Vistagen Therapeutics, Inc.

Greetings and welcome to the Vistagen Therapeutics Fiscal Year 2024 First Quarter Corporate Update Conference Call. During the presentation, all participants will be in a listen-only mode. Afterwards, we will conduct a question and answer session. At that time, if you have a question, please press the 1 followed by the 4 on your telephone. If at any time during the conference you need to reach an operator, please press star 0. And as a reminder, this conference is being recorded Thursday, August 10th 2023. I would now like to turn the conference over to Mark Flather, Vice President of Capital Markets. Please go ahead.

Thank you, Jennifer. Good afternoon, everyone, and welcome to Visigyn's first quarter fiscal year 2024 corporate update conference call and webcast. This afternoon, we issued a press release providing an overview of our progress this last quarter. We encourage you to review this, which can be found on the investors section of the Visigyn website. Before starting today, We want to remind you that we may make forward-looking statements regarding our business based on our current expectations and information. The forward-looking statements speak only as of today and except as required by law, we do not assume any duty to update in the future any forward-looking statement made today. 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 may make today. Additional information concerning risks and factors that could affect our business and financial results is included in our fiscal year 2024 first quarter Form 10-Q for the period ending June 30, 2023. And in future filings, that will make with the SEC from time to time, all of which will be, which are and will be available on our website and the SEC's website. With that taken care of, I'd like to thank and welcome all the stockholders, analysts, and everyone taking an interest in BISGEN. I'm joined on the call today by Shawn Singh, our Chief Executive Officer, and Josh Prince, our Senior Vice President of Business Operations. Shawn will provide an overview of our progress, focusing specifically on the results from our positive Phase III Palisade II trial, evaluating the efficacy, safety, and tolerability of Fasadienol pH 94B nasal spray in adults with social anxiety disorder, or SAD, followed by a brief opportunity for questions from cell site analysts. We want to remind you that this call is being webcast and will be available for replay after the call is completed. The replay link can be found in the Investors Events section on our website. Now I'd like to turn the call over to our Chief Executive Officer, Sean Singh, to update you on our recent inspiring news regarding the Palisade II Phase III study results.

Thank you, Mark, and good afternoon, everyone, and thanks for joining our call. As I've said before many times, our team has remained steadfast in our core mission, which is to radically improve the mental health and well-being of millions of individuals around the world who are suffering from a wide variety of anxiety, depression, and other CNS disorders that severely disrupt their daily lives. And as we've recently announced, we've solidified a major cornerstone in that mission focused on improving the lives of the over 25 million individuals in America who are affected by social anxiety disorder or SAD. There's indeed an active and growing need for a new, faster acting option for treatment of SAD without abuse potential or the side effects and safety concerns that often are associated with the currently approved medicines. We remain focused on addressing the significant unmet mental health need for individuals across a broad range of demographics, and in a diverse range of communities across the globe. We're committed to innovation of multiple differentiated treatments in alignment with our mission to shift the treatment paradigm for anxiety, depression, and multiple other CNS disorders. So a lot's changed since our last conference call, and let's get right to the biggest news in our company's history. It's been a long time since a positive phase three study has brought new optimism for treatment of a social anxiety disorder. And we are thrilled to be in a leadership position with the compelling top line results from our phase three Palisade II trial that were announced on Monday. These phase three results highlight the potential for Fasadienol with its innovative proposed mechanism of action to transform what's possible for millions of individuals living with SED in the US and millions more who are affected worldwide. In the Palisade II study, Fasadionol demonstrated a rapid and clinically meaningful reduction in the subjective units of distress score, or SUD score, indicating that a single administration of Fasadionol has the potential to reduce rapidly anxiety symptoms during an anxiety-provoking situation, similar to perhaps how a rescue inhaler used on demand helps a person with asthma. To recap, this was a U.S., multi-center, randomized, double-blind, placebo-controlled phase three trial consisting of four visits by subjects to a clinic that were spaced out a week apart. A screening visit, a baseline setting public speaking challenge after administration of a placebo nasal spray, a second public speaking challenge where patients were randomized to either fastidionol or placebo, then a follow-up safety visit. Stud scores were captured at one-minute intervals throughout each public speaking challenge, and physician and patient assessment of improvement were captured after the second speaking challenge was completed at visit three. In order to