Good afternoon. Thanks so much for joining our 45th Annual Healthcare Conference. I'm Stacy Ku, part of the biotech team with my colleague Vishal, and we'd like to welcome Prashant Kohli, CEO of Grace Therapeutics. Obviously, you recently disclosed some really interesting results, but we want to take a step back and maybe just talk about the disease indication, maybe some background on your products, just to set the stage as we kind of drill down.
Yeah, happy to. Thank you for having me today. We're targeting a rare disease called subarachnoid hemorrhage. It's a devastating condition, life-threatening, with high disease burden. Eventually, a third of the patients do not survive. A third end up living with long-term disability. It largely afflicts a far younger population. Average age is less than 60 years old. For reasons not entirely well known, it afflicts more women than men. The condition really strikes out of the blue. There's an aneurysm that typically is building deep inside the brain, that all of a sudden ruptures and spills blood where it's not supposed to. Quick medical intervention is key to survival. A lot of the patients end up throwing up and getting unconscious.
Ideally, these patients are triaged, even if it's a community hospital, then taken to a comprehensive stroke center. It requires a highly specialized clinical staff, neurosurgeons, neurocritical care, to care for this, for a subarachnoid hemorrhage.
Okay. Our sense is you're doing a lot of work around pinpointing the size of the market, trying to understand, as we think about prevalence, how it translates to the number of patients that end up going to hospital, getting treated. I just want to talk about the size of the market first before we then talk about your product.
Yeah, no, happy to. We recently just had some claims data that we evaluated. In terms of the size of the market, there are 70,000 patients that get admitted to the hospital. So these are 70,000 patients that survive and make it to the hospital. It's a rare disease. We have an orphan drug designation for the condition. There are literature estimates that peg the number closer to 50,000 patients. However, those numbers are dated. Ten, fifteen-year-old does not factor into account population growth and aging population. Based on our most recent claims analysis, the market size is about 70,000 patients.
Okay, understood. As we dig into GTX-104, just, real quick, our KOLs tell us that nimodipine is the standard of care, to prevent delayed cerebral ischemia. Maybe walk through background on nimodipine, the value proposition of 104, and clinical evidence for using this drug in nearly all your patients.
Yeah, so nimodipine is a calcium channel blocker, the only FDA-approved pharmacotherapy for improving neurological outcomes in subarachnoid hemorrhage. The molecule itself is written into the care guidelines by American Heart and Stroke Association. The Joint Commission, when it monitors, certifies a hospital, tracks the adherence to the care guidelines. In the US, if a patient has subarachnoid hemorrhage, they will receive nimodipine. In terms of the unmet need, if I can talk about that and put it in context with GTX-104, nimodipine is only available in oral dosage form in the US, either as a capsule or a liquid solution. Both of them are administered orally or enterally. Since most of the patients are unconscious, the drug is given, administered through the nasogastric tube.
A lot of challenges are associated with administering a drug that is dosed very frequently, several times a day, up to 21 days to be administered, in a very sick patient population in neurocritical care, that is obtunded and or dysphagic via the nasogastric tube. In addition, there are a significant amount of clinical liabilities when the drug is given orally. Specifically, what we found in our multiple phase one trial, we have exposure data in over 160 subjects head to head, with GTX and oral. Specifically with oral, it has high pharmacokinetic variability, suffers with cytochrome P450 liability. When the drug is administered through the nasogastric tube, the bioavailability suffers tremendously because of gut motility or ileus issues. The additional issue that we found, the only major side effect of the drug is hypotension.
When patients develop hypotension frequently, in fact, over half of the patients do not receive the full therapeutic dose of nimodipine due to the hypotension issue. The only FDA-approved drug either is not in sufficient therapeutic dose quantity in the patient because of hypotension and missed doses, or has low bioavailability, especially with the NG tube, all of which we believe impedes in creating efficacy of the drug. We started developing GTX-104, which is a novel aqueous infusion of nimodipine. It's the first time nimodipine has been solubilized in an aqueous form, and the clinical value proposition is with GTX-104, you have better pharmacokinetics, consistent concentration of the drug, and also the ability to better manage hypotension.
Understood. Maybe talk about the phase three STRIVE-ON study, obviously a safety trial. Maybe talk about main goals for the study and what were the key takeaways.
