Earnings Call Transcript - VTGN Q3 2023

Operator, Operator

Greetings. Welcome to VistaGen Therapeutics Third Quarter Fiscal Year 2023 Results Conference Call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. Please note, this conference is being recorded. I will now turn the conference over to Mark Flather, Vice President of Investor Relations. Thank you. You may begin.

Mark Flather, Vice President of Investor Relations

Thank you, Sherry. Hello, and welcome to VistaGen's conference call covering our third quarter of fiscal year 2023 financial results and a business update. Thank you for joining us today, and welcome to our stockholders, analysts, and anyone taking an interest in VistaGen. Joining me today are Shawn Singh, our Chief Executive Officer; and Jerry Dotson, our Chief Financial Officer. The format for this call will consist of prepared remarks from management, followed by a brief opportunity for questions from sell-side analysts. This call is being webcasted and will be available for replay. The link to access the replay can be found in the Investors Events section of our website, vistagen.com. On today's call, we will 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 that we may make today. Additional information concerning risks and factors that could affect our business and financial results is included in our most recent quarterly report on Form 10-Q filed earlier today with the Securities and Exchange Commission, or SEC, and in future filings that we make with the SEC from time to time, all of which are or will be available on our website and the SEC's website. Now I'd like to turn the call over to our Chief Executive Officer, Shawn Singh.

