Welcome to Virtual Investor Conferences. My name is John Vigliotti, and on behalf of OTC Markets, as well as our co-host, Zacks Small Cap Research, we're very pleased you joined us for our next presentation from Acasti Pharma. Their session will be moderated by John Vandermosten. He's the senior biotechnology analyst with Zacks Small Cap Research. Please note you can submit questions for the presenter in the box to the left of the slides, and you can also view a company's availability for one-on-one meetings through the Schedule Meetings tab found on the conference platform. At this point, I'm very pleased to welcome Prashant Kohli. He's the Chief Executive Officer of Acasti Pharma, Inc, which trades on NASDAQ under the symbol ACST. Welcome, Prashant and John. Thank you. Great. Thank you for the intro, John. Acasti is a development stage biotech company with a focus on rare disease. It's investigating a new formulation of an already approved drug, nimodipine, to treat aneurysmal subarachnoid hemorrhage, or aSAH for short. Prashant, welcome to the OTC Life Sciences Investor Forum. Thank you, John. Let's start out with your lead indication because I think, most investors probably haven't heard of it. What is aSAH, and how rare is it? Thank you, John. Excited to be here today. aSAH stands for aneurysmal subarachnoid hemorrhage, and it's a rare form of brain bleed. An aneurysm developing deep inside the brain unexpectedly ruptures, spilling blood into the brain, which is what causes the hemorrhagic stroke. It's a rare disease, and that's why it's called aneurysmal subarachnoid hemorrhage. What are some of the symptoms that a patient might see if they've suffered aSAH? Can we see it coming, or is it something that happens unexpectedly? Yeah, yeah, good question. So the disease doesn't have very well quantified known causal factors. It really strikes out of the blue, unexpectedly. There is no disease etiology that develops over a period of time like you do with other forms of stroke, ischemic stroke in particular. So the patients unexpectedly will experience the worst, absolutely the worst headache in their life, typically classified as a thunderclap headache. Most of them might even get unconscious at this point in time or throw up. For reasons not very well understood, it afflicts a younger population. Average age is 59 years old, and more women, slightly more women than men. It's a disease that afflicts a younger population, carries a very high mortality and morbidity risk, and a huge cost and burden to not only the patient's family, but also society as a whole. It sounds expensive when it happens. So after a patient is diagnosed with aSAH, what does their journey look like? It sounds like it probably is a difficult one because that's pretty serious, you know, blood on the brain. So eventually, a 1/3 of the patients do not survive the insult. Mm-hmm. Another third end up living with long-term morbidity. So you have two-thirds of patients with poor outcomes, and as you correctly pointed out, it is one of the most expensive diseases to treat in a hospital setting. So a patient ideally, you know, upon the insult, gets to a comprehensive stroke center, or even if they're triaged at their local regional hospital, they will invariably be sent to a tertiary hospital. And a CT angiogram is the definitive diagnosis for aneurysmal subarachnoid hemorrhage. There is an active rupture bleed in the brain. As you would expect, there's nothing that's gonna really stop it from a therapeutic standpoint. A neurosurgeon ideally goes in either endovascularly, which is more of the standard of care in the United States now, but there is open brain or craniotomy that's used as well, where they would go in and clip the aneurysm to stop the bleed. And endovascularly, they would go in and typically insert a coil, again, to stabilize the ruptured aneurysm, which eventually leads to stoppage of the bleeding. The patients are in a very serious condition, so they are in a neurocritical ICU. These neuro ICUs at these comprehensive stroke centers are some of the best of the best in the country. They have very well-trained, skilled, highly skilled, not only neurosurgeons, but also neurointensivists, the neuroscience nurses, and the care and the support staff with the appropriate technology to monitor the patient. The only FDA-approved therapy to improve outcomes is a calcium channel blocker called nimodipine, and the patient is put on this nimodipine therapy for up to 21 days, so besides surgical intervention, extensive medical management, this pharmacotherapy of nimodipine is what's used extensively as standard of care in the U.S. ... So does the patient, you know, you said 21 days of treatment, does the patient recover fully, or is there always kind of, there's some loss, you know, due to the magnitude of the insult? So the patient, as I mentioned earlier, a third of the patients will eventually not survive, and another third end up living with long-term morbidity. Okay. and about a third rule of thumb is that they will end up, you know, with good recovery. So it's across the spectrum, but it is a serious, life-threatening disease, with potentially poor outcomes if the patients are not adequately treated, on a timely basis. About 50,000 cases a year of aSAH in the country. That number has been fairly consistent year- over- year, in the U.S. So even all the advances that we have made for other kinds of strokes, the incidence in aneurysmal subarachnoid hemorrhage has been fairly consistent year- over- year, going back, several years now. Okay, so