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spk08: Greetings and welcome to VistaGen Therapeutics' second quarter of fiscal year 2022 results conference call. At this time, all participants are on a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during a conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Mark Flather, Vice President of Investor Relations. Thank you. You may begin.
spk05: Thank you, Doug. Hello, and welcome to Vistagen's conference call covering its fiscal year 2022 second quarter financial results and recent accomplishments. I'm Mark Flather, Vice President of Investor Relations at Vistagen. Thank you for joining us today, and welcome to our shareholders, analysts, and anyone taking an interest in Vistagen. Joining me today are Shawn Singh, our Chief Executive Officer, Jerry Dodson, our Chief Financial Officer, Dr. Mark Smith, our Chief Medical Officer. The format for this call will consist of prepared remarks from management, followed by an opportunity for questions. To ask a question during the Q&A portion of this call, be sure to hit star followed by the one key at any time to be placed into the queue. This call is being webcast and will be available for replay. The link can be found in the Investors IR Calendar 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 current information. The forward-looking statements speak only as of today and accept as required by law and 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 statement 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 10Q filed earlier today with the Securities and Exchange Commission, or SEC, and 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, with the formalities out of the way, I'd like to turn the call over to our Chief Executive Officer, Sean Singh.
spk04: Thank you, Mark. Good afternoon, everyone. On behalf of our entire team at Vistagen, thank you for joining this call today. We sincerely hope you are all safe, healthy, and doing well. The current mental health treatment paradigm requires new, faster-acting medicines, medicines without the negative side effects and safety concerns that are often associated with currently approved options. As the prevalence of anxiety and depression disorders has grown considerably over the last 20 months, both in the US and across the globe, the unmet need has become more acute than ever. During the second quarter of our fiscal 22, we continued our strong performance and continued to build momentum across all aspects of our business. As we head toward the end of 21 and into 2022, we are increasingly confident and excited about the potential of our CNS pipeline to mitigate many mental health challenges and make meaningful improvements in the lives of millions of individuals around the world who are suffering from the debilitating effects of anxiety and depression. Among the milestones we achieved during the second quarter of fiscal 22 was the initiation of Palisade 2, the second major phase 3 trial in our Palisade phase 3 program for PH94B in social anxiety disorder, or SAD. Like Palisade 1, Palisade 2 is a U.S. multicenter, randomized, double-blind, placebo-controlled Phase III clinical study designed to evaluate the efficacy, safety, and tolerability of our PH94B nasal spray for the acute treatment of anxiety in adults with SAD. As a reminder, according to the U.S. National Institute of Health, SAD is the third most common psychiatric condition in the U.S. after depression and substance abuse. and it now affects over 23 million Americans. The initiation of Palisade II is another important step forward in our efforts to confirm the positive efficacy and safety data we observed in Phase II development of PH94B in SAD. It successfully developed in our Palisade Phase III program. PH94B has the potential to be the first FDA-approved, fast-acting, non-sedating, acute treatment of anxiety for millions in the U.S. who suffer from the debilitating effects of SAD. PH-94B is designed to be used as needed, on demand, as an acute treatment of anxiety for adults with SAD, treating their anxiety and fear of embarrassment, judgment, or humiliation in the context of an anxiety-provoking interaction, situation, or event in a manner similar to how a rescue inhaler is used to prevent the onset of an asthma attack. or as an acute migraine treatment is used to prevent the onset of a migraine episode. A market approval of PH94B in the U.S. would also pave the way for potential regulatory approvals in numerous additional high-value markets around the world. All ongoing studies in our Palisade Phase III program for PH94B and SAD are progressing well, and we remain on track for top-line data from Palisade 1 in mid-22, and from Palisade 2 in the second half of 2022. With its unique mechanism of action and safety profile we've observed in all clinical studies to date, we believe PH94B also has therapeutic potential across a broad range of anxiety disorders beyond SAD. During the quarter, we launched our exploratory phase 2A clinical development program for PH94B, with the initiation of a phase 2A clinical trial in adjustment disorder with anxiety. With emotional stress and impaired functioning brought on by sudden changes