progress to randomization at the second public speaking challenge, or visit three, subjects had to exhibit high levels of anxiety during the first public speaking challenge, the baseline challenge. Patients in the study were confirmed SED patients. with a score of 70 or above on the Leibowitz Social Anxiety Scale, which is commonly referred to as the LSAS, without other primary psychiatric disorders and not currently receiving active CNS medications. In total, 141 subjects were randomized in the trial, 70 on Fasadienol and 71 on placebo. The total enrollment reflects the pause in enrollment after we received top-line results from Palisade 1, to allow for independent biostatisticians to conduct an interim analysis of the 141 patients who were randomized and had completed the trial up to the date of the pause. Although the results of the independent interim analysis indicated the continuation of Palisade 2 would not be futile, for business reasons, we elected to extend our pause of Palisade 2, pending our assessment of the then impending top line results of our Palisade open label safety study, the results of two SAD public speaking challenge studies conducted by peer companies, further discussions with the FDA regarding the continuing acceptability of the LSAS as the primary efficacy endpoint in phase three studies for the treatment of SAD, as well as a comprehensive assessment, very important assessment, of the expense, time, statistical and regulatory implications, and logistical challenges associated with resuming policy two. Following positive results from our Palisade open label study, the results of the two SAD public speaking challenge studies conducted by peer companies, each of which did not meet their primary efficacy endpoint as measured by the SUDS, and our positive discussions with the FDA in early 2023 about the continuing validity and reliability of the LSAS as a primary efficacy endpoint, For strategic reasons, we chose to close Palisade 2 with 141 completed subjects rather than resume the study and randomize an additional 67 subjects for a total of 208 subjects as originally planned. It's very important to note that through this process, Palisade 2 was not altered in any way. It was simply stopped early with an intention to treat population of 141 subjects instead of the originally planned 208. The statistical analysis plan was followed as originally planned. It was similar to Palisade 1 and did not require a type 1 error correction because the study was not altered and the blind was never compromised as a result of the interim analysis. The primary endpoint in Palisade 2 was a difference in mean SUD score during the public speaking challenge at visit 2 baseline and visit 3 treatment for patients who received facet INL compared to placebo. Pathodontal treated patients demonstrated a statistically significant greater change in least squares means SUD score with a reduction of 13.8 points compared to a reduction of 8 points for a difference between groups of 5.8 with a p-value of 0.015. We believe these results to be clinically significant, especially considering the They're based on a single dose of fastidinol in a highly provocative public speaking challenge and are supported by high responder rates captured in the secondary and exploratory endpoints. The study had a secondary endpoint, the Clinical Global Impressions Improvement Scale, or CGII. Fastidinol demonstrated a statistically significant difference in the proportion of clinician-assessed responders versus placebo as measured by the CGII. Responders were identified as those who were rated as very much less anxious, or much less anxious after visit three, with 37.7% of Fasadionol-treated patients rated as responders as compared to 21.4% of those treated with placebo, with a p-value of 0.033. To watch these results clearly demonstrate that physicians were able to recognize the improvement in patients on Fasadionol, even with a full week between the two public speaking challenges. The PALS-A2 study also had an exploratory endpoint, patient's global impression of change scale, or PGII. Very excited by the patient's ability to recognize their improvement on fasodionyl because responders were identified on that scale as those who self-rated very much less anxious or much less anxious after visit three. An impressive 40.6% of fasodionyl-treated patients rated themselves as responders. as compared to only 18.6% of those treated with placebo with a p-value of .003. This responder rate of more than double the rate of placebo clearly illustrates to us that patients could appreciate the improvement in their ability to deliver their speech and is highly relevant clinically. When you think about the potential for patients to engage with less fear and reduced avoidance of their anxiety-provoking events and situations, especially as they continue to use Fasadionil over time, as we saw from LSAS data in our placebo-controlled Phase II crossover study and our open-label, palisade open-label study. In addition, other than the other important exploratory endpoint, the percentage of Fasadionil patients who improved by 20 or more SUDS points at visit three was almost double the rate of placebo, with 35.7% of fasciodontal patients dropping by 20 or more points compared to 18.6% on placebo. A 20-point drop is very clinically relevant and likely makes a difference in improving patients' ability to engage in an anxiety-provoking event. From a safety standpoint, similar to all of the prior studies of fasciodontal completed to date, including our large palisade open-label study, that included 481 subjects and