Greetings, and welcome to the Vistagen Therapeutics Fiscal Year 2024 Q1 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 zero. As a reminder, this conference is being recorded Thursday, August 10, 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 Vistagen's Q1 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 Vistagen 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 Q1 Form 10-Q for the period ending 30 June 2023, and in future filings that we make with the SEC from time to time. All of which are and will be available on our website and the SEC's website. With that taken care of, we'd like to thank and welcome all the stockholders, analysts, and everyone taking an interest in Vistagen. 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 3 PALISADE-2 trial, evaluating the efficacy, safety, and tolerability of Fasedienol, PH94B, nasal spray in adults with social anxiety disorder, or SAD, followed by a brief opportunity for questions from sell-side 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, Shawn Singh, to update you on our recent inspiring news regarding the PALISADE-2 Phase 3 study results.
Thank you, Mark, good afternoon, everyone, 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. 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 this 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. 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 3 study has brought new optimism for treatment of social anxiety disorder, and we are thrilled to be in a leadership position with the compelling top-line results from our Phase 3 PALISADE-2 trial that were announced on Monday.
These Phase 3 results highlight the potential for Fasedienol, with its innovative proposed mechanism of action, to transform what's possible for millions of individuals living with SAD in the U.S. and millions more who are affected worldwide. In the PALISADE-2 study, Fasedienol demonstrated a rapid and clinically meaningful reduction in the Subjective Units of Distress Score or SUDS, SUDS score, indicating that a single administration of Fasedienol 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 3 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 Fasedienol or placebo, then a follow-up safety visit. SUDS 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 SAD patients with a score of 70 or above on the Liebowitz 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 Fasedienol 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 a primary efficacy endpoint in Phase 3 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 PALISADE-2. 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. 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 randomized 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 I 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 SUDS score during the public speaking challenge at visit two baseline and visit three treatment for patients who received Fasedienol compared to placebo. Fasedienol-treated patients demonstrated a statistically significant greater change in least squares means SUDS score, with a reduction of 13.8 points compared to a reduction of eight 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 they're based on a single dose of Fasedienol 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 CGI-I.
Fasedienol demonstrated a statistically significant difference in the proportion of clinician-assessed responders versus placebo, as measured by the CGI-I. Responders were identified as those who were rated as very much less anxious or much less anxious after visit three, with 37.7% of Fasedienol-treated patients rated as responders, as compared to 21.4% of those treated with placebo, with a p-value of 0.033. To us, these results clearly demonstrate that physicians were able to recognize the improvement in patients on Fasedienol, even with a full week between the two public speaking challenges. The PALISADE-2 study also had an exploratory endpoint, Patients' Global Impression of Change scale, or PGI-I. Very excited by the patient's ability to have recognized their improvement on Fasedienol 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 Fasedienol-treated patients rated themselves as responders, as compared to only 18.6% of those treated with placebo, with a p-value of 0.003. 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 reduce the avoidance of their anxiety-provoking events and situations, especially as they continue to use Fasedienol over time, as we saw from LSAS data in our placebo-controlled Phase 2 crossover study and our open-label PALISADE open-label study.
In addition, other than the other important exploratory endpoint, the percentage of Fasedienol patients who improved by 20 or more SUDS points at visit three was almost double the rate of placebo, with 35.7% of Fasedienol 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 Fasedienol completed to date, including our large PALISADE open label study that included 481 subjects and over 30,000 doses of Fasedienol that were administered in that study. Fasedienol 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%.
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 PALISADE-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 result of the primary endpoint in PALISADE-1 was a least squares mean change in SUDS from visit two to visit three of 15.6 points for Fasedienol 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 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 contributed to logistical issues caused by COVID-19 in 2021, such as high site and CRO employee turnover, absenteeism, changes in raters, time lapses between visit two and visit three 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.
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 Fasedienol in future studies, given multiple positive Phase 2 studies, efficacy seen on the exploratory endpoint in the PALISADE open label study, and now the strong results in our placebo-controlled Phase 3 PALISADE-2 trial. This is especially meaningful after the recent multiple failures in SAD studies by peers that 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 Fasedienol, but to confirm what we've also long believed, that the acute use of Fasedienol for SAD events continued over time, will lead to a reduction in disease severity. Coupled with the safety and tolerability profile we have already demonstrated, we believe Fasedienol 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.
