Hello everyone, welcome today to the latest in a series of HCW@Home events. Today our featured company is NervGen Pharma Corp. My name is Ram Selvaraju, and I'm a senior equity research analyst in the healthcare team within the equity research department here at H.C. Wainwright. I'm also a managing director at the firm. It's my pleasure to introduce NervGen, a publicly traded company traded on the Nasdaq under the ticker symbol NGEN. Representing the company today is Adam Rogers, MD, Chief Executive Officer. Adam, it's a pleasure to have you with us. Thank you, Ram. It's a pleasure to be here today. I think it would perhaps be best to start off with a brief overview of NervGen, its technology platform, and its focus in particular on an area of very high unmet medical needs, spinal cord injury. Perhaps you could take us through the salient points of that, please. Sure. Thank you, Ram. NervGen has been developing NVG-291, which is a 35 amino acid peptide that we inject. It's delivered as a subcutaneous injection in the abdomen. The goal of NVG-291 and its mechanism of action is to interfere with the CSPG cascade. CSPGs are chondroitin sulfate proteoglycans, are part of the normal central nervous system, and they act as an inhibitor to neurons, but keep them going in the direction that they are supposed to go to their area of innervation. In neurotrauma, these CSPGs are upregulated and will interact with sprouting neurons and prevent them from reinnervating, remyelinating, and regenerating. The goal of our drug is to not get rid of the CSPGs, but we remove the inhibitory factor of the CSPG so that neurons can regenerate, and we can improve function in individuals with spinal cord injury. There is upregulation of CSPG in other neurotraumas and neurodegenerative disorders as well that we will touch on later in the company as we progress. With respect to the lead candidate, excuse me, NVG-291. My understanding is that the company has already completed a phase I-B/IIa trial, the CONNECT study, and has reported extensive findings from that trial. Perhaps you could walk us through three aspects of these findings. Firstly, the motor evoked potential amplitude data that demonstrates biological activity and connects to the underlying pathophysiology of disease in spinal cord injury. If you could also maybe make the distinction between spinal cord injury as a whole and the specific patient subpopulation that was chosen to be studied in the CONNECT trial. Secondly, if you could give us a sense of the functional translation of the biological activity of NVG-291 to a clinical endpoint that would be commensurate with functional recovery, as you plan to use in the upcoming phase III trial. Lastly, if you could say a few words perhaps about the patient experience on NVG-291. Some of the anecdotal evidence that's been reported on a blinded basis from the CONNECT trial, patients who went through the study and who were treated with your drug. Also, if you could talk a little bit about the safety profile of NVG-291 as seen from that trial. Sure. Thank you, Ram. NVG-291 was enrolled in our CONNECT SCI study. We looked at individuals who had chronic spinal cord injury, who are 1-10 years out from their injury. These are individuals with chronic tetraplegia or what we would consider motor incomplete cervical spinal cord injury of C7 or higher. It was a one-to-one randomization. It was performed at one single site in Chicago. It was an 80% power. The primary endpoint was motor evoked potential in either the upper or the lower extremity. We had to hit one or the other. These individuals received daily subcutaneous NVG-291. They received it for 12 weeks, so the injection period was 12 weeks. We evaluated them at week 12 with the MEPs. We also looked at some functional outcomes as well as secondary outcomes and our secondary endpoints, that was done at week 12 as well as week 16. At week 12, we discontinued the drug, then we wanted to look from a functional standpoint how these individuals performed at week 16. As you noted, Ram, we also did blinded exit interviews that were performed on average 250-260 days out from the study. The individuals were still blinded to their treatment effect. What we saw in these individuals, from an MEP standpoint, was that in the upper extremity, meaning measuring an electrical impulse from around or just above the area of injury to the first dorsal interosseous muscle, which is between the thumb and the forefinger. We saw an improvement of motor evoked potential that was statistically significant. We had to hit a p-value of 0.025 or higher. We did that in the upper extremity. This indicates that we were improving neuronal connectivity. It demonstrates neuroplasticity of the drug and remyelination. We had an improvement there. In addition, we looked at startle MEPs. In spinal cord injury, the corticospinal tract is much more affected than the reticulospinal tract. The corticospinal tract is what controls