Shawn Singh, CEO

Thank you, Mark, and good afternoon, everyone. Thank you for joining the call. There is an active and growing need for new, faster-acting treatment options for anxiety and depression disorders. Treatment options without negative side effects and safety concerns that are often associated with the currently approved medicines. We remain focused on addressing the significant mental healthcare need for individuals across a broad range of demographics and in communities across the globe. Our team is committed to developing and commercializing multiple differentiated treatments that align with our mission to shift the treatment paradigm for anxiety and depression disorders and improve the trajectory of mental healthcare, One Mind at a Time. We'll start this call with a brief update on PH94B and our Phase III program in Social Anxiety Disorder or SAD. During the quarter, we further analyzed PALISADE-1 to obtain a better understanding of the unexpected results from that study. As a reminder, the study involved only a single dose of PH94B to subjects who were randomized to the treatment arm in the study. All subjects were given a highly provocative public speaking challenge conducted only in a clinical setting before a group of strangers, and their change in the subjective units of distress or SUDS score was determined and measured as the primary endpoint. We moved forward with this study methodology following our discussions with the FDA back in mid-2020, during the early phase of the COVID-19 pandemic, when the world was sheltered in place and social interactions and even exposure to the outside world were not encouraged. Following are among the hypotheses we believe are potential explanations for the unexpected outcomes in PALISADE-1: The study was conducted through surges of the COVID-19 pandemic, introducing significant additional variability in terms of changing social dynamics, subject stress, study site, and CRO personnel turnover, mask-wearing, and scheduling and monitoring complexities. Also, the public speaking challenge study design may not have been scalable to a large Phase III study, especially during the pandemic, given the various complexities of consistently administering the highly provocative challenge and the requirements for rigorous adherence to the study protocol across numerous sites and over an extended period. Furthermore, some subjects in the study may have had a reduced response to PH94B due to impaired olfactory cell function, potentially caused by the COVID-19 virus or even nasal swab testing for COVID-19 or influenza. After receiving the topline results from PALISADE-1, we paused PALISADE-2, which involves the same single dose, post-randomization public speaking challenge methodology as PALISADE-1. We then engaged independent biostatisticians to conduct an interim analysis of available data from the 140 subjects randomized in the study at that time. Based on their independent review of the unblinded data from those 140 subjects, data we've not yet seen, independent statisticians recommended that we continue PALISADE-2 as planned. Accordingly, during the quarter, we submitted protocol amendments to the PALISADE-2 study protocol to the FDA, aimed at minimizing the potential issues that may have played a part in the unexpected results we saw in PALISADE-1. If we decide to resume PALISADE-2, we believe these protocol changes could considerably increase the probability of favorable results in the remaining one-third of the trial subjects. However, another important factor to note regarding our considerations for potentially resuming PALISADE-2 is that in December 2022, a couple of months ago, two of our peers announced topline results of their recently completed SAD studies using a single administration public-speaking challenge study design with SUDS as the primary endpoint. Neither study achieved its primary efficacy endpoint. After reviewing the information and data available to us at this time, we believe it is not yet advisable to resume PALISADE-2 before discussing our broader Phase III development plan for PH94B in SAD with the FDA and assessing the results of the other two recently completed SAD public-speaking challenges conducted during the pandemic that also did not achieve their primary efficacy endpoints. We remain confident in PH94B's potential to be a game changer for individuals affected by social anxiety disorders. We have been and will continue to explore all of our options for what we believe will be the best path forward with the highest probability of success for our Phase III program in SAD. We are currently preparing to meet with the FDA to discuss our broader Phase III development plan, which includes the possibility of conducting a multiple administration, randomized double-blind placebo-controlled Phase III study of PH94B in adults using the Liebowitz Social Anxiety Scale, or LSAS, as the primary measure to evaluate the efficacy of PH94B over time in patients with SAD to support a potential PH94B NDA for treatment of SAD. Unlike the PALISADE-1 and 2 Phase III studies, which involved assessment after only a single administration of PH94B in a clinic-based public speaking challenge, with SUDS as the primary outcome measure, the Phase III study contemplated as part of our broader plan would involve multiple administrations of PH94B on an as-needed basis up to four times a day in a real-world setting over multiple weeks, with the LSAS as the primary efficacy endpoint. Using the LSAS would be consistent with the design of all registration trials supporting the FDA’s three precedent-setting approvals of treatments for SAD. Given that the LSAS measures overall improvement in disease severity by assessing both the reduction in fear and anxiety over time about social and performance situations, as well as the reduction in avoidance of those anxiety-provoking situations, we believe the LSAS is appropriate to measure and reflect the true impact of PH94B on patients' daily lives. We expect to announce our plan for PALISADE-2 concurrently with other updates to our broader PH94B Phase III development plan for SAD. Another important component of our Phase III program in SAD is the PALISADE Open Label Study, which we initiated back in October 2021 to evaluate the safety and tolerability of PH94B in adult subjects with SAD taken as needed prior to anxiety-provoking social and performance situations in daily life over a period of up to 12 months. In addition to assessing safety and tolerability of PH94B in that study, we also included several exploratory objectives, including PH94B's potential to achieve overall symptom reduction and improvement in severity of SAD as measured by the LSAS. The primary endpoint is required by the FDA for all prior SAD approvals. In August 2022, we closed recruitment and enrollment in the PALISADE Open Label Study. A preliminary analysis of the final dataset observing nearly 400 subjects in that study is encouraging, and although it is an open-label study, when considered with our prior placebo-controlled multiple assessment Phase II study of PH94B in a real-world setting, that study has helped inform many important aspects of our broader Phase III development plan for PH94B in SAD. The open-label study results reinforce our beliefs in the potential of PH94B used over time as needed up to four times per day in daily life to provide rapid onset, clinically meaningful and sustained response with a favorable safety and tolerability profile. We expect to have the final data readout of observations from this study in the first quarter of calendar 2023. Moving next to our exploratory target indication for PH94B adjustment disorder with anxiety, we've completed our small Phase IIa double-blind, placebo-controlled clinical trial to evaluate the efficacy, safety, and tolerability of PH94B as a potential treatment for adults with adjustment disorder with anxiety. Subjects self-administered PH94B at prescribed intervals four times per day for 28 days. We anticipate announcing topline data from this exploratory Phase IIa trial by the end of the first quarter of calendar 2023. During recent months, we achieved several milestones in our PH10 program in major depressive disorder or MDD. We submitted our U.S. IND and subsequently received the U.S. FDA's green light to conduct the Phase I randomized, double-blind, placebo-controlled safety study in healthy volunteers. That study is now underway and is intended to both confirm the favorable safety profile of PH10, establishing three previous clinical studies conducted in Mexico, including a positive published Phase IIa study of PH10 for the treatment of MDD, as well as to facilitate our plans for Phase IIb development of PH10 in the U.S. as a novel standalone treatment for MDD. We anticipate completing that Phase I study by the end of the first quarter of 2023. In all clinical studies to date, PH10, like PH94B, has been well-tolerated and has not caused psychological side effects such as disassociation, hallucinations, or other safety concerns that may be associated with other rapid onset depression therapies such as ketamine. Also of note, we recently received the FDA's Fast Track designation for development of PH10 for MDD. Similar to the large and growing anxiety market, there is significant unmet need for patients with MDD, where the current treatments are either undesirable or inadequate. With a differentiated mechanism of action that is designed to be fast-acting, non-systemic and non-sedating, we believe that PH10 has the potential to shift the treatment paradigm for MDD considerably. Having PH10 in the clinic in the U.S. and under the FDA's Fast-Track designation are important recent milestones in our plan to bring PH10 to many individuals battling MDD and potentially other depression disorders. As to AV-101, our Phase Ib drug-drug interaction clinical study with oral probenecid is ongoing. We anticipate completing that study during the second quarter of calendar 2023. After its conclusion, assuming no unexpected safety issues, we will crystallize the final components of our plan for exploratory Phase IIa development of AV-101 alone or in combination with probenecid and on our own or with a collaborator as a potential oral treatment for one or more CNS disorders involving the NMDA receptor. Finally, I'd like to make a few comments about our recent acquisition of Pherin Pharmaceuticals. Now that this transaction has been completed, we have full ownership of worldwide intellectual property rights to PH94B and PH10, which previously were under exclusive licenses to us from Pherin that included customary milestone and royalty payment obligations over time. As a result of the acquisition, we've eliminated all future royalty and milestone payment obligations for PH94B and PH10, which significantly improves the potential commercial profile of these late-stage assets should they be approved downstream. In addition, we will retain all licensing revenues, including pre-commercial licensing revenues should we enter into such transactions as we have in the past. Further, as a result of the Pherin acquisition, we've added three early clinical-stage pherine product candidates to our pipeline: PH15 for cognition improvement, PH80 for migraine and hot flashes, and PH284 for appetite-related disorders. Also of note, VistaGen did not assume any debt as part of this transaction, nor did we bring on any Pherin employees or take on any Pherin facilities. I would now like our CFO, Jerry Dotson, to summarize some highlights from our financial results for the third quarter of our fiscal year 2023.