over 30,000 doses of Fasadionol that were administered in that study. Fasadionol in Palisade 2 was well tolerated with no serious or severe adverse events, and there was no treatment emergent adverse event occurring at a rate above 1.5%. So, now let's compare the primary endpoint in Palisade 2 to the primary efficacy endpoint result in Palisade 1. As many of you know, it's not uncommon in mental health studies to have both positive and negative studies in separate studies of similar design, particularly true of the subject scales that, given the subject scales that have to be used in such studies and the potential for high and unexpected variability and placebo effects as we saw in PAL-SAID-1. This becomes even more likely when you add the task of consistently administering a complex public speaking challenge across numerous sites, during an unprecedented pandemic, public health crisis, and mental health epidemic. The key difference in the outcome of Palisade 1 compared to Palisade 2 was a much higher placebo effect in Palisade 1. The drug effect in both studies was similar. This was generally true across the primary, the secondary, and the exploratory endpoints. The end results of the primary endpoint in Palisade 1 was the least squares mean change in suds from visit two to visit three of 15.6 points for Fasadinol and 17.3 points for placebo, with a p-value of 0.506. We firmly believe that the systemic variability introduced by the pandemic contributed to these very unexpected and very different results between these two studies. A large portion of Palisade 1 was fielded in 2021, through the height of the second wave of the pandemic, while the vast majority of Palisade 2 was fielded in 2022, as the acute phase of the pandemic had subsided. This dynamic likely impacted Palisade 2 disproportionately in terms of patient mindset, study protocol execution, and study oversight. Subjects randomized in 2021 likely were given were different. given the overall level of anxiety and uncertainty and general unrest, restrictions, mask wearing, and the like during the acute phase of the pandemic. The high placebo rate in Palisade 1 also may have attributed to logistical issues caused by COVID-19 and 21, such as high site and CRO employee turnover, absenteeism, changes in time lapses between visit 2 and visit 3 due to unpredictable and intermittent clinical site closures. and patients postponing travel, delayed monitoring visits, and the like. As these dynamics became apparent as the acute phase of the pandemic subsided in early 2022, we also initiated retraining and renewed monitoring of sites as is customary with staggered start replicate studies. And that, too, may have had a much larger impact on Palisade 2 since it was completed before the majority of patients went through that study. We view the results of Palisade 1 as an outlier. driven by the aforementioned reasons, and we are highly confident in the potential of FASTA-DINL in future studies, given multiple positive Phase II studies, efficacy seen on the exploratory endpoint in the Palisades open-label study, and now the strong results in our placebo-controlled Phase III Palisade II trial. This is especially meaningful After the recent multiple failures in SED studies by peers, it may have been subject to similar systemic variability from the pandemic. With the statistically significant and clinically meaningful results of Palisade 2, we're now positioned to move our Phase 3 development plan forward with the additional studies needed for a potential NDA submission, including a Palisade 3 trial and a fearless trial. allowing us to not only confirm the acute benefit of Fasadionol, but to confirm what we've also long believed, that the acute use of Fasadionol for SAD events continued over time will lead to a reduction in disease severity. Coupled with the safety and tolerability profile we've already demonstrated, we believe Fasadionol will be the ideal approach to SAD treatment in the future. Preparations are now underway to initiate these next studies. Protocol for Palisade 3 will be substantially similar to Palisade 2, with SUDS, again, as the primary efficacy endpoint in clinic-based public speaking challenges. And the study design of FEARLESS will be substantially similar to the multi-week real-world registration trials for the only three drugs approved for the treatment of SAD decades ago, using the LSAS as the primary endpoint. As a new class of medicines, our five-candidate ferrine nasal spray pipeline holds the potential to transform the treatment landscape across numerous therapeutic areas. At the head of the class stands Fasadienol's potential, as demonstrated in the Phase III Palisade II trial. That set the stage for the first fundamentally new class of medicine for individuals living with SAD in more than 20 years. Positive Palisade II data bolster our growing collection of evidence, supporting future clinical studies of Fasadienol across several disorders and gives us further confidence in the promise of our fairing pipeline's untapped potential overall. We've had some recent advancements in our other fairing programs, so let's take a brief look at those. Results from our successful U.S. Phase I trial of Ytruvone, previously referred to as PH10, built on successful Phase I studies and a positive, randomized, double-blind, placebo-controlled Phase IIa study of itruvone in major depressive disorder, or MDD. It was previously conducted in Mexico. And stage itruvone now for Phase IIb development in the United States as a standalone, rapid-onset, varying product candidate for the treatment of MDD. The