fine motor function. We hit statistical significance in both the upper and lower extremity in the startle MEP. What that is is we put headphones on these individuals. There is a very loud 100-110 decibel noise. What we do is we run the MEP again. What this demonstrated, the statistical significance, is that we are having a rebalancing or an improvement in the corticospinal tract functioning, also demonstrating a drug effect as well. What we looked at, our primary, the functional endpoint. Yes, we're showing that we are improving neuronal conductivity, we're showing that we are hooking up more neurons. How does that lead to a functional outcome? We looked at something called GRASSP quantitative prehension, which is a series of four tests that look at very fine motor function, putting pegs in a hole, key in a lock, and turning it, grasping a water bottle and pouring it into a glass, and putting a nut on a bolt and turning it. What we found was that we had an improvement of about 825% in those individuals in GRASSP quantitative prehension at week 12. We had a 3.7 point improvement from day zero to week 12 in these individuals compared to a 0.4 point improvement in the placebo arm. That really was a dramatic functional improvement in these individuals. At week 16, we discontinued treatment at week 12. We follow these individuals for another four weeks, we reperform the test at week 16. What we found was that there was an improvement from 3.7 to +4.4 on those individuals that received drugs. We see a gradual improvement in these individuals as well in GRASSP quantitative prehension. We also conducted blinded exit interviews, as you described, Ram. These individuals, what they described from a really global holistic approach. How did this drug impact their lives really on a day-to-day basis? There were really two really main findings that we got out of this. Number one, that two-thirds of the individuals reported an improvement in bladder function and bladder control. Less catheterization, less leaking, ability to understand and know when they needed to void, and confidence that they weren't going to have an episode of leaking so that they could drive in a car and go to bed and not have any accidents in the middle of the night. The second was a reduction in muscle spasticity identified in 56% of the individuals that were in the study. Given the reticulospinal tract overactivity, these individuals have significant muscle spasticity. So we saw a nearly 60% reduction in muscle spasms in these individuals, which is really dramatic as well. In addition, we had two individuals that could not complete the 10-meter walk test. Both of those were able to complete the 10-meter walk test at the end of 12 weeks of the study. Maybe just to elaborate on the safety profile, the safety and tolerability- Yes of NVG-291. Thank you. No individuals dropped out of the trial, all 20 individuals remained in the study. This was a difficult study to remain in because all of these individuals had to move. They had to go to Chicago, live in a hotel across from the clinical trial site for four and a half months. Of all of the injections, 99.8% of all injections were given. Really, just a couple of injections were missed in the study. There were no SAEs, and really the only issue we had was very mild injection site reactions that were sporadic, did not occur with every injection, and pretty much resolved on their own. It was really very irregular when the individuals got this. We couldn't predict when they were going to get an ISR. I think it's important to frame this within the context of the fact that we have a debilitating, chronic, very, very discommodious disease that doesn't currently have any approved effective pharmacotherapy. What you could conceivably offer based on the results of the CONNECT trial is a drug that provides functional recovery without imposing a meaningful side effect safety burden. That is correct. I think one thing that gets missed in individuals, and I think you hinted on this, Ram, and you'll hear this when you speak to individuals or their family members. People with spinal cord injury consider themselves to be snowflakes because no two injuries are identical. The forces are different. The location of the injury is different. What it affects in that level of the spinal cord, where they have the injury is slightly different. All of these individuals in and of themselves are unique. We're taking a very heterogeneous population, and we're homogenizing them as much as possible by taking a small subset, which is cervical motor incomplete spinal cord injuries of C7 or higher. The reason that we're identifying at this point just cervical spinal cord injury is that for the most part, these individuals all have hand dysfunction. As we go forward, grasp quantitative prehension or testing their hand function to evaluate the functional improvement in this drug is going to be vital. You mentioned earlier the significant