Earnings Call Transcript - VTGN Q4 2024

Operator, Operator

Greetings, and welcome to the Vistagen Therapeutics Fiscal Year-End 2024 Corporate Update Conference Call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Mark McPartland, Senior Vice President of Investor Relations.

Mark McPartland, Senior Vice President of Investor Relations

Thank you, Joe. Good afternoon, everyone, and welcome to Vistagen's fiscal year-end 2024 corporate update conference call and webcast. This afternoon, we filed our annual report with the Securities Exchange Commission or SEC on SEC Form 10-K for our fiscal year ended March 31, 2024, and issued a press release providing an overview of our progress during our fiscal year 2024. We encourage you to review the press release and our 10-K, both of which can be found in the investor section of our website. During today's call, we'll make forward-looking statements regarding our business based on our current expectations and information. These 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 statements 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 make today. Additional information concerning risks and factors that could affect our business and the financial results is included in our fiscal year-end 2024 Form 10-K filed today with the SEC, and in the filings that we'll make with the SEC from time to time in the future. All of which are available in the Investors section of our website and/or on the SEC's website. With the formalities out of the way, we offer a warm welcome to all of our stockholders, sell-side analysts, and others interested in Vistagen. I'm joined on our call today by Shawn Singh, our Chief Executive Officer; Cindy Anderson, our Chief Financial Officer; and Josh Prince, our Chief Operating Officer. Shawn will provide an update on our lead programs in our diversified neuroscience pipeline. After the conclusion of the prepared remarks, there will be a brief opportunity for questions from the sell-side analysts. The call is being webcast and will be available for replay after completion. The replay link can also be found in the Investor section of our website. With that, I'd like to turn the call over to our Chief Executive Officer, Shawn Singh.

