VistaGen at Stifel 2025: Pioneering Acute SAD Treatment

On Tuesday, 18 March 2025, VistaGen Therapeutics (NASDAQ: VTGN) participated in the Stifel 2025 Virtual CNS Forum. The company outlined its strategic focus on developing Fasadienol, a potential breakthrough in the acute treatment of social anxiety disorder (SAD). While the company expressed confidence in its innovative approach, challenges such as dose selection and regulatory alignment were also discussed.

Key Takeaways

• VistaGen’s lead product, Fasadienol, aims to be the first approved acute treatment for SAD.
• The company plans to submit a New Drug Application (NDA) in the first half of 2026.
• Financially, VistaGen has $88 million in cash, supporting operations through Q1 2026.
• Phase 3 trial readouts for Palisade III and IV are expected by the end of the year.
• VistaGen is focusing on telehealth as a key component of its commercial strategy.

Financial Results

• VistaGen reported $88 million in cash at the end of the last quarter.
• This cash is expected to support operations until Q1 2026.
• The company plans to submit an NDA in 2026, pending successful Phase 3 trials.

Operational Updates

• Phase 3 Trials: VistaGen is on track for Phase 3 data readouts for Palisade III and IV by the year’s end. The company emphasizes quality enrollment and adherence to protocols.
• Device Validation: The metered dose spray device for Fasadienol has been certified for consistent delivery, targeting nasal receptors effectively.
• Enrollment Efficiencies: VistaGen has implemented efficiencies to ensure quality enrollment, crucial for addressing social anxiety disorder.

Future Outlook

• NDA Submission: VistaGen aims to file an NDA in the first half of 2026, contingent on positive trial results.
• Commercial Strategy: The company is leveraging telehealth to enhance patient engagement and prescription management. Pricing strategies consider the unique nature of an acute treatment used chronically.
• Anticipated Challenges: Balancing consumer demand with payer concerns is a focus, with no major issues anticipated over existing antidepressants.

Q&A Highlights

• Trial Indexing: The company views Palisade II as more representative of the current environment, while Palisade I is considered an outlier.
• Regulatory Strategy: VistaGen has aligned with the FDA on study design and endpoints, addressing dose selection challenges with supporting studies.

For more detailed insights, please refer to the full transcript below.

Full transcript - Stifel 2025 Virtual CNS Forum:

Paul, Moderator: Excellent. Thanks, everyone, for listening in today. It’s my pleasure to be moderating this panel with Sean Singh, CEO of Visions Therapeutics, a company that has a big Phase three readout this year for their lead product in social anxiety disorder. And so I’m going to ask Sean to give a quick update and overview of the company, and then we will do Q and A. So Sean, take it away and thank you for

Sean Singh, CEO, Visions Therapeutics: just You bet. Thanks a lot, Paul. Always great to to join you. I know it’s just a bit of a speed date, so we certainly encourage folks to to talk to us afterwards. So obviously, I’ll be making forward looking statements today, so assess our 34 act filings as well.

We’re laser focused on developing and commercializing an entirely new class of fast acting, non systemic intranasal drug candidates that we call pharynx and that whole class up and down multiple therapeutic indications each with fairly stale standards of care. We’re moving into a zone where we can harness the power of nose to brain neurocircuitry in ways that we just haven’t seen before. Each of these assets that we are advancing has had at least one Phase two positive study in the case of the lead program that we’re in a registration directed program for the acute treatment of social anxiety disorder. It’s also had a positive Phase three study. So this as you noted, it’s an exciting year for us.

We’ve got a couple of Phase three readouts by the end of the year in the social anxiety program. So we think we’re able to move into a zone if those are successful where the first ever approved acute treatment is on the horizon possibly.

Unidentified speaker: Yes. Okay. Great. Well, I think when

Paul, Moderator: I talk to investors about your story, Sean, it feels like the crux of the debate here is which trial should we index to? Should we index to Palisade II or should we index to Palisade I’ll leave that as an open ended question and would love your perspective.

Sean Singh, CEO, Visions Therapeutics: Well, the world’s different obviously now than it was when we saw the effects of the Black Swan or the pandemic on a lot of work in the early days when Palisade One was being executed mostly. Things changed and Palisade two is a reflection of that when the world changed and the masks came down and insight surveillance was a lot more possible, less turnover at sites with staff, CRO staff turnover. So a lot of issues that others were affected by, especially in neuropsych studies. But we see the world now a lot more like PALCADE2 backend and Phase two. So we see PALSADE1 more as an outlier in a lot of ways that impacted the placebo side of the ledger and things that we’re doing now in PALSADE3 and four that are enhancements to the programs that allow execution just really a much different way than even at the back end of Palisade two.