improvement on this GRASSP quantitative prehension outcome measure and how that compared to the data that was obtained from the placebo group in the CONNECT study. How does that effect size inform the design parameters of the upcoming pivotal study? Now, for our audience, I'll just recap that the company has had a successful end-of-phase II meeting with the FDA, has had consistent dialogue with the agency in formulating the registrational path for NVG-291, and is now on the cusp of initiating a phase III trial deemed the RESTORE study, which is slated to enroll roughly 150 patients. I think it would be helpful for our audience to better understand the statistical powering assumptions that went into the design of the RESTORE trial and the selection of the primary endpoint based on the data from the phase I-B/IIa trial and the feedback that you recently received from the FDA. Sure. Ram, we've had two meetings with the FDA over the last six to eight months, one back in the early fall, and then one again towards the end of Q1 of 2026 of this year. Really the first meeting, and both of them were very collaborative. Obviously, FDA understands this, we understand this, and you even made mention. There are no therapeutic options for individuals with spinal cord injury. After their initial injury and a little bit of physical therapy in the first few months after the injury, they're basically out there on their own. There are no options for them whatsoever. GRASSP quantitative prehension or hand function is very important. Hand function for individuals with cervical spinal cord injury is probably the most important functional improvement that they can gain. That was the last two meetings that we've had with the FDA, that we had a lot of discussions around the importance of hand function. We held focus groups that we reported back to the FDA on, and these focus groups touched on individuals with cervical spinal cord injury, their caregivers, their family members, to discuss with FDA how important hand function is. We then utilized the GRASSP quantitative results that we got from the CONNECT SCI, which is our phase I-B/IIa study, and we were able to power those results. By the way, those results exceed what physicians or KOLs would consider the minimally important difference of plus two. We got a plus 3.7. Above a +2 is where an individual can use a fork to feed themselves, open up a bottle of water, opening up the bottle cap, combing their hair, brushing their teeth. The results that we saw quantify or translate into really functional improvements on a day-to-day basis. We were able to use these results at week 12 and power our clinical trial. Basically, we have a 90% power that brings us to 150 individuals. The RESTORE study, which is a single registrational study, will be a 1-to-1 randomization of 75 individuals that will receive drug and 75 in the placebo arm. Again, it'll be daily injections for 12 weeks. Instead of MEPs as the primary endpoint, it'll be GRASSP quantitative prehension. In our discussions with FDA, really the FDA wants to know two things. One, they want a functional endpoint, and that's our primary endpoint, GRASSP quantitative prehension. Our secondary endpoints are really hierarchically aligned, and the FDA wants to understand how does this drug globally impact an individual. Great, you've got a number, you improve hand function X amount, but how does it improve their day-to-day living? That's really what our discussions with FDA hinged around. Just in terms of the statistical powering, if you look at the 150-patient sample size in the RESTORE trial, can you comment on what you expect to use from a statistical parametric perspective in analysis of the primary endpoint, and what the confidence interval might be, if you can define it in that manner, and the degree of statistical powering that is assumed in this 150-patient period of study to detect a predefined signal output? What I'll get into, Ram, is that we are able to detect, and we're powering for a 2.5-point difference in treatment at 12 weeks. Right now, we saw a 3.3-point improvement, so I think we're pretty conservatively within the area where we can very successfully run a phase III trial here. As far as the limits, I won't get into it right now on this call. Okay, understood. With respect to the phase III evaluation window, and A, how this compares to the evaluation window that was used in the CONNECT trial, and what we should anticipate looking at kind of the natural history of the evolution of the disease course in patients with chronic tetraplegia. Maybe you could say a few words about the selection of the 12-week endpoint and what went into making that decision and how confident you feel about that evaluation window in the context of the pivotal trial being sufficiently lengthy to capture the principal therapeutic impact of the drug relative to the course of the disease. Sure. The one thing I think that there's a misnomer, and