VistaGen Therapeutics, Inc. Aktie

Good day, everyone. Thank you for standing by. Welcome to the Vistagen Therapeutics Corporate Update Conference Call and Webcast. Please note that today's conference is being recorded. At this time, I'd like to turn the conference over to your host, Mark McPartland, Senior Vice President, Investor Relations at Vistagen. Mark, please go ahead.

Thank you, Michelle, and good morning, everyone. Welcome, and thank you for joining us. In a press release issued earlier this morning, Vistagen announced top line results and post-hoc analyses of data from our PALISADE-4 Phase III public speaking challenge trial, evaluating fasedienol for acute treatment of social anxiety disorder as well as our planned next steps in fasedienol program. The announcement is available in the Investors section of our website.

During today's call, we will briefly review the PALISADE-4 top line and post-hoc data, provide perspective on the findings within the broader fasedienol clinical development program and outline the company's planned regulatory and development plans. During today's call, we will make forward-looking statements regarding our business development programs, regulatory strategy, financial outlook and other matters based on our current expectations. These forward-looking statements speak only as of today and involve risks and uncertainties that could cause actual results to differ materially from those anticipated.

Additional information regarding these risks and uncertainties is included in our most recent filings with the SEC, including our annual report on Form 10-K and 10-Q, today's current report on Form 8-K. Except as required by law, we undertake no duty to update any forward-looking statements.

With the formalities out of the way, we welcome our stockholders, investment community and others joining us today. I'm joined on the call with Shawn Singh, our President and Chief Executive Officer; Dr. Angel Angelov, our Chief Medical Officer; and Josh Prince, our Chief Operating Officer.

Shawn will provide some opening remarks, and then Dr. Angelov will provide an overview of the primary and post-hoc analyses from our PALISADE-4 top line results and his perspectives on their significance, along with the full post-hoc data from our PALISADE program. Followed by a brief operational commentary and closing remarks by Shawn. After that, we'll open up the call for questions from the sell-side analysts. And with that, I would like to turn the call over to Shawn.

Thank you, Mark, and good morning, everyone. As disclosed in today's press release, PALISADE-4 did not achieve its primary or secondary endpoints in the overall trial population. Those results certainly were disappointing. However, our multiple post-hoc analyses of the data in patients with very severe social anxiety disorder amounting to slightly over half of the patients randomized in the trial demonstrates significant findings we believe are important from a clinical and regulatory perspectives. Today's call and the slide deck covered by our Form 8-K just filed this morning are intended to share those findings with you.

Although these findings do not change the primary outcome of PALISADE-4, they provide us important scientific insight into the broader fasedienol development program, and they have helped us inform our plans to meet with the FDA to discuss a transition from our previous registrational pathway for fasedienol in social anxiety disorder involving an acute symptom treatment to a potential registrational pathway focused on the overall treatment of social anxiety disorder over time.

Today's call has 2 key objectives: first, to review the PALISADE-4 results; second, to share the additional analyses we conducted and explain how those findings fit within the large body of data and totality of evidence generated across our development of fasedienol in social anxiety disorder over the years.

We will discuss how that data and evidence support our plan to meet with the FDA with the goal of mapping a clear registrational pathway forward for fasedienol to help improve the lives of patients with this highly prevalent disorder who have not seen a new FDA-approved treatment alternative in over 20 years. With that, it's my pleasure to turn the call over to our Chief Medical Officer, Dr. Angel Angelov, to walk you through primary and post-hoc data from PALISADE-4 and pooled post-hoc data from across the PALISADE program in patients with very severe social anxiety disorder. Angel?

Thank you, Shawn. Before reviewing PALISADE-4 specifically, I would like to briefly place today's results in the context of the broader PALISADE development program. The PALISADE program was designed to evaluate fasedienol as an on-demand acute treatment for social anxiety disorder using a standardized 5-minute public speaking challenge, a minute-by-minute assessment using the subjective units of distress scale, or SUDS, with a one-time drug administration model.

Across the PALISADE program, we've accumulated a substantial efficacy and safety database, including more than 1,500 exposed participants. Today's discussion focuses primarily on our PALISADE-4 trial, but our interpretations and current plans are informed by the complete body of evidence generated across the entire fasedienol development program, including the PALISADE program, Phase II studies, large open-label studies on an outpatient basis and Phase I electrophysiological studies. As Shawn mentioned, the primary analysis of PALISADE-4 did not achieve statistical significance on the primary or secondary endpoints in the overall trial population. These are the results we reported this morning, and I'd like to begin by reviewing those data.

In the overall study population of 238 patients, the least-squares mean change from baseline on the SUDS was minus 9.5 points for patients receiving fasedienol compared with minus 11.4 points for patients receiving placebo, resulting in a treatment difference of 1.9 points, which was not statistically significant.

Similarly, we did not observe statistically significant treatment difference between fasedienol and placebo on the secondary endpoints evaluated in the study, although there is a noticeable difference in the patient perspective on efficacy in the PGI-C data. Importantly, safety and tolerability data for fasedienol remained favorable, consistent with observations throughout the entire clinical development program. No new safety signals were identified, and the overall safety findings were consistent with previous placebo-controlled studies.

While the results in the primary analysis were not what we had hoped for, completing the primary analysis represented the first step in understanding the study. As is customary following any large Phase III trial, we conducted a comprehensive scientific review of the complete data set to better understand the findings and evaluate whether additional observations might help inform future development decisions.

I'd now like to provide important context for the additional analysis that follow. During the data review, we examined several factors, including the overall distribution of treatment responses, placebo variability, site operations, baseline disease characteristics and the consistency of treatment effects observed across the data set. That review identified several observations that we believe warranted additional evaluation.

The first of those observations is placebo response variability. We believe that is very important for understanding the overall study results. While the treatment effect observed among patients receiving fasedienol was generally comparable with prior studies, placebo responses exhibited greater variability, contributing to a broader distribution of outcomes.

We also observed notable differences between the mean and median placebo responses, indicating there's a relatively small number of extreme values for placebo that influence the overall distribution of placebo outcomes. That led us to a deeper exploration of placebo behavior related to severity subpopulations in the trial and in the context of the public speaking challenge, which is designed to detect an acute anxiolytic effect.

