Good day ladies and gentlemen and welcome to the call to discuss the neurobiology of postpartum depression, the treatment landscape and LPCN 1154, a short duration treatment option for PPD which is currently in phase III. 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. Dr. Patel is joined by Dr. Deligiannidis, Professor and Director, Women's Behavioral Health, Zucker Hillside Hospital, Northwell New York. In addition to Dr. Deligiannidis, Lipocine's Medical Director Dr. Anthony DelConte and the company's Vice President of Clinical Development, Dr. Benjamin Bruno will be presenting. Dr.
Chidu Chidambaram, the company's Vice President of Research and Product Development is also in line and will be available during the Q& A session. The presentation to accompany today's discussion was released by Lipocine earlier today, is available on the corporate website at www.lipocine.com and has been filed on Form 8-K with the SEC and is available on the SEC's website at www.sec.gov. An archive of this webcast will be made available on the website later today. I will now turn the call over to Dr. Mahesh Patel. Mahesh, please go ahead.
Thanks, Peter. Good morning, everyone, and thanks for joining. I'm Mahesh Patel, President, CEO, and Co-Founder of Lipocine. Today we'll discuss a potential paradigm-shifting 48-hour treatment option for postpartum depression, also known as PPD, a serious condition in need of rapid relief. PPD can be a life-threatening condition, especially in severe cases. Currently, in the U.S. alone, annually about a quarter million women are diagnosed with PPD, and about 80,000 are seeking intervention. First, I would like to go over today's agenda. Following my introduction, Dr. Deligiannidis will discuss the PPD landscape. Dr. Deligiannidis' presentation will be followed by a discussion on LPCN 1154 target product and label attributes by Dr. DelConte, and followed by Dr. Ben Bruno, our Vice President of Clinical Development. We'll talk about the development program and next steps. I'll provide some concluding remarks and then open up the call for Q&A.
Before we get into the discussion, I'd like to remind you that certain statements we will be making in this presentation are forward-looking statements within the meaning of the Private Securities Litigation Reform Act. Also note, no material non-public information about a publicly traded issuer of security will be discussed during the webcast. No solicitation for purchase of any securities will be made during the webcast and the meeting. Participants and any materials shared during the meeting have been authorized by the company. Before we dive into today's discussion, I'd 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. They're all based on our proprietary oral delivery technology.
This pipeline includes our most advanced candidate, that's LPCN 1154 for postpartum depression, which we anticipate submitting an NDA in mid-2026 and is the topic of today's discussion. Other key therapeutic candidates in our pipeline include LPCN 2401 for obesity management, comprising a novel bioidentical androgen that is a physiological regulator of myostatin. We plan to initiate a phase II proof-of-concept study with LPCN 2401 as an adjunct to a GLP agonist to enable quality weight loss via improved body composition in obesity management. In addition, our pipeline includes LPCN 1148 with groundbreaking positive phase II results demonstrating improvement in sarcopenia and lower recurrence of hepatic encephalopathy events in patients with decompensated cirrhosis. Let's get started on today's topic with some background on oral enablement of brexanolone, the active ingredient in LPCN 1154. Next slide. Brexanolone, also known as allopregnanolone, is a poorly water soluble neuroactive steroid.
Despite proven robust efficacy in PPD within major depressive disorder via an IV route, the development of effective oral delivery of brexanolone has historically been a significant barrier to patient preferred oral therapy option. Our delivery technology presents brexanolone for most effective absorption by efficient transportation across the aqueous barrier layer through a proprietary oral delivery technology which is validated by an approved product TLANDO on the market. The first effective oral delivery of brexanolone has been achieved by Lipocine and as Dr. Bruno will describe later today, now it's my pleasure to introduce you to our expert on PPD, Dr. Deligiannidis. She's a Professor at Feinstein Institute for Medical Research in New York and Professor of Psychiatry, Molecular Medicine and Obstetrics and Gynecology at Donald and Barbara Zucker School of Medicine also in New York. Dr. Deligiannidis, please go ahead.
Thank you so much.
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It's a pleasure to provide a synopsis today on the PPD treatment landscape.
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Start off with [CSARMA] relations and affiliations.
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Thank you. In the U.S., perinatal mental health disorders, including perinatal depression, are among the most common complications of pregnancy in the year after delivery, affecting one in five women globally. Rates of perinatal depression, i.e., depression occurring either in pregnancy or in the year after delivery or PPD, are one in four. The cost of not treating perinatal depression, which is often comorbid with anxiety amongst U.S. births, is $14.2 billion annually, with the average cost per affected mother-child dyad through age five being about $32,000. As you can see, some of these factors are here listed below, but they're due to these and some additional ones that are not listed as well.
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For many years, professional organizations have recommended screening for depression both in pregnancy and the postpartum period. Recently, and very excitedly, in 2023, the American College of Obstetricians and Gynecologists updated their clinical practice guideline. ACOG now recommends screening for depression and anxiety using a validated scale during pregnancy at the initial prenatal visit, so when they first show up to prenatal care, and then again later in pregnancy and at a postpartum visit. The guideline additionally calls for increased diagnosis and initiation of treatment and referral to community mental health care. These updated guidelines will result in increased screening and initiation of pharmacotherapy by OB/GYNs, and we've seen increased screening that was evident even before these guidelines were issued. I noted a study here that shows those increased trends from the period from 2016 to 2018. About 70% of postpartum women do start treatment for PPD.
However, far fewer receive what we consider adequate dose and duration of treatment. By this we mean women may not receive the adequate dose of the antidepressant to achieve the full antidepressant effect, or they may not stay on the antidepressant for as long as they need to to fully recover or stay well.
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Depression during pregnancy and PPD are associated with many adverse maternal, obstetrical, infant, and child developmental outcomes that are adverse. I listed only a few examples here, but they include decreased maternal functioning and symptoms of psychosis or suicide ideation, which may lead to psychiatric hospitalization or maternal death by suicide. Untreated depression worsens other medical conditions, including diabetes and hypertension, and untreated depression leads to worse birth outcomes. PPD is also associated with poor maternal-infant bonding, lactation failure or unplanned weaning, and impair a child's cognitive, behavioral, and emotional development.
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As I noted, PPD is a major depressive disorder, a major depressive episode that has onset either in pregnancy or after delivery. It's important to point out that PPD is not the baby blues. The baby blues is not a clinical diagnosis and it's experienced by approximately 80% of women in the first two weeks following delivery. Although it can include fluctuation of mood, it resolves on its own without treatment and does not impair functioning. I'd like to share a clinical example of how PPD presents just to have clarity. An example would be Abby. She's a 34-year-old married female with a history of depression and anxiety who presented for clinical care eight weeks after delivering her second child. Her mood was well prior to and during pregnancy, but she developed severe, severe depressive symptoms soon after delivery.
She reported constant sadness with crying spells, feelings of hopelessness that she'd never get better and that this was the deepest depression she ever had. She felt helpless and worthless with intense guilt. She felt no connection with her baby and it took hours to fall asleep due to ruminative worry. She was so exhausted that she didn't have the energy to brush her teeth or shower and she could not care for her infant or her toddler. She experienced significant weight loss since her delivery. She was weighing less than her pre-pregnancy weight when we saw her. She no longer sensed hunger, so her husband had to urge her to eat small snacks throughout the day. Her body felt weighed down and she could not concentrate. During her interview she stated, I don't know how much longer I can fight this.
I just want to disappear so that the pain will go away.
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How can we help Abby? For decades, psychotherapies and the serotonergic or traditional antidepressants have been the cornerstone of PPD treatment. We have strong scientific evidence that a variety of psychotherapies or talk therapies can be used as treatment for mild to moderate PPD. The serotonergic antidepressants may be used alone or in combination with psychotherapy for moderate to severe PPD. A recent meta-analysis of the 11 postpartum RCTs for SSRIs concluded that there may be a benefit of SSRIs over placebo in both depression response, which is a 50% or more improvement in depression severity, and in remission rates at 5 weeks- 12 weeks.
Follow up. Next slide.
There are challenges. The use of traditional serotonergic antidepressants for postpartum depression, and actually they mirror many of the challenges that we have with their use in major depressive disorder outside of the postpartum period. Serotonergic antidepressants are known to have a slow onset of action, taking on average 6 weeks-8 weeks. For patients to experience depression relief or improvement, we prescribe SSRIs and SNRIs for several months or longer depending on the clinical situation. They're associated with low rates of response and remission, and many patients experience bothersome side effects. The side effects listed here are some of the more common side effects of serotonergic antidepressants, and in many women can lead to premature antidepressant continuous discontinuation.
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I will transition to the neuroactive steroid- based antidepressants for the treatment of PPD and I'd like to review just a couple of slides for their biology. Neuroactive steroids are natural or synthetic steroids. They're made from cholesterol centrally in the brain, but also peripherally in the ovaries, the placenta, the testes, the adrenal glands. They are positive allosteric modulators of the GABAA receptor. What this means is that they enhance inhibition of the postsynaptic neuron by facilitating negatively charged chloride ions to flow into the neuron. We have decades of preclinical research that indicate that these neuroactive steroids, especially the best studied is allopregnanolone, that they have important roles in modulating brain responses to both acute and chronic stress. This is really important because depression is a stress disorder.
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Neuroactive steroids enhance both tonic and phasic inhibition through their interaction with two types of GABAA receptors, synaptic and extrasynaptic receptors. GABAA receptors are comprised of five different components, which you can see in the figures here. The composition and configuration of these five receptor components determines the pharmacology and the location of those GABAA receptors in the brain. This provides selectivity for what they bind and where. Preclinical data suggests that the delta component-containing extrasynaptic receptors are important in both the cause of PPD and the mechanism of allopregnanolone's antidepressant effect. Unlike benzodiazepines, which also bind GABAA receptors, neuroactive steroids bind both synaptic and extrasynaptic GABAA receptors and do not bind the benzodiazepine binding site.
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In summary, under stressful life conditions, failure of the brain's GABAergic system to adapt to physiologic or abnormal neuroactive steroid levels may lead to brain circuit dysfunction in areas important for emotional regulation, resulting in clinical PPD.