about fifty thousand. So, as you mentioned, there is an approved drug for the disease. However, it's got some shortcomings, the oral form of nimodipine. But you and Acasti are using a new formulation of the drug, one that can be infused, which solves some of the shortcomings of the oral form. Can you explain why the oral form isn't good enough? So nimodipine, as you rightly pointed out, is available as oral capsule or as an oral solution. Nimodipine, as a molecule, is highly hydrophobic. It has other liabilities, clinical liabilities, when it's given orally. And I'll explain on the... you know, take a few minutes just to kind of explain what the challenges with oral nimodipine is, and then talk about our technology with GTX-104. So when the drug is given orally to this patient population. Now, keep in mind, majority of the patients are unconscious, or they're obtunded, they're dysphagic, they have a hard time swallowing. Now, nimodipine has very high first-pass metabolism. What that means is the drug has to be administered very frequently, every four hours, so that equates to about 6x a day for up to twenty-one days. It has other cytochrome P450 liabilities. The drug has to be metabolized in the liver before it can get into the systemic circulation, the bloodstream, and it needs to get there in order for it to get to the brain, which is where it's required to improve outcomes. Nimodipine, you know, has been proven to be efficacious in multiple well-controlled clinical trial, so it's a drug that is really critical to make sure that the patients get the oral form. Now, when the patients are unconscious, the only way to get this drug is through a feeding tube, which these patients- Hmm ... sometimes have. And nurses have to shove it down the nasogastric tube, wash it down with saline. A lot of times, the drug, the full therapeutic dose doesn't get to the patient. The oral capsules are the, you know, big capsules, one gram each, just 60 mg every four hours. So it's two 30-mg capsules, the biggest size that is approved by the FDA. So it's a challenge even for a normal subject to swallow these two big capsules. And in these critically ill patient population, it becomes a real dosing burden for nurses to get the drug into the patient. The other issues with nimodipine. Nimodipine is a well-known vasodilator, acts in the neurovasculature- Hmm ... you know, causes hypotension, a drop in blood pressure. Now, in this particular patient population, if they become too hypotensive, that becomes a huge safety risk for these patients. So oftentimes, in fact, published literature has shown in over 55%-60% of the patients, nimodipine is withheld. The dose of nimodipine is withheld to prop up their blood pressure, to stabilize the blood pressure. In about a 1/3 of those patients, they have to be administered highly invasive rescue therapy, again, to stabilize their blood pressure. It could be intra-arterial vasopressors, angioplasty, very invasive, very risky, and also very expensive rescue therapy to manage their blood pressure in response to nimodipine therapy. Those instances, the only FDA-approved drug is currently being routinely withheld in this patient population to better manage the side effect profile. In a way, it's no wonder that patients have poor recovery because of some of these challenges. Nimodipine also has drug-to-drug interaction and food effect liabilities. When it's given orally, patients have gastric motility or ileus issues as well, which significantly either impedes or exacerbates the absorption rate into the bloodstream. There is, again, well-quantified published literature. When the drug is given specifically through the feeding tube, you see oftentimes it's barely detectable in the blood. And if it's not, again, in the blood, it's not gonna be in... you know, get to the brain where it needs to do its job. So there are some significant clinical liabilities, not to mention, you know, very high dosing burden and potential risk of medication errors, which have, you know, which do occur in practice, that creates unmet medical needs in this particular case with the oral formulation. So in response to that, our scientists figured out a way to solubilize the hydrophobic molecule, nimodipine, and create an aqueous formulation of nimodipine. What this aqueous formulation allows for now is a infusion of nimodipine directly into the systemic circulation for these patients, which addresses a lot of the challenges, the clinical challenges that I outlined just a few seconds ago. From a clinical standpoint, the feedback we hear from neurosurgeons, neurointensivists, and physicians is real excitement around better able to manage hypotension with an IV form. As you know, it's far more easily titratable versus someone's- Be more precise, I guess, right? You can be more precise with the dosing. Correct. You can be more precise, reduce medication error, cut back on dosing burden. So those are some of the benefits of the GTX-104, our IV, novel IV formulation of nimodipine. Okay. And, as we've mentioned, the underlying API, the underlying drug, nimodipine, has already been approved by the FDA, just it's in this oral form. So with that in mind, what's the regulatory pathway that you need to follow to get this approved? So just to you know highlight your point exactly, it's nimodipine is already standard of care. It's written in the care guidelines by the American Heart and Stroke Association, so physicians do not have to be convinced to use nimodipine. In fact, the Joint Commission routinely monitors hospitals' usage of