Shawn Singh, CEO

Thank you, Mark. Good afternoon, and thank you for joining our call. Vistagen's fiscal 2024 was filled with a series of remarkable accomplishments. Most notably, with the positive results from our PALISADE-2 U.S. Phase 3 study of fasedienol for the acute treatment of social anxiety disorder, Vistagen became the first company to achieve a positive Phase 3 study with a drug candidate for the acute treatment of SAD. In addition, with the potential to complement PALISADE-2, we recently launched our PALISADE-3 Phase 3 trial, marking that as the next major step forward in our registration-directed PALISADE-Phase 3 program for fasedienol and SAD. These significant achievements and progress across our diversified pipeline of novel neuroactive pherine candidates reflect our commitment to pioneering neuroscience that's anchored in a deep understanding of nose-to-brain neurocircuitry, focused on developing differentiated drug candidates with the potential to set new standards of care for underserved patients affected by high-prevalence neuroscience disorders. As a brief reminder to some and as an introduction to others, our diverse clinical-stage neuroscience pipeline features a new class of neuroactive intranasal product candidates known as pherines. Exclusively designed as nasal sprays, our pherine pipeline leverages an innovative approach to treating psychiatric and other neuroscience disorders by using the nose as a portal for the administration of novel rapid-onset, neurocircuitry-focused drug candidates that do not require systemic absorption or binding to neurons in the brain to achieve desired therapeutic effects. Administered in microgram-level doses within milliseconds, each member of our new class of pherines activates peripheral chemosensory neurons in the nasal cavity, influencing fundamental neurocircuitry in both the olfactory system and the brain. With unique proposed mechanisms of action or MOAs, our non-systemic, neurocircuitry-focused pherines have demonstrated favorable and differentiated safety profiles in all clinical studies completed to date. Our aim is to develop and commercialize a diversified pipeline of neuroactive pherines for multiple high-prevalence CNS disorders, such as social anxiety disorder, major depressive disorder, and menopausal hot flashes, indications with limited differentiated FDA-approved treatment options and inadequate or even non-existent current standards of care. For example, social anxiety disorder, which is a neuropsychiatric disorder that's marked by profound fear and anxiety of social and performance situations in everyday life, often triggered by social media and team orientation in the workplace or in academic settings, affects more than 30 million U.S. adults. Yet, despite the high and seemingly ever-growing prevalence of SAD, there is still no FDA-approved acute treatment to help individuals rapidly and safely manage their anxiety symptoms when faced with social and performance stressors in their everyday life, especially when they are faced with multiple different anxiety-provoking stressors during any single day. Our Phase 3 program for fasedienol intends to help close that treatment gap for the millions of underserved individuals affected by SAD without an adequate option for a rapid, flexible, and patient-controlled treatment. Building on our success during fiscal 2024, our registration-directed PALISADE-Phase 3 program for fasedienol for the acute treatment of SAD is progressing on track, including enrollment in our recently launched PALISADE-3 trial, which is on track for top-line data mid-year in calendar 2025, as well as preparations for our upcoming PALISADE-4 trial that we expect to initiate in the second half of this year and complete before the end of calendar 2025. Both Phase 3 trials are designed with the potential to replicate the successful PALISADE-2 Phase 3 trial. While the public speaking challenge design of PALISADE-2 and the use of the subjective units of distress scale or SUDs as the primary efficacy endpoint remain unchanged, we have built in some notable enhancements to PALISADE-3 and PALISADE-4 and made some operational changes we believe will help optimize quality enrollment, enhance surveillance, and control potential variability, as well as drive rigorous protocol adherence during the execution of PALISADE-3 and PALISADE-4, all against the backdrop of what is now a far more favorable and stable clinical research environment than at any time during the pandemic. During the second half of 2024, we're also planning to initiate a small placebo-controlled repeat-dose study in alignment with our discussions with the FDA to evaluate the effects of a second dose of fasedienol administered 10 minutes after the first dose prior to a public speaking challenge. Like PALISADE-4, we anticipate completing this study in the second half of calendar 2025 with a top-line readout near the end of calendar 2025. We believe success in either PALISADE-3 or PALISADE-4, combined with the positive results from PALISADE-2 and additional open-label safety data from all fasedienol clinical trials to be completed next year, may provide substantial evidence of fasedienol's effectiveness and safety to support submission of a potential U.S. new drug application for the acute treatment of SAD during the first half of 2026, which, if approved, could be the first approval of its kind. As a reminder, the FDA has granted Fast Track designation for our development of fasedienol for the acute treatment of SAD. We are also actively exploring the therapeutic potential of our pherine itruvone, another non-systemic pherine candidate with the potential to be a new and fundamentally differentiated therapy for major depressive disorder or MDD. Preparations and planning for U.S. Phase 2B development of itruvone in MDD are ongoing. Our mission in this large and increasingly prevalent neuropsychiatry market is to transform the standard of care, expediting the timeframe in which individuals may find relief of their MDD symptoms with a new rapid-onset product candidate with a differentiated safety profile that is not associated with unwanted side effects and safety concerns, such as sexual side effects, weight gain, or abuse liability. We also see significant medical and commercial potential in PH80, our rapid-onset, non-systemic, hormone-free pherine nasal spray candidate for women's health indications. During fiscal 2024, we announced positive data from two previously unreported placebo-controlled, exploratory Phase 2A studies conducted outside the U.S. PH80 demonstrated statistically significant results both as a treatment for vasomotor symptoms or hot flashes that are due to menopause and for the management of premenstrual dysphoric disorder or PMDD. We're currently conducting U.S. IND-enabling non-clinical studies with the potential to facilitate further Phase 2 clinical development of PH80 for menopausal hot flashes in the U.S., which is another high-prevalence indication affecting approximately 80% of women ages 45 to 65. Current treatment options that are not satisfactory or suitable for millions of those women worldwide. We're also pleased to enter into an exclusive negotiation agreement with Fuji Pharma, which is a leading women's health-focused company in Japan during fiscal 2024, focused on negotiating exclusively for a potential license agreement with them for the development and commercialization of PH80 in Japan. On a corporate level, Vistagen received Mental Health America's prestigious Platinum Bell Seal Award during the first quarter of fiscal 2024, and again in the first quarter of the current fiscal year. We also received the esteemed Great Place to Work certification, each of these awards reflecting our commitment to be a company that exceeds workplace practices and standards intended to promote and support the mental health and well-being of our employees, while also playing a key role in promoting and advancing a broad societal shift toward destigmatizing mental illness. With that, I'll now turn the call over to our CFO, Cindy Anderson, to summarize some of the highlights from our fiscal 2024. Cindy?

