Vistagen Therapeutics Inc (VTGN) 2025 Q3 法說會逐字稿

Good day. Thank you for standing by. Welcome to Vistagen Therapeutics third-quarter fiscal year 2025 corporate update conference call. (Operator Instructions) Please note that today's conference is being recorded.

I will now hand the conference over to your speaker host, Mark McPartland. Please go ahead.

Thank you, operator. Good afternoon, everyone, and welcome to Vistagen's fiscal year 2025 third quarter corporate update conference call and webcast. Earlier this afternoon, we issued a press release for the third quarter of our fiscal year 2025 ended December 31, 2024, providing an overview of our progress across our lead clinical neuroscience programs. We encourage you to review the release, which can be found in the Investors section of our website.

Based on the current expectations and information, we will make forward-looking statements regarding our business during today's call. These forward-looking statements speak only as of today. Except as required by law, we do not assume any duty to update any forward-looking statements made today and-or in future.

Of course, forward-looking statements include risks and uncertainties, and our actual results could differ materially from those anticipated by any forward-looking statements that we make today. Additional information concerning risks and factors that could affect our business and financial results will be included in our fiscal year 2025 third quarter Form 10-Q for the period ending December 31, 2024, and in future filings we will make with the SEC from time to time, all of which are or will be available in the Investors section of our website and on the SEC's website.

Now with the formalities complete, we warmly welcome our stockholders, sell-side analysts, and others interested in our programs and progress. I'm joined on our call today by Shawn Singh, our President, Chief Executive Officer; Cindy Anderson, our Chief Financial Officer; Josh Prince, our Chief Operating Officer. Shawn will discuss recent highlights in our lead neuroscience programs, and Cindy will discuss our fiscal third quarter financial results. After our prepared remarks, as the operator has already noted, there will be a brief opportunity for questions from the sell-side analysts participating on the call today.

As a reminder, this call is being webcast and will be available for replay after completion. The replay link can also be found on our website's Investors section under Events. I will now turn the call over to our President and Chief Executive Officer, Shawn Singh. Shawn?

Thank you, Mark, and good afternoon, everyone. Thank you for joining our call.

We had a very productive quarter. As many of you know, we are developing a new class of intranasal product candidates that are called Pherines. And these are designed to harness the power and the potential of nose-to-brain neurocircuitry to achieve a broad and diverse range of therapeutic benefits without requiring systemic absorption or binding to neurons in the brain.

So let me start by discussing our most advanced pherine, fasedienol, and our ongoing registration-directed PALISADE Phase 3 program for that asset for the acute treatment of social anxiety disorder or SAD. Currently, as I've mentioned before, there is no FDA-approved medication for the treatment -- for the acute treatment of SAD, which is a very serious and a potentially life-threatening condition that's recognized by the FDA, and one that post-COVID is estimated to affect over 30 million adults in the US, who struggle with intense and debilitating anxiety and fear of embarrassment, humiliation, judgment when they're dealing with stressful, social and performance situations.

And with fasedienol, our goal is to address this critical and very long neglected treatment gap by providing a novel, convenient, safe, and rapid onset as-needed solution to help individuals who are affected by SAD face the challenges in their everyday lives.

In 2023, we reported positive results from our PALISADE-2 Phase 3 trial of fasedienol for the acute treatment of SAD. In 2024, to build on the success of PALISADE-2 in our registration-directed Phase 2 program for fasedienol, we initiated PALISADE-3 and PALISADE-4 as Phase 3 trials, each designed as a replicate public speaking challenge with the same primary endpoint, and in each case, an open-label extension. And today, I'm pleased to report that both PALISADE-3 and PALISADE-4 are currently continuing to advance towards expected top line results later this year.

In addition, we recently announced initiation and enrollment of the first subjects in an exploratory Phase 2 repeat dose study of fasedienol in SAD. And besides the addition of a repeat dose arm, it is similar in design to our Phase 3 PALISADE-3 and PALISADE-4 studies for the acute treatment of adults with SAD, again, including in open-label extension.

With these studies advancing, we believe either PALISADE-3 or PALISADE-4, if successful, together with PALISADE-2, may establish substantial evidence of the effectiveness of fasedienol in support of a potential new drug application submission to the US FDA for the acute treatment of SAD in adults.

In addition to advancing our fasedienol Phase 3 program in SAD, we made progress in our development programs for itruvone as a stand-alone treatment for major depressive disorder and PH80 as a nonhormonal, nonsystemic treatment of vasomotor symptoms or hot flashes that are due to menopause.