As noted, when we compare PALISADE-4 with prior studies in the PALISADE program, the level of improvement observed among patients receiving fasedienol remained relatively consistent. In contrast, greater variability appeared to be concentrated within placebo responses rather than the active treatment responses. In our subpopulation analysis, we focused on patients with very severe social anxiety disorder defined as having a baseline score on the Liebowitz Social Anxiety Scale, or LSAS, of 95 or greater at visit 1 screening. We wondered whether subjects having more severe anxiety would be less likely to show a large improvement on placebo. This very severe LSAS subgroup included 123 patients, just over half of the overall study population.

The LSAS is one of the most used clinician-rated measures of social anxiety disorder severity in clinical research and has served as the primary efficacy endpoint in the registrational trial supporting all currently approved pharmacologic therapies for the treatment of social anxiety disorder. In this post-hoc analysis of very severe social anxiety disorder patients, fasedienol demonstrated a nominally statistically significant improvement compared with placebo on the trial's primary efficacy measure. The least-square mean change from baseline in the SUDS score.

Patients receiving fasedienol achieved LS mean change from baseline of minus 12.8 points compared with only minus 3.7 points for placebo, representing a treatment difference of negative 9.1 points with a nominal p-value of 0.036. PGI-C percent responders, a patient-reported secondary endpoint also showed nominal statistical significance in this very high severity subpopulation.

The largest driver of efficacy for the post-hoc subpopulation was the filter for disease severity. The additional filters who saw ceiling effects and [indiscernible] improvement of placebo at Visit 2 when worsening anxiety is expected by the anxiety-provoking public speaking challenge contributed less but widened the separation of fasedienol from placebo.

We applied the same filter approach to a post-hoc pooled analysis, first for PALISADE 3 and 4, then for PALISADE 1, 3 and 4 and finally, for all 4 Phase III trials in the PALISADE program. The totality of data to date from the fasedienol development program, including the post-hoc pool data in the very severe patient subpopulation, supports the hypothesis that fasedienol's acute anxiolytic signal may be the most detectable when the study population has sufficient baseline trait anxiety like that in the very severe social anxiety subpopulation. And the endpoint is not overwhelmed by noise from the public speaking challenge.

These findings should be interpreted in the context of the overall data set for the development program. When viewed together with the favorable safety and tolerability data observed throughout the PALISADE program, our positive PALISADE-2 Phase III trial and other clinical evidence generated across the development program, we believe these data provide important scientific and clinical basis for discussions with the FDA regarding the potential future registrational pathway for fasedienol.

Before I turn the call back to Shawn to discuss our planned FDA engagement, I'd like to briefly comment on another important component of the overall development program, our accumulated safety knowledge. In addition to the efficacy data we've discussed, fasedienol development program has now accumulated a substantial safety database with more than 1,500 participants exposed to fasedienol, including more than 300 with at least 6 months of exposure and more than 100 with at least 12 months of exposure in outpatient settings.

No new safety signals have been identified in PALISADE-4, and the favorable safety and tolerability data have remained consistent throughout the clinical development program. We believe this safety database, together with the efficacy observations discussed today and the broader body of evidence generated across the PALISADE program provide important context for our planned discussions with the FDA regarding future development of fasedienol. With that, I'll turn the call back to Shawn.

Thank you, Angel. Evaluating the totality of evidence across the fasedienol development program with a goal of establishing a clear registrational pathway forward for this asset.

Based on the totality of data to date, our immediate priority is to engage with the FDA to discuss a plan to transition away from the acute treatment of social anxiety disorder measured by the SUDS to the treatment of social anxiety disorder measured by the LSAS, consistent with regulatory precedent supporting the 3 FDA-approved antidepressants for treatment of social anxiety disorder.

We plan to seek agreement to pursue a single trial registrational pathway with confirmatory evidence under the FDA's draft guidance to industry published just a little over a week ago. That trial would be designed to evaluate fasedienol's potential to treat social anxiety disorder over time in a Phase III outpatient trial with the LSAS as the primary endpoint.

Confirmatory evidence would include positive data from our PALISADE-2 Phase III trial, the data that we've shared with you today, our placebo-controlled Phase II clinical trials, LSAS related open-label data and the aggregate safety data Angel just discussed with you.

We also continue to expect top line results from the randomized portion of our Phase II repeat dose study later this quarter -- next quarter.

As we previously shared, the design of that study was informed by FDA feedback to evaluate repeat dosing, dosing interval, dose response and duration of effect. At the same time, we will remain financially disciplined based on our current operating plans and previously announced cost management initiatives we continue to expect our cash resources to support our operations into 2027.

Beyond fasedienol, we remain confident about and committed to advancing our broader Pherine pipeline, including preparations for the continued clinical development of our nonsystemic pherine, itruvone for major depressive disorder and refisolone for menopausal hot flashes.

We believe the totality of evidence from our fasedienol development program, including the post-hoc analysis and insights we've discussed with you today, support confidence in fasedienol's therapeutic potential to improve the lives of over 30 million individuals in the U.S. living day after day, most for many years, with the impact of social anxiety disorder has on their daily lives. We are grateful for all involved with PALISADE-4. Your participation made a difference, a very big difference, and we look forward to engaging with the FDA and updating investors as we move forward.

With that, I'll turn the call back to Mark to begin a brief Q&A period.

Thank you, Shawn. Operator, we are now ready to open the call for questions from the sell-side analysts participating today.

Thank you. [Operator Instructions] And the first question will come from Paul Matteis with Stifel. Your line is now open.

On the switch to the LSAS, can you talk about some of the historical data with fasedienol and LSAS?

I thought I remember that in some of the earlier studies, this was a more challenging endpoint or a less sensitive endpoint, which might be why you went with the SUDS.

My second question is just in this severe population subgroup, it looks like there might be a site excluded or certain patients excluded from that analysis. So maybe just talk about the rationale there.

And then third, I guess, given the lack of difference overall in the study, if the fact that there seems to be the signal in severe, does that mean that the mild -- in the milder population or the moderate to mild population placebo did better? And if so, how would you reconcile that?

Great. Thanks a lot, Paul. Appreciate the question. So your first question refers to, I think, the placebo-controlled Phase II crossover study. So I'll let Dr. Angelov address that.

Yes. So we did study in the Phase II program where beyond the SUDS that was used in that study, we also had LSAS assessment that came at the weekly intervals that the study was ongoing.

It was a 2-week study where patients received fasedienol or placebo. And after 2 weeks, they switched to the opposite group's drug.