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The FDA approval of IV brexanolone in 2019 was a breakthrough for the field. It was a first-in-class antidepressant, had rapid antidepressant actions, and those were maintained even after the acute 60-hour treatment course was complete. However, IV administration of brexanolone mainly required patients to come into the hospital for a 72-hour inpatient stay. The cost of both the medication and the inpatient stay and logistics of administration really ultimately limited access to patients. In the IV brexanolone studies, loss of or altered state of consciousness occurred in 4% of patients, so IV brexanolone was prescribed through a REMS safety program. The company that developed brexanolone then developed zuranolone, a synthetic structural analog of allopregnanolone, which could be dosed orally once daily for 14 days at home. It was FDA approved for PPD in 2023.
IV brexanolone was withdrawn from the clinical market, I believe due to the availability of oral zuranolone and not due to safety or efficacy reasons.
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For the clinical characteristics, neuroactive steroid antidepressants are characterized by rapid onset of action measurable within days. Zuranolone does not require up or down titration, though IV brexanolone did, and neuroactive steroids have a different side effect profile compared to serotonergic antidepressants, which is limited to the time around that short treatment course, which is unlike the more chronic dosing we use with SSRIs. I mentioned the common side effects of SSRIs and SNRIs including weight gain, sexual dysfunction, insomnia, and emotional blunting. These are not reported with neuroactive steroid antidepressants. The most common side effects for zuranolone include sedation and dizziness, diarrhea, and fatigue. IV brexanolone had a boxed warning for excessive sedation and sudden loss of consciousness. Zuranolone has a box warning for impaired ability to drive or engage in other potentially hazardous activities.
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Thank you. For many women with PPD, the safety of antidepressants while breastfeeding is a very important consideration. The National Library of Medicine at the NIH maintains a wonderful database on drugs and lactation, and we use this all the time clinically to assess the safety of medications and breastfeeding. A relative infant dose, that's the weight-adjusted percentage of the maternal dose, of less than 10% is considered compatible with breastfeeding. Here you can see on the left the RIDs for some of the most common antidepressants prescribed for PPD. The relative infant dose for brexanolone is between 1% and 2%, and the relative infant dose for zuranolone is less than 1%, indicating very low passage into the breast milk.
According to NIH LactMed, this database, because of the low amounts of brexanolone or zuranolone in the milk, neither would be expected to cause adverse events in breastfed infants, and if either is required by the mother, it's not a reason to discontinue breastfeeding. However, until more data are available, LactMed recommends that zuranolone should be used with careful infant monitoring for excessive sedation during breastfeeding, especially in newborn or preterm infants. Zuranolone's 14-day treatment course may be problematic for some breastfeeding women, since it'd be challenging to pump and dump the breast milk for that duration for those women who want to avoid 100% of medication exposure through the breast milk.
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In summary, PPD is common. It's associated with myriad adverse outcomes for mother and child. Oral neuroactive steroid antidepressants are rapid acting medications that require a shorter course of treatment without titration, and they're associated with time limited side effects. Thank you for your attention. I'll now turn it over to Dr. Tony DelConte. Dr. DelConte is an OB/GYN by training and is Lipocine's Medical Director. Thank you.
Thank you Dr. Deligiannidis. Before Dr. Ben Bruno shares Lipocine's clinical development plans, I want to provide some additional patient and physician insights on the limitations of current therapies and the product profile of LPCN 1154. As we just heard from Dr. Deligiannidis, it's important to consider the significant medical, social, and economic impact of how postpartum depression, a condition that affects many pregnancies. Let's explore how LPCN 1154 might make a difference in families affected by postpartum depression. As discussed earlier, screening and treatment for postpartum depression are increasingly recognized in clinical guidelines. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists advocate for routine screening during pregnancy and the postpartum period. Notably, ACOG's approach allows for diagnosis without a structured clinical interview using validated questionnaires. Instead, this flexibility can lead to earlier identification and treatment of postpartum depression.
The recommendation for brexanolone or zuranolone within the first year postpartum highlights the urgency of addressing this condition. Early diagnosis is crucial as it could significantly impact the well-being of both the mother and the infants. Insights from market research reveal some important observations from OBs and psychiatrists regarding postpartum depression. Patients with a history of major depressive disorder (MDD) are at a higher risk for developing postpartum depression, yet many feel unprepared to discuss their symptoms. Both OB/GYNs and psychiatrists can conduct screening, but OBs will take the lead in diagnosing postpartum depression, and psychiatrists are referred and involved in more severe cases. There has historically been a preference for SSRIs as a first-line treatment practice, but there's a clear demand for safer and more effective options. Recently, a growing number of prescribers are shifting their practice toward a product approved specifically for postpartum depression.
Healthcare professionals are particularly focused on dosing and speed of symptom relief when considering new treatments. Patient observations provide valuable insights into the challenges faced by those dealing with postpartum depression. Concerns about side effects and the stigma of taking antidepressants often hinder open discussions about symptoms. Many patients experience a less than adequate follow-up, leading to low adherence to treatment plans. The desire for faster relief from symptoms is evident as current options often fall short of expectations. Additionally, limitations such as driving restrictions and breastfeeding considerations can deter patients from accepting treatment. Understanding these patient perspectives is essential for developing more effective and acceptable treatment options. The efficacy of brexanolone in the treatment of postpartum depression has been well established in clinical studies.
As illustrated in the accompanying graph, treatment with brexanolone is associated with significant reductions in the Hamilton Depression Rating Scale from baseline, and remission rates are also shown here. In addition to remission, researchers have assessed response rates and other clinical outcomes not shown here to further evaluate treatment efficacy. These data highlight the therapeutic value of brexanolone and underscore the potential impact of an oral formulation in improving clinical outcomes for patients with PPD. The low percentage of patients currently treated with oral neuroactive steroids, as seen on the left panel, suggest a gap in awareness or accessibility that could be addressed on the right panel. Data on NAS users for treating PPD reveal that a significant majority have not previously received treatment for PPD, and these findings highlight a potential opportunity for outreach and education regarding available treatment options.
As we evaluate the market potential, it's important to consider how we can support access to effective treatments for postpartum depression. The product profile of LPCN 1154 is designed to address critical unmet need in treating PPD, as we heard. As a positive allosteric modulator of the GABAA receptor, it binds to both postsynaptic and extrasynaptic sites different from the benzodiazepam, and its unique formulation allows for oral administration without the need for any titration or tapering, making it user friendly. The 48 hour outpatient dosing regimen is a significant advantage as it eliminates the need for hospital stays and potential dosing errors. The innovative Lipocine proprietary oral delivery technology that enhances drug absorption allows for oral delivery, and it's also its differentiated product attributes. Let's discuss now how these features position LPCN 1154 as a possible game changer in PPD treatment.
LPCN 1154 offers a viable alternative to current therapies for postpartum depression. This slide compares the target profile of LPCN 1154 with existing treatments, highlighting its unique points of differentiation. Unlike traditional SSRIs/SNRIs, which have longer onset times and lower remission rates, LPCN 1154 should provide faster onset of action and a higher remission rate within days. The oral administration route is a significant advantage. The data presented here, including projected outcomes based on previous studies, position LPCN 1154 as a potential preferred option for the treatment of PPD. Would now like to turn it over to Dr. Ben Bruno to discuss the development status and next steps for LPCN 1154. Ben, thanks.
Thanks Tony. I'm now going to cover the developmental history of LPCN 1154 including the design and updates on the phase III study. As Tony just highlighted, the molecule brexanolone is highly efficacious in the treatment of postpartum depression. However, the previously FDA- approved product has only been available via 60- hour IV infusion, which limited patient access and commercial success. We first set out to determine if we could enable the oral bioavailability of brexanolone using Lipocine's proprietary oral delivery technology. Next slide. To that end, we initially performed two formulation screening studies in postmenopausal women. We found both our capsule and tablet formulations enabled the oral bioavailability of brexanolone and that the tablet formulation allowed for higher daily doses. Further, brexanolone exposure increased with dose and was higher with post meal administration. All other studies discussed here were carried out with the tablet formulation.
Next, after confirming oral enablement, we proceeded to perform some dose finding studies in postmenopausal women. The first was a three arm crossover study that included two LPCN 1154 dosing regimens as well as an IV brexanolone. We found that the multi dose oral regimens were both well tolerated and resulted in similar brexanolone exposure as the IV product administered per the label. However, we determined that it would be necessary to modify the dose and dosing regimen slightly in order to better match the blood levels of the IV brexanolone product. To that end, we conducted an additional single arm study with the to be marketed dose and dosing regimen, which allowed us to confirm the dosing regimen to be used in future studies.
Next, if we look at the data across the previously discussed studies, you can see that there was dose linear exposure across all of the single and multi dose regimens evaluated. In the left panel are the data for the single dose studies showing linear dose response for Cmax and total exposure AUC with doses ranging from 27 mg- 500 mg, and on the right are the data for the multi dose studies showing linearity with regimens of 300 mg, 400 mg, and 500 mg doses. These linear dose responses demonstrate that a dose and regimen can be selected to fit a desired brexanolone exposure profile. Next, after completing the dose finding studies, the next step was a dosing regimen confirmation study with IV brexanolone. This allowed us to determine if the LPCN 1154 dosing regimen results in comparable exposure as the approved efficacious IV product.
This was a standard two period crossover design that enrolled 24 healthy postmenopausal women. Half were randomly assigned to receive LPCN 1154 during the first period and half received IV brexanolone administered per the product label at a maximum dose of 90 micrograms per kilogram per hour. After a washout period, the participants returned for the second dosing period where they received the alternate intervention. Next, the results are presented here. LPCN 1154 met all standard bioequivalence criteria to IV brexanolone. Standard bioequivalence criteria require that the 90% confidence interval of the geometric mean ratio of the test to reference product is within 80%- 125%. As you can see, this was met for all three standard Cmax, AUC0-∞ , and AUC0-t . LPCN 1154 was well tolerated with no sedation or somnolence events observed.