Currently, we are preparing and planning for potential Phase 2b clinical development of itruvone in the US, and we are conducting customary nonclinical studies that we need to support our planned submission of an investigational new drug application, or IND, to the US FDA to facilitate further Phase 2 clinical development of PH80 for menopausal hot flashes.

I'm now going to turn to some other corporate highlights. We recently reported positive results from an exploratory Phase 2a trial of PH284 in cancer cachexia. PH284 is our fifth clinical stage, neurocircuitry-focused intranasal pherine product candidate with a positive efficacy signal and differentiated safety in all the studies that have been completed to date.

And this recent announcement underscores the breadth and diversity of our clinical stage pherine pipeline with five innovative, nonsystemic, investigational, intranasal pherine product candidates, all supported by positive Phase 2, and in the case of fasedienol, one Phase 3 positive clinical study, the clinical data and the placebo-like tolerability that we've seen across all these studies gives us tremendous confidence in the range and the diversity and the therapeutic potential of our neuroscience pipeline.

The positive studies from our five pherines with clinical data across various indications drive our optimism and our confidence in the power and the promise of nose-to-brain neurocircuitry and the enormous potential of our intranasal pherine pipeline. As always, we are optimistic about the potential of our product candidates to address multiple significant treatment gaps and to transform standards of care to improve lives.

I'll now hand it over to Cindy Anderson, our CFO, to summarize our financials from the last quarter. Cindy?

Thank you, Shawn.

As Shawn mentioned, I will highlight a few financial results from our fiscal year 2025 third quarter. Research and development expenses were $11.3 million for the quarter ended December 31, 2024, compared to $4.5 million for the same period last year. The increase in R&D expenses was primarily due to an increase in research, development, and contract manufacturing expenses related to our PALISADE Phase 3 program for fasedienol in SAD as well as IND-enabling programs for itruvone in MDD and PH80 for the treatment of menopausal hot flashes.

General and administrative expenses were $4.0 million for the quarter ended December 31, 2024, compared to $3.8 million for the same period last year. The increase in G&A expenses was primarily due to increased headcount. Our net loss attributable to common stockholders was $14.1 million for the quarter ended December 31, 2024, compared to $6.4 million for the same period last year. As of December 31, 2024, we had $88.6 million in cash, cash equivalents, and marketable securities.

I will now hand the call back over to Shawn.

Thanks, Cindy. So we are more optimistic than ever here at Vistagen with five clinical-stage pherine product candidates, each with positive patient data and differentiated safety. We have now multiple opportunities to disrupt treatment paradigms, enhance patient outcomes, and create value for our stockholders.

So I'd like to thank you all once again for your continued interest and support in what we're doing here at Vistagen. And on behalf of everyone on our team, we look forward to keeping you updated on our progress.

Operator, we'd like to now open the call to questions from the sell-side analysts who are participating today.

(Operator Instructions) Andrew Tsai, Jefferies.

Congrats on the quarter. I just -- this is Matt on for Andrew. And I just wanted to ask real quick if you're confident that the data from PALISADE-3 and 4 will still be in the second half of this year? Or are you expecting any delays? And also, I've got a follow-on to that after this.

Thanks, Matt. Good to talk to you. So as we've guided, we're confident that we'll see data from both PAL-3 and PAL-4 in 2025. So no change in that guidance.

Okay. Perfect. And then I guess, is there anything that keeps you up at night in terms of what more could be done on these studies in terms of execution?

Interesting question. No, it doesn't keep me up at night because of the enhancements and the team that we've got executing on these studies, especially surveillance associated with rigorous adherence to the protocol. These are all very important, execution-related initiatives that we've got in place, reduced reliance on CRO surveillance, expansion of our internal team, and just the way that we've been seeing the conduct of the studies with rigorous training even upfront of any enrollment at any of the sites. It's just actually been significantly different than what we've seen in the past in a very positive way.

Josh Prince is on the line with me. Josh, why don't you go and say a few things. You are driving a lot of the execution.

Sure. Thanks, Shawn. It is a very interesting question. And actually, to your point, we have more visibility into what's happening with these studies than we did before running PALISADE-1 and 2 in the pandemic and with the enhancements that we've put in place.