Our objective, very, very clearly is, for STRIVE-ON to be a registration trial. That was the objective right at the onset. As you mentioned, it's a safety trial, a comparative safety trial between IV GTX-104 and oral nimodipine. The primary endpoint is hypotension. Patients that develop clinically significant hypotension, GTX-104 versus oral nimodipine. In addition, we are collecting a number of additional outcome measures, neurological outcome measures, as well as pharmacoeconomic outcome measures. From a data perspective, GTX-104 had almost 20% fewer patients that developed fewer clinically significant hypotensive events relative to oral nimodipine. We met the primary endpoint, with fewer hypotensive patients.
What has been some of the KOL responses to some of the data?
Yeah, so just to kind of put it in perspective, you know, we have additional data that we reported as part of our top line. To put that in perspective, when we had our scientific advisory board and other KOLs that reviewed the data, we have a drug that has, with IV form, fewer patients that develop hypotension. What we also observed is that there were patients that received more of the therapeutic dose of GTX-104. In fact, 54% of the patients received 95% or higher relative dose intensity as opposed to only 8% on the oral side. Significant difference between the two arms. The next question arises, is there more drug being administered to patients, does it have any effect? The answer is yes.
When we evaluated the outcome measure, modified Rankin Scale, which is the gold standard metric for evaluating neurological outcomes in subarachnoid hemorrhage, it's at 90 days since a patient developed subarachnoid hemorrhage. We had almost 30% patients with better recovery on the IV side relative to oral. It's a physician-assessed neurological scale at day 90. Another outcome measure is patient-reported outcomes, quality of life. We had far superior outcome from patient-reported measure as well. We had zero patients that were bedridden day 90, as opposed to 12% on the oral nimodipine side. Additional parameters such as patients being able to take care of their personal hygiene, go about on their day-to-day daily activities, significant benefit as well, fewer patients on the IV side versus oral that had those morbidities. Then the third domain was pharmacoeconomic measures, things such as ICU length of stay.
We had 1.5 fewer ICU length of stay days on the IV side versus oral, five fewer ventilator days. When physicians, when our KOL and SAB members looked at the holistic picture of the STRIVE-ON data, it was very encouraging. They were very, very encouraged, very excited about the potential of GTX-104 to really make an impact in this terrible disease. To see consistently strong signal from an efficacy perspective, as well as from a pharmacoeconomic perspective, is truly, you know, exciting. There has been no innovation in subarachnoid hemorrhage in almost 40 years now. We believe GTX-104 can really, you know, when approved, can be a really impactful therapeutic option for physicians and for patients.
KOL perspective, quality of life measure is always one that's very important for them when they kind of look at the data and pharmacoeconomic will be very important, I think, as we move on to maybe the reimbursements and commercial strategy for your team. Okay. Our best understanding is NDA submission in the first half. What are kind of the next steps to get approval for 104?
Right now, our team is heads down, operationally, putting together all the data packet for the NDA submission. We have a we are on schedule for a pre-NDA meeting with the FDA in the next several weeks and then, everything going well, right to an NDA submission, end of second quarter of this year. We anticipate everything going well up to, in the second quarter, you know, to mid next year, 2026.
Okay. How do you expect, and again, this is early days, but as you're talking to KOLs and members of your SAB, how do you expect GTX-104 is going to be integrated into standard of care? How are docs telling you they're going to use it? We'll start there.
Yeah, so just to kind of couch it, a lot of our work has been pre-data since the data just came out, you know, a few weeks ago. So our next step that we are working towards is a lot of the pre-commercial development and planning and further, use the data to establish a body of evidence that feeds into the commercialization process. In terms of the use case at a real simplistic level, almost 55-60% of the patients that are either obtunded, dysphagic, unable to tolerate oral nimodipine is perfectly in the sweet spot for GTX-104. You know, from a serviceable market standpoint, that's our core market pre-data.
We believe as we test the market post data that that could expand, probably, into a little wider serviceable market. The clinically relevant issue of hypotension management resonates very strongly within the physician community. It's a real challenge, has not only a high complexity associated with it, issues around medical management, but also cost. When patients develop hypotension, the first thing physicians do is to titrate the dose down from 60 milligrams every four hours. Sometimes they go down to 30 milligrams, oftentimes even 15 milligrams every hour. That all adds to the dosing, the nursing burden. In addition, creates challenges from a quality perspective as well, medical safety to be able to make sure that the appropriate amount of drug is being given to the patient at the right time frame.