All AEs reported were mild to moderate in severity and no event was reported by more than two participants. Next, if you look at the safety of oral brexanolone in our clinical program to date, you can see that LPCN 1154 is well tolerated. In total, 58 unique participants have been dosed with LPCN 1154 in PK studies. On the left hand panel you can see that there were low rates of CNS depressant related events with no instances of excessive sedation or loss of consciousness. On the right are the non-CNS depressant events, the most common of which was venipuncture site reaction related to the blood draws for PK sampling. All AEs were mild to moderate in severity. There have been no serious or severe AEs reported.
With this encouraging safety profile and establishment of a dosing regimen based on PK bridge to IV brexanolone, the next step is completing a phase III efficacy study and I'll share some details of that on the next slide. The phase III trial is a two arm outpatient randomized blinded placebo-controlled study in women with severe postpartum depression. The study is designed to enroll approximately 80 women age 15 and above. Participants will be randomized one to one to receive either LPCN 1154 or placebo. The duration of treatment administration is 48 hours utilizing the dose and regimen confirmed in the dosing regimen study. The primary endpoint, change from baseline in HAM-D, will be evaluated at 60 hours post first dose. Additional endpoints being evaluated include another measure of depression, MADRS, as well as anxiety evaluation. Safety, tolerability, and efficacy will also be evaluated through day 30 of the study.
Next slide. We believe the study will yield positive efficacy findings for LPCN 1154 for a few reasons. First, the molecule brexanolone has previously demonstrated efficacy as a treatment for PPD. Second, as this study utilizes the same dose and dosing regimen as was used in the prior dosing regimen confirmation study, the levels of brexanolone are expected to be similar to those achieved with the IV product. Third, the study size, duration, and population are similar to those of the IV infusion products. phase III study, we initiated the study in late March of this year and the first patient was dosed in June. The first data and Safety Monitoring Board meeting is expected to occur this year and top line efficacy and safety data are expected in the second quarter of 2026. Next, I'll share some regulatory updates in terms of the clinical development plan.
The FDA has agreed with our plan for a single phase III study to be sufficient to support NDA submission provided positive results, of course. Further, FDA has reviewed and provided feedback on the phase III design we submitted, which included at-home dosing without the need for continuous medical monitoring. The dosing regimen confirmation study will act as supporting data in this submission for clinical pharmacology and labeling studies. We previously discussed the single and multi-dose PK studies in postmenopausal women, but we also completed a PK study in women with postpartum depression. The latter shows that brexanolone levels were similar in the two populations, women with PPD and postmenopausal women. We also completed a food effect study, which informed our administration. In the phase III study, patients are being instructed to take the product with fat-containing food or snack.
For nonclinical development, the 505(b)(2) pathway allows us to leverage much of the data previously generated during the development of IV brexanolone. Therefore, limited additional studies are needed, including a repeat dose local toxicity study and in vitro studies including plasma protein binding and GABA binding. For manufacturing, three registration batches have been manufactured and have adequate stability for submission. Now I'll turn it back to Mahesh for his concluding remarks.
Thanks Ben. Why LPCN 1154 is a compelling opportunity, here are some of the reasons. PPD is a life-threatening condition as mentioned earlier, especially in severe cases where these mothers have homicidal or suicidal tendencies, and approximately 10%- 12% of births could result in PPD, and that number holds good worldwide. Currently in the U.S. alone, as I mentioned earlier, about a quarter million women are diagnosed with postpartum depression. About 60,000- 80,000 are seeking active intervention. Another thing to note is that awareness and diagnosis are on the rise. A recently launched neuroactive steroid comprising of an oral option is registering a significant uptake in this first year of its launch. Given the limitations of the available options, there remains significant unmet need for the treatment of PPD, especially for rapid relief of symptoms.
Differentiated bioidentical oral LPCN 1154 represents a compelling opportunity with significant and growing market potential with strong pharmacoeconomic justification, works factory pricing and coverage. In summary, next slide, Lipocine is developing a product with a paradigm changing potential to successfully treat postpartum depression. LPCN 1154, comprising bioidentical neuroactive steroid, if approved, is designed to provide a rapid relief option that restores level of this mood-stabilizing neuroactive steroid consistent with the third trimester of pregnancy levels and could be a therapy option that results in significantly improved outcomes for women and the family suffering from postpartum depression. Furthermore, breastfeeding limitations, if any, would be of short duration due to treatment duration of only 48 hours and is not expected to interrupt mother's milk production.
Besides being a significant market opportunity with ultra-short treatment duration with expected robust efficacy via a convenient oral route, LPCN 1154 has the potential to establish a new standard of care should it get approved. Following our discussions with FDA, we are now conducting a single clinical trial as Ben discussed, and we anticipate using the data from this study to support an NDA submission targeted in mid-2026. Before I wrap up, let me briefly discuss the potential utility of LPCN 1154 or brexanolone for other depression indications. Next slide. I would like to point out that PPD is an episodic form of major depressive disorder. Given the novel mechanism of action, if that's proven, oral bioidentical brexanolone with known safety profile has significant promise for treating MDD by providing faster relief relative to currently available options for MDD, which take weeks to take effect.
Moreover, LPCN 1154 has a potential to treat treatment-resistant depression by helping patients who are refractory to currently available options. This also represents a significant unmet need as approximately 3 million patients in the U.S. have treatment-resistant depression. With this, we conclude our prepared remarks for the day, and at this point we'll turn over the call to our operator for Q& A.
Thank you, Mahesh. Before we transition to verbal questions, I just had a few written-in questions that I'd like to pose to the group here. I'll start with the first one. Given the side effect concerns that have limited the market adoption of brexanolone, can you talk about the safety and tolerability profile of LPCN 1154 so far, and how does it compare to brexanolone?
Sure, Peter, I'll have Ben take that question. Yeah, go ahead.
Sure. Thanks both. As I mentioned in our presentation, we have dosed 58 unique participants, but this has been hundreds and hundreds of doses of LPCN 1154 administered, and we have observed very limited CNS depressant effects. All the adverse events reported have been mild to moderate in severity. We've had no serious or severe adverse events reported, no cases of excessive sedation or loss of consciousness. There has always been this question of what is the cause of excessive sedation and loss of consciousness noted in the clinical studies of IV brexanolone. In clinical practice, they really haven't been noted that frequently or at all to our knowledge. It may be more of a route and a formulation effect of the IV product rather than a class effect of these neuroactive steroids. To date, our safety has been, the drug has been very well tolerated.
We'll see in this phase III study, we're generating the safety data needed to confirm that in the target population.
Thanks. Awesome. Thank you. The other question that came in is, can you just talk about the key prescribing dynamics between OB/GYNs and psychiatrists in the treatment of PPD today?
Sure.
I'll give it a shot and then I'll pass it on to Dr. Deligiannidis to add anything she wants to. Our market research suggests that the prescribing is mostly done 50/50 between OB/GYN and psychiatrist with respect to a product that was oral and recently launched. Quite a few scripts have come from OB/GYN and that's because of the focus of detailing. We are pretty confident based on our market research that there is an opportunity for psychiatrists as a detailing target with this. I'll pass it on to Kristina if she wants to add anything.
Sure, yeah. Part of it is understanding where these patients are seen and cared for. As was noted, there's such increased screening now of postpartum depression. The obstetricians, because of their repeated interactions with pregnant and postpartum women, are key to the screening. The pediatricians too, when they're bringing their children for the well child checks. We have many types of physicians following up on them, but a lot of the treatment's happening within OB/GYN. That's because of those postpartum visits that they're seeing their patients for. If they've been screened throughout, then you can actually see if the depressive symptoms have risen, then they can initiate treatment. What has been, I think, a challenge, and I mentioned it, was that many women start the medicine but don't continue it. That's because still the SSRIs are the lion's share of prescriptions for PPD in the United States.
Because of that, because it takes an OB/GYN, and for me too, to titrate the SSRI or SNRI, we're looking at tolerability. If the patient's improving, there's many interactions, many visits to get them to sort of the key dose that they need to be on for efficacy. That's why so many don't get that adequate dose and many fall out of treatment and stop the medications before they even get to that adequate dose of an SSRI. Because of side effects, which I mentioned, are burdensome and they really get in the way of treatment. For women with postpartum depression, short acting alternatives sort of cut around those difficulties and the challenges that women are facing in getting accessible full treatment of their PPD. Shorter duration allows obstetricians to prescribe the medication within the realms and in the architecture of obstetrical practices.
I think that's been key to the increased use of these therapeutics for psychiatry. I can't speak for the field, but we're very excited about these rapid acting, novel therapeutics in the area of depression and other psychiatric illnesses. They too will be well poised to utilize novel therapeutics, including neuroactive steroid options.
Thanks.
Thanks, Mahesh. And Kristina. Kristina, maybe one more that seems directed at you, but can you talk about how you see the PPD treatment landscape evolving in maybe the next three to five years, given some of the things you just touched on?
Yeah. I've worked as a perinatal psychiatrist for the past 20 years and over this time, there's just been an evolution as well. The evolution has really been increased screening in obstetrics, family medicine, pediatric practices. In the past, like, you know, in the early days, most PPD was referred to psychiatry and psychology. It was really the patient would voice concerns about their feeling. I'm not feeling well, can you refer me to somebody? It wasn't detected typically in the obstetrics office, but the OBs would help get those patients to more specialty care, community mental health, psychiatry as such. I would just say over the past 20 years, there's been increasing efforts to train obstetric clinicians in PPD screening. This is not just obstetricians, but this is obstetric nurse practitioners, PAs, social workers, midwifery to screen, diagnose and now initiate treatment.
With the recent clinical practice guidelines, the reason why I get so excited about them is that it's a huge change from what the recommendations were in the past. I expect that this is going to give a huge thrust to that of screening. Increasingly, PPD is going to be treated outside of psychiatry with referrals to specialists like me for the more high risk individuals or complex cases where there's multiple diagnoses or medical comorbidities where we have to look at multiple things and for individuals who might need more long term treatment. I do see a shifting where it was sort of refer, refer, refer to screen, detect, initiate and then triage. Right. Who needs a subspecialist and who can be treated within primary care. We saw a really similar evolution in primary care. The lion's share of major depressive disorders is treated in primary care, not psychiatry.