that I think we have to address is individuals with chronic spinal cord injury. People with chronic spinal cord injury that are over a year out. They have an immense ability for neuroplasticity. That was identified by Jerry Silver in his lab. He discussed it many, many times. That one would think, Ram, that just because you would think. Listen, as a physician, I was a retina specialist, you used to think, look, when there's an injury, you need to address it immediately. In spinal cord injury, obviously, that's the thought, like, "Hey, let's attack this right away." Actually, the body's ability and the central nervous system's ability to have neuroplasticity persists and actually improves as time goes on. These individuals that are out more than a year, they actually have more sprouting of neurons that are occurring, than those that are in the immediate or say, within three-month period. We actually have a really a very optimal window to address the injury and improving the neural connections that we think can occur. Getting into the duration of time, in animal models, they used a seven-week period and showed a dramatic improvement in animal function, in a spinal cord injury model. In humans from the CONNECT SCI study, with just 12 weeks of drug, we saw really dramatic improvements in hand function, improvements in bladder function, reduction in spasticity. We saw a lot of improvements in these individuals with just 12 weeks. We want to stick with the 12-week point. The other reason we want to stick at that point as well is that there are no drugs out on the market at this point in time. We can power a study to show a statistical improvement at 12 weeks. We want to keep it in this 12-week mark so that we can get a drug to market as rapidly as possible. I think that's an important delineation to make, that there are considerations surrounding the time it's likely to take to conduct a pivotal trial, and the fact that these patients are waiting anxiously for anything to help them. Ultimately, especially if you have a treatment modality that can reasonably be expected to achieve an efficacy onset within a reasonable period of time, it doesn't really appear to me to make much sense to conduct a very long-term trial with a very lengthy evaluation window, especially when you anticipate being able to see effects of the drug treatment within the initial days of the treatment being administered. I would say that's a reasonable summary of the situation, right? I think even when we look back and when I look back at the results of our CONNECT SCI study and I read the blinded exit interviews, they were really a wealth of knowledge in understanding the impact of the drug. When you listen to the individuals, you read their transcripts, the individuals that received the drug, many of them noted improvements at six, seven, eight weeks after receiving the drug. For example, one woman whose hand was really in a contracted formation since she had her injury, and her injury was from a fall on a rug. Six weeks after receiving the drug, her hand opened up, and it was the first time she was able to lay her palm flat on a table. We're seeing results very early after treatment. Like I said, we can power the study. We can see an improvement at 12 weeks. There is no therapeutic option out there for these individuals. We had extensive discussions with the FDA on this, and our stance was we want to get a drug to market as soon as possible to help individuals. Given the context of the fact that there appears to be not only durability of effect, but durability of effect long after dosing has ceased, and this may speak to the underlying impact of the drug on residual neuroplasticity in the system. Is there a plan to look at some or all of the patients who might be enrolled in the RESTORE trial on a longer-term basis and capture some long-term follow-up data, even if they might not necessarily be within the official evaluation window of the study? If so, what does that look like, and how do you anticipate potentially using such long-term follow-up, assuming, as we anticipate, it elucidates even more additional therapeutic effects, therapeutic benefits of NVG-291? Right now, Ram, our plan is the primary endpoint is at 12 weeks. We will follow the individuals off drug for another four weeks and then do quantitative prehension, and then we will do another blinded exit interview in those individuals roughly a month after that. In this study alone, we're only going out to the 20-week mark. Again, there are no options at this point to look long-term, but obviously, that may change with time. Just one last aspect to tackle here. Going back to the CONNECT trial results. Yes I just wanted to see if you had a defined plan for the publication and presentation of these results, and if so, in what fora or in what context, particularly from a peer-reviewed publication standpoint, significant scientific journal, high impact factor, et cetera, you