialty pharmacy, it's mail order. You've got to get the medication, and there's a couple of steps and phone calls that have to happen between the patient and the pharmacy and things to get it to the patient. I think that that's a little bit of a barrier. Penetrance is still on the lower side, but it's growing is what I understand. I think it's just a matter of time. This, again, is first in class. It's not just a new SNRI. This is a completely different category and class of antidepressants. It will grow, and it is growing. It's just, I think for the reasons Dr. Jain mentioned and we've mentioned, there's been more hesitancy with this, which I think differentiates potentially from LPCN 1154. Okay. Great feedback. Thanks. Really appreciate that from both of you. Excellent to have you on. One question for you, Mahesh. Sure. I share the concerns of an obvious rogue clinical trial site. Stuff happens. If you do the trial again, maybe there would be some guardrails put in place from the idea of would you max out participation from any one clinical site just to prevent the impact that a rogue trial, which can always happen, could have on the results. Thank you. Yeah. Scott? Was that a question? Yeah. Yes. What is the question? What would you typically- No. Scott- Doing it again, yeah. We learned a lot executing the previous trial, and issues and risk were identified. We have a mitigation strategy in place and an implementation plan. Ben, you want to highlight some of the key ones? Sure. Of course, Scott, step one is not inviting this site not to participate in the next trial. Also capping enrollment at each individual site to make sure no site's bringing in more than 10% of the participants at the site. Inclusion of more academic sites into this study, as well as working with third-party consultants in terms of site selection. Another thing we're looking at doing or planning on doing is limiting the percentage of de novo PPD participants in the study, so capping that at about 20% in the study population. Third, we're looking at the issue of the PK, the no evidence of drug in their blood at that hour 60 time point. We're going to have a pre-specified analysis set looking at just those that did have drug if they were randomized to 1154. Also having unblinded study personnel that can screen for issues at the site level to see if any particular sites are having high number of participants that don't have drug in their system. Finally is a interim analysis planned at about 50% of participants who have completed the primary analysis time point. That'll allow us to make some decisions on the trial in terms of continuation as planned, potential resizing, or even calling the trial a success at that interim analysis. Okay. You've obviously thought a lot about that question. Those seem some very good adjustments. Thank you all for taking the question. Thanks, Scott. Thank you for the question, Scott. Our next question comes from Katie Deegan at H.C. Wainwright. Please go ahead, Katie. Hey, good morning. Thank you guys for the call and taking questions. I'm on for Yee today. I know you guys are still in the middle of post-hoc analyses. Are you seeing any synergies with current medications in the patients' histories? Are there any trends of prior treatment that are indicative of response to therapy? Thanks, Katie, for asking the question. We are in the midst of doing that analysis, you're right. I'll pass it on to Ben. Do you want to comment in terms of- Sure. Yeah. People that are on antidepressant use, et cetera? Okay. Yeah. One thing we have looked at is the effects in those that were on concomitant antidepressants while they were in the study, and the effect is very similar in that population compared to the overall study population. We haven't looked back to see does history of response to a certain medication predict response to LPCN 1154. That being said, as Dr. Dee was saying, that this is a very different mechanism of action. I'm not sure if we would see synergies or predictability based on previous therapies that they've tried. Got you. That makes sense. My only other question was, at one point. One of the KOLs, I apologize, mentioned that this might be a useful therapy for men as well, expanding beyond postpartum. Would you be able to elaborate on that a little bit further? That was me. Yeah. Yeah. Dr. Jain, go ahead. I can comment on that. There is, and you mentioned this before, obviously, placenta plays a profoundly important role in the partum period and the postpartum period. Men equally are quite responsive to their own neuroactive steroids. If you look at the neurobiology of the GABAergic system in depression in men, it is as abnormal in depression as that of women. If you look at some of the preliminary data we have from zuranolone and other, remember, there's been other molecules that have been studied, men tend to respond quite well. Yeah, that's as a researcher, as a clinician, I am deeply wanting LPCN 1154 to be available for postpartum depression, I don't want men left out. We too need quick onset. We don't want side effects like sexual dysfunction and weight gain. We too want sustained benefit. We too do not want to take medication on a regular basis. Therein lies the reason why I had made that particular comment. Yeah. I can add to that if there's time. Neurosteroidogenesis and that pathway with the GABAergic system is a shared mechanism. Dr. Jain showed that this is a multi-hypothesis mechanism, right? A disease hypothesis. There are many different ways you can come in to get a major depressive episode. Neurosteroids are one of them, and critical because neurosteroids naturally modulate acute and chronic stress in the brain. We believe, or I believe, and it's not blasphemy, I tell people, because I'm a perinatal psychiatrist, I have been working in the field of novel therapeutics development and PPD for years, but it's a unique trigger for a major depressive episode is this hormonal change. It is very likely that that is not necessary, that hormonal trigger may not be necessary for other forms of depression to manifest. We've seen zuranolone approved in Japan by their regulatory authorities. Obviously, there have been many trials in the U.S. that did not reach FDA approval for a variety of reasons. I think most of us in the neurosteroid field believe that there is a neurosteroid sensitive biotype of major depressive disorder. We see it in this phenotypically enhanced patient population of perinatal depression. I agree with Dr. Jain that there are obvious implications for MDD more broadly. Perfect. Thank you, guys. Of course. Great. Thanks for the questions, Katie. I'll now turn the call over to PJ Kelleher at LifeSci to read the written questions from the webcast. Hi, all. I think just one question because a lot of them have already been answered in the discussion. Thanks again. Mahesh, this one might be for you. Can you just talk about what next steps are with the FDA and remind folks what ultimately gives you guys the confidence that the FDA could potentially advise you guys to file an NDA and potentially subsequently approve LPCN 1154? Sure. Thanks, Peter, for asking. I mentioned earlier, we have already requested a pre-NDA guidance meeting to address the feasibility of the completeness of the package. Our outlier analysis of the efficacy data have already been submitted to the IND, and the initial interaction is basically saying that, it's not totally out of question, our approach. That seems to be we need to make arguments as to justify why the outlier site is an outlier and how you could use the post hoc data. The other initiative, of course, is should our approach and completeness of the package be confirmed at a pre-NDA meeting, our next step would be to submit NDA ASAP after the meeting. Although Ben talked about the design of the other trial that we are planning in parallel, that would be a supportive trial, and should we need that during the review, the information from the interim results, we could always have the option of updating the NDA at that time. That's a dual approach that we are thinking and executing. The other thing is that in the background, we have applied for fast track and breakthrough designation. That would help if the designation approved or designated, we will have a rolling review and a possibility of getting there faster. These are the three approaches, multiple approaches. We feel pretty confident of the arguments we have about the outlier site, given the extreme placebo response and not seeing the PK blood levels. Of course, the demographics didn't match the real world population. With regards to our 505(b)(2), I guess, as I mentioned, the drug is known to work. I mean, through an IV approval. We have established a bridge with the efficacy of the IV brexanolone. Of course, our data has got this kink about the outlier site. If you look at every other way, it's coherent, it's consistent, it's pretty strong. We feel pretty good about submitting the NDA. We do want to have the confirmation of the completeness of the package of the pre-NDA meeting. That's the plan. Fantastic. That's it for the written questions. Mahesh, I'll turn it back to you. Right. Thanks, Peter. Thanks, Tara. Thank you all for participating today. Thank you all again