I think we're following a similar path.
Thanks.
Fantastic. Thank you. At this time, we'll change over to some of the verbal questions. Our first question today comes from Scott Henry of AGP. Scott, you can unmute yourself.
Thank you and good morning. I'm not sure who this would be for, but historically how predictable is brexanolone in the clinic, particularly at, say, 60 hours for the HAM-D score? Just trying to get an idea of how the variability of this molecule is. A lot of antidepressants are not that predictable in the clinic. Perhaps you could give us an idea for this specific molecule. Thank you.
Thanks, Scott. I think we, going by the published data and zuranolone label, it just shows robust efficacy. I'll have Ben add on to comments. Go ahead, Ben.
Sure.
Yeah.
You know, Tony had shared a graph showing the responder rates. There's a very high responder rates. There were numerous studies done as part of the brexanolone development, and the results were fairly consistent across those studies in terms of reduction in HAM-D. That was actually across a range of severities of postpartum depression as well. I would say it's fairly consistent based on the data we have seen to date in terms of brexanolone having an effect and helping these women with postpartum depression.
Okay, that's great. I just have one follow-up question, then I'll hop into the queue. With regards to the phase III clinical trial, you mentioned a DSMB meeting in the second half of 2025. Will that involve an interim analysis for efficacy, or will that be strictly a safety analysis?
Yeah, Ben, go ahead.
Okay.
That'll be a safety analysis. Of course, the DSMB will be unblinded to treatment groups, and they will be able to look at the safety data to date in the study to give us a bit of a readout in terms of the safety of oral LPCN 1154 in this population in order to determine if the trial can proceed as planned or if any changes are needed. There will not be an interim efficacy readout in this study.
Okay, great. Thank you. I'll jump back in. Thank you.
Thank you, Scott. Our next question comes from Eduardo Martinez- Montes of H.C. Wainwright, please go ahead.
Hi there.
This is Eduardo on for Yi.
Quick question.
This might be for Kristina. You've mentioned a few times how SSRIs are generally the first line of therapy in PPD. There's obviously a lot of advantages to using these faster acting, you know, drugs like zuranolone. I'm curious what the rationale is for using SSRIs. Is it just kind of tradition set in their ways or what's the rationale for physicians prescribing?
Yeah, so there are multiple things. I think that part of it is that, you know, zuranolone was FDA approved in 2023. I would say that the penetrance of brexanolone IV into, you know, into physician practice was very limited. There were only a limited number of REMS approved treatment sites across the country. You kind of had to know that and know how to operate that and send patients and refer them. It was very complicated to connect patients to those treatment sites. We're really talking about from 2023, you know, fall 2023 to today. I think it's still early. A lot of it is education, getting education to a myriad of prescribers, right, from OB/GYN to psychiatry to NPs, family practice. There are so many that could be, that are screening and are detecting PPD.
I think that, you know, what I have seen is that the SSRIs have just been so pervasive in treating all depression, sort of, you know, that many providers have become familiar and comfortable with, especially outside of psychiatry, with two or three antidepressants and continue to use the same antidepressants over and over. Because they have not had the training to, you know, look at other types of interventions. That's usually when, if, you know, we see a treatment failure in primary care, they come to psychiatry and we're able to look more broadly at other options. I think there's a lot of enthusiasm for these agents because they're so simple to use.
I think that with zuranolone, because it's the only FDA approved oral neuroactive steroid right now, it is going to see growth in this area, as with any oral neuroactive steroid that has a short, you know, treatment course. As I mentioned before, I think a benefit of these neuroactive steroids is that it fits sort of the life of the OB/GYN, the OB/GYN practice, how they bill, how they set up visits. While many OB/GYNs initiate treatment, the SSRIs, we just don't see those women really be on adequate treatment sometimes or for the duration that they need. There are some cost challenges. I think it was Dr. Patel shared the cost of zuranolone and there are some physicians who are, you know, for generic sertraline or other SSRIs, just say, you know what, I'm comfortable with it, it's inexpensive, just keep doing what I do.
I think there are many factors, but I think a lot of it is just time and provider knowledge of the available options that are available for PPD.
That's really helpful. Thanks so much. If I could have one other, I'm curious, obviously you have the 48-hour, if I understand correctly, duration of treatment. Is there any possibility that you would get deeper or more durable responses by extending that dosing period?
Yeah, thanks, Eduardo. Currently, our dosing regimen is based on confirmation of levels that were comparable to zuranolone, which had robust efficacy. I'll pass on to Ben to comment on durability. I think we are monitoring for 30 days, right?
Yeah, that's right, Matt. We're monitoring up to 30 days looking for the durability of the efficacy, which was again noted in the IV studies with this short duration treatment of 60 hours for the IV product. We do expect to see duration of efficacy out to 30 days. There are always research questions out there. There could be a longer treatment regimen. We've also discussed, you know, are there opportunities to treat more than once during an episode of postpartum depression for somebody who would have recurrence of PPD. In this study right now we are looking to test and see if this 48 hour dosing regimen is efficacious in the treatment of postpartum depression, as well as to see the durability of that effect out to 30 days.
I would say from a safety perspective, there's no limitation with regards to the duration of therapy. That's something, you know, down the road or post approval as we target other indications, we would want longer duration effects.
Got it.
Thank you so much, and thanks for the presentation.
Thanks, Eduardo.
Just one other additional follow up from Scott Henry of AGP.
Thank you for taking the follow up. I think this would be for Dr. Kristina Deligiannidis, not going to try that last name. It's pretty straightforward with regards to IV brexanolone versus zuranolone because IV brexanolone just had challenges in the marketplace in terms of administration. As someone that would treat patients based on the data, could you talk a little bit how you would compare oral brexanolone versus zuranolone and you know, how you would think about that kind of competition between those options. Thank you.
Yeah. I have extensive experience with IV brexanolone and oral zuranolone. I served as a study PI on all of the clinical trials that were done leading to FDA approval for those two products. I have zero experience with the product of discussion today. This will be hypothetical. I think this is, you know, if you were to do the market research maybe on me is what the question is. I know that some of that research was presented earlier. I think that, you know, for the rapid onset, it's really important for clinical. I would have to see how it, how this molecule behaves compared to zuranolone for the rapid onset. Obviously, we had time points to measure very frequently in those trials, the change in HAM-D very frequently once we started ramping up the IV brexanolone, which was different than in the oral. Right.
We had like day three, day eight. We didn't have those very early hours for comparison. The onset's going to be fast, right, especially when you compare it to sort of the mainstay of treatment for decades, the serotonergic antidepressants. If this is faster, fantastic. I think the treatment duration, like the 48 hours, can be very compelling for especially some women. If the data, which look very good for breastfeeding for the relative infant dose for brexanolone, and it looks good for zuranolone as well. If the oral brexanolone looks similar to IV brexanolone, that would be fantastic for women who are not able to pump and dump for a 14-day course of zuranolone. Is there a need to pump and dump with zuranolone? The NIH doesn't really advise us. It's not in the labeling. It just says it's a risk benefit analysis. It's a discussion.
It shouldn't bar women from breastfeeding. Nonetheless, even with education, women are hesitant. There are some prescribers that are hesitant too, because right now we don't have infant data. What happens is, while medications are in development, we're able to do the breastfeeding studies and lactation studies. It's the case reports that this database puts all together over the years of infant reports. For zuranolone, we just don't have that data yet because they've not been used in enough lactating women. We haven't, as academicians, written up those case reports of how women and their babies are doing with a shorter treatment course, though, even if a woman had to pump and dump until the medication cleared through breast milk, that physiologically you got just as a physician would be possible where 14 days, if somebody wanted to or needed to.
With zuranolone, the milk supply really diminishes because you're waiting for that to, you know, to come out at the milk supply. I think those are things. Also, we don't have medications that work for 100% of our patients. Right. For whatever percent of patients don't have that rapid response or remission. Right. We saw that not everybody responded or remitted with IV brexanolone or oral zuranolone. We're going to know right away, and we can have plans, you know, B, C, and whatever, ready to go. This provides just such a quick way of getting in there and bringing down depressive symptoms, bringing down risk that, you know, whatever your rapid acting therapeutic is, this is a way, this is where everybody is, and this is where the field is moving. I think that again, the 48 hour is going to increase adherence if this is efficacious.
Also, just anything about the breast, if that works out, that the RID is really similar to IV, that could be very beneficial for breastfeeding women because it's always a topic, OBs, psychiatrists, patients, and they get so many opinions from everybody. It doesn't matter on the education. Sometimes that really can make a difference.
Okay, great. Thank you. That's perfect.
Mahesh, one final corporate question. We can wrap things up here, but can you just touch base on if the FDA has formally agreed to using a single phase III to be sufficient for an NDA approval? Kind of complementing that, can you just talk about cash runway, and what funding, if any, might be required to get you to NDA submission and beyond?
Yeah, sure. Thanks, Peter. First, I'll address the financials question. This trial is fully funded, and conducting and executing the trial won't really change our historic burn rate. That's about roughly $3 million a quarter. Through extensive bidding and contracting, we were able to, with a quality CRO, get this study going. With regards to single study, as Ben mentioned, that's based on the FDA feedback, and I'll have Chidu, you know, interacting with the FDA for this product, jump in and want to add any comments.
Thanks, Mahesh. Yes, based on our meeting with the FDA, FDA voluntarily recommended us to do a single phase III study, safety and efficacy as Ben mentioned, along with the supporting data from the dosing confirmation study, and they said that should suffice for the NDA submission.
Wonderful. Thank you, Mahesh. I'll turn it back to you for any final closing remarks, and then we can wrap things up.
Oh, thanks, Peter. Yeah, this concludes our prepared remarks. I'll thank Peter and all of you for participating in this event today. Appreciate it. Thanks.