So 2 weeks of fasedienol after that 2 weeks of placebo and then in the other arm, the opposite way. What we saw in that study was that the LSAS improved at a level that was statistically significant for a relatively small study that showed that LSAS did improve over time and really generated a lot of interest in the possibility of LSAS as a primary endpoint in future studies.

Paul, you might remember that was Dr. Liebowitz in that study. He's the innovator, of course, of the Liebowitz Social Anxiety Scale or the LSAS. And so that -- what we liked in that study was the folks that got the drug first before they crossed over to placebo.

We actually saw a carryover effect, which is consistent with how we think this drug's MOA operates, which is that you build confidence over time and your symptoms knock down in acute settings. And then as you continue to engage and not avoid your stressors, you see that confidence cognitively build over time.

Yes. To the second question, in the exclusions that we had, we had one site excluded. However, it was because of unreliable data, and it was all flagged before database lock. When we excluded that site, there was no change from placebo on the data that we're reviewing. We excluded the site unreliable data and not as part of the severe subpopulation review.

The subpopulation review dramatically diverged when we have the LSAS 95 and above cutoff. The additional the additional filters of ceiling subscores, just to give you a sense, when you're at 90 to 100, you're at the max of that scale. And then you go through a public speaking challenge that is supposed to induce additional anxiety.

There's no way that, that scale can continue going up. So we excluded patients with that type of ceiling effect, and there was only 5 of them that had that. And then the additional filter brought in just one more person because of the way that huge placebo response observed in the visit 2, which was all placebo run-in. So overall, the biggest effect comes from the LSAS 95 and above cutoff and then the other filters just nominally contributed but didn't create the separation that the severity subpopulation did.

And to your last point, one of the things that is important to understand is that it's just -- it's not that the drug may not work in milder cases. It is easier to see the signal when you have this higher level of anxiety based on. So that is why it's much more prominent and less variability was seen with the placebo response with the severe subpopulation.

And our next question is going to come from Myles Minter with William Blair. Your line is open.

Just back on like the excluded data in that post-hoc analysis as well. I think you exclude a handful of patients that coming into the public speaking challenge, I think they were scoring subscores of greater than 90 and maybe that the public speaking challenge because you're so anxious to start with didn't get that rise and fall that we'd expect in the anticipation performance sort of stage of that. Maybe you can talk about the effect on that. And then if I break down PAL 1, 2, 3, 4 individually and don't pool them, do you have on a post-hoc basis a static effect in PAL 2 for this severe population given that is your positive trial from the overall population?

The first question related to the ceiling effect, I think, Myles. Is that accurate? The scale -- the subscale 0 to 100 and those that, there's a handful that were 90 to 100. And when you are starting at that spot at your baseline, there isn't really any potential for the instrument to measure a benefit because there's not much room between 90 and where you are between 90 and 100. So that ceiling effect did impact and we excluded -- what was it?

5 patients.

5 subjects in that regard.

Yes. And from the -- just to really go through those 3 numbers, 15 were excluded from Site 1. However, only 12 of those had actually LSAS 95 and above. then 5 were excluded for the ceiling SUDS scores that Shawn just talked about. And there was one additional patient that was excluded for this pronounced really placebo response where they paradoxically improved while they're getting provoked with the public speaking challenge.

So this is really the total numbers of PALISADE-4 in terms of exclusions. And the overall number that you see is primarily driven by 98 subjects that came from the cutoff of the LSAS 95 and above.

Then the next question goes to the severity in PAL-2 alone on a stand-alone basis.

Correct.

Yes, we looked at that, and we did not see the same type of separation that we see in PAL-4, really the combined data of 3 and 4 and really the total full data. Why do we think that is? We didn't have the variability of placebo responses that we see in PAL-4. That was really the biggest driver for the results that we saw in the overall population. In PALISADE-2, there was no such variability in the placebo responses. Hence, there was really no specific subpopulation that carried the overall results.

Angelov, I would add to that, too, PALISADE-2 had a smaller sample size. So when you start cutting, you're getting to much smaller n's. And that's one of the advantages, obviously, of pooled is you have bigger ends to show that separation.

Yes, correct. Because directionally, as you can imagine, when you have a positive trial, actually all the subpopulation, the severe and the less severe, they all were directionally pointing in the same way, fasedienol was better than placebo. But when you have the lower ends, getting to statistical significance makes it much, much harder.

And the next question is going to come from Andrew Tsai with Jefferies.

The first one in terms of the history of the development program, I feel like there was a period of time, maybe right after PALISADE-1, but actually before PALISADE-2, where you did consider pivoting to LSAS and you had FDA discussions back then. So can you remind us the degree of alignment or agreement you got with the FDA to look at LSAS just as a reminder? And then I have more follow-ups.

Yes. Thanks, Andrew. Good to hear from you. The meeting that we had with the FDA in the spring of 2023 was focused primarily on whether or not the LSAS remained a valid and reliable endpoint for a registrational pathway similar to the antidepressants, 3 antidepressants that were approved at that point about 20 years ago.

And so because the agency has not approved anything since over 20 years from now, 23 now at this point, I think Effexor was the last one. We needed to -- in case we wanted to move to that direction, we need to understand whether the agency was still aligned on that endpoint being valid and reliable. And we've got a definitive yes on that one.

Makes sense. And now that you're pursuing an LSAS in the next Phase III, would this be a daily kind of fixed dosing paradigm? Or is it still treat as needed? And is it fair that the study duration might be a little bit longer, more consistent with the prior previous drugs, the antidepressants, maybe it's like an 8-week paradigm. I don't know. But maybe talk about that different.

Yes, that's certainly something we'll be addressing with the agency. The MOA and building the program around the MOA has always been central to our thinking. And the way this drug works is with rapid onset effect that we see. So we discussed that with the FDA and certainly, an over time perspective with the LSAS being more of a movie as opposed to a quick snapshot, we would expect the study it doesn't necessarily have to be exactly the same as the 12-week structure that the approved drugs have.

That's something we'll discuss with the agency. Those obviously have a different MOA takes a lot longer, as you know, for those types of drugs to kick in. But we'll have that discussion with the FDA, and we'd expect it to be more along the lines of the crossover study, but it's something certainly will be discussed with them as an immediate priority.