Jerry Dotson, CFO

Thank you, Shawn. As Shawn mentioned, I'd like to highlight a few of the financial results from the third quarter of our fiscal year 2023. I would also encourage everyone to review our quarterly report on Form 10-Q that we filed with the SEC earlier this afternoon for additional details and disclosures. During the three months ended December 31, 2022, we recognized $179,600 of revenue related to the AffaMed Agreement, compared to recognizing $357,900 of revenue for the three months ended December 31, 2021. As a reminder, the revenue recognized in both of those periods is non-cash in accordance with the applicable accounting standards. We received the related cash from AffaMed back in August of 2020. Research and development expense decreased by $0.9 million from $7.9 million to $6.9 million for the quarters ended December 31, 2021, and 2022, respectively. This decrease is primarily due to reduced expenses related to the PALISADE Phase III program for PH94B, which, as Shawn has described, includes PALISADE-1, PALISADE-2, and the PALISADE Open Label Study, as well as the PH94B Phase IIa study in adjustment disorder with anxiety and other non-clinical development, regulatory, and outsourced manufacturing activities for both PH94B and PH10. We expect R&D expense in the final quarter of our fiscal 2023 to decrease as well as we wind down these trials that Shawn has mentioned earlier. Our general and administrative expense was flat at approximately $3.1 million for each of the quarters ended December 31, 2022, and 2021. Our net loss attributable to common stockholders for the quarter ended December 31, 2022, was approximately $9.8 million versus a net loss of approximately $10.7 million for the quarter ended December 31, 2021. At December 31, 2022, the company had cash and cash equivalents of approximately $25.0 million. Again, please refer to our quarterly report on Form 10-Q filed earlier today with the SEC for additional details and disclosures. I'll now turn the call back to Shawn.