Good day ladies and gentlemen and welcome to the call to discuss the neurobiology of postpartum depression. The treatment landscape in LPCN 1154, a short duration treatment option for PPD which is currently in phase III. 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. Dr. Patel is joined by Dr. Deligiannidis, Professor and Director, Women's Behavioral Health, Zucker Hillside Hospital, Northwell New York. In addition to Dr. Deligiannidis, Lipocine's Medical Director, Dr. Anthony DelConte and the company's Vice President of Clinical Development, Dr. Benjamin Bruno will be presenting. Dr.
Chidu Chidambaram, the company's Vice President of Research and Product Development is also online and will be available during the Q& A session. The presentation to accompany today's discussion was released by Lipocine earlier today, is available on the corporate website at www.lipocine.com and has been filed on Form 8-K with the SEC and is available on the SEC's website at www.sec.gov. An archive of this webcast will be made available on the website later today. I will now turn the call over to Dr. Mahesh Patel. Mahesh, please go ahead.
Thanks, Peter. Good morning, everyone, and thanks for joining. I'm Mahesh Patel, President, CEO, and Co-Founder of Lipocine. Today we'll discuss a potential paradigm shifting 48-hour treatment option for postpartum depression, also known as PPD, a serious condition in need of rapid relief. PPD can be a life-threatening condition, especially in severe cases. Currently, in the U.S. alone, annually, about a quarter million women are diagnosed with PPD and about 80,000 are seeking intervention. First, I would like to go over today's agenda. Following my introduction, Dr. Deligiannidis will discuss the PPD landscape. Dr. Deligiannidis' presentation will be followed by a discussion on LPCN 1154, target product and label attributes by Dr. Anthony DelConte, and followed by Dr. Benjamin Bruno, our Vice President of Clinical Development. We'll talk about the development program and next steps. I'll provide some concluding remarks and then open up the call for Q&A.
Before we get into the discussion, I'd like to remind you that certain statements we'll be making in this presentation are forward-looking statements within the meaning of the Private Securities Litigation Reform Act. Also note, no material non-public information about a publicly traded issuer of security will be discussed during the webcast. No solicitation for purchase or any securities will be made during the webcast and the meeting. Participants and any materials shared during the meeting have been authorized by the company. Before we dive into today's discussion, I'd 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. They're all based on our proprietary oral delivery technology.
This pipeline includes our most advanced candidate, that's LPCN 1154 for postpartum depression, which we anticipate submitting an NDA in mid-2026 and is the topic of today's discussion. Other key therapeutic candidates in our pipeline include LPCN 2401 for obesity management, comprising a novel bioidentical androgen that is a physiological regulator of myostatin. We plan to initiate a phase II proof-of-concept study with LPCN 2401 as an adjunct to a GLP agonist to enable quality weight loss via improved body composition in obesity management. In addition, our pipeline includes LPCN 1148 with groundbreaking positive phase II results demonstrating improvement in sarcopenia and lower recurrence of hepatic encephalopathy events in patients with decompensated cirrhosis. Let's get started on today's topic with some background on oral enablement of brexanolone, the active ingredient in LPCN 1154. Next slide.
Brexanolone, also known as allopregnanolone, is a poorly water soluble neuroactive steroid despite proven robust efficacy in PPD within IV route. The development of effective oral delivery of brexanolone has historically been a significant barrier to patient preferred oral therapy option. Our delivery technology presents brexanolone for most effective absorption by efficient transportation across the aqueous barrier layer through a proprietary oral delivery technology which is validated by an approved product, TLANDO. On the market, the first effective oral delivery of brexanolone has been achieved by Lipocine and as Dr. Bruno will describe later today, now it's my pleasure to introduce you to our expert on PPD, Dr. D eligiannidis. She's a Professor at Feinstein Institute for Medical Research in New York and Professor of Psychiatry, Molecular Medicine and Obstetrics and Gynecology at Donald and Barbara Zucker School of Medicine also in New York, Dr. Kristina Deligiannidis. Please go ahead.
Thank you so much.
Next slide.
It's a pleasure to provide a synopsis today on the PPD treatment landscape.
Next slide.
Start off with [CSARMA] relations and affiliations.
Next slide, thank you.
In the U.S., perinatal mental health disorders, including perinatal depression, are among the most common complications of pregnancy in the year after delivery, affecting one in five women globally. Rates of perinatal depression, i.e., depression occurring either in pregnancy or in the year after delivery or PPD, are one in four. The cost of not treating perinatal depression, which is often comorbid with anxiety amongst U.S. births, is $14.2 billion annually, with the average cost per affected mother-child dyad through age five being about $32,000. These costs, as you can see, some of these factors are here listed below, but they're due to these and some additional ones that are not listed as well. For many years, professional organizations have recommended screening for depression both in pregnancy and the postpartum period. Recently, and very excitedly, in 2023, the American College of Obstetricians and Gynecologists updated their clinical practice guideline.
ACOG now recommends screening for depression and anxiety using a validated scale during pregnancy at the initial prenatal visit, so when they first show up to prenatal care, and then again later in pregnancy and at a postpartum visit. The guideline additionally calls for increased diagnosis and initiation of treatment and referral to community mental health care. These updated guidelines will result in increased screening and initiation of pharmacotherapy by OB/GYNs, and we've seen increased screening that was evident even before these guidelines were issued. I noted a study here that shows those increased trends. In the period from 2016 to 2018, about 70% of postpartum women do start treatment for PPD. However, far fewer receive what we consider adequate dose and duration of treatment.
By this we mean women may not receive the adequate dose of the antidepressant to achieve the full antidepressant effect, or they may not stay on the antidepressant for as long as they need to to fully recover or stay well.
Next slide.
Depression during pregnancy and PPD are associated with many adverse maternal, obstetrical, infant and child developmental outcomes that are adverse. I listed only a few examples here, but they include decreased maternal functioning and symptoms of psychosis or suicide ideation, which may lead to psychiatric hospitalization or maternal death by suicide. Untreated depression worsens other medical conditions including diabetes and hypertension, and untreated depression leads to worse birth outcomes. PPD is also associated with poor maternal infant bonding, lactation failure, or unplanned weaning and impair a child cognitive, behavioral and emotional development.
Next slide.
As I noted, PPD is a major depressive disorder, a major depressive episode that has onset either in pregnancy or after delivery. It's important to point out that PPD is not the baby blues. The baby blues is not a clinical diagnosis and it's experienced by approximately 80% of women in the first two weeks following delivery. Although it can include fluctuation of mood, it resolves on its own without treatment and does not impair functioning. I'd like to share a clinical example of how PPD presents just to have clarity. An example would be Abby. She's a 34-year-old married female with a history of depression and anxiety who presented for clinical care eight weeks after delivering her second child. Her mood was well prior to and during pregnancy, but she developed severe depressive symptoms soon after delivery.
She reported constant sadness with crying spells, feelings of hopelessness that she'd never get better and that this was the deepest depression she ever had. She felt helpless and worthless with intense guilt. She felt no connection with her baby and it took hours to fall asleep due to ruminative worry. She was so exhausted that she didn't have the energy to brush her teeth or shower and she could not care for her infant or her toddler. She experienced significant weight loss since her delivery. She was weighing less than her pre-pregnancy weight when we saw her. She no longer sensed hunger so her husband had to urge her to eat small snacks throughout the day. Her body felt weighed down and she could not concentrate. During her interview she stated, I don't know how much longer I can fight this.
I just want to disappear so that the pain will go away. Next slide. How can we help, Abby? For decades, psychotherapies and the serotonergic or traditional antidepressants have been the cornerstone of PPD treatment. We have strong scientific evidence that a variety of psychotherapies or talk therapies can be used as treatment for mild to moderate PPD. The serotonergic antidepressants may be used alone or in combination with psychotherapy for moderate to severe PPD. A recent meta-analysis of the 11 postpartum RCTs for SSRIs concluded that there may be a benefit of SSRIs over placebo in both depression response, which is a 50% or more improvement in depression severity, and in remission rates at 5 weeks- 12 weeks.
Follow up. Next slide.
There are challenges with the use of traditional serotonergic antidepressants for postpartum depression. They mirror many of the challenges that we have with their use in major depressive disorder outside of the postpartum period. Serotonergic antidepressants are known to have a slow onset of action, taking on average six to eight weeks. For patients to experience depression relief or improvement, we prescribe SSRIs and SNRIs for several months or longer, depending on the clinical situation. They're associated with low rates of response in remission, and many patients experience bothersome side effects. The side effects listed here are some of the more common side effects of serotonergic antidepressants and in many women can lead to premature antidepressant discontinuation.
Next slide.
I will transition to the neuroactive steroid based antidepressants for the treatment of PPD. I'd like to review just a couple of slides on their biology. Neuroactive steroids are natural or synthetic steroids. They're made from cholesterol centrally in the brain, but also peripherally in the ovaries, the placenta, the testes, the adrenal glands. They are positive allosteric modulators of the GABAA receptor. What this means is that they enhance inhibition of the postsynaptic neuron by facilitating negatively charged chloride ions to flow into the neuron. We have decades of preclinical research that indicate that these neuroactive steroids, especially the best studied is allopregnanolone, have important roles in modulating brain responses to both acute and chronic stress. This is really important because depression is a stress disorder.
Next slide.
Neuroactive steroids enhance both tonic and phasic inhibition through their interaction with two types of GABAA receptors, synaptic and extrasynaptic receptors. GABAA receptors are comprised of five different components, which you can see in the figures here. The composition and configuration of these five receptor components determines the pharmacology and the location of those GABAA receptors in the brain, and this provides selectivity for what they bind and where. Preclinical data suggests that the delta component containing extrasynaptic receptors are important in both the cause of PPD and the mechanism of allopregnanolone's antidepressant effect. Unlike benzodiazepines, which also bind GABAA receptors, neuroactive steroids bind both synaptic and extrasynaptic GABAA receptors and do not bind the benzodiazepine binding site. Next slide.