A lot of the patients are refractory to dosing down nimodipine from a hypotension standpoint. In those instances, rescue therapy has to be administered to these patients. It could take the form of intraarterial vasopressor use. If that doesn't work, angioplasty. It is a very invasive, high care burden to manage hypotension. That is what, from an IV perspective, connects a lot of dots for physicians. In an ICU setting, the usual way of giving a drug is by sticking a needle and infusing a drug. That way, physicians know the right amount has been administered, especially when the dosing frequency is very high. That's what's really compelling about GTX-104 from the physician community standpoint.
And to confirm, when you say kind of the 50%, you know, that's including those that are maybe unconscious, those that are unable to swallow the oral nimodipine, is that a fair way to characterize that number?
Correct. You know, we believe it's somewhere in the 50-60% range. You know, the combination of patients that are currently receiving their drug via the nasogastric tube, that are dysphagic, that have unable to swallow. There are a fair number of patients that just don't tolerate oral nimodipine, you know, very well. That's how we frame the serviceable market.
Okay. I know we covered the size of the population of patients that might be appropriate for GTX-104, but still early days, so we'll caveat that. Need to have conversations with payers. What's your thinking around GTX-104 pricing? Remind us the price of oral nimodipine, as well as the oral solution.
Yeah, so as you mentioned, still early days, you know, for us from a commercial development perspective, you know, but the reimbursement in a hospital setting is DRG driven. Based on our recent claims work, what we also discovered is, subarachnoid hemorrhage is one of the most expensive DRGs, tipping it at over $500,000. So significant reimbursement there for a hospital.
Given that this is a rare disease, we fully intend to price responsibly and, at the same time, make sure that we capture the value for GTX-104 based on the strong body of evidence that we have accumulated not only from our STRIVE-ON trial, but also our multiple phase one trial where we have established a very strong pharmacokinetic basis of the clinical signal that we see with GTX-104. To answer your question, based on our current preliminary assessment, and again, you know, we'll dig deeper into it over the next several months, the oral capsule, nimodipine capsule, is relatively inexpensive. You know, we believe the price point to be somewhere in the $50-$100 per day range. Nimodipine on label is indicated for up to 21 days of therapy.
It's administered, as I mentioned today, several times, every four hours, six times a day. There is a liquid formulation on the market that bypasses the extraction of the liquid from the capsule to squirt it down the feeding tube. That oral solution does command a significant price premium over the generic oral capsule, anywhere from, you know, 8-10x of the current pricing of the capsule. From our perspective, based on the assessments that we have done and preliminary market research, we believe that the market has already accepted a significant price premium for the liquid solution. All the liabilities that I talked about, the challenges with oral nimodipine, are consistent between the capsule and the liquid solution.
The additional challenge with the liquid formulation is the way it was solubilized does create an additional side effect of diarrhea. Managing that complexity along with other issues with the patient can be a real challenge on the ICU floor. We believe a responsible pricing that takes all of that into account is how we are approaching it.
Okay. You alluded to the different, let's say, treaters of subarachnoid hemorrhage that you need to address. Maybe talk in more detail. Who are those that would choose GTX-104 when a patient presents? Is it a neurologist? Is it a neurosurgeon? Is it a nurse? Who are the potential champions that would get 104 added formulary?
Yeah, so great question. As we dissect the potential buying center in a hospital setup, for us, clearly, the neurocritical care center ICU is the hub of the wheel. This is where the patients are treated. At a very simplistic level, the chief of the neurocritical ICU would be the champion. Now, there are some hospitals where the neurosurgeons, you know, are really calling the shots when it comes to therapeutics and medical management. You know, in that instance, we can certainly see someone on the neurosurgery side to step up.
From a process standpoint, typically, the clinical, hospital pharmacist, you know, who's affiliated with the neuro ICU, would be the one that does a lot of the work from a pharmacoeconomic standpoint and presents that to the P&T committee, for a new therapeutic to be added to the hospital formulary.
Okay. The process would be started kind of post-approval?
Correct. Post-approval. There are strong regulatory guardrails in place that preclude us from having any commercial conversations prior to FDA approval.
Okay. As you work through the P&T process, is this a knife fight? Is it one by one? Can you walk through how many institutions you need to target? It's kind of a small salesforce type of strategy?