Shawn Singh, CEO

Thanks, Jerry. We remain unwavering in our core mission to improve mental health and well-being worldwide. As we continue to advance the next stage of our corporate development, we move forward with a strong team, a strong pipeline, and a strong mission that drives us to innovate better solutions for mental health disorders, all with significant unmet need. This is an exciting endeavor for our company, and we believe that we are very well positioned for 2023. On behalf of the VistaGen team, I want to thank you for the privilege and the opportunity to make a difference, One Mind at a Time.

Mark Flather, Vice President of Investor Relations

Thank you, Shawn. This concludes our prepared remarks. Sherry, we would like to now open the call up for questions from sell-side analysts.

Operator, Operator

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

Andrew Tsai, Analyst

Thanks. Hi, everyone. Good afternoon. Appreciate you taking the questions. First one is that your upcoming FDA meeting, in terms of discussing a possible pivot in the Phase III design using LSAS and then multi-dosing over a long period of time. So can you kind of talk about the scenarios here if the FDA says, okay, do a pivot, what would you do with PALISADE-2? And if the FDA says no, what would you do with PALISADE-2? So basically, what I'm trying to get at is, in what scenario could we see the PALISADE-2 results at the end of the day? Even though it hasn't finished, you did see a signal in the interim analysis. So that's why I asked? Thanks.

Shawn Singh, CEO

Thanks, Andrew. Good question. Look, we still have to assess really what would be the best path forward after not only we take a look further at what happened in the peer studies. There are questions associated with scaling up that methodology and executing on a very highly provocative challenge that requires exquisite adherence to protocol. We've submitted some protocol amendments to the FDA. So we'll see what their feedback is on that, things that we think can overcome some of those methodological challenges. We'll see what their opinion is on that, as well as which direction things go in the meeting, where we're discussing a potential next step forward with LSAS as the basis, just like with the three approvals. So it's possible that we would simply unblind PALISADE-2 as it is and in the study there and see what we find from those unblinded data on 140 subjects. It could be denting, it could be a soft trend, it could be a positive signal, decent effect size, it could be a lot of things. We know what the interim analysis said, but we haven't seen the data. It's also possible of resuming PALISADE-2 depending on which direction things go with the FDA. Look, the good thing going into the discussions with the FDA is that there is a lot of evidence already; there are Phase II placebo-controlled studies in PH94B in SAD that have substantial evidence showing its rapid onset of effect following the acute administration. That was – we talked about that study quite a bit. Then the placebo-controlled crossover study that was two weeks of real-world use, then that amplified by what we've seen so far, we haven't yet reported, but we'll assume observations from the long-term safety study in the LSAS component of that study in particular. So there's a lot of things to ask the FDA. There's a lot of things to get feedback from the FDA on, and we'll make some decisions based on that interaction, as well as what we might learn more about. We need to do some work again with sites. We need to figure out some more information about what sites are around and are willing to be involved. And if we were going to resume, would we want changes to be made, that they may or may not be able to execute, depending on staffing and expertise. So we're set to see.

Andrew Tsai, Analyst

Right. Okay. Very, very helpful. And so speaking of the open label data coming up, what exactly do you plan to share with us? Basically, how much data can we expect to see in the topline release? And then secondly, part of my – this long kind of question, but one of the issues – underlying issues, in general, of the open label study is, there's no placebo. We don't necessarily know what the placebo would trend. That said, I can think of the epilepsy space, where there is an efficacy measure called seizure freedom because placebo can barely achieve seizure freedom in epilepsy. So that is perhaps why looking at seizure freedom rates in an OLE could make sense. So as we get back to the social anxiety space, I guess the question is, what percentage of placebo patients can achieve remission in theory over, let's just say, six to 12 months? Because – and I guess, would you agree looking at remission rates could be valuable of a data point basically?