in health, safety, economic and social circumstances that many have experienced at heightened levels since the beginning of the pandemic, the increasing prevalence of adjustment disorder with anxiety has become very apparent to our team and the clinicians within our ecosystem. We believe PH94B has potential to offer hope to the growing number of individuals whose ability to function in their daily lives has been impaired by the onset of adjustment disorder. We expect top line results for this Phase IIa study in the second half of 2022. In the coming quarters, we plan to initiate additional small exploratory Phase IIa studies to assess PH94B's potential in populations suffering from anxiety disorders beyond SAD and adjustment disorder where we believe the current treatment alternatives are inadequate. During the quarter, we also reported important new preclinical data on PH94B's potential mechanism of action. Data from a tissue distribution study in laboratory rats demonstrate that a single intranasal administration of radiolabeled PH94B was largely confined to the nasal passages, with minimal or undetectable levels in most other tissues, including the CNS. And importantly, no appreciable activity was observed in the brain. We believe these results further highlight how the mechanism of action of PH94B is fundamentally differentiated from that of all current anxiety therapies. Because PH94B administered intranasally involves binding to peripheral neurons in the nasal passages, we believe there is limited transport of PH94B molecules to the circulatory system, thereby minimizing systemic exposure. When this radiolabeled PH94B data is combined with previously announced preclinical electrophysiology data demonstrating that the mechanism of action of PH94B does not involve direct activation of GABA-A receptors, which is in distinct contrast to the mechanism of action of benzodiazepines, we see a growing body of evidence suggesting that PH94B has potential to achieve anti-anxiety effects without requiring systemic uptake and distribution. and without causing benzodiazepine-like side effects and safety concerns. Regarding our other clinical stage drug candidates, PH10 nasal spray and our oral prodrug AV101, we are on plan to initiate our Phase IIb study for PH10 as a potential standalone rapid-onset treatment of major depressive disorder in mid-22, and to initiate our drug-drug interaction study of the combination of AV101 with probenicid near the end of this calendar year. We believe our current cash position is sufficient to advance our CNS pipeline well beyond a steady stream of potential data and regulatory catalysts from our Palisade Phase III program for PH94B and SAD, not only in calendar 22, but into calendar 2023, as well as other important clinical opportunities across our pipeline. We believe we have the flexibility and options to further strengthen our balance sheets beyond the multiple key data readouts with potential to be significant value-creating catalysts for the company. As we advance development of mental health treatments with groundbreaking potential, we've added to our strong team of great people with extensive experience in CNS drug development, clinical operations, CMC, commercial operations, and medical and regulatory affairs. During our last quarter, we also expanded leadership expertise on our board of directors with the additions of Mary Rotundo and Maggie Fitzpatrick to our board. which now has a female-led majority, significant distinction in board representation within the biopharmaceutical space. Our experienced team is well-positioned to advance our programs through important late-stage clinical and regulatory milestones and navigate a responsible path forward to potential commercialization of PH94B and social anxiety disorder. Our team is comprised of amazing individuals who not only possess vast knowledge and experience within our industry, but who also share our passion for social change and align with our corporate values. As we forge forward as changemakers in the mental health arena, we are confident and very excited about the potential of our CNS pipeline to make meaningful transformations in the daily lives of those impacted by mental illness. I'd now like to turn it over to Jerry Dodson, our CFO, to summarize some highlights from our fiscal year 22 second quarter financial results. Jerry?
spk03: As Sean mentioned, I'll highlight a few items from the second quarter of our fiscal year 2022 financial results. 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. For the second quarter of our fiscal year 2022, ending on September 30th, 2021, Vistagen recognized approximately $0.4 million in non-cash sub-license revenue from the $5 million upfront payment that we received in the second quarter of fiscal 2021 related to our PH94B development and commercialization agreement with Afamed Therapeutics. We recognized approximately $0.3 million related to this agreement in the second quarter of fiscal year 2021 that ended on September 30th, 2020. Our research and development expenses increased by about $7.7 million from $2.4 million to $10.1 million for the second quarter ended September 30th, 2020 and 2021 respectively.