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 pherine nasal spray pipeline holds the potential to transform the treatment landscape across numerous therapeutic areas. At the head of the class stands Fasedienol's potential, as demonstrated in the Phase 3 PALISADE-2 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-2 data bolster our growing collection of evidence, supporting future clinical studies of Fasedienol across several disorders and gives us further confidence in the promise of our pherine pipeline's untapped potential overall.
We've had some recent advancements in our other pherine programs. Let's take a brief look at those. Results from our successful U.S. Phase 1 trial of Itruvone, previously referred to as PH10, build on successful Phase 1 studies and a positive randomized, double-blind, placebo-controlled Phase 2A study of Itruvone in major depressive disorder or MDD that was previously conducted in Mexico. Stage Itruvone now for Phase 2B development in the United States as a standalone, rapid onset, pherine product candidate for the treatment of MDD. U.S. Phase 1 trial was randomized, double-blind, placebo-controlled, and investigated the safety and the tolerability of a single dose and multiple doses of Itruvone 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, Itruvone nasal spray was well tolerated and demonstrated a favorable safety profile, consistent with all prior clinical studies of Itruvone. For Itruvone, we also reported important preclinical data of radiolabeled intranasal Itruvone 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 Itruvone nasal spray as binding to receptors of peripheral chemosensory 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 flibanserin, these preclinical data further the substantial body of evidence supporting Itruvone's favorable safety profile. We're continuing our preparations for advancing into Phase 2B development of Itruvone for MDD in 2024.
We're also very excited about our PH80 pherine 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, that was designed to explore the efficacy, safety, and tolerability of PH80 for the acute treatment of menopausal hot flashes at 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. 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 pherines, was well tolerated, with 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 in 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. 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 10-Q shortly. 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-2 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 2021.
We will continue to be very judicious in how we use this vehicle going forward, and we have plenty of capacity remaining under our ATM 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. 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, strong pipeline, and an unwavering drive to innovate better solutions for CNS disorders in large primary care markets with significant unmet needs. On behalf of the Vistagen team, I'd like to thank you again for the privilege, for the opportunity to make a difference.
Thank you, Shawn. Jennifer, we'd now like to open up the call for questions from the sell-side analysts participating on the call today.
Thank you. If you would like to register a question, please press the one followed by the four on your telephone keypad. You will hear a three-tone prompt to acknowledge your request. If your question has been answered and you would like to withdraw your registration, you can press the one followed by the three. Our first question is from the line of Andrew Tsai from Jefferies. Please go ahead.
Hey, everyone. Good afternoon. Thanks for taking my questions, I wanted to offer a big congratulations on the recent data. N ow that you have PALISADE-2 on hand, how confident are you this study could be one of two traditionally supportive, placebo-controlled, pivotal Phase 3 studies for a filing? Then second to that is, do you think you'll meet with the FDA? If so, when could we get a resolution on the next steps in the NDA package? Thanks.
Well, thanks, Andrew. I appreciate the question, and thanks for the congratulations. It's certainly enabling. Whether the FDA accepts the trial as pivotal, that's always to be determined downstream by the FDA. There's no doubt in our mind, we didn't change anything. It's the only difference, as I noted, was the number of subjects. There's no Type I error, there's no protocol amendment, there was no deviation at all from the original plan other than the number of subjects.
Having a highly stat sig result with the profound safety profile that we've seen now in hundreds and hundreds of patients that have been exposed to Fasedienol, you already remember, we had FDA feedback regarding abuse liability and a favorable amount of feedback from the FDA, and that was even before our open label study delivered the results we reported. I like where we stand. Having something in this disorder with a validated endpoint, with highly stat sig data and clean safety data, I really like our chances. It's certainly going to be a key pillar in our NDA submission downstream, should we get to that point with additional studies. At least one additional study.