Shawn Singh, CEO

That's something we can discuss with the FDA. All of the approval studies were registrational studies for the three antidepressants approved for SAD. Those are all 12-week studies. Again, look, we obviously acknowledge the absence of a control group in any open-label study by definition. But the data from – again, I noted this before, nearly 400 subjects observed in that study provide very important additional information regarding PRN dosing of PH94B. We take that together with the data from the placebo-controlled Phase II study, where the real-world study provides a lot of evidence on how SAD patients would use PH94B; for example, the frequency of use in the real-world setting and the appropriateness also of assessing improvement in SAD over time, utilizing the LSAS, obviously, as the key measurement. For that, given that, that's the historical precedent, that's the historical compare to three of them now. We know each SAD patient is different. We know SAD treatment is individualized and tailored to the situations that patients encounter in their daily life. We think PRN use is the most appropriate dosing strategy for the treatment of SAD, unlike the single highly provocative administration assessment that was in the PAL-1 and PAL-2 studies. And that these feared situations that people encounter, they are very predictable and are awaited with fearful and anxious anticipation. So the LSAS, which again, long established by Dr. Liebowitz, who is the PI of the Phase II studies and also currently working with us, that remains the most appropriate outcome measure for the type of study we might next do, right, a double-blind, placebo-controlled study that evaluates efficacy of as-needed use of PH94B, but over time for the treatment. Because what we're trying to essentially do is reset the mind, similar to how cognitive-behavioral therapy works. And rather than taking, say, a snapshot with SUDS and with the public speaking challenge, they all assess more like a movie, assessing the improvement of the patient over time. And again, having the LSAS as the primary endpoint is consistent with the registrational trials for the existing approved treatment. So it may be prudent, as you said, to follow beyond 12 weeks. We know this is a chronic disorder. So repeat dosing is exactly the way we've long envisioned using PH94B to help people. And again, a lot of the reason we moved into the PAL-1 was where the world was at the time, in the middle of 2020 when we last met with the agency about Phase III study design that you couldn't even go outside as you all remember. So exposing people to stressors over a long period of time, six weeks was probably what we would see in a Phase III study. Given the way that PH94B's onset is rapid, what we would see say in the six-week study would be really what the antidepressants achieved in a 12-week period, since they have a long onset of action. So what we would show to your first part is, we would certainly want to show improvement on the LSAS at least one month and probably two months, given that we're aiming for a study design somewhere in the four to six-week range. What we're looking for there is, are we seeing a significant drop? Again, this is observed data. We understand how the control group, but it definitely informs when you have nearly 400 subjects. It gives us a lot of information to tack on top of really the other crossroad we were at back in 2020. We could have gone to the real-world study then, but for the fact that we're in COVID. Now, I think we have that opportunity given that the world settled down a bit; vaccines are okay, and we have a lot more understanding of the safety associated with having people record their stressful events and having LSAS assessments for a long period of time.

Andrew Tsai, Analyst

Right. Thanks. Last one and then I'll hop in the queue is, on the adjustment disorder data coming up, it is also dosed chronically placebo-controlled 40 subjects, I believe. So I think the primary endpoint is day 20 HAM-A scores. So can you kind of give us a reminder what existing drugs show at four weeks, just so we can have a comparator when that data comes?

Shawn Singh, CEO

They have not a lot of competitors. That's a challenge with this disorder. It's in DSM-5, but there really aren't a lot of controlled studies. That's why this really lands in exploratory study zone. HAM-A, you had to have somewhere around 20 to be enrolled, and people had to be on if they were on anything, there were stable background antidepressants, but we'll – it's an exploratory study. It's a small study, as you said, around 40 subjects. We're looking for a signal, as you'd expect from a Phase IIa study. It's not heavily powered as you'd expect with the exploratory design. So we'll see. The 300 meds are used. But unfortunately, they're just – it's the same sort of collection of meds that we see in social anxiety disorder that folks that had never really had experience with anxiety, but for, in most cases, something here associated with the chaos, the domino effect from COVID, job loss, relationship loss, isolation – those things started to impair their functioning. That's adjustment disorder and anxiety that disrupted routines and so forth. So benzos, beta blockers, antidepressants, alcohol, all kinds of things that really aren't optimal for SAD or also not optimal for adjustment disorder.

Andrew Tsai, Analyst

Thanks, Shawn. Appreciate that progress.