spk00: This increase
spk03: results primarily from conducting our Palisade Phase III program for PH94B in SAD with the continuation of Palisade I and the initiation of Palisade II and Palisade Long-Term Safety Study, as well as the initiation of our Phase IIA study of PH94B for the treatment of adjustment disorder with anxiety. While we continued, Non-clinical development and outsourced manufacturing activities for both PH94B and PH10. All of that accounting for increased expenses of approximately $5.9 million during the quarter ended September 30th, 2021, compared to the same quarter of the previous fiscal year. Salaries and benefits expense for the quarter ended September 30th, 2021, increased by approximately $1.6 million versus the expense for the comparable prior year quarter, primarily due to the hiring of additional senior management and other personnel focused on clinical operations, outsource manufacturing activities, and regulatory affairs. General and administrative expenses increased to approximately $3.1 million from approximately $1.3 million for the quarters ended September 30th, 2021 and 2020, respectively. The increase was primarily due to the hiring of additional senior management personnel and expenses incurred in connection with various customary pre-commercialization activities for PH-94B. Our net loss for the second quarter of fiscal 2022, the quarter ending September 30th, 2021, was approximately $12.8 million versus a loss of $3.3 million for the comparable quarter of fiscal year 2021. At September 30th, 2021, the company had cash and cash equivalents of approximately $93.6 million. I'd also note that between October 1st, 2021 and today, the company has received approximately $1.1 million in additional cash proceeds from the exercise of outstanding warrants. 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.
spk04: Thanks, Jerry. So we continue to march forward, determined and resilient and unwavering towards several significant and potentially transformative milestones across our pipeline. With patients and investor-focused priorities guiding our mission to improve the lives of millions of people who battle mental health challenges every day, our team at Vistagen is thankful for the privilege and for the opportunity to make a difference for those needing changes in their treatment options. Our accomplishments this year, and as we advance towards our goal of becoming a top-tier biopharmaceutical company, would not at all be possible without the commitment and hard work and endurance of our entire Vistagen team, our collaborators, and our stockholders. We thank you for your continued support, and we look forward to creating life-changing value for patients and for all of our stakeholders.
spk05: Thank you, Sean. This concludes our prepared remarks. Operator, we'd now like to open up the call for questions.
spk08: Thank you. Ladies and gentlemen, at this time, we will begin an answer session. If you'd like to ask a question, you may press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key. Once again, that is star 1 to ask a question. Our first question comes from the line of Brian Scorny with Robert W. Baird. Please proceed with your question.
spk10: Hey, good afternoon, everyone. Thank you for taking my question. I guess on the initiation of the long study, I was just hoping you could kind of walk us through how to think about sort of how randomized patients and screened-out patients are handled in the follow-up and how you kind of look at monitoring the drug exposure levels that they have. And then I think the gating factor on the study was animal tox studies. I guess, was there anything of note in those studies to speak of? And can we assume that being cleared to enroll patients in this study means there was nothing of note?
spk04: Hey, Brian, thanks for the question. So, no, there was nothing of note in the six-month tox studies that support us getting into the long-term safety study. Mark Smith, our CMO, is on. I'll let Mark address some of your questions regarding the study. It's on track.