Shawn, I would just also add to that, that back then and obviously still holds true now, from the crossover study that Angelov mentioned, we had -- in 2 weeks, we had about the same magnitude of effect that the approved SSRIs had in 12 weeks. And so to your point, we've looked at what's the potential study duration, potentially less than 12 weeks, but obviously longer than what we did recently. And then I think the other piece is just the continued open-label data that we've driven, granted it's not placebo-controlled, but it's the other thing that gives us some confidence in hopefully the future study where you see LSAS decline over time.

Okay. And very last question. I think there was this separate redosing study that could read out soon, too, also in Q3. Would you still plan to share those results regardless of the outcome? Or is that kind of in the back burner for now?

Absolutely. Yes, absolutely. That is on track with prior guidance. So absolutely, we would. And it would also be part of the overall totality of data and discussion with the FDA as we map out under the single trial guidance, which really is extremely helpful to have this draft guidance and its recency is also very important to us about a single trial pathway.

So those are the things that we want to get in front of the FDA as soon as we can and discuss what we and they believe is an appropriate path forward given the body of work that's been generated up to this point, which is absolutely robust. So looking forward to it.

Thank you and I am showing no further questions in the queue at this time.

Thank you, operator, and thank you, everyone, who joined us on the call today for your thoughtful questions. If anyone on today's call has additional questions, please feel free to contact us at [email protected] or through the Contacts section of our website. Thank you again for your time and participation and your continued interest and support in Vistagen. This concludes today's conference call. Have a great day.

Thank you, and you may now disconnect.

Good day, everyone. Thank you for standing by. Welcome to the Vistagen Therapeutics Fiscal Year 2026 Third Quarter Corporate Update Conference Call and Webcast. Please note that today's call is being recorded.

At this time, I'd like to turn the call over to your host, Mark McPartland, Senior Vice President, Investor Relations at Vistagen. Mark?

Thank you, Lisa, and good afternoon, everyone, and welcome to our conference call and webcast.

Earlier this afternoon, we filed our quarterly report on Form 10-Q and issued a press release for our fiscal year 2026 third quarter, which ended December 31, 2025, and provided an update of our progress across our clinical stage neuroscience program. We encourage you to review the PR and 10-Q which are both available in the Investors section of our website.

Before we begin, please note that we'll be making forward-looking statements regarding our business during today's call based on current expectations and information. These forward-looking statements speak only as of today. Except as law requires, we do not assume any duty to update any forward-looking statements made today or in the future.

Of course, forward-looking statements involve risks and uncertainties, and our actual results could differ materially from those anticipated by any forward-looking statements we make today. Additional information concerning risks and factors that could affect our business and our financial results are included in our fiscal year 2026 third quarter Form 10-Q. And for period ending December 31, '25, and in future filings that we make with the SEC from time to time. Again, all of which are available in the Investors section of our website or, of course, on the SEC's website.

With the formalities completed, we warmly welcome our stockholders, sell-side analysts and others interested in our programs in progress. I'm joined on our call today by Shawn Singh, our President and Chief Executive Officer; Josh Prince, our Chief Operating Officer; and Nick Tressler, our Chief Financial Officer. Shawn will provide a brief business and clinical update and Josh and Nick will be available to provide additional feedback during the Q&A portion of our call. After our remarks, we'll take questions from the sell-side analysts participating on the call. A replay of the webcast will be available in the Events section of the Investor page of our website.

With that taken care of, I'd now like to turn the call over to our President and CEO, Shawn Singh.

Thank you, Mark, and good afternoon, everyone. It's been an important quarter for our team with the completion of the randomized portion of our PALISADE-3 Phase III trial in social anxiety disorder, as guided and focused efforts to learn from the study's results and drive high-quality and efficient execution of our ongoing PALISADE-4 Phase III trial.

We have reviewed available data from PALISADE-3 and implemented moderate refinements, including retraining, site rationalization and operational enhancements to PALISADE-4. We've also been working with third-party collaborators on the implementation of innovative approaches to analyze the available data sets, not only from PALISADE-3, but also from the factional studies across the PALISADE program, including both the randomized and the open-label trials.

Our objective is to better understand the drivers of both fasedienol and placebo response using the substantial data collected from these studies to potentially inform optimized statistical models that consistently incorporate covariants and explanatory variables across all PALISADE studies which could anchor future weight of evidence discussions with the FDA.

The analyses are ongoing with our collaborators and involves the use of their proprietary artificial intelligence and machine learning technologies to identify nonspecific responses and understand and predict susceptibility to placebo response and likelihood of response to active drug in the context of the public speaking challenge study design.

Overall, the full complement of ongoing work is focused on delivering practical operational understanding, predictors of response and enhanced statistical models with the potential to impact both PALISADE-4 and our regulatory strategy based on the totality of data from the PALISADE program.

The open-label extension portion of PALISADE-3 and PALISADE-4 remains ongoing and is designed to evaluate the safety and tolerability of repeated as-needed intranasal administration of fasedienol in adults with social anxiety disorder, but in real-world daily life situations. In addition to safety assessments, the study includes exploratory longitudinal measures using validated instruments such as the cognition administered Liebowitz Social Anxiety Scale, or LSAS, and the patient-reported Social Phobia Inventory or SPIN.

While open-label data are inherently in controlled and exploratory, the OLE portion of the PALISADE-3, Phase III study, could provide important context on patient experience with repeated use over time in real-world anxiety provoking situations to patients encounter. Together with our broader analytical work across the PALISADE program, insights from open-label studies should contribute to our enhanced understanding of fasedienol drug effect and usage patterns.

Once again, we'd like to thank the patients who participated in our PALISADE studies as well as the clinical investigators, the site staff and our contract research organization for their ongoing dedication and professionalism as we complete PALISADE-4 and advance our broader analytical efforts.

As we've previously stated, PALISADE-4 is successful, together with PALISADE-2 in the broader body of evidence generated across the PALISADE program, these data may support a potential new drug application submission to the U.S. Food and Drug Administration for the acute treatment of social anxiety disorder in adults. The significant unmet need in social anxiety disorder, where effective treatments are very limited, continues to guide our work and our long-term focus.

Turning to our women's health program. We received an official USAN adoption statement, designating PH80 as refisolone. Refisolone is our hormone-free nonsystemic intranasal product candidate with potential for the treatment of moderate to severe vasomotor symptoms, commonly referred to as hot flashes due to menopause. We believe refisolone may also have therapeutic potential across other women's health indications.