Cindy Anderson, CFO

Thank you, Shawn. As Shawn mentioned, I will highlight a few financial results from our fiscal year 2024. I also encourage everyone to review our report on Form 10-K, filed with the SEC earlier this afternoon for additional details and disclosures. Research and development expenses were $20 million for the year ended March 31, 2024, compared to $44.4 million for the year ended March 31, 2023. This decrease in R&D expenses was primarily due to a decrease in clinical and development expenses related to the timing of expenses incurred in our Phase 3 trials of fasedienol and SAD. General and administrative expenses were $14.1 million for the year ended March 31, 2024, compared to $14.7 million for the year ended March 31, 2023. The decrease in G&A expenses was primarily due to a decrease in professional fees and stock-based compensation expense, offset by an increase in compensation expenses. Our net loss attributed to the common stockholder was $29.4 million for the year ended March 31, 2024, compared to $59.2 million for the year ended March 31, 2023. As of March 31, 2024, we had cash and cash equivalents of $119.2 million. As a reminder, please refer to our annual report on Form 10-K that was filed today with the SEC for additional details and disclosures. I will now turn the call back over to Shawn.

Shawn Singh, CEO

Thanks, Cindy. As we conclude our prepared remarks, I just want to underscore the hard work and the commitment, as well as the pride and enthusiasm of our team around our potential to improve the lives of the patients we are focused on helping and to deliver value to our stockholders. With the commencement of our PALISADE-3 and the pending launch of our PALISADE-4 Phase 3 trials for fasedienol targeting the acute treatment of SAD, a market with increasing prevalence now topping 30 million Americans, we are systematically executing our registration-directed program with the potential to achieve the first FDA approval for that indication. We have great confidence in our team's expertise in executing our PALISADE-3 and PALISADE-Phase 3 program and all the programs across our neuroscience pipeline. So on behalf of the entire team at Vistagen, I'd like to thank you for your ongoing interest and support.

Mark McPartland, Senior Vice President of Investor Relations

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

Operator, Operator

Thank you. Our first question comes from Andrew Tsai with Jefferies. Please proceed.

Unidentified Analyst, Analyst

Hey, good afternoon and congrats on the progress. This is Matt on for Andrew, and I just had a couple of questions if you don't mind. In PALISADE-3, how many patients have you enrolled so far? And is enrollment cadence looking stronger or slower than the first couple of studies? And then also, if you don't mind commenting on the screen failure rate and how that compares to the prior studies as well? Thank you.

Shawn Singh, CEO

I'm sorry, I didn't catch your name.

Unidentified Analyst, Analyst

Matt, thank you.

Shawn Singh, CEO

Oh, hey, Matt. So we haven't given any guidance on enrollment at all on specifics of enrollments and screen fail rates and the like. But what I can tell you is what I emphasized during the prepared remarks, which is we're very happy with the way that PALISADE-3 has kicked off. We've been able to build in some really important efficiencies, not only throughout the execution of the study, but upfront even between lead generation and actual enrollment through Visit 1 and the screening. We've been able to achieve a lot of the things that reflect and leverage the lessons learned through the course of the prior execution of studies of this particular design, leading all the way back to Phase 2 time. So I think our team is extremely well positioned to continue this study on track and the same be the case for PALISADE-4 with the ability to achieve the readouts right around the time that we've guided, which would be mid-2025 and then near the end of 2025 for PALISADE-4.

Unidentified Analyst, Analyst

Okay, got it. Thank you.

Shawn Singh, CEO

Josh, do you have anything to add to that? Josh?

Josh Prince, COO

Yes, hello, Shawn. Thank you. I just want to express our satisfaction with the startup of PALISADE-3. It is meeting our expectations regarding recruitment rates and screen failure rates, among other aspects. At this stage, we are very pleased with our progress.

Shawn Singh, CEO

Thanks, Josh.

Operator, Operator

And the next question comes from the line of Paul Matteis with Stifel. Please proceed.