spk00: Yeah, so the placebo-controlled studies, you know, we are looking for patients who, you know, get very stressed out by public speaking. So we're kind of, you know, self-selecting some of those patients. But for the long-term safety, we're really looking for all comers, pretty much everybody with social anxiety disorder. We want to give them a try on this medication. those that maybe didn't quite make the inclusion-exclusion for the placebo-controlled, maybe because they were not quite sick enough, or maybe they were already taking like an SSRI. They were on some background medications that were not allowed in the placebo-controlled setting. We're allowing all those people now to come in to the long-term safety. So a lot of those people who Screen failed for the two randomized trials. We will allow them to go in now to the long-term safety now that the FDA has given us the green light on that. So I think it'll be very interesting to see how some of these other patients respond to the medication and also those with, we want to make sure that it's safe to use on top of background antidepressants. which we believe it will be, but this will provide some evidence for that. And you also asked about how do we monitor how much they're taking. So it's two ways. The old-fashioned way, we essentially weigh the vial before and after each visit. That will give us an indication of how many administrations they delivered And the second way is we're asking them to actually record on a cell phone app. So they'll each have an app on their smartphone and we ask them at the end of each day to record how many times they took it. In the previous outpatient study, on average, even though they can take it up to four times a day, On average, they took it about one and a half times a day. So we'll see if that continues in this long-term safety. That'll be important information, I think, for us as to guiding folks how to take this medication.
spk10: Great. And then maybe if I could just ask a follow-up on just trying to get some granularity on sort of how to think about the timeline for Palisade readout. I think in the protocol, it allows for up to seven weeks from screening to last visit of a patient. Should we also expect maybe another six weeks on top of that for data lock and scrubbing? I'm just trying to figure, like, once you announce the completion of enrollment, would we think it's about a quarter from that completion to top-line data?
spk00: Yeah, I'd say four to six weeks, you know, after we enroll our last patient, yeah. So, you know, the protocol itself could go fairly quickly. But, yes, you're right. I mean, there could be a little prolonged screening period. So, yeah, four to six weeks, I would expect.
spk09: Okay. Thank you.
spk08: Our next question comes from the line of Andrew Tsai with Jefferies. Please proceed with your question.
spk06: Hey, good afternoon. I'm Andrew Tsai. I just have a few questions and appreciate your time today. If I could begin, you know, you did briefly talk about the carbon-14 radiolabel study to see where the drug goes. To confirm, it does stay in the peripheral neurons and does not get into the brain. Do you know how it gets eliminated by the body?
spk00: Good question. Good question. The short answer is no. We really don't know. In this particular study, most was gotten eliminated through the feces and some in the urine. Now, I'm not sure that's true in man, to be honest, because I think in this particular study, we were giving a lot of volume to these rats. And I think some of it went back down their nasopharynx and into their gut. That could happen in humans as well if they sniff too hard or something. But the shorter answer is we don't believe it's taken up into the brain. That was very clear in this study, that most of it was contained in the nasopharynx, and then some of it went back down the throat. But a lot of people try to give drugs through the nose, like oxytocin, hoping that some will get across and then into the brain. That is not why we're giving this in the nose. We're giving it in the nose because that's where the receptors are. But back to your question, how it's eliminated. Honestly, we don't know completely. We actually, I was just, we were just researching this, and much to my surprise, we learned that the nose actually has a lot of cytochrome P450 enzymes in it, not as much as the liver, but quite a substantial amount. And so obviously this is a mechanism by which drugs can be metabolized. So it may be metabolized locally, right in the nose, much to my surprise, to be honest, and we may investigate that. So that actually may be how it's eliminated. And one other caveat for that C14 experiment, We were measuring C14, so we don't know if the PH94B was modified. It could have been metabolized. And so what small amount we were seeing in the body, we're not even sure that was parent drug. So still a lot to be learned here.
spk06: Thank you for the explanation. To follow up just briefly on that, do you know if there's any changes in heart rate or blood pressure after administration into the nasopharynx?
spk00: Early experiments that Dr. Monti did, the discoverer of these pharynx, early experiments when he was back in academia, he did see some transient changes in blood pressure and heart rate, and mainly to a slight decrease in blood pressure, slight decrease in heart rate and heart rate variability. So yes, there were some transitory effects. So we do believe this does affect the sympathetic, parasympathetic nervous system. And we're actually looking forward now to some small studies, not part of the placebo control because we didn't want to complicate that, but some smaller studies where we will be examining this. And heart rate, blood pressure, skin conductance was a consistent change. We'll be also looking at this in an upcoming PTSD study where we enroll PTSD patients and look at some biomarkers like this because we believe this drug, part of its mechanism of action is to tone down the fight or flight response. And so we'll be measuring these biomarkers in upcoming studies.