nimodipine in this patient population, so there's a self-governance mechanism to making sure the patients are getting nimodipine in the U.S. From a regulatory standpoint, we have had extensive conversations with the FDA and they have been very consistent in giving us the guidance on what it would take to get an approval or file an NDA application. We met with the agency face-to-face pre-pandemic in early 2020 where we negotiated a path towards an NDA. Two steps. Step one was to establish a pharmacokinetic bridge in a phase I trial to make sure that pharmacokinetically we bridge the IV to the oral dosage form, which we successfully accomplished in 2022, and the second step is to conduct a phase III pivotal trial. It's a safety trial in patients, a 100-patient safety trial, so that is what we are currently enrolling for, our second and final step towards an NDA application. Okay. Yeah, and I think you mentioned the, you know, obviously, the phase II trial. It's the, I think STRIVE-ON is what you've named it. What's... How is it designed? And, you know, it's a safety trial, right? So obviously, those are gonna be the endpoints, but maybe you can clarify some of the other endpoints, perhaps, that are part of the STRIVE-ON trial. So it's not a statistically powered trial, FDA agreed. You know, it's the design, you know, nimodipine is already proven to be efficacious. So once we met the scientific bridge in our phase I trial, that qualified us for the 505(b)(2) pathway. And the trial design of STRIVE-ON is safety. All of our endpoints are safety, where we need to demonstrate that GTX-104, the IV formulation of nimodipine, is just as safe as oral in the patient population. 50 patients are being administered GTX-104, are on the 104 arm, another 50 on the oral arm. It's a randomized, one-to-one, open-label, safety trial. The primary endpoint, number of patients that develop hypotension, between the two arms, and in addition to the other AEs and SAEs that we are capturing, as part of our trial design. The patients are on treatment for up to 21 days, both IV or oral, and there's a follow-up period, day 30 and day 90. We're also collecting other data, such as health, economic, and outcomes data, the challenges that I mentioned about oral, with the dosing burden, therapeutic intensity, rescue therapy use, length of stay. So additional pharmacoeconomic measures that can really help us with commercialization as well, potentially upon approval. So it's a robust trial design. However, we believe it to be relatively de-risked. We have done multiple phase I studies in over 160 subjects, where GTX-104 head-to-head with oral has already shown to be comparably safe. So we have strong confidence going into the STRIVE-ON trial. Okay. And I think you provided guidance that, you'll be, submitting an NDA, or you're gonna try... Your target is to submit an NDA in the first half of 2025. Does that mean that, you- we'll see top line from that trial around the end of the year sometime? So several weeks ago, we announced that we are way over 50% enrolled in the trial. We anticipate fully enrolling 100 patients in the next few weeks, and that leads us to a data readout very, you know, early next year, followed by, if everything goes well, an NDA application soon, soon thereafter, by the middle of the year, 2025. Okay, great. And the value that Acasti is bringing to the table, you know, your platform is the technology behind your IV formulation, and you gave us a kind of a quick peek at it a few minutes ago. Can you provide a more in-depth summary of how that works and, you know, how it's different from other types of IV formulations that may try to do the same thing? So, nimodipine, as I mentioned, is hydrophobic. There have been a lot of attempts made to try and crack the formula on how to create an aqueous formulation. They have been all either unsuccessful or subpar, that have created more complications for patients. What our team did, you know, brilliant formulators, drug delivery scientists located in New Jersey, created micellar technology with GRAS excipients, generally regarded as safe excipients. So these are excipients that have already been used in other approved drugs, and created a first ever aqueous formulation of nimodipine. We wanted to make sure when we designed the formulation, that it was going to be commercially very attractive, both from a manufacturing cost perspective, but also from a ease of manufacturing as well. So it was going to be not overly complex. As you know, most sterile injectables require special handling. Refrigeration can be very expensive, tricky to manufacture. Our aqueous formulation is room temperature stable, doesn't require- Hmm ... any of those special handling and bells and whistles, for other sterile injectables, which we believe will create a very competitive differentiation for us and give us a lot of flexibility, even from a pricing standpoint, to not have to carry all that extra cost that comes with an injectable. So we're very proud of the scientific breakthrough that has gone into developing this technology in a life-threatening disease, where we know that there are some very serious clinical challenges and unmet medical needs that GTX-104, you know, is ideally positioned for and then potentially become the standard of care. You've commissioned a study not too long ago about just some of the benefits that the hospitals might see if they shift to the infused IV formulation that you have. Can you summarize the findings of that study that you commissioned, and also give us your impression of what hospitals are looking for in this patient population to, you know, improve treatment? Yeah. So we conducted a survey of P&T committee members of hospitals. So this is the Pharmacy and Therapeutics Committee. Hospitals routinely evaluate new technology, new drugs, via this P&T process. We wanted to make sure that GTX-104, the target product profile, was gonna be compelling and for hospitals to embrace the technology for patient use. So in over 80% of the respondents, it was a 30-person survey that was conducted at these top academic medical centers of P&T committee members. 