anticipate these results ultimately making their way into the public domain in a more detailed manner than have already been presented? Sure. We are in the works of putting together a manuscript for the CONNECT SCI, the phase I-B/II-A study. That is ongoing. It will be submitted, and we anticipate, depending on the time that it takes for acceptance, maybe in the next six to 12 months. Got it. Just one last point regarding the previous discussions that you've had with FDA and the design parameters of the RESTORE trial. In terms of statistical sensitivity, the quantitative prehension dynamic, or quantitative prehension parameter appears to be more sensitive than some other historical measures that have been used. For example, generalized motor scores and things of that nature. For example, if we look at the ASIA scale. I was wondering if you could maybe just comment about the additional statistical sensitivity of this outcome measure. Clearly, it's a very specific functional recovery outcome that you are monitoring for, and how that played into the overall study design, particularly as this pertained to the target enrollment size. Sure. Well, obviously, listen, from a target enrollment size, we use quantitative prehension. The results that we received, that's how we powered the phase III study. Quantitative prehension was very, very helpful. It is a very sensitive test. It's very, very good at evaluating fine hand function. It's those four tests that I described. You cannot fake the test. There are no compensatory mechanisms that an individual spinal cord injury can invoke. If you put a key into a keyhole and turn it, there's really nothing that you can do from a compensation standpoint. That's one of the issues with some of the other tests, some of the more gross motor skill tests that are employed, like the UEMS. It's just not as sensitive a test. It's a physician measuring someone's strength. It's off of their historical, subjective process of how strong they think the person is. From the standpoint GRASSP, each of the four tests are validated. They're very sensitive. It was a test that was designed up in Toronto specifically for individuals with spinal cord injury, also can be used for individuals with stroke. It really is the best evaluation for the effect of this drug, and not only for the improvement in neural regeneration, but also in the functional improvement that one sees. Very helpful. Now if we can talk a little bit about the history of drug development in spinal cord injury, because I'm sure that's something that is on our audience's minds. Maybe you could talk a little bit about previous challenges, pitfalls that have been encountered by drug developers who came before NervGen, and how you've incorporated some of the learnings from those failed trials into your own drug development efforts in this indication. Maybe comment a little bit about how the RESTORE trial design is different, how you are using a functional outcome measure that is different. You earlier just said, when you compare quantitative prehension to an upper extremity motor score, for example, that there are significant executive challenges associated with evaluating the UEMS in a quantitative and uniform reproducible way. maybe you could talk through some of the learnings from prior trials and how the RESTORE study and the mechanism of action of NVG-291 are both risk mitigating factors in the context of the drug development effort that NervGen is engaged in doing in SCI. Sure. I think one of the greatest challenges that I see in most of the other drugs that have failed is the fact that they required that they be administered within the acute period, within the first 48 to 72 hours. I'm a physician. I took care of a lot of traumatic injuries in the eye as a retina specialist. When you are thinking in the line of a spinal cord injury, let's say you're skiing, Ram, and you have the injury. You get taken to a local hospital. You get evaluated. The clock is ticking. You then get transferred to another regional hospital. Maybe that does spinal cord injury, maybe it doesn't. Then, there's a second or third transfer that goes on. It is not easy to enroll individuals in that first 48 to 72 hours, especially if there's not someone that has power of attorney to sign consent forms and other things. I think, one, there's that barrier right there. Number two is a lot of these drugs that were used, they may not have really been specific for what the underlying issue is in spinal cord injury. That's I think really where the strength of NervGen is. We target chondroitin sulfate proteoglycans. They are in the normal nervous system. When there's an injury, they get upregulated. They interact with neurons that are resprouting and prevent them from reconnecting. Our drug directly targets that inhibitory nature and really making those CSPGs, we're attacking their cascade. We're diminishing their inhibitory effect so that the neuron can regenerate. The