spk04: And we'll provide more guidance on that as we go forward. Okay.
spk06: Thank you. Just a few more questions. So we know that the Palisade 1 and 2 studies are ongoing. Do both U.S. Palisade studies need to be successful for you to file an MDA? Because we asked only because the Phase 2 had a very high p-value. So could that be a supporting study? And what do you do if one of the two studies fail? Do you have some sort of hedge or backup that you can leverage?
spk04: Good question. Mark, let me address this. The standard requirement is what applies here. So obviously, as is the case normally, you need two adequate, well-controlled studies to anchor your NDA. Palisade 1 and Palisade 2 are intended to suit that purpose. If one of them doesn't read out as supportive, then we also have Palisade Global that will start sometime in the middle of next year. That would be to support regulatory submissions outside the United States. but it could also be further supportive of what we might need to do in the U.S. I don't think it's safe at the moment. We certainly haven't had guidance from the agency that the phase two study could be used to support just adding one more phase study, a phase three study on top of that. So I think we have to just assume that the track we're on is intended through this whole program is intended to ultimately, if successful, support the NDA in the United States in mid-23. Palisade Global would launch, we expect, sometime in the middle of next year.
spk09: Gotcha. That's the Global Phase 3 trial.
spk04: Yeah, it'll be a replicate of what we see in Palisade 1, Palisade 2, or just involve other jurisdictions besides the United States.
spk06: Wonderful. Okay, thank you. And again, just a few more questions. The next question is, can you talk a little bit about the competitive landscape in SAD other than SSRIs benzos, beta blockers. We see that companies are starting up anxiety studies. So what's your messaging around that competitive environment?
spk04: Well, look, there's never a one-size-fits-all for any of these neuropsychiatric indications. We are considerably downstream, as you know. We're certainly not aware of anybody in the phase three arena who's got the type of product profile that we're advancing with PH94B. So We certainly hope the world continues to get as many anxiety and depression treatment options as possible because we do know that no one size fits all. But on the other side, we're extremely confident about where we're positioned with PH94B and social anxiety disorder.
spk06: Gotcha. Thank you. Thank you. And so for PH94B for adjustment disorder, you started the phase two study with How did you end up choosing kind of the four times a day dosing regimen rather than, you know, two or six? And what makes you kind of feel that four times a day dosing will be safe and efficacious?
spk04: Well, remember, our objective with the program, the Phase IIa program, is to be able to explore PH94B's potential in a fairly broad range of anxiety disorders beyond SAD. So these are exploratory Phase IIa studies, which means first time in these populations. So it may not be that 94B is used the same way in all different anxiety disorders. And if this one is designed from a different perspective, as you just noted, I'll let Mark add a little more color to that. But our purpose here, remember, these are small exploratory Phase IIa studies to try to get some information to be able to assess potential to move into Phase 2B as we want to see additional indications for PH94B as we build on top of what we hope to be the initial first and foremost focus in social anxiety disorder. Mark?
spk00: Yeah, so the way we chose the dose was really based on our preclinical talk studies. So we gave that four times a day intranasally in our talk studies. So we knew that we had coverage for that preclinically. So this is the highest recommended dose, 3.2 micrograms intranasally four times a day. So we decided, you know, because this was the first time, actually one of the very first placebo-controlled trials I'm aware of in the U.S. in adjustment disorder, we decided to just push our dose, you know, because it's been so well-tolerated and give it the best chance in this disorder beyond SAD.
spk06: Gotcha. And, you know, what data have you seen to kind of show that this drug will have an effect kind of throughout the day given kind of, you know, our long work days anywhere from like 8 a.m. wake up, 6 a.m. wake up to, you know, 10, 11 p.m. sleep time?