Unidentified Analyst, Analyst

Hi there, this is Julian on for Paul. Thanks so much for taking our question. You described a couple of notable enhancements that you made, things like operational changes, enhanced surveillance, et cetera. Do you mind just providing a little bit more color on what exactly you're doing and why that gives you greater confidence as you continue enrolling PALISADE-3 and soon PALISADE-4? And then just really quickly, one quick question. On the repeat dose study, do you mind telling us just what you're looking to achieve here, and is this more about building the safety database, or is this more about replicating efficacy with a multi-dose paradigm? Thank you.

Shawn Singh, CEO

Great. Hey, thanks, Julian. Appreciate the questions. So just to be clear right up front, the public speaking challenge design will remain the same across PALISADE-2, PALISADE-3, and PALISADE-4, as will the SUDS as the primary efficacy endpoint. So no changes there. Those will continue to remain consistent throughout the development of fasedienol for the acute treatment of SAD. And that's been the case all the way back to Phase 2. The refinements that we made to PALISADE-3 and PALISADE-4 really are based again on experience that we have very unique and extensive experience scaling up to a large Phase 3 study that come from our observations of the conduct of the PALISADE Phase 3 program from the early through the late stages of the pandemic in particular. So the enhancements to PALISADE-3 and PALISADE-4 apply primarily to ensuring that we've got optimal subjects in the study, with extensive, precise, and universally applied screening, inclusion-exclusion criteria, and that the public speaking challenge protocols are administered properly and consistently with limited variability. For example, one of the exclusion criteria that's been added is limiting high-frequency smoking or vaping, THC use, signs of COVID, or any recent nasal swabs, all of which could have some sort of an impact possibly on receptors and impact a single-dose public speaking challenge. Josh, maybe talk about some of the other things that you and the team have been seeing some really significant benefits on as we've even pre-start up and now as we've gotten into the execution of PALISADE-3.

Josh Prince, COO

Yes, absolutely. I think two of the key things you touched on, Shawn, are our experience of going through PALISADE-1 and PALISADE-2, but then also being able to operate in a pandemic-free environment as we got PALISADE-3 up and running and as we look forward to getting PALISADE-4 up and running allows us to really drive consistent execution across sites to reduce potential variability. It’s really around changing our approach to both study monitoring and our staffing model, right? It gives us rigorous training of sites and then oversight of study conduct. So, if you think about where we are with PALISADE-3 compared to PALISADE-1 or PALISADE-2, we had an in-person investigator meeting for PALISADE-3. We had that face-to-face in-person training of PIs, raters, and study coordinators, which we couldn't do in one and two. As we've gotten sites up and running, we’ve already had more in-person site visits in PALISADE-3 than we did in either PALISADE-1 or PALISADE-2, because of the restrictions of the pandemic. So, that new site-facing staffing model is giving us a lot more oversight and increased level of site communication to ensure that the studies are going the way we want them to.

Shawn Singh, CEO

I would also add that we've eliminated mask-wearing in these PALISADE-3 and PALISADE-4 studies by either the subject or the public speaking audience. The drug dose will be administered by the healthcare provider just to ensure proper dosing for the study. So a lot of little things, as well as some significant changes, are all intended to really enhance and optimize surveillance, control variability, and other factors that make a difference in outcomes. But those are some significant mitigators we think will help alleviate some of the risks typically associated with scaling up to a multicenter study. For the repeat dose study, I'll let Josh speak to that in a minute, but again, we're in line with what the FDA has been discussing with us for a while. While there could be some safety benefits from the study, we also believe it could provide labeling benefits. So, Josh, why don’t you just amplify a little more on what we’ve been thinking on the repeat dose study.

Josh Prince, COO

Yes, absolutely. It's essentially the same design as PALISADE-3 and PALISADE-4, just with the addition of an additional dose 10 minutes after the first, and then the subject moves into the public speaking challenge. The reason we're doing the study is that the FDA specifically asked, stating that in the real world, a patient might still feel nervous after a first dose and want to take another dose. So, we'd like to assess what happens in that instance. So that is the primary goal of the study, to inform the label for how physicians should advise patients. Additionally, we plan to have an open-label extension for that study. This will help us understand what happens in the real world when patients are able to use the product again within 10 minutes, and whether or not they actually do. So again, it informs the label and how physicians can guide their patients. To clarify, there are three arms in the study: placebo followed by placebo, fasedienol dose followed by placebo, and fasedienol dose followed by fasedienol.