Got it. Then, now that you're going to do a PALISADE-3, as we think about the potential outcomes, do you think PALISADE-3 would look similar to what you saw in PALISADE-2 or something even better? Because, I don't know, PALISADE-2, there's maybe some COVID going on, but the counterargument would be maybe there's some expectation bias, due to the positive results. How are you thinking about the outcome of PALISADE-3 and why?
Well, I think there's a lot of reasons, of course, to be confident about our next couple of steps in the PALISADE-3 direction. First, certainly, the world isn't really controlled anywhere near to the degree it was in the pandemic, and that obviously impacts the entire ecosystem associated with executing successful clinical studies. There's a lot of lessons learned that we have been able to gather from a deconstruction of PALISADE-1, for sure, and I suspect we will from PALISADE-2. Things like subjects will have an olfactory smell test. W e'll have restrictions on use of nasal swabs up front of the event. There's several things that are associated with just modest amendments to the protocol, but they're positive lessons that you typically learn when you stagger starts of studies.
That plus the training that we've done, the proprietary training models that we have, all up and down every aspects of conducting that type of study, I don't think there's anybody better to conduct and more expertised to conduct a public speaking challenge in a Phase 3 setting than we are. I have no reservations about that. I like our chances going into the study. I like the expertise we have internally. I like the four sixth standards that we've got in our network outside the company. Certainly, Dr. Liebowitz plays a key role in our ability to be successful with this clinical program, with this drug. Yes, we're excited.
Got it. Okay. Speaking of PALISADE-2, going back to the data, when could we expect you to share detailed results at a medical meeting or a publication? I t would be great to see the curves of SUDS and so forth. Secondly , you've compared PALISADE-2 to PALISADE-1 and explained the differences, but can you also compare to the prior Phase 2 study and maybe compare and contrast any efficacy differences that you saw? Were there different baseline SUD scores, for instance, between these two studies? Help us reconcile any differences. Thank you.
Thanks. Well, first to your question about the data w e're this obviously falls into industry standard breaking news, we're trying to find a nice place to present the Phase 2 data, in a breaking news context. Hopefully, sometime this fall, I think, would probably be the earliest. We'll have more information on that as we go forward. Certainly, abstracts and the like are already, in circulation. Then as to your questions about as to PALISADE or to the Phase 2 studies, obviously, it's a different environment. That's a three study or three-site study. Josh Prince, I want you to actually just address this, just briefly, some of the things that we see.
Yes. Hi. Thanks, Shawn. Hi, everybody. Just to fill in the, space there, I think the key is the time difference. When we think about how long it's been since those earlier Phase 2 studies were done, and you think about just the environment that we live in today versus then and through the pandemic, we think that has an effect. Overall, the efficacy seen for both PH94B and placebo in that Phase 2 study was everything was shifted up compared to what we've seen with PALISADE- 2 and PALISADE- 1. We really do think it has to do with , again, the times and t he types of patients and conducting a study through the pandemic.
All right. Thank you very much.
Thanks, Andrew.
Our next question is from the line of Joanne Lee from Maxim Group. Please go ahead.
Hi, good afternoon. Thanks for taking the questions, and congratulations on the successful outcomes of the recent Phase 3. The results were truly remarkable. Just, given Fasedienol achieved positive results in now both PAL2 and the open label study, could you provide some insight on the rationale behind choosing to pursue both SUDS and LSAS as primary measures in the PAL3 and FEARLESS studies? Was this decision influenced by any guidance from the FDA? Just curious on that.
Well, thanks, Joanne, first of all, for the question. It's a great question. Look, we've long held the way that we think Fasedienol can help people is two distinct ways. It can certainly help people, as we've shown in PALISADE-2, in an acute setting. A s they take it out of their pocket or their purse or their backpack, and they use it on demand in a patient-tailored way, it has the ability to knock down very rapidly those symptoms. That's what PALISADE-2 showed. We also have placebo-controlled Phase 2 data and some exploratory data from the open label, lots of subjects, that also when it's used acutely, but used over time, it increases the confidence of a person. It increases their resilience, and it reduces their tendency to avoid situations that could benefit their lives.