And so if anything, I would say it's easier to sleep at night now than it was back then without COVID in place, with masks down, with the review that we have of subject's eligibility, making sure that scales are administered properly, making sure that the rigorous public speaking challenge script is followed to the T, and then having the ability to do quick interaction and retraining with sites if they start to deviate from that protocol. So we feel like we're giving these studies the best chance we could at success with those changes.

Fantastic. And then also, you're starting to see a little bit -- we're starting to see a little bit more competition in terms of novel drugs for social anxiety disorder. Can you talk about how you think about the competition and how fasedienol doesn't have -- is immune to this competition?

Thanks for the question, Matt. Unfortunately, we've got a robust market here in the United States in terms of the number of people affected by the disorder, over 30 million. It's a lot of adults that struggle from time to time with what most people consider everyday social and performance situation.

So one thing always is the case with neuropsychiatry, there's no one size fits all. And it's also the case, certainly, that there's plenty of room for a lot of treatments to come into play to try to make a difference.

One very major difference with this pipeline, and this is not just as to fasedienol for SAD, but it's for up and down the pipeline in each of the standards of care and the treatment paradigms currently we're trying to disrupt, whether it's depression, whether it's menopausal hot flashes, or certainly, SAD is that it's the mechanistic difference.

So being able to rely on nose-to-brain neurocircuitry and having a pipeline of drugs that don't have to go through your whole body that are activating neurons in your nose within milliseconds, that project to neurons at the olfactory bulb, neurons at the base of the brain, and then project to different regions of the brain to achieve different therapeutic outcomes, it's a critical distinction. There's no other drug approved that has this kind of mechanism of action.

And what's important about that is it doesn't rely on a case like, say, an oral systemic where you've got to occupy and thread the needle just right of receptors in the brain, 1 or 2 that are associated with different indications, depression, for example. So we think we've got a very unique mechanistic approach to a broad range of therapeutic areas where we've just not seen much of anything. There hasn't been a single drug approved in SAD for a long time.

And the same thing in terms of menopausal hot flashes, depression, nothing with the kind of nonsystemic and rapid onset approaches that we're trying to achieve in the clinical studies we've seen.

So certainly, there are oral systemic approaches with different receptors in the brain that are targeted at different doses and different time frames to onset. I think we're very confident where we stand in terms of time to onset and the ability to avoid a lot of the issues you typically see pop up in REMS or in black boxes or even things that are more common associated with, say, drug-drug interactions.

So not having to go through the liver, not having to go through the kidney, not have to really go across the brain, into the brain, it's a big difference compared to what we see in the field and have seen in the field for decades.

So we think we're in pretty good shape, if we can get to the point where we can provide this product candidate to people who have been struggling with this disorder for most of their lives. Remember, the mean duration is about 20 years with onset in adolescents. So I think there's a lot of room for improvement based on where the market sits today.

John Boyle, William Blair.

This is John on for Myles. So a few from us. To start, can you give us some color on the potential path forward for AV-101 in neuropathic pain now that you've received a patent for the indication? And what gives you confidence for 101 in the indication given the prior failures of Aptinyx's NMDA modulators in DPN?

And then maybe on the PALISADE program, could you remind us of the rationale for the clinician administration in PAL-3 and 4? And specifically, is there any expected difference on the placebo response for clinician versus self-administering?

Okay. Any other ones, just those two?

I've got some more, if you want, after.

Always happy to talk to you, John. So look, with respect to AV-101, as we've announced, that's a candidate for partnering, and our confidence drives not just in pain but also in dyskinesia associated with L-Dopa therapy for Parkinson's. And we've got not only Phase 1 data telling us that this is a compound that we think is pretty safe, but also one that we've seen in preclinical models, not yet in any patient-based studies, but in preclinical models, the MPTP monkey model in terms of the Parkinson's-related dyskinesia, and then in some conventional pain models that have been published that we see it's a different approach.

And it's -- these are NMDA receptor at the glycine site, seven-chlorokynurenic acid, which is what the prodrug produces when astrocytes take it up in the brain. That is a very selective and potent glycine site antagonist, but not so much so, say, like a ketamine or an amantadine where it's blocking the ion channel.

So we think it's got modulatory capabilities at that site, both NR1 and NR2, and we're in a spot with this one where while it's not in line with the pherine assets that we've got in with clinical stage and Phase 2 or later positive data, this is one that we think there is some potential for those who are focused on those neurological indications. And I'd refer you to the publications that are in pain that we can send to you that will give you a little bit more comfort on the preclinical data.