other issue with a lot of these drugs is that they either have to be put in the area of the injury or surgery is needed to administer them. Again, the mode of administration is very difficult. With NVG-291, it's a very straightforward, simple, subcutaneous injection. I love drugs that are easily administered. It overcomes an enormous barrier to either participation in a study, the fact that we can give our drug at home by either the individual or a caregiver or a family member is really fantastic. Those are really the main issues that we have to affect. I think really where we excel is we are targeting the main issue, this chondroitin sulfate proteoglycans, that are impairing the ability of the central nervous system to recover, remyelinate, and regenerate. We think about from a regulatory perspective, the concept of minimally clinically impactful difference, and how the FDA views, for example, the 2.5 point difference on the quantitative prehension outcome measure that you mentioned earlier that went into the design of the phase III RESTORE trial. Maybe just frame for us what that difference looks like in the eyes of regulators. If they consider that to be an MCID or if, frankly, their threshold is way lower than that, as I suspect it might be, given the nature of this indication and the fact that there are no available pharmacotherapies. From an MCID, we discuss it on our website, in our PowerPoint presentation, the MID, which I think are very similar. From a powering standpoint, we use that. From an MID, which came from the Up-LIFT study evaluating the ARC-EX device, Ram, they defined it as a plus two improvement from baseline in GRASSP quantitative prehension. If you discuss with KOLs, and we discussed this with the FDA, anything plus two or above is what is considered to be clinically important for an individual. I hit on this, and we saw this in our blinded exit interviews, that these individuals, for example, were able to comb their hair, brush their teeth, make a meal for themselves, button their clothes, zipper a zipper so that they don't have to wear sweatpants, and they can wear normal pants. The FDA just wants to understand from a whole body effect how it's impacting it. Above that two, and that's really just something that came from the study, from the Up-LIFT study. That plus two is above that threshold of which individuals see what's really a clinically meaningful benefit from the drug. We exceed that in our GRASSP quantitative prehension in our 3.7 point improvement. Turning now to the secondary endpoints that are essentially enumerated in the disclosed design parameters of the RESTORE trial. Perhaps you can frame for us the hierarchy with which, from a regulatory standpoint, these secondary endpoints are likely to be evaluated, and also from a broader, more commercial perspective, which of these endpoints are likely to be considered the most important, which are likely to have the most resonance for key opinion leaders, for medical practitioners who might ultimately wind up prescribing NVG-291. I'll just remind investors that these include, for example, instruments like the Patient Global Impression of Change or the Clinician Global Impression of Change, among other endpoints. Perhaps you could just take us through the key secondary endpoints and with what hierarchy they might be weighted in the eyes of both regulators and ultimate end consumers. When you look at our RESTORE study and in our discussions with FDA, we really had a very robust discussion, Ram, around key secondary endpoints with the FDA. It was probably our number one greatest discussion that we had with them. They understand hand function, the importance of it. The FDA understands GRASSP quantitative prehension, KOLs understand that. Really what our discussions with FDA were over the last six months is they want to understand how does this drug impact an individual on a day-to-day basis. They understand we improve hand function, okay, how does this impact someone with a cervical spinal cord injury on a day-to-day basis? How does it make their life better? From key secondary endpoints, we agreed on a very hierarchical scale of starting with Patient Global Impression of Change. They allowed us to use PGIC because the study is only 12 weeks long, they felt that an individual could look back and evaluate their change that they underwent over a 12-week period, followed by Clinician Global Impression of Change. We have the SCIM-III and the Modified Ashworth Scale. They're on our website. They are labeled in a very hierarchical fashion for a reason due to our interactions with FDA. That's what they felt were the most important ones from the top down. From a medical practitioner's standpoint, would you say that this would dovetail with the manner in which physicians would hierarchize, if I can use that word- Yeah the importance of the secondary endpoints too? I definitely think so. I think from a patient standpoint, like I