Shawn Singh, CEO

It's important to remember that these pherines activate the chemosensory neurons within milliseconds. There's also a limited capacity for the nose to accept the volume of spray, so we're not expecting significant safety-related concerns associated with the multiple dosing. But it does, as Josh noted, have the potential to help inform labeling, providing guidance on safe usage if someone were to dose it more frequently than, say, every hour, which is the typical duration of effect of fasedienol that we've observed in prior studies.

Unidentified Analyst, Analyst

Excellent. Thank you for the details.

Operator, Operator

And then the next question will come from the line of Tim Lugo with William Blair. Please proceed.

Tim Lugo, Analyst

Thank you for the question, and congratulations on all the progress for PAL-3. My question relates to PAL-3: How many sites are up and enrolling patients? Of those sites, and maybe the planned sites for PAL-3, how many of those sites also overlap with PAL-1 and PAL-2?

Shawn Singh, CEO

Thanks, Tim. I appreciate the question. One of the good things about having the experience that we've got within the clinical research community is the ability to assess sites that we think are top-tier and others that may not be quite there. The emphasis for both of these Phase 3 studies is to try to replicate PALISADE-2, which we hope and believe has a strong lineup. Some of them do overlap from the prior studies. Right now, we publicized that we should be right around 10 sites up. It's on a good pace. Some of these sites will have been in PALISADE-1 or PALISADE-2. However, all of them uniquely, as we talked about, even if they have been before, we know there's always a benefit. This is the third time that this protocol is being tested after a long period where there was little to no progress in social anxiety disorder, let alone treatment for the acute condition. There’s a lot of good experience and understanding we’ve observed at many scientific conferences where we presented PALISADE-2 data. A great level of awareness exists, even at sites and principal investigators not involved in the program. This fundamentally differentiated approach offers practitioners the chance to provide patients with a medication that can fit their lives and the stressors they encounter. So, the bottom line is that we really expect to have top-tier programs on both PALISADE-3 and PALISADE-4. A lot of that is due to the way we've managed these studies. It's not just a quick in-person investigators meeting. We maintain ongoing communication with the sites to ensure comprehensive support. We aren't facing the level of attrition in staff turnover at sites that we saw during the pandemic. There's a sense of normalcy in the clinical research community focused on our neuropsychiatric program that excites us, combined with protocol enhancements leading to a more stable environment.

Tim Lugo, Analyst

Thank you for that. One more question about the repeat-dose study. You mentioned it's for labeling purposes. Will there be a SUD score recorded prior to the repeat dose and then after the repeat dose, or is it more of a safety and tolerability type of study?

Shawn Singh, CEO

Yes, there absolutely are SUD scores collected, identical to those in PALISADE-3 and PALISADE-4. We collect scores pre-speech and once the speech starts, obviously capturing those scores for the primary endpoint. The actual endpoints will be identical to those in PALISADE-3 and PALISADE-4.

Tim Lugo, Analyst

Will a certain non-response after the first dose trigger that second dose, or will you just collect all the data and let people redose if they feel they need to?

Shawn Singh, CEO

In the public speaking challenge portion of the study, there is a 15-minute waiting period after the subject takes the initial dose. The second dose will be administered during that waiting period. The study design returns to the original structure for PALISADE-3 and PALISADE-4.

Tim Lugo, Analyst

Okay. Thank you so much.

Mark McPartland, Senior Vice President of Investor Relations

Operator, I believe that's all the time we have for questions today. If there's any additional questions, please do not hesitate to contact us by email at ir@vistagen via the contact section of our website. We also encourage you to register for email updates on our website to stay connected to the latest news from Vistagen. Again, thank you all for participating on our call today. We appreciate everyone's interest and support. We look forward to keeping you current on our continued progress. This concludes our call. Have a magnificent day.

Operator, Operator

This concludes today's conference. You may now disconnect your lines at this time. Enjoy the rest of your day.