We are currently preparing to submit our U.S. Investigational New Drug Application, or IND, for refisolone to the U.S. FDA and with a planned submission in the first half of 2026. This IND is intended to support further potential Phase II clinical development of refisolone in the U.S. for the treatment of moderate to severe vasomotor symptoms due to menopause. Building on a previously completed placebo-controlled exploratory Phase IIa clinical trial conducted in Mexico by Pherin Pharmaceuticals, which is now our wholly owned subsidiary and that trial demonstrated clinical benefit in the vasomotor symptoms indication.

We believe that indication in women's health represents a significant area of unmet need, and we remain committed to advancing refisolone as a nonsystemic hormone-free product candidate with a disciplined data-driven approach as we prepare for the potential next phase of clinical development.

Turning briefly to our financial position as of December 31, 2025, we had $61.2 million in cash, cash equivalents and marketable securities. During the quarter, we implemented company-wide cash preservation measures intended to enhance our operational efficiency extend our runway and maintain strategic flexibility across our Pherin pipeline. We believe we are well positioned to complete PALISADE-4 and to advance preparations and planning for our preparing pipeline.

In closing, our mission remains unchanged to deliver transformative treatments and improved lives. The path forward requires discipline, rigor thoughtful analysis, and we believe the steps we have taken and are taking position Vistagen to make informed decisions and responsibly advanced programs with the potential to deliver meaningful value to patients and to shareholders.

So I want to thank you for your continued interest in the company and your support, and we look forward to updating you on our progress in the quarters ahead.

Thank you, Shawn. Operator, we would now like to open up the call for questions from the sell-side analysts joining us today.

[Operator Instructions] The first question today is coming from the line of Andrew Tsai of Jefferies.

Thanks for the update. So maybe in the PALISADE-3 data, you had a chance to look at it maybe descriptively, how did the individual curves look at every interval out to 5 minutes? Was there a separation at all across any of those time points with n2 versus placebo?

Thanks for the question, Andrew. Josh?

Andrew, we -- at this point, what we've released publicly is the top line results. So we're still looking into a lot of that data. We haven't released the individual curves publicly.

We do know that there's what really -- where we find information is looking into individual respondents and subgroups of respondents. And again, that analysis continues. So that's where we do see definite differences.

Okay. And it sounds like you're looking at ways for PALISADE-4 to tweak around the SAP plan, and let's just say you did would you need to notify and then talk to the FDA to potentially get an official buy-in from them that the changes can be done? Is there a risk to modifying the SAP plan, basically?

Yes, it's a great question. The SAP and the just like with PALISADE-3 already been submitted and approved or no feedback from FDA. So that's set. So any future changes, to your point, would absolutely require a resubmission and alignment with the FDA before we locked the database and got the top line results.

Understood. And then my last question is, should you modify the plan, would you need to backfill -- back to the original enrollment target of around [ 2.36 ] or [ 2.38 ]. Or are there no changes to the enrollment?

Yes. The change to the SAP would not change the enrollment or the planned enrollment for the study. The key there is that it's whatever that SAP in is, like I said, locked in before you get to database lock and then applied to the total population for the study.

Next question is coming from the line of Emily Chudy of Stifel.

This is Emily on for Paul Matteis from Stifel. We just had a quick question. Maybe could you remind us where you guys are in terms of enrollment for PALISADE-4 and if you like plan on telling -- or plan on puring when that has completed or like dosing has completed? And then also, could you maybe share on like what details you saw in PALISADE-3 that kind of led you to refine to the refinements that you outlined in the PR?

Thanks, Emily. Appreciate the question. So it will be consistent with the pattern for PALISADE-3. Once we hit the last patient's last visit and then proceed towards top line. So that will be -- we're on track with guidance that we've previously given with respect to PALISADE-4 [ TOR ], the randomized portion of PALISADE-4.

Josh, you can address the second part.

I'm sorry, I missed the second part. Can you rephrase that?

For -- you guys discussed like refinements, including like retraining of some sites. Could you maybe provide any color on what details you saw from PALISADE-3 that kind of led to that decision?

Yes. I don't think -- we can't go into too much detail given PALISADE-4 is ongoing. But at a high level, one of the things that PALISADE-3 different than PALISADE-2 was a higher placebo response. So as one example, making sure that our training is reinforced and up-to-date with sites in terms of potential ways to minimize that, in particular, kind of how the protocol is followed. The script is followed to the letter, making sure that there's no chatting with the subjects as they come in, anything that could potentially lend to a comfort for a subject or that could drive a higher placebo effect.

So it's those types of things that we're able to implement quickly based on what we see from PALISADE-3. And also because we're listening to what's happening at each site through the audio recordings that we've talked about previously, gives us the opportunity, again, to be hyper focused feedback and any intervention where we see something deviating from the prescript that we've put in place.

In addition to that, some -- a focus on centralized recruitment and making sure that gets and stays completely tight or rationalized. So the kinds of things that can impact in stream execution especially, as Josh noted, with high focus on placebo mitigation strategies and best practices across -- especially from really experienced sites.

Our next question is coming from the line of Myles Minter of William Blair.

This is John on for Myles. I was wondering if you could talk a little bit more through your regulatory path forward and your confidence in it in the event that PALISADE-4 hits and you have a 50% program success? And alternatively, if PALISADE-4 misses, do you see any regulatory path forward with PALISADE-2 alone?

Thanks, John. Appreciate the question. So look, the Fundamentally, we believe that the regulatory outcomes always depend not only on FDA regulations and guidance, but the totality of data, the weight of evidence, the risk benefit, the nature of the in-need population. So these kinds of assessments -- that is what we align our regulatory strategies to accordingly.

So we're not really in a position to speculate on any approval scenarios, but what we can tell you, of course, is we're very mindful not only of the evolving the way that AI is evolving within the agency and how that is emerging is part of and factoring into the regulatory decision-making. We on top of that and very closely focused on that but also just, again, the weight of evidence, once we see where we are with the randomized portion of PALISADE 4, we'll be able to look across the totality of the program.

And the primary objective in the primary regulatory strategy remains, as we've said, which is complementing if PALISADE-4 is successful complementing PALISADE-2 with a broader base of information from the totality of the program for the acute treatment of social anxiety disorder. PALISADE-4 doesn't hit and separate from placebo. It's still the same. It's a totality of evidence focus. It's a way of evidence focus across the program and what we see from all data we can possibly see and analyze relating to the drug.

Helpful. And a quick follow-up. Is there anything that you're seeing in the blinded data of PALISADE-4, that gives you a little bit more confidence in that study over PALISADE-3?