80% came back highly favorable and did not see any challenges adopting GTX-104 at their hospitals. And we think there are some strong reasons for that. Patient safety, making sure that the patients get the full therapeutic dose of the only approved drug for a debilitating disease state, cutting down on hospital resources, reduction in dosing burden, improving outcomes and safety, better compliance, and management of hypotension, are some of the strong value proposition and differentiators that were cited as being favorable for GTX-104 relative to the challenges of, you know, oral nimodipine. Okay. You know, actually, the point that you brought up that was most interesting to me was that, you know, these patients that may be unconscious can- Mm-hmm ... can receive their treatment, you know, and otherwise, they have to do it orally every four hours. So I think, you know, it seems like you- Mm-hmm ... you've solved one of the bigger issues there. Well, you know, I was gonna ask you about some of the other things in your portfolio. I know your main focus is on GTX-104, but there are other things you're doing. There's GTX-102 for ataxia t elangiectasia, which is another rare disease. I think only symptomatic treatments are now available for that. Tell us about that asset and what might, you know, be the next steps for that. GTX-102 is our second late-stage clinical asset. It's for a rare, ultra-rare pediatric neurodegenerative disease called ataxia t elangiectasia, or A-T for short. The prevalence of A-T in the U.S. is about 5,000 patients, children. It's a terrible condition, a genetic defect that children are born with. Patients get usually diagnosed month eighteen or twenty-four month, when parents start noticing poor development, oculomotor, you know, physical development, gait disturbances. There's a genetic test where that's a definitive test for flagging patients with A-T. And the prognosis is dire. These patients are wheelchair-bound within the first five years of their life. They're highly prone to infections, cancers, leukemias, and eventually, unfortunately, succumb to those comorbidities in their twenties. There is no FDA-approved therapy currently on the market for A-T. Our team identified a proof of concept clinical trial at the University of Siena in Italy, where they administered a corticosteroid called betamethasone and found a statistically significant improvement in outcomes with that drug in patient population. So we secured the exclusive worldwide license to that proof of concept trial and created our own novel formulation of betamethasone that can be given, administered as a very easy, simple-to-use oral mucosal spray, either by the patient or the caregiver directly. And this program, GTX-102, we successfully conducted a phase I trial in 2022, and we believe that it's ideally teed up for what we think should be the pivotal phase III efficacy and then safety trial for GTX-102. So we're equally excited about our second program, which is, you know, late stage as well and ready for what we believe to be its pivotal trial. Is that something that you might pick up after you file your NDA for GTX-104? So over a year ago, in terms of making sure that we better stay focused and allocate our capital resources, we prioritized GTX-104 since that was the closest to a potential NDA approval, and allocated our resources to this program. Our plans absolutely are to get the second program, you know, back online once we have made more progress with GTX-104 and are able to raise capital on better terms. Obviously, for this program, opportunistically, we're also looking at either outlicensing or selling the second asset as well, the GTX-102 program. Okay. We want to make sure that we preserve, create, and capture shareholder value, but we believe that it's a differentiated program. We're getting a lot of interest and excited to bring this program back online at the right time. Something we didn't talk about yet is your financial profile, what's your cash level and your capital structure. Can you spend one minute or two on that, sharing how that looks? Sure. So, as of June thirtieth of this year, we announced a little over $19 million in cash. We're fully funded. The company has no debt. The STRIVE-ON trial is fully funded with the cash on hand, including filing our NDA application middle of next year. In fact, if we do not take on any other programs, our cash runway takes us into calendar 2026. So we have a healthy cash position relative to our core asset and our core program. The company has no debt, a relatively clean cap table. So we're, you know, we're fully funded. The key point is on our STRIVE-ON and our GTX-104 program. Okay, great. Well, I think we've come just about to the end of our time today, Prashant, and thank you so much. Again, for our viewers, we had the CEO of Acasti, Prashant Kohli, ticker symbol ACST. Thanks so much, and look forward to working with you again. Thank you, John. Appreciate it, and enjoyed our talk today.