spk00: Yeah. So, again, Most of our studies have been single dose, but we did have one outpatient study in social anxiety disorder where they were allowed to take it up to four times a day. And like I said, on average, they took it one and a half. There were a few people that took it two or three times a day. I can't recall anybody that needed to take it boom, boom, boom, You know, so it seemed, and this is anecdotal, but it seemed from that study that people were taking it, you know, one, two times a day, and that seemed to be sufficient. But again, we do plan to do another study next year where we address the question you've just posed to see, you know, what happens when people do redose. How long does the dose last? And so we'll be addressing those, some of those questions next year in some ancillary studies.
spk04: One of the key benefits of the product profile that we envision for PH94B is the fact that it does have a shorter duration of effect than, say, a benzodiazepine, and that allows us some hope and some confidence that it's going to be a very flexible treatment alternative for people. There are not only multiple different events within a particular day where people might have anxiety-provoking triggers, but it could be the very same event throughout a longer period in a day. So the ability to use the drug up to four times a day is very important, and that it should not, as we've seen so far in all clinical development, impair cognitive functioning or sedation. It's really distinct from what a benzodiazepine delivers. and even as to the rapidity of the onset. So faster onset, but without the side effects and safety concerns of benzodiazepines is a critical component of why we are advancing a PH94B forward in SAD.
spk06: Yeah, thank you. And I mean, there definitely seems to be an unmet need in that category. I just want to ask, do you have time for a few more questions?
spk09: Mark? Yeah, sure. I wanted to listen to
spk05: Yeah, let's come back. Yeah, we're happy to take additional questions. But, yeah, we've got a few more in the queue, and we'll come back if the questions aren't answered. Is that good?
spk09: Yeah, wonderful. Thank you. Excellent. Our next question comes from the line of Tim Lugo with William Blair.
spk08: Please proceed with your question.
spk07: Thanks for taking my question, and congratulations on the progress in the quarter. Mark, I think you mentioned, given the prior experience, you were expecting a 1.4 or maybe one and a half times a day use. Is that roughly what's occurring in the open label study as of now? And I guess as a follow-up, I know there's a maximum of four times a day. Is there also a minimum in that study for how much patients use per day?
spk00: It's too early to tell, you know, what the average dose is going to be. We'll be monitoring that, though, throughout the study. But, no, there's no minimum. And, you know, we instruct patients they don't have to take it every day. And, you know, that's the beauty of this drug is that, you know, they only take it when they need it. I mean, they may go several days and not, you know, encounter a social stressor. So in those days, there's no need to take it. but then another day they may have a very stressful day and they may need to take it two or three times that day. So there's no minimum. There is a maximum of four based on our TOCS work, but no minimum. And we will be monitoring this through the app regularly, but I don't have any data to share with you right now.
spk07: Okay, that's understandable. And in the long-term study, Since you don't have a public speaking requirement and that trigger, are you collecting through the app what is kind of triggering use?
spk00: No, not per se. We are actually looking into that. We are discussing that. That was measured in the Phase 2 study. And there was various things. That study was all done in New York. So there were things like being on subways and stuff that were individual maybe to that environment. But we're discussing that, whether that would be feasible. But currently, we're not collecting that information.
spk07: Okay. And can you just roughly describe how enrollment is going in Palisade 1 and your happiness with the site conduct to date?
spk00: Yeah, I mean, it's going according to plan. And, you know, we're pretty confident we will deliver as planned, you know, next summer.
spk07: Okay. That's great to hear. And maybe one last question. Can you just talk about, I know you have the adjustment disorder study up and running. And I also know that you're planning a number of other Phase 2As. Can you kind of give us a map of those? additional phase twos, when we expect to start them, and when we can start seeing some data coming out of those?
spk04: Yeah, so Tim, most of those studies we've mapped out for you before. 2022 will be initiating really the remaining components from the phase 2A, exploratory phase 2A program for 94B. So some will start in the first half of the year and others in the second half of the year in 22. But they all should be up and running. during the course of 22. The adjustment disorder study should read out near the end of 22. The others won't read out in 22 most likely, but adjustment disorder study will.
spk07: Okay, great to hear. Congrats on the progress.