In summary, under stressful life conditions, failure of the brain's GABAergic system to adapt to physiologic or abnormal neuroactive steroid levels may lead to brain circuit dysfunction in areas important for emotional regulation or resulting in clinical PPD.
Next slide.
The FDA approval of IV brexanolone in 2019 was a breakthrough for the field. It was a first-in-class antidepressant, had rapid antidepressant actions, and those were maintained even after the acute 60-hour treatment course was complete. However, IV administration of brexanolone mainly required patients to come into the hospital for a 72-hour inpatient stay. The cost of both the medication and the inpatient stay and the logistics of administration really ultimately limited access to patients. In the IV brexanolone studies, loss of or altered state of consciousness occurred in 4% of patients. IV brexanolone was prescribed through a REMS safety program. The company that developed brexanolone then developed zuranolone, a synthetic structural analog of allopregnanolone, which could be dosed orally once daily for 14 days at home. It was FDA approved for PPD in 2023.
IV brexanolone was withdrawn from the clinical market, I believe due to the availability of oral zuranolone and not due to safety or efficacy reasons.
Next slide.
For the clinical characteristics, neuroactive steroid antidepressants are characterized by rapid onset of action measurable within days. Zuranolone does not require up or down titration, though IV brexanolone did. Neuroactive steroids have a different side effect profile compared to serotonergic antidepressants, which is limited to the time around that short treatment course, which is unlike the more chronic dosing we use SSRIs. I mentioned the common side effects of SSRIs and SNRIs, including weight gain, sexual dysfunction, insomnia, and emotional blunting. These are not reported with neuroactive steroid antidepressants. The most common side effects for zuranolone include sedation and dizziness, diarrhea, and fatigue. IV brexanolone had a boxed warning for excessive sedation and sudden loss of consciousness. Zuranolone has a boxed warning for impaired ability to drive or engage in other potentially hazardous activities.
Next slide.
Thank you. For many women with PPD, the safety of antidepressants while breastfeeding is a very important consideration. The National Library of Medicine at the NIH maintains a wonderful database on drugs and lactation and we use this all the time clinically to assess the safety of medications in breastfeeding. A relative infant dose, that's the weight-adjusted percentage of the maternal dose of less than 10% is considered compatible with breastfeeding. Here you can see on the left the RIDs for some of the most common antidepressants prescribed for PPD. The relative infant dose for brexanolone is between 1% and 2% and the relative infant dose for zuranolone is less than 1%, indicating very low passage into the breast milk.
According to NIH LactMed, this database, because of the low amounts of brexanolone or zuranolone in the milk, neither would be expected to cause adverse effects in breastfed infants and if either required by the mother, it's not a reason to discontinue breastfeeding. However, until more data are available, LactMed recommends that zuranolone should be used with careful infant monitoring for excessive sedation during breastfeeding, especially in newborn or preterm infants. Zuranolone's 14-day treatment course may be problematic for some breastfeeding women since it'd be challenging to pump and dump the breast milk for that duration. For those women who want to avoid 100% of medication exposure through the breast milk.
Next slide.
In summary, PPD is common. It's associated with myriad adverse outcomes for mother and child. Oral neuroactive steroid antidepressants are rapid acting medications that require a shorter course of treatment without titration, and they're associated with time limited side effects. Thank you for your attention. I'll now turn it over to Dr. Tony DelConte. Dr. DelConte is an OB/GYN by training and is Lipocine's Medical Director. Thank you.
Thank you. Dr. Deligiannidis, before Dr. Benjamin Bruno shares Lipocine's clinical development plans, I want to provide some additional patient and physician insights on the limitations of current therapies and the product profile of LPCN 1154. As we just heard from Dr. Deligiannidis, it's important to consider the significant medical, social, and economic impact of how postpartum depression, a condition that affects many pregnancies. Let's explore how LPCN 1154 might make a difference in families affected by PPD. As discussed earlier, screening and treatment for postpartum depression are increasingly recognized in clinical guidelines. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists advocate for routine screening during pregnancy and the postpartum period. Notably, ACOG's approach allows for diagnosis without a structured clinical interview, using validated questionnaires instead. This flexibility can lead to earlier identification and treatment of PPD.
The recommendation for brexanolone or zuranolone within the first year postpartum highlights the urgency of addressing this condition. Early diagnosis is crucial as it could significantly impact the well-being of both the mother and the infants. Insights from market research reveal some important observations from OB/GYNs and psychiatrists regarding postpartum depression. Patients with a history of major depressive disorder are at a higher risk for developing PPD, yet many feel unprepared to discuss their symptoms. Both OB/GYNs and psychiatrists can conduct screening, but OBs will take the lead in diagnosing PPD and psychiatrists are referred and involved in more severe cases. There has historically been a preference for SSRIs as a first-line treatment practice, but there's a clear demand for safer and more effective options. Recently, a growing number of prescribers are shifting their practice toward a product approved specifically for PPD.
Healthcare professionals are particularly focused on dosing and speed of symptom relief when considering new treatments. Patient observations provide valuable insight into the challenges faced by those dealing with postpartum depression. Concerns about side effects and the stigma of taking antidepressants often hinder open discussions about symptoms. Many patients experience a less than adequate follow-up, leading to low adherence to treatment plans. The desire for faster relief from symptoms is evident as current options often fall short of expectations. Additionally, limitations such as driving restrictions and breastfeeding considerations can deter patients from accepting treatment. Understanding these patient perspectives is essential for developing more effective and acceptable treatment options. The efficacy of brexanolone in the treatment of postpartum depression has been well established in clinical studies, as illustrated in the accompanying graph.
Treatment with brexanolone is associated with significant reductions in the Hamilton Depression Rating Scale from baseline, and remission rates are also shown here. In addition to remission, researchers have assessed response rates and other clinical outcomes not shown here to further evaluate treatment efficacy. These data highlight the therapeutic value of brexanolone and underscore the potential impact of an oral formulation in improving clinical outcomes for patients with PPD. The low percentage of patients currently treated with oral neuroactive steroids, as seen on the left panel, suggests a gap in awareness or accessibility that could be addressed on the right panel. Data on NAS users for treating PPD reveal that a significant majority have not previously received treatment for PPD, and these findings highlight a potential opportunity for outreach and education regarding available treatment options.
As we evaluate the market potential, it's important to consider how we can support access to effective treatments for postpartum depression. The product profile of LPCN 1154 is designed to address critical unmet need in treating PPD. As we heard, as a positive allosteric modulator of the GABAA receptor, it binds to both postsynaptic and extrasynaptic sites different from the benzodiazepine, and its unique formulation allows for oral administration without the need for any titration or tapering, making it user friendly. The 48-hour outpatient dosing regimen is a significant advantage as it eliminates the need for hospital stays and potential dosing errors. The innovative Lipocine proprietary oral delivery technology that enhances drug absorption allows for oral delivery and it's also its differentiated product attributes. Let's discuss now how these features position LPCN 1154 as a possible game changer in PPD treatment.
LPCN 1154 offers a viable alternative to current therapies for postpartum depression. This slide compares the target profile of LPCN 1154 with existing treatments, highlighting its unique points of differentiation. Unlike traditional SSRIs/SNRIs, which have longer onset times and lower remission rates, LPCN 1154 should provide faster onset of action and a higher remission rate within days. The oral administration route is a significant advantage. The data presented here, including projected outcomes based on previous studies, position LPCN 1154 as a potential preferred option for the treatment of PPD. Would now like to turn it over to Dr. Ben Bruno to discuss the development status and next steps for LPCN 1154. Ben, thanks.
Thanks Tony. I'm now going to cover the developmental history of LPCN 1154, including the design and updates on the phase III study. As Tony just highlighted, the molecule brexanolone is highly efficacious in the treatment of postpartum depression. However, the previously FDA approved product has only been available via 60 hour IV infusion, which limited patient access and commercial success. We first set out to determine if we could enable the oral bioavailability of brexanolone using Lipocine's proprietary oral delivery technology. Next slide. To that end, we initially performed two formulation screening studies in postmenopausal women. We found both our capsule and tablet formulations enabled the oral bioavailability of brexanolone and that the tablet formulation allowed for higher daily doses. Further, brexanolone exposure increased with dose and was higher with post meal administration. All other studies discussed here were carried out with the tablet formulation.
Next, after confirming oral enablement, we proceeded to perform some dose finding studies in postmenopausal women. The first was a three arm crossover study that included two LPCN 1154 dosing regimens as well as an IV brexanolone. We found that the multidose oral regimens were both well tolerated and resulted in similar brexanolone exposure as the IV product administered per the label. However, we determined that it would be necessary to modify the dose and dosing regimen slightly in order to better match the blood levels of the IV brexanolone product. To that end, we conducted an additional single arm study with the to be marketed dose and dosing regimen, which allowed us to confirm the dosing regimen to be used in future studies.
Next, if we look at the data across the previously discussed studies, you can see that there was dose linear exposure across all of the single and multi dose regimens evaluated. In the left panel are the data for the single dose studies showing linear dose response for Cmax and total exposure AUC with doses ranging from 27 mg- 500 mg, and on the right are the data for the multi dose studies showing linearity with regimens of 300 mg, 400 mg, and 500 mg doses. These linear dose responses demonstrate that a dose and regimen can be selected to fit a desired brexanolone exposure profile. Next, after completing the dose finding studies, the next step was a dosing regimen confirmation study with IV brexanolone. This allowed us to determine if the LPCN 1154 dosing regimen results in comparable exposure as the approved efficacious IV product.
This was a standard two period crossover design that enrolled 24 healthy postmenopausal women. Half were randomly assigned to receive LPCN 1154 during the first period and half received IV brexanolone administered per the product label at a maximum dose of 90 micrograms per kilogram per hour. After a washout period, the participants returned for the second dosing period where they received the alternate intervention.
Next.