Operator, Operator

Our next question is from Tim Lugo with William Blair. Please proceed.

Timothy Lugo, Analyst

Thanks for taking the question. For the upcoming adjustment disorder study, can you remind me how many doses these patients are taking per day? And I guess, following up with the prior question, do you have a sense of what the placebo rate is in this setting? I guess there's any sort of historical that you can compare to?

Shawn Singh, CEO

Yes. I'll take that part first, Tim. There's just isn't a lot of traffic historically in this disorder. So I can't really give you a well-grounded number. In terms of the dosing regimen, we had, again, a small study that showed a lot of safety from PH94B taken up to four times a day. So we sort of forced that into this exploratory study. There wasn't a lot grounded that necessarily said four times is what was needed. But part of it was to also establish safety associated with taking the drug four times a day because that crosses over into thoughts about safety related to taking PH94B four times a day in multiple different SAD-related anxiety-provoking episodes. So there was a little bit of crossover intention by that study regimen. So in this one, it's four times a day, and it's recommended to be spaced out an hour or so between doses in the morning, early late morning, early afternoon, and evening, so four times is kind of spread out for an hour so in between. We know PH94B has a rapid onset. We also know it has a fairly short duration of effect. So that's part of the benefit of it being sort of a better benzo without the baggage, right, rapid onset, but without the lingering cognitive impairment. So it's four times a day split by a few hours over 28 days.

Timothy Lugo, Analyst

Okay. That's helpful. And so outside of the upcoming PH94B meeting, it sounds like you got a couple of assets through the Pherin acquisition, PH80 specifically. Can you just – outside of PH94B, can you rank kind of where the rest of the pipeline is in terms of priorities for the company?

Shawn Singh, CEO

Yes, sure. Well, PH94B, of course, is way top of the list and across multiple indications in the two that we've acted on in the clinic, SAD and adjustment disorder, PH10 following right after that. We have a IIa that was done outside the U.S. That's the POC study for that asset in major depressive disorder. We had to bring it back to the U.S. to a full IND enabling program, optimize the formulation a bit. The small Phase I that we're doing should be done here within a few months, and we'll announce on that probably early second quarter. That then lets us hopefully move right back into late-stage Phase IIb development with that asset as a standalone treatment option for MDD with the rapid onset and the same similar features in terms of no systemic uptake and to sedation as PH94B. And then it's kind of leveled out. There are early – there's early clinical data for PH15, PH80, and PH284 done again outside the U.S. in most cases and some cases here. But we're going to need to do some IND-enabling work for those three assets, similar to what we had to do for PH10. We expect to be able to achieve some grant support for that work. That was non-clinical work that gets us back into the clinic. AV-101 we see probably more advanced than PH80, PH15, and PH284 at this point, because if we see the safety that we're hoping with this combination, we have a lot of preclinical data, really solid preclinical data across a few indications involved in the NMDA receptor. So levodopa-induced dyskinesia, neuropathic pain, some of the models that we've done in MPTP monkeys as well as in models for pain against Lyrica and gabapentin. We'll have to decide which direction we want to go. But I think the IIa would be the next priority after PH10 for IIb with AV-101, and then we'll see how things go. We haven't had our hands on the new Pherin assets for too long, so we want to do a little more digging into the data sets that exist. But there are clinical data across all those that are fairly encouraging, and we just need to get more direct touch on all three of those as we see what we might want to do there. There's a lot of grant opportunities for those assets. The core focus, however, predominantly is on PH94B followed by PH10.

Andrew Tsai, Analyst

Thanks, Shawn. Appreciate that progress.

Operator, Operator

There are no further questions at this time.

Mark Flather, Vice President of Investor Relations

Thanks so much. If you have any additional questions, please do not hesitate to get in touch with us by emailing ir@vistagen.com or contacting the individuals listed on our press release issued today. We also encourage you to sign up on our website to stay connected with the latest news from VistaGen. Thank you for tuning in, and we appreciate everyone's attention and support. We look forward to keeping you current on our continuing progress. This concludes our call. Have a great day. You may all disconnect.