spk09: Thanks, Tim.
spk08: Our next question comes from the line of Jason McCarthy with Maxim Group. Please receive your question.
spk01: Hey, guys. Thanks for taking the question. A lot of questions asked and answered. Sounds like a lot of progress has been made. Maybe a very broad, general question, Sean or Mark. Maybe you guys can talk a little bit about your thoughts on the mental health space, particularly what happened after the Compass readout the other day and, you know, the views of the space around the need for safety and With some of these drugs, it was a big deal on the psychedelic side, but there's a lot of positive safety aspects around 94B and the drugs that you're developing. Can you talk a little bit about that impact?
spk04: Yeah, absolutely. It's a critical component of every screen that we put in to each candidate across the pipeline, and the safety is a critical component of the success we think of any drug in either neuropsych or neurology. The tradeoff you typically have to make between the benefit for the underlying condition and the cost associated with the side effects and safety concerns, it's a tough challenge sometimes, especially as it affects compliance. So each of our three candidates, as in all clinical work to date and all preclinical work supportive of that, has just had an exceptional response. side effects and safety profile. And a lot of that has to be really driven towards the mechanism of action. And whether it's the fairings or whether it's AV101, there's a differentiation from what's out there today that has very well-established concerns associated with their use. We just don't see those. And to be able, especially what we've seen recently with 94B in the GABA-A study and in the C14 study, It just continues to fortify what we had thought about these candidates going into them early on. It's just they're completely different. To not have to require systemic uptake and distribution of 94B and 10 to achieve anti-anxiety and antidepressant effects, that's radical. And it's something that we think if we're successful in this Phase 3 program with 94B, it will carry us quite well into the commercial arena. It's a big deal. We've seen, again, as Mark laid out to you, some of the rationale we think that supports why we're seeing such an excellent safety profile. And I think as things continue in the program, I don't think we anticipate seeing anything different than what we've seen so far through clinical development. But, of course, we're going to be watching it carefully.
spk09: Great. Thank you, Charles. Our next question is a follow-up from Andrew Tsai with Jefferies.
spk08: Please proceed with your question.
spk06: Thank you. I just wanted to note, I appreciate the time that you've taken today to answer all these questions very thoroughly. I'm sure that the street appreciates it as well as investors do. Just one last question for you. You know, presumably in the Phase II study for PH94B, there were patients that did not respond to the drug. Did you ever figure out why that may be the case? And if so, how did you address it in the phase three study? Just trying to wonder how you can maximize essentially the probability of success for those phase three trials.
spk04: Mark, go ahead and address that.
spk00: Yeah. Well, I'll take the second part of your, how do we maximize probability of success? I mean, we, it's really through a two-step inclusion-exclusion criteria. So we're including patients, you know, who have pretty severe social anxiety disorder. We, you know, that's based on the Leibowitz scale. And so we're looking for patients like that. But on top of that, We're also making sure that they have a sufficient stress response to the public speaking itself. We're looking for people who get pretty stressed out by the five-minute talk we ask them to do. We're asking a lot of these subjects. We appreciate them participating in this study. I think the fact that they have high scores coming in makes them more sensitive to see a drug effect. So that's sort of how we're maximizing our success and really following on the Phase II protocol very closely. Now, back to your question. Yes, there were some patients who didn't respond. I'm trying to remember. I think it was about 25%, 30%. who did not respond completely to the drug in the phase two. And it's a good question. We don't know exactly what will predict response and not response genetically or physiologically. I think that's an interesting question. But it is a minority of people who did not respond, luckily. and didn't seem to be related to gender, that we can tell because in the open label study, both males and females responded to the drug. Doesn't seem to be related to age or gender, but we'll continue to look into that, because I agree, it is an important question. But it is a minority, thankfully, at least from that phase two data.
spk09: All right, that's all the time we have for questions today.
spk05: If you have any additional questions, please contact us at ir.bistagen.com or call any of the phone numbers listed on our press release today. 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, and you may all disconnect now.
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