Yeah, so from a commercialization perspective, this is a rare disease. These patients are treated at very high-end, comprehensive, ideally stroke centers or advanced stroke centers, academic medical centers. Based on the claims analysis that we recently concluded, there is a high concentration of patient volume at a number of hospitals. In fact, 250 or so hospitals treat about 50% of the patients. We believe with a very highly experienced, targeted, hospital salesforce, 15-20, this drug could be commercialized very effectively. In our STRIVE-ON trial, we had 30 high-volume hospitals that participated in the trial. We had a lot of demand, in fact, over 100 hospitals that wanted to be part of the trial. We picked the 30. We believe these could be the early adopters to really prime the market.
This is a very small clinical community of neurosurgeons, neurocritical care. We've been building relationships with these institutions for a number of years now. Our scientific advisory board is stellar neurosurgeons and neurocritical care. Besides boots on the ground, very targeted boots on the ground, we believe a strong medical affairs, medical communication strategy with thought leadership at medical congresses would be an effective way for us to commercialize cost-effectively.
Okay. You talked at kind of at the onset of our discussion, maybe national treatment guidelines. What work can be done on your end to kind of grow awareness for 104?
Yeah, great question. The American Heart and Stroke Association does put out care guidelines for aneurysmal subarachnoid hemorrhage. The most recent one was updated in 2023. Even though there is no intravenous formulation of nimodipine currently approved in the U.S., the guidelines do allude to an IV formulation. We believe that there is a natural parlance to getting into the guidelines. Typically, you need a body of real-world evidence once the drug is on the market, for a certain period of time, to be included in that.
That would be our plan as well for IV once it's on the market with a strong body of real-world evidence, to make it into the care guidelines, which, in our plan would be for GTX-104 to be the only dosage form, the standard of care for nimodipine.
Okay. As we think about 104, and the opportunity as you enter kind of different hospitals, are there examples of other agents that are branded and are able to get bundled into a hospital visit in lieu of generic options?
You mean analogs?
Analogs, yeah. Other agents with very similar kind of launch trajectory.
Yeah, so, I mean, you know, not not, you know, head to head necessarily, but there might be certain, you know, anti-infectives or antibiotics that, you know, could come to mind. The other one, which is much more pedestrian, is Ofirmev , you know, the Tylenol, IV Tylenol. Most of the drugs typically go from IV to an oral dosage form, and here we are going the other way around for what we believe to be very sound, clinically relevant value proposition because of just the inherent challenges of the molecule with its GI liability and the fact that this is a very, very sick, you know, patient population.
Okay. Understood. Any other studies that you plan on running, post-approval, registry study, anything else that you think will be helpful for the value proposition?
Yeah, you know, from our perspective, you know, we view this as a very long-term franchise. You know, we have very strong patent protection in addition to an orphan designation that should translate into an exclusivity for seven years post-approval. We believe that there are ways to engage with the medical community with evidence, ongoing generation of data either via company-sponsored trials or investigator-initiated trials. We have a number of such ideas, you know, that are in early planning stages. We also anticipate engaging with the medical community in Congress settings. We already have neuro ICU physicians coming to us with some ideas.
So we'll evaluate, you know, all of those and prioritize them, you know, where we, you know, where we believe it'll, you know, make a meaningful contribution to patient care and create value for the company as well.
Okay. Wonderful. In the last few moments, maybe talk about your pipeline program, which I know you obviously completely focused on GTX-104, and then timing of next catalyst.
Yeah, I'll address your last question. From a timing, the upcoming catalyst for us right now, it's heads down GTX-104, getting to our pre-NDA meeting and NDA submission, middle of the year is what our target is by the end of second quarter. An anticipated PDUFA, 2026, mid-2026. In terms of our pipeline program, we do have two additional clinical stage pipeline assets. Both of them were deprioritized, as we allocated our capital and our resources towards our biggest value driver program, which is GTX-104. The second of those programs is also a very late-stage program. It's ready for its pivotal phase 3 safety and efficacy trial. It's for an ultra-orphan neurodegenerative disease called ataxia telangiectasia.
We received feedback from an end-of-phase one meeting from the FDA several weeks ago, and that is ready for its pivotal phase three efficacy and safety trial. Our third asset is also a clinical stage program, that has completed a phase one trial for chronic pain management. It's a non-narcotic, topical spray formulation of bupivacaine. Both of those programs, as I mentioned, are on the back burner for now. We'll, you know, evaluate BD opportunities for them.
Okay. Wonderful. Thank you so much for the time and look forward to seeing, hopefully, approval and launch.
Thank you, Stacy. Really enjoyed talking to you as well.
Thanks.