It was a big deal when the mask came down. So Palisades three and four have no masks involved, but we’re also able to train in person, surveil in person with our own team at sites, less reliance on CROs and CRAs from CROs. Some things that are again more like Phase two with the IP being administered by the PI directly like in Phase two. We’ve got the audio recordings of the speeches to be able to make sure that there’s rigorous adherence to the protocol, which is key. The fact that in Palisade three and four, this isn’t the first lap with this protocol and this endpoint in Phase three setting for the public speaking challenge.

So all those things, a confluence of things, being able to have a different degree of scrutiny upfront, prescreening even is a whole different ballgame. So we lead to the latter, of course, and that’s what we’re aiming to replicate PALSATE two with three or four.

Paul, Moderator: Yeah. Do you want to give, do you want to give some color to folks on just the backstory around this public speaking design? Why was this leveraged? How standardized is it? And if you guys succeed and file for approval, it’ll be new from a regulatory perspective.

So what’s your confidence that the agency is fully on board?

Sean Singh, CEO, Visions Therapeutics: Well, we aligned with the agency early on about what affects again this population. And we’re aiming again at the acute treatment of SAD, not the overall treatment like the long onset antidepressants that were approved a couple of decades ago. That was a scale, the lebod social anxiety scale that’s more really a movie of their experience rather than some scale and a design that can assess minute to minute changes. And so with the acute treatment indication in mind, aligning with the agency that the people who suffer from this disorder and it’s a chronic disorder with the mean duration of about twenty years for the thirty million people that are affected by this in the adult population, that you can they fear talking to people, right? This is a fear of judgment, humiliation, embarrassment in many everyday social and performance situations.

And secondly, that you can provoke anxiety consistently across sites with the public speaking challenge. And so that there’s one trigger that and one stressor that’s being assessed across the participants in the study and across the sites. So with that in mind, what’s the appropriate endpoint? Well, we aligned that the appropriate endpoint for measuring minute to minute benefit potential of a drug is the Suds, the Subjective Units of Distress scale. So again, each minute during the public speaking challenge, the subject reports how they feel on that scale zero to 100 with the 75 being more than a little uncomfortable each minute.

And so that’s helpful not only for us to make sure we can enrich the population with appropriate subjects that can be affected by the disorder in a beneficial way. But it really is it provides a standardized paradigm really for assessing a provocation that’s commonly experienced by folks.

Paul, Moderator: Yes. And as it relates to the FDA, any thoughts there on the agencies comfort with it would be helpful? And I guess maybe even just bridging on that, right, like how well do we understand what a clinically significant effect size is on this scale? And how might that come into also the regulatory prospects of Fasadienal if you do hit a P value?

Sean Singh, CEO, Visions Therapeutics: Yes. Well, there’s standard assumptions, I think, around effect size, somewhere around a four in neuropsych studies has been pretty commonly embraced as you’ve seen. But And

Paul, Moderator: you mean like you mean a Cohen’s D of 0.4?

Sean Singh, CEO, Visions Therapeutics: Cohen’s D of 0.4, yes. The key for us again from very early on was making sure that we could align with the agency on the study design. Others behind us also have had input from the agency about using the suds in the public speaking challenge for acute treatment. Those were some oral systemic drugs, a couple of different companies you probably know about. So we’ve seen it, we’ve seen guidance from the agency, not just to us, but to other sponsors about the appropriateness of the study design and the endpoint associated with that design.

And of course, the Leewood scale, which is really the only other scale to anchor approvals, those were for totally different types of drugs in a totally different indication for the long onset. No old school antidepressant is going to give the acute treatment benefit.

Unidentified speaker: Yeah. Okay. Makes sense.

Paul, Moderator: And then from a regulatory perspective, how important is it to also show maintenance of benefit? Considering that this is an acute treatment, you also, I think, would like people to be able to use it as much as they would like. How do you satisfy the agency on showing that repeat dosing over time still works, repeat dosing over time is safe? What’s going on there at this, Jim?

Sean Singh, CEO, Visions Therapeutics: Well, we did align with the agency on a repeat dose study, mostly for safety oriented reasons and sort of a common sense thought perhaps that people might think more is better and to try to assess whether or not using a couple of doses within a short period of time within ten minute window has any potential effect on safety. And if it is the case that the dosing in the redose scenario may inform labeling, it may be a guide to the fact that a second dose administered within ten minutes is safe as we anticipate it will be based on everything we’ve seen. So again, the acute treatment dynamic though and the acute communication is grounded in the public speaking challenge and the suds full stop. So we have wonderfully seen in the open label study that we already talked about with about 30,000 in about five hundred patients, four eighty one patients that people using the LSAS, again, it’s open label, so it’s a little different scenario than placebo controlled. But we think people do get better the more they use it.