It reduces the opportunity costs in their lives. T he reduction in avoidance of engaging in social and performance situations, is important. The Liebowitz scale captures both of those. We're at a perfect spot right now because we've got one successful study in Phase 3, and you only need two adequate and well-controlled studies to get an approval of a drug. It could either be from a PALISADE -3 or it could be from a FEARLESS. Either way, what we're trying to do is look to the most efficient path to get this drug to patients as soon as possible, onend it's one of those two tracks. It could be both, but you only need one other besides the one we've got. At least that's our opinion at this point.
Doing the LSAS-based study, again, it's consistent with the only three drugs ever approved for treatment of social anxiety disorder. That was the primary efficacy endpoint. We needed to make sure, and we did find this out in the Q1, that the FDA still believed that to be a valid and reliable endpoint, and they do. That provides optionality there. The other side is, well, we already know what they think about the SUDS endpoint in the PALISADE program. Importantly too, we have a keen interest, given that social anxiety disorder is normally, the onset is typically in adolescence, between, say, ages eight and 17. There's a huge number, as we know, of minors who are affected with mental health disorders, especially social anxiety disorder.
The Liebowitz scale, there's an LSAS-CA, which is for children and adolescents, so much easier down the road when we want to extend our treatment opportunity to pediatrics to run a Liebowitz scale-based study using a modified version of that scale, similar to the way that the adult study was run. Very difficult to envision a 10-year-old giving a public speech to a group of strangers. Just a much easier to execute down the road in a pediatric setting as well. It's really a nice combined set, either one of the two. Ideally, we see both, and then you have a very robust commercial opportunity that extends into the pediatric arena.
Got it. That was really helpful. C learly lots of excitement around the SAD program, but we're also really enthusiastic about the broader pherine platform as well. Could you shed some color on the current statuses and progress of those programs, PH10, PH15, and PH80, particularly on the latter, PH80, with the positive preclinical data? W e see the hot flash and other symptoms of menopause receiving a lot more attention in the area of women's health. Curious if you could walk us through some of the timelines around those programs. Thank you.
Sure. Well, first, with respect to Itruvone or PH10, that's now, after a bit of a long run, it's staged to go into Phase 2B development in the U.S. T he efficacy study was run outside the U.S., we really had to start back to the point of a U.S. IND-enabling program. For that one, because there had been no prior U.S. activity or no prior U.S. IND, we did a whole standard battery of non-clinical studies followed by a small Phase 1 to then now be able to leap back over, we believe, the Phase 2A that was done and move into Phase 2B. It's a tremendously exciting program, given what we just also learned, that 94B or Fasedienol, there's no meaningful systemic exposure.
The kinds of safety profile benefits that we see from Fasedienol are also in the Itruvone zone. Meaning that we don't anticipate sexual side effects, we don't anticipate weight gain, we don't anticipate many of the types of side effects and safety concerns that are associated with the currently approved systemic therapy. I'm very excited about that as a standalone treatment for major depressive disorder. As to PH80, again, you hit it. Hot flashes is hot right now. With the new NK3 antagonist that was approved, there's been a lot more interest of late in that space. There's an enormous population, of course, that's affected by hot flashes for many years, with very limited options that don't cause some concern, whether it's hormonal therapy or the new class.
PH80 is majorly distinguished from both of those, current treatment options and the antidepressants that are used for hot flashes. Again, like Fasedienol and Itruvone, we don't believe it's systemically absorbed. We think, again, that it also has the ability, with neural circuitry that's associated with temperature, to be able to reduce the daily number of hot flashes that, just as we saw in the Phase 2A study, but also the severity of those hot flashes and the types of things that disrupt lives, so sweating and function and the like.
It's exciting that the challenge with that one is, like PH10, we've got to go through what probably will be about a 12 to 15 months IND-enabling program, where we do the CMC work and the preclinical work that's needed to get back into a Phase 2B setting. The difference with this one is that there was a prior U.S. IND, we don't think we need to do a Phase 1 study in order to get into Phase 2B for this indication. I t's not a lot of money. It's less than $2 million for these IND-enabling programs. We have to do similar work with PH15 and PH284, the other two pherine assets in the pipeline. That's the status of both.