The results are presented here. LPCN 1154 met all standard bioequivalence criteria to IV brexanolone. Standalone standard bioequivalence criteria require that the 90% confidence interval of the geometric mean ratio of the test to reference product is within 80%- 125%. As you can see, this was met for all three standard criteria: Cmax, AUC0-∞ , and AUC0-t . LPCN 1154 was well tolerated with no sedation or somnolence events observed. All adverse events reported were mild to moderate in severity, and no event was reported by more than two participants. Next, if you look at the safety of oral brexanolone in our clinical program to date, you can see that LPCN 1154 is well tolerated. In total, 58 unique participants have been dosed with LPCN 1154 in pharmacokinetic studies.
On the left-hand panel, you can see that there were low rates of CNS depressant-related events with no instances of excessive sedation or loss of consciousness. On the right are the non-CNS depressant events, the most common of which was venipuncture site reaction related to the blood draws for pharmacokinetic sampling. All adverse events were mild to moderate in severity. There have been no serious or severe adverse events reported with this encouraging safety profile and establishment of a dosing regimen based on pharmacokinetic bridge to IV brexanolone. The next step is completing a phase III efficacy study, and I'll share some details of that on the next slide. The phase III trial is a two-arm outpatient randomized blinded placebo-controlled study in women with severe postpartum depression. The study is designed to enroll approximately 80 women age 15 and above.
Participants will be randomized one to one to receive either LPCN 1154 or placebo. The duration of treatment administration is 48 hours utilizing the dose and regimen confirmed in the dosing regimen study. The primary endpoint, change from baseline in HAM-D, will be evaluated at 60 hours post first dose. Additional endpoints being evaluated include another measure of depression as well as anxiety evaluation. Safety, tolerability, and efficacy will also be evaluated through day 30 of the study. Next slide, we believe the study will yield positive efficacy findings for LPCN 1154 for a few reasons. First, the molecule brexanolone has previously demonstrated efficacy as a treatment for postpartum depression. Second, as this study utilizes the same dose and dosing regimen as was used in the prior dosing regimen confirmation study, the levels of brexanolone are expected to be similar to those achieved with the IV product.
Third, the study size, duration, and population are similar to those of the IV infusion products. phase III study, we initiated the study in late March of this year and the first patient was dosed in June. The first data and Safety Monitoring Board meeting is expected to occur this year, and top line efficacy and safety data are expected in the second quarter of 2026. Next, I'll share some regulatory updates in terms of the clinical development plan. The FDA has agreed with our plan for a single phase III study to be sufficient to support NDA submission, provided positive results, of course. Further, FDA has reviewed and provided feedback on the phase III design we submitted, which included at-home dosing without the need for continuous medical monitoring. The dosing regimen confirmation study will act as supporting data in this submission for clinical pharmacology and labeling studies.
We previously discussed the single and multi-dose PK studies in postmenopausal women, but we also completed a PK study in women with postpartum depression. The latter shows that brexanolone levels were similar in the two populations, women with PPD and postmenopausal women. We also completed a food effect study, which informed our administration. In the phase III study, patients are being instructed to take the product with fat-containing food or snack. For non-clinical development, the 505(b)(2) pathway allows us to leverage much of the data previously generated during the development of IV brexanolone. Therefore, limited additional studies are needed, including a repeat dose local toxicity study and in vitro studies, including plasma protein binding and GABA binding. For manufacturing, three registration batches have been manufactured and have adequate stability for submission. Now I'll turn it back to Mahesh for his concluding remarks.
Thanks, Ben. Why LPCN 1154 is a compelling opportunity. Here are some of the reasons. PPD is a life-threatening condition, as mentioned earlier, especially in severe cases where these mothers have homicidal or suicidal tendencies, and approximately 10%- 12% of births could result in PPD, and that number holds good worldwide. Currently, in the U.S. alone, as I mentioned earlier, about a quarter million women are diagnosed with postpartum depression. About 60,000- 80,000 are seeking active intervention. Another thing to note is that awareness and diagnosis are on the rise. A recently launched neuroactive steroid comprising of an oral option is registering a significant uptake in this first year of its launch. Given the limitations of the available options, there remains significant unmet need for the treatment of PPD, especially for rapid relief of symptoms.
Differentiate bioidentical oral LPCN 1154 represents a compelling opportunity with significant and growing market potential with strong pharmacoeconomic justification for factory pricing and coverage. In summary, next slide, Lipocine is developing a product with a paradigm-changing potential to successfully treat postpartum depression. LPCN 1154, comprising bioidentical neuroactive steroid, if approved, is designed to provide a rapid relief option that restores level of this mood-stabilizing neuroactive steroid consistent with the third trimester of pregnancy levels and could be a therapy option that results in significantly improved outcomes for women and the family suffering from postpartum depression. Furthermore, breastfeeding limitations, if any, would be of short duration due to treatment duration being only 48 hours and is not expected to interrupt the mother's milk production.
Besides being a significant market opportunity with ultra-short treatment duration with expected robust efficacy via a convenient oral route, LPCN 1154 has the potential to establish as a new standard of care should it get approved. Following our discussions with the FDA, we are now conducting a single clinical trial as Ben discussed, and we anticipate using the data from this study to support an NDA submission targeted in mid-2026. Before I wrap up, let me briefly discuss the potential utility of LPCN 1154 oral brexanolone for other depression indications. Next slide. I would like to point out that PPD is an episodic form of major depressive disorder. Given the novel mechanism of action, and that's proven, oral bioidentical brexanolone with known safety profile has significant promise for treating MDD by providing faster relief relative to currently available options, which take weeks to take effect.
Moreover, LPCN 1154 has a potential to treat treatment-resistant depression by helping patients who are refractory to currently available options. This also represents significant unmet need, as approximately 3 million patients in the U.S. have treatment-resistant depression. With this, we conclude our prepared remarks for the day, and at this point, we'll turn over the call to our operator for Q and A.
Thank you, Mahesh. Before we transition to verbal questions, I just had a few written-in questions that I'd like to pose to the group here. I'll start with the first one. Given the side effect concerns that have limited the market adoption of brexanolone, can you talk about the safety and tolerability profile of LPCN 1154 so far, and how does it compare to brexanolone?
Sure, Peter, I'll have Ben take that question. Go ahead, sure.
Thanks both. As I mentioned in our presentation, we have dosed 58 unique participants, but this has been hundreds and hundreds of doses of LPCN 1154 administered and we have observed very limited CNS depressant effects. All of the adverse events reported have been mild to moderate in severity. We've had no serious or severe adverse events reported, no cases of excessive sedation or loss of consciousness. There has always been this question of what is the cause of excessive sedation and loss of consciousness noted in the clinical studies of IV brexanolone. In clinical practice they really haven't been noted that frequently or at all to our knowledge. It may be more of a route and a formulation effect of the IV product rather than a class effect of these neuroactive steroids.
To date, our safety has been the drug has been very well tolerated and, you know, we'll see in this phase III study we're generating the safety data needed to confirm that in the target population.
Thanks.
Awesome. Thank you. The other question that came in is can you just talk about the key prescribing dynamics between OB/GYNs and psychiatrists in the treatment of PPD today?
Sure, I'll give it a shot and then I'll pass it on to Dr. Deligiannidis to add anything she wants to. Our market research suggests that, you know, the prescribing is mostly done 50/50 between OB/GYN and psychiatrist. With respect to, you know, a product that was oral and recently launched, quite a few scripts have come from OB/GYN and that's because of the focus of detailing. We are pretty confident based on our market research that there is an opportunity for psychiatrists as a detailing target with this. I'll pass it on to Kristina if she wants to add anything.
Sure, yeah. Part of it is understanding where these patients are seen and cared for. As was noted, there's such increased screening now of postpartum depression. The obstetricians, because of their repeated interactions with pregnant and postpartum women, are key to the screening. The pediatricians too, when they're bringing their children for the well child checks. We have many types of physicians following up on them, but a lot of the treatment's happening within OB/GYN. That's because of those postpartum visits that they're seeing their patients for. If they've been screened throughout, then you can actually see if the depressive symptoms have risen, then they can initiate treatment. What has been, I think, a challenge, and I mentioned it, was that many women start the medicine but don't continue it. That's because still the SSRIs are the lion's share of prescriptions for PPD in the United States.
Because of that, because it takes an OB/GYN, and for me too, to titrate the SSRI or SNRI, we're looking at tolerability. If the patient's improving, there's many interactions, many visits to get them to sort of the key dose that they need to be on for efficacy. That's why so many don't get that adequate dose and many fall out of treatment and stop the medications before they even get to that adequate dose of an SSRI because of side effects, which I mentioned are burdensome and they really get in the way of treatment. For women with postpartum depression, short acting alternatives sort of cut around those difficulties and the challenges that women are facing in getting accessible full treatment of their PPD. Shorter duration allows obstetricians to prescribe the medication within the realms and in the architecture of obstetrical practices.
I think that's been key to the increased use of these therapeutics. For psychiatry, I can't speak for the field, but we're very excited about these rapid acting, novel therapeutics in the area of depression and other psychiatric illnesses. They too will be well poised to utilize novel therapeutics, including neuroactive steroid options.
Thanks.
Thanks, Mahesh. And Kristina. Kristina, maybe one more that seems directed at you, but can you talk about how you see the PPD treatment landscape evolving in maybe the next three to five years, given some of the things you just touched on?
Yeah. I've worked as a perinatal psychiatrist for the past 20 years and over this time, there's just been an evolution as well. The evolution has really been increased screening in obstetrics, family medicine, pediatric practices. In the past, like, you know, in the, I'll call them the early days, most PPD was referred to psychiatry and psychology. It was really the patient would voice concerns about their feeling. I'm not feeling well, can you refer me to somebody? It wasn't detected typically in the obstetrics office, but the OBs would help get those patients to more specialty care, community mental health, psychiatry as such. I would just say over the past 20 years there's been increasing efforts to train obstetric clinicians in PPD screening. This is not just obstetricians, but this is obstetric nurse practitioners, PAs, social workers, midwifery to screen, diagnose and now initiate treatment.