And the confidence that builds from knocking down acutely the symptoms that are associated with them being judged or humiliated, embarrassed, and you get that over and over again. And the LIBORDS scale can capture that. We had seen that in the placebo controlled crossover where there was stat sig on reduction in avoidance. And the LIBORDS scale captures whether people are engaging in their stressors more or less and whether their fear and anxiety levels are decreasing or sustaining. And so I think what we like out of this, especially the PGIC, which is a secondary endpoint in PALCADE three and four, where the patients are saying how they thought they did second speech after first, combined with the CGI, which is the clinicians also assessing whether they thought the subjects were less stressed, less anxious, second speech versus first.

And this is in a double blind setting, so nobody knows who’s on what. But what we saw from PALISADE2 contextualizing even the group level change on the suds, you get to a very clinically meaningful conclusion for this particular disorder. And that’s done with one dose in a highly provocative challenge. So

Unidentified speaker: Right. Right. Okay.

Paul, Moderator: Very good. I think the other questions you and I have talked about, Sean, relate, again, on the regulatory side, assuming that you are successful with one of these two studies. The two let’s ask the most important one first, and that’s really, you know, let’s say, look, anxiety is really hard. Right? I think good drugs and anxiety can fail in half their clinical trials.

So let’s say you split the difference in PALISADE three and PALISADE four again. Do you feel like you have a fileable package? And do you feel comfortable that PALISADE II in the context of stopping enrollment early would count as a pivotal trial?

Sean Singh, CEO, Visions Therapeutics: The answer is yes on both of those. Look, we were able to accomplish with PELSIAD two and probably a more statistically challenging scenario than what’s currently in play for three and four stat sig and a clinically meaningful difference on the suds with a safety profile that’s remarkably distinct from any anxiolytic that we’ve ever seen. And so to guide through our advisors, former FDA folks and counsel and everybody that we look to for guidance, one of the two has to hit to complement it. We’re not yet in this disorder where it’s the case where one would probably carry the day. Part of the reason we have the redundancy built in with three and four is to be able to capture in the open label extensions some additional exposures that top off to the ICH guidelines at 1,500 total exposures and one hundred and twelve hundred and twelve months, three hundred and six months.

So yes, we believe that if Palisade three or four, ideally, we’re driving for both are positive studies that they complement what we’re able to deliver on PALCAD2. And assuming that we hit the safety database numbers and even I think there’s an advocacy argument and even if we’re not quite at the full complement of the guidance given what we’ve seen so far. So remember, we went to the agency a while back and asked if we had to do a human abuse liability study based on everything that we tendered. The answer to that was no at this time and nothing since has driven that in our opinion is driven off that initial assessment from the agency. So again, it’s just the typical remaining components.

We have a couple of non clinical studies that are to roll the CARC and the repro tox and then the REG batches, which are already on their way. So

Paul, Moderator: Yes. Okay. Makes sense, Sean. The other regulatory question here that I bugged you guys about a lot when I was first doing work on Vistigen just goes back to this question of dose selection. Right?

The FDA, I think, wanted you guys to do this other sort of repeat dose study. And the beauty of facadienal, right, is that the systemic exposure is almost nonexistent. The side effect profile looks very benign. The challenge that that might raise, right, is how do you actually know you’re in the efficacious dose range? Can you actually elucidate a biological effect?

You can’t look at receptor occupancy. So and then I guess from just even a repeat exposure perspective, you can’t detect the drug. Like, how do you validate the device is behaving reliably and as planned? So what what are you guys doing to prepare to tackle all of those inevitable questions from a regulatory perspective?

Sean Singh, CEO, Visions Therapeutics: A lot of things. As you can imagine, it’s busy. Well, I mean, remember, this Fasadienol offers a completely new MOA that’s not really amenable to typical bioavailability data requirements, right. Unlike the typical CNS products, their Fasadienyl is acting as an agonist on receptors directly. It doesn’t follow the typical pathway to absorption and circulation and receptor activation.

So our work has not we haven’t been able to detect this drug systemically even a very low levels of detection. So we know it’s metabolized in the nose. We developed an FDA agreed on assay that showed it’s not absorbed and can’t be detected in plasma at one nanogram per ml. This is not detectable in the brain in our C14 radio labeled studies. So we’ve got to the point where we’re also using a meter dose spray device that’s been already certified to ensure consistent spray delivery.