U.S. Phase I trial was randomized, double-blind, placebo-controlled, and investigated the safety and the tolerability of a single dose and multiple doses of vitruvone nasal spray in healthy adult subjects. There were no reported serious adverse events or discontinuations that were due to adverse events in the study. Overall, vitruvone nasal spray was well tolerated and demonstrated a favorable safety profile consistent with all prior clinical studies of vitruvone. For vitruvone, we also reported important preclinical data of radiolabeled intranasal vitruvone in laboratory rats which further validate its potential to treat MDD without systemic absorption. These new data additionally support the proposed mechanism of action of a true bone nasal spray as binding to receptors of peripheral hemisensory neurons in the nasal cavity, but not to neuronal receptors in the brain, thereby limiting transporter molecules to the circulatory system and minimizing potential systemic exposure. As was the case when We completed a similar study with vasodilinol. These preclinical data further the substantial body of evidence supporting iTrueBone's favorable safety profile. We're continuing our preparations for advancing into phase 2B development of iTrueBone for MVD in 2024. We're also very excited about our PH80 fairy nasal spray, which has been highly studied in multiple indications. We recently reported a positive exploratory phase 2A trial of PH80 nasal spray, which provides new optimism for the acute treatment of moderate to severe vasomotor symptoms or hot flashes in women due to menopause. In a randomized double-blind placebo-controlled exploratory phase 2A clinical study of PH80, it was designed to explore the efficacy, safety, and tolerability of PH80 for the acute treatment of menopausal hot flashes in women. PH80 induced a significant reduction in the daily number of hot flashes compared to placebo at the end of the first week of treatment, and the improvement was maintained through each treatment week until the end of the treatment period. Baseline subjects reported a mean daily number of hot flashes of 7.7 in the PH80 group of 18 subjects and 8.0 in the placebo group of 18 subjects as well. After one week of treatment, the number of hot flashes dropped to 2.8 in the PH80 group and 6.4 in the placebo group for a p-value of less than 0.001. And after four weeks of treatment, the number of hot flashes dropped to 1.5 in the PH80 group and 5.1 in the placebo group for a p-value of less than 0.001. PH80 treatment also significantly reduced the severity and the disruption in function and sweating related to hot flashes during the treatment period as compared to placebo. PH80, as our other pharynx, was well-tolerated, no serious adverse events, and the adverse event profile comparable between PH80 and placebo. All 36 subjects completed four weeks of treatment, and no subject discontinued participation in the study as a result of adverse events. One of the favorable aspects of running additional trials in this particular indication is that there will be objective measures for these studies. That is to say, it's easier to measure how many hot flashes are experienced and their frequency of those symptoms versus more subjective endpoints that we have seen in some of the other studies and different indications. Given the depth of our entire CNS pipeline and the robust body of successful safety and efficacy studies to date, We are also pursuing multiple potential strategic development and commercialization partnerships, both global and regional, to efficiently unlock the full value of our product candidate portfolio. We believe global and regional partnerships, especially for commercialization, to amplify our internal expertise and development activities and potentially accelerate key development timelines and enhance overall our efforts to deliver differentiated treatment options. So now for some brief comments about our financials. We've been able to reduce our cash burn rate, as you will see in our to-be-filed 10Q shortly, and we've been implementing corporate initiatives to streamline operations in order to conserve our resources. We do not anticipate any significant near-term cash burn increases. As for our cash position, we've recently taken advantage of the unusually high trading volume in our stock to strengthen the cash position on our balance sheet by over an expected $30 million in gross proceeds. To put this high trading volume into perspective, more than $1 billion worth of our stock has traded since the announcement of the Palisade II results on Monday, four trading days ago. As is industry standard, we established an at-the-market agreement with Jefferies over two years ago, back in May of 2021. Until just recently, we'd only used this very sparingly back in calendar Q3 of 21. We will continue to be very judicious in how we use this vehicle going forward, and we have plenty of capacity remaining under ITM to further strengthen our balance sheet, should we wish to do so, as well as other strategic financing options and potential non-dilutive grants and partnering arrangements. So in closing, we remain steadfast in our core mission to improve mental health and well-being worldwide. As we continue advancing the next stages of our corporate development plan, we move forward with a solid team, a strong pipeline, and an unwavering drive to innovate better solutions for CNS disorders in large primary care markets with significant unmet needs. So, on behalf of the Visigyn team, I'd like to thank you again for the privilege, for the opportunity to make a difference.