With the recent clinical practice guidelines, the reason why I get so excited about them is that it's a huge change from what the recommendations were in the past. I expect that this is going to give a huge thrust of screening. Increasingly PPD is going to be treated outside of psychiatry with referrals to specialists like me for the more high risk individuals or complex cases where there's multiple diagnoses or medical comorbidities where we have to look at multiple things for individuals who might need more long term treatment. I do see a shifting where it was sort of refer, refer, refer to screen, detect, initiate and then triage. Right. Who needs a subspecialist and who can be treated within primary care. We saw a really similar evolution in primary care. The lion's share of major depressive disorder is treated in primary care, not psychiatry.
I think we're following a similar path.
Thanks.
Fantastic. Thank you. At this time, we'll change over to some of the verbal questions. Our first question today comes from Scott Henry of AGP. Scott, you can unmute yourself.
Thank you and good morning. I'm not sure who this would be for, but historically how predictable is brexanolone in the clinic, particularly at say 60 hours for the HAM-D score. Just trying to get an idea of how the variability of this molecule is. A lot of antidepressants are not that predictable in the clinic, but perhaps you could give us an idea for this specific molecule. Thank you.
Okay, thanks, Scott. I think we, going by the published data and zuranolone label, it just shows robust efficacy. I'll have Ben add on to comments. Go ahead, Ben.
Sure.
Yeah.
You know, Tony had shared a graph showing the responder rates. There's a very high responder rates. There were numerous studies done as part of the brexanolone development, and the results were fairly consistent across those studies in terms of reduction in HAM-D. That was actually across a range of severities of postpartum depression as well. I would say it's fairly consistent based on the data we have seen to date in terms of brexanolone having an effect and helping these women with postpartum depression.
Okay, that's great. Now just one follow up question, then I'll hop into the queue with regards to the phase III clinical trial. You mentioned a DSMB meeting in second half of 2025. Will that involve an interim analysis for efficacy or will that be strictly a safety analysis?
Yeah, Ben, go ahead.
That'll be a safety analysis. Of course, the DSMB will be unblinded to treatment groups, and they will be able to look at the safety data to date in the study to give us a bit of a readout in terms of the safety of oral LPCN 1154 in this population in order to determine if the trial can proceed as planned or if any changes are needed. There will not be an interim efficacy readout in this study.
Okay, great. Thank you. I'll jump back in.
Thank you, Scott. Scott, our next question comes from Eduardo Martinez- Montes of H.C. Wainwright, please go ahead.
Hi there, this is Eduardo on for Yi. Quick question. This might be for Kristina. You've mentioned a few times how SSRIs are generally the first line of therapy in PPD. There's obviously a lot of advantages to using these faster acting, you know, drugs like zuranolone. I'm curious what the rationale is for using SSRIs. Is it just kind of tradition set in their ways or what's the rationale for physicians prescribing?
Yeah, so there are multiple things. I think part of it is that, you know, zuranolone was FDA approved in 2023. I would say that the penetrance of brexanolone IV into physician practice was very limited. There were only a limited number of REMS approved treatment sites across the country. You kind of had to know that and know how to operate that and send patients and refer them. It was very complicated to connect patients to those treatment sites. We're really talking about from 2023, fall of 2023 to today. I think it's still early. A lot of it is education, getting education to a myriad of prescribers, right? From OB/GYN to psychiatry to NPs, family practice. There are so many that could be screening and are detecting PPD.
I think that what I have seen is that the SSRIs have just been so pervasive in treating all depression, that many providers have become familiar and comfortable with, especially outside of psychiatry, two or three antidepressants and continue to use the same antidepressants over and over. Because they have not had the training to look at other types of interventions, that's usually when, if we see a treatment failure in primary care, they come to psychiatry and we're able to look more broadly at other options. I think there's a lot of enthusiasm for these agents because they're so simple to use. I think that with zuranolone, because it's the only FDA approved oral neuroactive steroid right now, it is going to see growth in this area, as would any oral neuroactive steroid that has a short treatment course.
As I mentioned before, I think a benefit of these neuroactive steroids is that it fits the life of the OB/GYN, the OB/GYN practice, how they bill, how they set up visits. While many OB/GYNs initiate treatment, the SSRIs, we just don't see those women really beyond adequate treatment sometimes or for the duration that they need. There are some cost challenges. I think it was Dr. Patel shared the cost of zuranolone, and there are some physicians who, for generic sertraline or other SSRIs, just say, you know what, I'm comfortable with it, it's inexpensive, just keep doing what I do. I think there are many factors, but I think a lot of it is just time and provider knowledge of the available options that are available for PPD.
That's really helpful. Thanks so much. If I could have one other, I'm curious, obviously, of the 48-hour, if I understand correctly, duration of treatment, is there any possibility that you would get deeper or more durable responses by extending that dosing period?
Yeah, thanks, Eduardo. Currently, you know, our posting regimen is based on, you know, confirmation of levels that were comparable to zuranolone, which had robust efficacy. I'll pass on to Ben to kind of comment on durability. I think we're monitoring for 30 days, right?
Yeah, that's right, Matt.
We're.
We're monitoring out to 30 days, looking for the durability of the efficacy, which was again noted in the IV studies with this short duration treatment of 60 hours for the IV product. We do expect to see duration of efficacy out to 30 days. There are always research questions out there. There could be a longer treatment regimen. We've also discussed, you know, are there opportunities to treat more than once during an episode of postpartum depression for somebody who would have recurrence of PPD. In this study, right now we are looking to test and see if this 48 hour dosing regimen is efficacious in the treatment of postpartum depression, as well as to see the durability of that effect out to 30 days.
I would say from a safety perspective, there's no limitation with regards to the duration of therapy. That's something, you know, down the road or post approval as we target other indications. We would want longer duration, effects.
Got it.
Thank you so much, and thanks for the presentation.
Thanks everyone.
There is just one other additional follow-up from Scott Henry of AGP.
Thank you for taking the follow up. I think this would be for Dr. Kristina . Not going to try that last name. It's pretty straightforward with regards to IV brexanolone versus zuranolone, because IV brexanolone just had challenges in the marketplace in terms of administration. As someone that would treat patients based on the data, could you talk a little bit how you would compare oral brexanolone versus zuranolone and how you would think about that kind of competition between those options. Thank you.
Yeah, I have extensive experience with IV brexanolone and oral zuranolone. I served as a study PI on all of the clinical trials that were done leading to FDA approval for those two products. I have zero experience with the product of discussion today. This will be hypothetical. I think this is, you know, if you were to do the market research maybe on me is what the question is. I know that some of that research was presented earlier. I think that, for the rapid onset, it's really important for clinical. I would have to see how this molecule behaves compared to zuranolone. For the rapid onset, obviously we had time points to measure very frequently in those trials. The change in HAM-D very frequently once we started ramping up the IV brexanolone, which was different than in the oral. We had day three, day eight.
We didn't have those very early hours for comparison. The onset's going to be fast, especially when you compare it to sort of the mainstay of treatment for decades with serotonergic antidepressants. If this is faster, fantastic. I think the treatment duration, like the 48 hours, could be very compelling for especially some women. If the data, which look very good for breastfeeding, for the relative infant dose for brexanolone, and it looks good for zuranolone as well. If the oral brexanolone looks similar to IV brexanolone, that would be fantastic. For women who are not able to pump and dump for a 14-day course of zuranolone, is there a need to pump and dump with zuranolone? The NIH doesn't really advise us. It's not in the labeling. It just says it's a risk benefit analysis. It's a discussion. It shouldn't bar women from breastfeeding.
Nonetheless, even with education, women are hesitant and there are some prescribers that are hesitant too, because right now we don't have infant data. What happens is, while medications are in development, we're able to do the breastfeeding studies and lactation studies. It's the case reports that this database puts all together over the years of infant reports. For zuranolone, we just don't have that data yet because they've not been used in enough lactating women. We haven't as academicians written up those case reports of how women and their babies are doing with a shorter treatment course, though, even if a woman had to pump and dump until the medication cleared through breast milk. Physiologically, you get just as a physician would be possible where 14 days, if somebody wanted to or needed to.
With zuranolone, the milk supply really diminishes because you're waiting for that to, you know, to come out of the milk supply. I think those are things. Also, we don't have medications that work for 100% of our patients. For whatever percent of patients don't have that rapid response or remission, we saw that not everybody responded or remitted with IV brexanolone or oral zuranolone. We're going to know right away and we can have plans B, C, and whatever, ready to go. This provides just such a quick way of getting in there and bringing down depressive symptoms, bringing down risk that, you know, whatever your rapid acting therapeutic is, this is a way, this is where everybody is and this is where the field is moving. I think that again, the 48 hour is going to increase adherence if this is efficacious.
Also, just anything about the breast, if that works out, that the RID is really similar to IV, that could be very beneficial for breastfeeding women because it's always a topic OB/GYNs, psychiatrists, patients, and they get so many opinions from everybody. It doesn't matter on the education. Sometimes that really can make a difference.
Okay, great. Thank you. That's perfect.
Mahesh, one final corporate question and then we can wrap things up here. Can you just touch base on if the FDA has formally agreed to using a single phase III to be sufficient for an NDA approval? Kind of complementing that, can you just talk about cash runway, and what funding, if any, might be required to get you to NDA submission and beyond?
Yeah, sure. Thanks, Peter. First, I'll address the financials question. This trial is fully funded, and conducting and executing the trial won't really change our historic burn rate. That's about roughly $3 million a quarter. Through extensive bidding and contracting, we were able to, with a quality CRO, get this study going. With regards to single study, as Ben mentioned, that's based on the FDA feedback. I have Chidu interacting with the FDA for this product. Jump in and want to add any comments?
Sure.
Thanks.
Yes, based on our meeting with the FDA, FDA voluntarily recommended us to do a single phase III study, safety and efficacy, as Ben mentioned, along with the supporting data from the dosing confirmation study. They said that should suffice for the NDA submission.
Wonderful. Thank you, Mahesh. I'll turn it back to you for any final closing remarks, and then we can wrap things up.
Thanks, Peter. This concludes our prepared remarks. I thank Peter and all of you for participating in this event today. Appreciate it.
Thanks.