So provided that the device is inserted properly in the nasal passage in the direction of the septum, the spray plume predictably contacts the nasal receptors. And we it’s the same way we target all these fairings. But as to dose, again, we arrived at the dose through a series of informative studies that include in this right from the beginning tissue culture studies with human nasal cells that show cellular response to the drug by imaging, increased calcium channel signaling. We then move to these we’ve talked about these electrogram of nasal receptors, these EGNR studies that we do in healthy volunteers that generate dose response curves that show variable receptor responses at increasing doses. So the eG and R has been a really important tool because your typical you know many of the chapters in your typical PK textbook they just they don’t apply in this with this platform of drugs.

And then again previous clinical studies also inform. So some of the early studies, the Phase two studies, the PALISADE2 study even with one point six and three point two micrograms that induced efficacy better than placebo. So it’s kind of a it’s a little bit of an end around way compared to your conventional small molecule that’s systemically absorbed and has to hit directly on receptors in the brain. And that’s a key piece of this puzzle is that there is no direct chemical activity on neurons in the brain, including the abuse liability receptor. So that’s the case for all these, the fairings up and down the pipeline.

Unidentified speaker: Yes. Okay. All right.

Paul, Moderator: So maybe let’s take a step back and get out of the weeds and more just on the practical element of timelines. Where are you at PALISADE three and four? What’s the updated timeline and top line? And what can you say about where you are with enrollment?

Sean Singh, CEO, Visions Therapeutics: Yes. Well, we guide to we’re guiding to both of these studies right now this year, and we’ll stick to that. We will certainly announce when we get to the last patient out, meaning the last patient that’s randomized in each of the studies. And typically there’s one more visit after that, which is a safety assessment and only the subjects who are randomized get included in the data set as we discussed. So we’ll guide on that.

We’re comfortable with our projections and our guidance and the fact that you’ve got a lot more efficiencies built into what we’re able to do on the execution side, it allows really the right amount of time to make sure we’re focused on quality enrollment, which is key with this disorder and any neuropsych disorder. And the fact that we have a couple of enrichment gates that are very important and then the audio taping of each of the speech has been a very significant factor in making sure we get the adherence to the protocol that is necessary for the study to be executed efficiently. And having our own people that we rely on, I have a lot of confidence in our own team to be able to be insights and dealing directly with those that have to execute the study at the sites.

Paul, Moderator: Yes. Okay, great. Well, we look forward to that. Maybe to wrap things up, do you want to look, I think it goes without saying, right, that anxiety is a huge market. Maybe the only sort of Nuance commercial questions here are it’s an acute treatment that someone might use chronically.

So what does that mean for how you might think about pricing something like this? And, you know, I guess, are there any good analogs, for a drug like this in psychiatry?

Sean Singh, CEO, Visions Therapeutics: Psychiatry, interesting. I mean, there’s certainly no analog for the acute treatment of SAD. And in psychiatry and anxiety, I mean, you know the other players, just watch an episode of White Lotus, you’ll get a sense of the impact of the benzos. But the answer is, we have to really understand the fact that the market has changed. When you talk to psychiatrists, just down the street from you there at Mass General, most of the interactions right now, if not all of them is online with that group.

And so the ability for the marriage of telehealth and mental health to be as tight as it is and sustain as tight as it is, is really important, especially if we have a drug that we would not expect to be scheduled based on everything so far. And the ability now for these engagements to be online and with recurring scripts that could come online, not like trying to get out of hand or another benzo. It’s a key piece of the overall make sure the consumer helps us and at the same time making sure we educate the market, the practitioners about it. But keeping it under prior authorization annually, we see maybe about six files a year. It’s not an all day every day type of disorder.

It’s very episodic. Weekends you see a decline in use in the open label depends on the life of the person whether what their job is if they’re in school socially what they do as to the use during the course of the week. But tracking utilization and tracking the kinds of things that drive your commercial assumptions. I think especially some of the work that we’ve done with payers, there’s no step at it expected because there’s no approval for an acute treatment. So it’s not like we got to step over with school antidepressants.

It’s informed us quite a bit on how we can put this in a zone where we kind of strike the right balance between pretty heavy consumer driven demand based on the way we can access people digitally, as well as the concerns or possible concerns of the payers.

Unidentified speaker: Yes. Okay. And then cash runway, Sean?

Sean Singh, CEO, Visions Therapeutics: Runway, we had $88,000,000 at the in our last Q we announced at the December that runs us through Q1 of twenty twenty six. So if either of these is a positive study or ideally both, the first half of twenty twenty six will be the target to drop down the NDA.

Unidentified speaker: Okay. Okay. Great. We’ve covered a lot.

Paul, Moderator: Thank you very much for taking the time, and thanks everyone for listening. And, yeah, best of luck. We’ll talk soon.

Sean Singh, CEO, Visions Therapeutics: Alright. Thanks again, Paul. Appreciate it.

Unidentified speaker: Alright. Thank you.

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