No comment on the blinded data, John.

[Operator Instructions] And the next question is coming from the line of Elemer Piros of Lucid.

Shawn, have you noticed any impact on enrollment since the announcement on December 17? Enrollment patterns.

Josh, you can address that.

Sure. The quick answer is no, definitely have not. Enrollment has continued as planned and projected for PALISADE-4.

Okay. And so what I'm trying to understand is how did the PALISADE-3 outcome and potentially PALISADE-4 be different by amending the SAP, would that mean that you would include some covariates that may influence the separation between the 2 arms? If you could just help me conceptually understand this a little bit better.

Sure. I mean part of what we're doing with AI and the machine learning, it's potential. It's not -- certainly not guaranteed. And if they're -- what you're looking for are there any co-variants that may have a potential fixed effect on the ANCOVA. And that's -- that may or may not evolve and emerge from the work that we're doing with our collaborators with their proprietary AI and ML. But it would be those kinds of things. Are there covariants that you notice when you look through the patient populations in each arm in prior studies in PALISADE-3, in particular, that may give you some sort of signal.

So the answer is we don't know yet. And as noted earlier, if we do make a modification to the SAP that's already been signed off by the agency, then we'd have to go back to them and socialize it with them. So that's part of what we're trying to find out. If there isn't, then again, we've got operational efficiencies and observations based on what we've seen across the studies that are being implemented into the PALISADE-3 or PALISADE-4 execution.

Josh, anything you want to add on that from the teams?

No, I think that captures it.

So just to summarize, you're looking at PALISADE-3 and maybe even PALISADE-2 for some covariants. If you find them, then you modify the SAP take it to the FDA before you were to analyze, I would say, 4 hypothesizing that those same covariants will be applicable to PALISADE-4? Am I understanding it correctly?

Yes. It has to be the -- not only whether it's timely, obviously, got to be timely before you lock the database, but it's also got to be appropriate. And there may also be potential changes that wouldn't be FDA regulatory appropriate. So it's got to be something that could be impactful at the same time, something that is reasonable with rigor and review from the FDA.

So, I would just add that we're actually -- we're looking across all the PALISADE studies. So PALISADE-1, -2 and -3 to see what we can learn. We've built -- now that we've had a third study complete. We've built continued size of data to examine which gives you more power when you're digging into different things. But you're 100% correct that it's essentially the covariants or the correction factors that you would apply in your statistical model.

I understand. And just a silly housekeeping question, if you may -- if I may.

At the end of December, you had 39.7 million shares outstanding but the weighted average for the quarter was 42 million. Can you help me to understand that?

Nick, are you on?

Yes, I am. Yes. So it's shares are outstanding at the end of the quarter. It's how we measure our earnings per share.

Okay. So -- share, I would say. But there are higher number of shares outstanding? Because we have reduced 42 million.

That includes the prefunded warrants, Elemer.

Operator, I believe that's all the time we have for today. We can wrap up the call.

So thank you, everyone, for joining today. and for your continued interest and support in Vistagen. Again, with our diverse innovative pipeline, we are encouraged about the future prospects of the company. If you have any additional questions, please don't hesitate to reach out to us at via e-mail, [email protected] or through the Contact Us section of our website. We also encourage you to register for e-mail updates and stay informed about the latest news and developments from Vistagen via our regular update.

We appreciate your time, engagement and ongoing support, and we look forward to keeping you updated on our continued progress. This concludes our call today...

One more thing, real quick. I just want to clarify. I think I misspoke. I think I said $61.2 million at the end of 12/31/25, it was $61.8 million as reflected in our Q.

Thanks, Shawn.

This concludes today's program. Thank you all for joining. You may now disconnect.

Good day, everyone. Thank you for standing by. Welcome to the Vistagen Therapeutics' Fiscal Year 2026 Second Quarter Corporate Update Conference Call and Webcast. Please note that today's call is being recorded. At this time, I'd like to turn the call over to your host, Mark McPartland, Senior Vice President, Investor Relations at Vistagen. Mark?

Thank you, operator. Good afternoon, everyone, and welcome to our conference call and webcast. Earlier this afternoon, we filed our quarterly report on Form 10-Q and issued a press release for our fiscal year 2026 second quarter, which ended on September 30, 2025, providing an overview on the progress in our PALISADE-3 program for fasedienol and social anxiety disorder across our other lead clinical neuroscience programs. We encourage you to review the PR and 10-Q, which are available in the Investors section of our website.

Now before we begin, please note that we will be making forward-looking statements regarding our business during today's call based on our current expectations and information. These forward-looking statements speak only as of today. Except as law requires, we do not assume any duty to update any forward-looking statements made today or in the future. Of course, forward-looking statements involve risks and uncertainties and other actual results could differ materially from those anticipated by any forward-looking statements we make today.

Additional information concerning risks and factors that could affect our business and financial results are included in the fiscal year 2026 second quarter Form 10-Q for the period ending September 30, 2025, and in future filings that we'll make with the SEC from time to time, all of which are available in the Investors section of our website or, of course, on the SEC's website.

Now with the formalities out of the way, we warmly welcome our stockholders, sell-side analysts and others interested in our programs and our progress. I'm joined on our call today by Shawn Singh, our President and Chief Executive Officer; and Josh Prince, our Chief Operating Officer. Shawn will provide a brief business update, clinical update, and Josh will be available to provide additional feedback during the Q&A portion of our call. After our remarks, we will take questions from the sell-side analysts participating on the call today. I remind you, a replay of the webcast will be made available in the Events section of our Investor page on our website.

With that taken care of, I'll now turn the call over to our President and CEO, Shawn Singh.

Thank you, Mark, and good afternoon, everyone. We've built a very strong momentum as we enter into what could be a potentially transformative period for Vistagen. Last week, we announced another major milestone in our PALISADE program. The last patient completed the randomized double-blind portion of our PALISADE-3 Phase III trial, evaluating our most advanced intranasal “pherines” product candidate, fasedienol for the acute treatment of social anxiety disorder.

We are now preparing for the release of top line results from the PALISADE-3 study by the end of this calendar year. We extend our sincere gratitude to the patients who participated in the study as well as the dedicated and experienced clinical investigators, the clinical site staff and our contract research organization. Their enthusiasm, their focus on detail and the collaboration throughout the study were notable and greatly appreciated and will remain so during the ongoing open-label extension of the study.