In terms of the clinician administration of the test drug in the context of PAL3, PAL4, Josh, why don't you go ahead and address that one?

Sure. Yes, I would love to. So with these studies compared to the prior ones, we were really focused on reducing any potential variability. And so when you think about a single-dose public speaking challenge or single dose at visit two, single dose at visit three, we really wanted to make sure that we reduce variability.

And rather than have to train each subject each time, you think about just having to train the raters or the clinicians at the site, and then they administer consistently throughout the duration. So that really drove that decision, again, just reducing variability. We really don't think there's any impact to the label or projected use because the open label that we have in place for all these studies has patients using it on their own every day, multiple times a day as needed. And so we don't expect any issues that -- issues there.

Similar to the math is coming down. Obviously, we want to -- this drug needs to be pointed right at the mid-septum, so not up into the sinuses in any way where it just would get in the respiratory system. So again, it just ensures that the drug has got the best opportunity to work in those that are in the treatment side. It shouldn't affect placebo, but to be determined, I suspect.

Very helpful. And I guess maybe just one more from us. How are you viewing your need to hit on both SUDS and CGI-I in PALISADE-3, 4? Kind of just wondering if there's any sense that you might need to show some anchoring -- some independent anchoring of the SUDS to the CGI-I.

Well, the SUDS is group level, right, and CGI-I is individual level. And it is -- you have seen in the past and we've seen in the past that how people do on their SUDS from time to time will tell you whether they are going to be a one or a two on the CGI-I. But they are really distinct assessments where we're focused, as the primary input, on the group level change between treatment and placebo. So CGI-I stands as does PGI-C, which is now a secondary endpoint in PALISADE-3 and 4. Those are all important to provide context as to what we've seen as the clinical meaningfulness at the group level.

Paul Matteis, Stifel.

This is Emily on for Paul. We were wondering if you could talk a little bit more about the ongoing repeat dose study and kind of what are you hoping to see in the rationale behind that? And also, if there would be any regulatory risk if fasedienol is safe but it kind of turns out 2 doses look a bit more efficacious than 1?

Sure. Josh, go ahead and hit this one.

Sure. So for repeat dose study, as we've noted before, it's really essentially identical to what we're doing in PALISADE-3 and 4, just with an additional arm so that we can see if a dose administered 10 minutes after the first dose would have an impact on the public speaking challenge.

And the FDA asked for that essentially because they felt in the real world, there's a good possibility that a subject may go ahead and still feel -- if they still feel nervous, take another dose. And so the thinking there is, is there any safety impact? We think there likely is not based on other higher doses that we've measured.

And then is there a potential efficacy benefit? There could be for some patients, but you also have to keep in mind that once those receptors are saturated with the spray, you don't really get any additional benefit. So it's to be seen as to whether or not we would see additional benefit in that arm.

At the end of the day, if PALISADE-3 or 4 are positive on that primary endpoint with 1 dose, we don't think that it would create any issues for approval to see potential benefit of a second dose. And what it would do is likely inform the label so that physicians are able to let patients know that they could dose again within that 10-minute time frame if they felt it might be beneficial. But beyond that, we really don't see impact. And it is a -- it's a smaller study as well. It's not powered or sized like our Phase 3 studies are.

It's a good point, Josh. And Emily, it's key that we align with the agency on this study. And I think the key takeaway for us is that it could inform labeling. It could help docs get -- the question is, how are you going to tell people to take it? Well, it could inform the labeling and guide whether the second dose within 10 minutes is safe. And that, as we -- as Josh noted, as we expect it would be.

And again, I think the anticipation is in the real world, people may think more is better. And so to know that it's okay and safe -- there's only so much volume the nose can handle anyway. And as Josh noted, once you occupy and activate those nasal canal sensory neurons, which happens in about 25 milliseconds, you're on your way to what we're trying to achieve when we -- the neural circuitry projects to the amygdala.

Thank you, everyone. This is all the time we have for questions today. If you have additional questions, please do not hesitate to contact us by e-mailing ir@vistagen.com or you can log into the website via the Contact section and submit questions through that portal. We also encourage you to register for e-mail updates on our website to stay connected with the latest news from Vistagen. Again, thanks for participating on the call today.

We appreciate everyone's interest and continued support. We look forward to keeping you updated on our ongoing progress. This concludes the call. Have a wonderful day.

Ladies and gentlemen, thank you for your participation. You may now disconnect.