Got it. Thank you for all the additional details. Once again, congratulations, and looking forward to more updates this year.
Thanks, Joanne.
Our next question is a follow-up from the line of Andrew Tsai with Jefferies. Please go ahead. Andrew, your line is live. Please proceed with your question.
Thank you. Just a couple of more questions. Thank you so much for the time. I mean, going back to PALISADE-2, there does seem to be a consistent efficacy signal across various endpoints. Just wanted to make sure, were there other pre-specified efficacy measures part of the study? If so, how did those look? Just wanted to make sure all pre-specified measures separated from placebo in a stat sig manner. Thanks.
Sorry, Andrew. You asked if there was a separation against placebo across all the endpoints. There was the primary, one secondary, and two exploratories, and we reported on all those, so four total.
Okay, great. G oing to the eventual label, if both PALISADE and FEARLESS succeeded, what would your eventual label look like for SAD? Would there be precedents around that label claim? Thank you.
No, there is no precedent for an acute treatment for social anxiety disorder. We would be the first to blaze that trail with Fasedienol. Drugs are used, benzodiazepines, for example, try to achieve that, but with considerable risk of abuse, misuse, and addiction. T hey're not approved for the treatment of social anxiety disorder. Only the three antidepressants, the two SSRIs and Wellbutrin, they are approved for the chronic condition. T here likely would be no limit, in our opinion, on how frequently somebody could use the drug acutely if it's PALISADE-2 plus PALISADE-3 that supports the label initially.
If later, eventually, FEARLESS came along and the staggered starts, is what we anticipate with PALISADE-3 first and FEARLESS second, sometime in 2024, it would be a case where the drug would be used acutely, as needed, but over time. What you try to achieve for someone ultimately at the end of the day, is they wouldn't have to take the drug. That's often and hopefully still also combined with talk therapy. T he PALISADE-2 hits the acute side of that match set. FEARLESS would hit the over time, although certainly people wouldn't be precluded from using Fasedienol over time if what's achieved is only the acute label.
Got it. Really quickly, as we think about the NDA package in the future, any peripheral studies that you would need to do, such as repeat just multiple dosing, per day studies, for instance? Thank you.
Sure. We'll do open label extensions on each of the two, the PALISADE-3 and the FEARLESS study, so that there still has to be a safety database that gets established. Then the redose study that you mentioned, sure, I think that's something we've reported before. FDA wants to see what happens if someone uses the drug twice instead of just once in that acute setting. That's something we will, before NDA, that's a small study that we'd likely be completing. Most likely, that'd be using a public speaking challenge as well. Not too many subjects, not too expensive, but again, trying to, not so much for safety, and we don't really worry about multiple uses in a short period of time, but I think there is some interest at the agency in wondering whether more is better.
We've certainly established that 3.2 micrograms use PRN, is good in PALISADE-2. If better is available, great, but it won't be an essential component for going forward in PALISADE-3 or the FEARLESS study.
Got it. Actually, very last one, because you don't have much opportunity on conference calls. In the study results, did PH94B work equally as well between males and females? That's the last question. Thank you.
I think that's something we'll be able to unpack. We don't have the full data set fully unpacked. We have the top-line results, so that takes a little bit of time. I don't think we see, and we've long held since. T hat was, I think, a long, long time ago, that was the question. We don't think there's any reason to believe the drug doesn't work as well in women as in men, or men as in women, whichever way you want to put it. FEARLESS will give us.
Great. Thank you.
Yes. Okay.
Thanks. Congrats.
Thank you.
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Excellent. Thank you, Jennifer, for your help today, thank you, Andrew and Joanne. We appreciate your questions. If there are any additional questions, please do not hesitate to contact us by emailing ir@vistagen.com or contacting the individuals listed in our press release issued today or on our website. We also encourage you to sign up on our website to stay connected with the latest news from Vistagen. Thank you for participating in our call today. We appreciate everybody's attention and support. We look forward to keeping you current on our continuing progress. This concludes our call. Have a fantastic day. You may all hang up.