Over the past several months, I've had the privilege of meeting in person with many of the dedicated teams conducting our PALISADE-3 and PALISADE-4 studies. The energy, the curiosity, the optimism that I've witnessed reaffirmed just how great the need remains for new treatment options for individuals whose daily lives are affected by social anxiety disorder and how differentiated and innovative fasedienol could be in meeting their needs. Together, our teams remain deeply focused on fasedienol's potential to become the first FDA-approved acute treatment of anxiety for the millions of adults with social anxiety disorder.

Looking ahead, we remain on track to report top line results from our PALISADE 4 Phase III trial in the first half of 2026. Both PALISADE-3 and PALISADE-4 share a similar public speaking challenge design and the same primary efficacy endpoint as our previously successful PALISADE-2 Phase III trial. In parallel, we are continuing preparations designed to advance our broader pherine pipeline, including itruvone for major depressive disorder and PH80 for menopausal hot flashes.

Both depression and women's health represent areas where far too many patients still struggle without adequate options. We're deeply motivated to bring forward the innovative nonsystemic neurocircuitry-focused potential of itruvone and PH80 to help address these important and widespread needs.

Turning now briefly to our financials. As of September 30, 2025, we had $77.2 million in cash, cash equivalents and marketable securities. We believe current cash covers all known aspects of our ongoing U.S. registration-directed PALISADE program for fasedienol for the acute treatment of SAD, including potential NDA submission if our PALISADE program is successful.

Before I conclude the business update, I'd like to welcome Mr. Paul Edick to our Board of Directors. Paul joins us at a pivotal time for Vistagen, bringing decades of experience leading successful FDA approvals, commercial launches and strategic transactions. His leadership will be invaluable as we prepare for our next phase of growth. I'd also like to extend our deep gratitude to Dr. Jerry Jin, who served on our Board from 2016 until his retirement earlier in September of this year.

In closing, our mission remains clear and unwavering: to redefine what is possible in neuroscience, to restore emotional well-being and improve quality of life for millions worldwide. With a diverse and innovative pipeline, experienced team, several key milestones approaching, we believe we are entering one of the most exciting and potentially transformative periods in our company's history with deep confidence in our ability to deliver meaningful value for patients and for our stockholders. I want to thank you all for your continued interest, your support and your engagement with Vistagen. It makes a lot of difference, and we look forward to sharing our progress with you in the weeks and the months ahead.

Thank you, Shawn. These are definitely exciting times at Vistagen as we continue to build momentum across our programs.

Operator, we would now like to open up the call for questions from the sell-side analysts joining us today.

[Operator Instructions]

Your first question comes from the line of Andrew Tsai with Jefferies.

Look forward to the top line data readout soon. And so I think you guys have mentioned before that we should expect 6 to 8 weeks after the last visit for the top line release. Is that still the case? Or could it come earlier than that actually?

Our guidance, I think we're just going to stick with it, Andrew. Thanks for asking the question, and thanks for coming on. But our guidance is that we'll see top line results released before the end of this calendar quarter, so by the end of this calendar year.

Okay. And for the top line analysis, how should we think about discontinuation rates, any protocol violations? Will that -- can we expect the top line to be pretty close in terms of the number of patients you've enrolled in the study? And then how should we also be thinking about the safety profile?

Well, you're going to hear as we did with PALISADE-2, right? So we're going to give you, obviously, top line results on the primary, the CGI-I, the secondary and also the PGI-C as a secondary. And obviously, pretty customary information regarding the safety profile that we've seen throughout the course of the study -- through the randomized portion of the study. So that's what we're printing out, and that's what we're reading out is -- are the top line results from the randomized double-blind portion, which is the public speaking challenge. So any safety data that we have from that study, similar to PALISADE-2, we'll be reading that out as well.

Okay. And then last question is from what you can tell, what have been the top reasons why patients screen failed in PALISADE-3? And are the top reasons different from what you saw in PALISADE-2?

So we can unpack that later. But what I can tell you, Andrew, is the reason that we made enhancements to the PALISADE-3 and 4 studies, again, was to make sure that there's very high-quality assessment for subject eligibility. And as a result of that, we had our own teams involved here with our teams for subject eligibility review. We had other enhancements into the execution of the study, of course, throughout the duration of the study.

So I think we've seen generally what we've expected to see and as we've modeled forward for not only screen fail, but also attrition rates throughout the course from enrollment through randomization through the end of the study. So I think we're comfortable with what we've typically seen and maybe more to come on that later. The important piece of the puzzle is -- yes, one more thing is obviously the important piece of the puzzle is that we got to the last patient class visit with the full complement that we had modeled for purposes of the studies. We've noted before, our end target was 236. So last patient class visit reflects our original thought.

The next question comes from the line of Paul Matteis with Stifel.

This is [ Matthew ], on for Paul. I guess for us, assuming one of PALISADE-3 or PALISADE-4 works, is there anything else gating registration -- gating filing? Is there anything else that you need to complete before then? How soon can you file?

Sure. Matthew, thanks for the question. So as you know, as we move closer toward completion of the Phase III development program, we always plan to interact with the agency. But we've said this before, obviously, it's the pivotal program data, it's a repeat dose study. It's the open-label data from our long-term safety study, a human factor study, the typical preclinical safety-related studies, reprotox and carc, all those are aspects that we expect to have wrapped up upfront, of course, of an NDA package.

So -- and we'll, of course, be meeting with the FDA as we get closer to make sure that we're in line with what's necessary regarding a submission package. So we estimate currently, and if everything goes according to plan that we've been executing on, we could see an NDA submission if PALISADE-3 is positive sometime around the middle of '26.

[Operator Instructions]

Your next question comes from the line of Myles Minter with William Blair.

Just the first one, is it your view that fasedienol would be eligible for commissioner's priority review voucher? It seems to me like SAD is potentially a public health crisis, and it's certainly a massive unmet need with over 30 million patients out there. That's the first one. And then second is just, I think in late October, you updated clinicaltrials.gov. You terminated a site in Arkansas and Kansas. I'm just curious whether that was because you've completed enrollment and you didn't need those sites anymore or just because of your site vigilance and you're going to see these sites in person? Was it something performance related that you terminated those sites?

Thanks, Myles. Thanks for the question. Josh, why don't you go ahead and take that last question first?

Sure. Yes. Thanks, Myles. As we've gone through the course of these studies for both PAL-3, PAL-4, it's a constant evaluation of fit with sites. And so we've had a few sites that, for whatever reason with regard to their ability to enroll the appropriate patients, whether it was their recruitment programs or other reasons, just they were not able to enroll. And so at some point, it makes sense to terminate those sites. There's been 1 or 2 like that.

And then also beyond that, as we -- to your point, as we get towards the end of the study, we definitely take a wind-down approach for a soft landing for the study to make sure it's well controlled. We're controlling variability and then making sure that we will be able to get from that end of study last patient out to top line results efficiently in the time line that Shawn mentioned. So for us, it's kind of course of business as we've gone through the process of the studies.

Thanks, Josh. So Myles, on your first question related to the voucher program, the CMPV program. So we're certainly aware of it and the criteria the FDA uses to evaluate eligibility. I think right now, while we don't expect that fasedienol falls within the typical scope of the CMPV programs, we, of course, believe the magnitude of unmet need and especially for a rapid situational treatment without the worrisome side effects and safety concerns, it's significant. But I think if the regulatory pathways evolve or additional guidance creates a relevant framework, then of course, we'll evaluate it at the appropriate time.

Your next question comes from the line of Elemer Piros with Lucid Capital Markets.

Shawn, this is Elemer dialing in for Elemer. What I'd like to ask you is if you have any indication on the usage patterns, this is coming from -- perhaps more likely from PALISADE-2 than maybe to a lesser extent from PALISADE-3 at this point for those who went out to complete the OLE up to 1 year?

Yes. Most of the usage pattern data is going to come from the open labels. And so what we can talk about, of course, is related to the reported open label, the long-term safety study that we had before. And the patterns established in the context of that study give some pretty good guidance to us about what we see going forward in the real world. Remember, this is a disorder that is -- it's chronic, but it manifests acutely and episodically.

And so a lot of it in terms of utilization depends on where people are in their particular phase of their journey, what is their job? What academic setting are they in? How frequently do they need to interact with people on a social basis? And you definitely see in that long-term safety study we've reported on more activity during the week, especially after people are back to work, back to school in the kind of rhythm of life that we're in now.

You see more utilization during a week, especially during work kind of hours. Weekends, it tends to taper off, obviously, because people are not in similar stressful settings or may be social situations, a barbecue at your friends or you go to a sporting event where there's worry about how you're looking, how you're -- whether you're being judged or not being judged, which is really the -- what anchors this disorder, unfortunately.

So more often during the week, less often during the weekend, and that's the pattern we saw early on in the open-label study we reported on, and it's reasonable to expect that sort of activity on a go-forward basis, at least that's what's anchoring a lot of our informed assumptions about how we could see the drug used in the real world.

Thank you, Shawn. And do you see any difference between the number of people entering the open-label phase between PALISADE-2 and PALISADE-3, and roughly what percentage is that?

Yes. I'm not going to remark on the percentages, but I can tell you, it's a high throughput rate we've seen historically in any open-label activity that we've got. And as to be expected, it's part of the reasons why people get interested in participating in the study in the first place is that they think if they complete it, there's an opportunity for the investigational agent to be part of their go-forward experiences.

So I think the reasons people don't tend to go into an open label historically are associated with a change in job, a change of living location, something significant that's a life-changing event that allows them to -- or causes them to not be proximate to the site that they were involved in the randomized study.

I see. I see. I just have 2 more if you have -- if you're okay with that. What would be the minimal effect size in terms of the SUDS or the CGI that would be deemed clinically meaningful?

So, we're going to try to, of course, replicate what we were able to accomplish in PALISADE-2, right? So you always have to contextualize whatever your primary is with the outcomes that are from the other endpoints, especially in this case, the cross association with CGI-I and PGI-C.

So you get to clinical significance or clinical meaningfulness when you look at all 3 of those, and we take a look at not only what happens with the SUDS, but also with the secondaries. So -- and it's -- I think we're targeting to try to replicate what we already believe is not only statistically significant, but a clinically meaningful outcome associated with the PALISADE-2 study.

Understand. And lastly, how do you think about commercialization at this stage? On your own, be a partner? Have you thought about this recently?

Companies -- yes, certainly we think about it all the time. Companies in positions like we are, if you have a contemplation for -- in the first commercial launch, you have to have a lot of good reasons for that. And here, as a company, we always position for optionality. There's many things that can happen. Key for us is to make sure we have the optimal opportunity to generate the value that could be associated with fasedienol if it gets approved. So there is certainly a very solid potential commercial plan. There's also opportunities should other strategic arrangements bring greater value potential.

But yes, as a company, we have the expertise. We have the planning. We have execution in certain cases already underway to be able to bring this extremely innovative asset into the treatment paradigm where there is just nothing sitting there that's interesting and exciting for patients to be able to recapture the agency that allows them to tailor the use of a medication to fit how these stresses are impacting their lives day-to-day.

And the world right now, it's a very interesting market out there in terms of the dynamics of telehealth and mental health, digital psychiatry, consumer-generated influencer-based activity across the socials, what we see with anxiety, very similar to what people see and hear about weight and a GLP-1 drug. So there's a transformed market environment over -- just even the last couple of years. And now you're also looking at a population of patients and maybe practitioners too, who really would prefer online engagement as opposed to in-person.

So there's some really unique opportunities, especially with what we would hope to be borne out as the target product profile and the way to access not only practitioners, but also raise awareness among consumers. So it's a really exciting opportunity for the company around this very unique asset that fits in so many ways for what we think are the clarion calls of not only practitioners, but certainly patients.

Yes. Exciting times. Looking forward to the read-out.

There are no further questions at this time. I would now like to turn the call back over to Mark McPartland for closing remarks. Please go ahead.

Thanks, operator, and thank you again, everyone, for joining us on the call today and for your continued interest and support. With a diverse and innovative pipeline and several key major milestones on the horizon, we believe Vistagen is entering one of the most exciting and potentially transformative chapters in our company's history. If you have any additional questions, please don't hesitate to reach out to us at [email protected] or through the Contact Us section of our website.

We also encourage you, of course, to register for e-mail updates to stay informed about our latest news and developments from Vistagen. We truly appreciate your time, engagement and ongoing support, and we look forward to keeping you updated on our continued progress.

This concludes the call. Have a great day.

Ladies and gentlemen, this concludes today's call. Thank you all for joining, and you may now disconnect.