said, when we did our blinded exit interviews, and we have blinded exit interviews as well. The problem is it's very hard to quantify an exit interview. From a qualitative standpoint, it's great. Otherwise, that would've been the number one secondary endpoint. Yes, I think how a patient is feeling, how they're doing, their impression of what's going on, I think will definitely impact how the drug is administered and given in the clinical setting once approved. Turning now to the ex-U.S. potential opportunity and interactions that you may or may not already have had with ex-U.S. regulators, like the European Medicines Agency. To what extent at this juncture do you anticipate the design of the RESTORE trial, the potential findings from that trial, are likely to be appropriately satisfactory to regulators ex-U.S. in order to facilitate potential international regulatory authorization of a drug like NVG-291? What additional work do you anticipate doing in the coming months in order to effectively harmonize regulatory expectations as you move the RESTORE trial forward? Sure. Now, listen, in the past, NervGen has had discussions with the EMA. We do have orphan drug designation with the European Medicines Agency, that reflects our early engagement with those regulators. Our focus has really been solely on the U.S. and North America at this point in time, it's the pathway that we're really putting all of our efforts in. GRASSP was developed in Toronto. It is recognized as a validated test in individuals with spinal cord injury, I don't anticipate that there will be any pushback from the EMA when we go back to them. What we've done internally and as our efforts are in the U.S. and in Canada at this point in time, but I've also brought in from a Chief Regulatory Affairs Officer, I brought in Shamim Ruff very recently, and she will help us and guide us as we start to expand to different countries worldwide. For those in our audience who are not familiar with Shamim Ruff's prior history, she has successfully shepherded multiple drugs through at the FDA for treatment of various neuromuscular conditions that were historically considered very much akin to SCI. In other words, they were areas of very high unmet medical need without pre-existing approved pharmacotherapies available, and certainly had significant patient advocacy impetus behind them, as would be the case also in the context of SCI. I think that's a fair statement, right, Adam? Correct. Absolutely. That's why I brought her on. In our discussions with the FDA, while this is not considered to be an orphan disease, given the fact that The way the FDA looks at this is they look at the total number of individuals with spinal cord injury, even though we're targeting cervical spinal cord injury. There's over 300,000 individuals with spinal cord injury in the United States, so they don't consider this to be a rare disorder in the eyes of the FDA. However, in our discussions with them, they look at this, that this is an enormous unmet need. It's almost very akin to a rare disease. This is really in the vein of someone like Shamim, which is why I brought her on, because of her enormous expertise at Sarepta and Stoke and getting drugs through the regulatory pathway. I think that's an interesting segue into what I believe our audience is going to be very interested to learn about, which is the segmentation of the spinal cord injury patient population. As mentioned before, you're addressing tetraplegia, you're addressing a specific subpopulation of spinal cord injury patients. As you yourself mentioned earlier, they themselves look at themselves as essentially snowflakes. No spinal cord injury is like any other spinal cord injury. Perhaps you could frame for us a little bit more the overall size of the spinal cord injury patient population, how you stratify or how NervGen stratifies that patient population, and what the size of the target subpopulation is that ultimately would be covered by a putative label supported by data from the RESTORE trial. Sure. Ram, in the United States alone, I'm only going to discuss the United States right now, there are roughly 310,000 to 320,000 individuals living with spinal cord injuries, and that's thoracic, lumbar, cervical, sacral spinal cord injuries. The incidence of that is around 18,500 new cases per year. Let's just say 17,000 to 19,000 new cases each year. Roughly 48%, about half of that population of spinal cord injury, has incomplete tetraplegia. Sometimes we'll call it motor incomplete cervical spinal cord injury. The subset of the population that we're targeting in the RESTORE study is roughly 50% of the prevalence of spinal cord injury, about 150,000 addressable patients. It's a large reservoir of patients, and there are roughly 9,000 to 10,000 new cases of acute cervical motor incomplete each year. Yeah. Now does that mean that from a standpoint that I think or NervGen thinks that we are only going to be addressing cervical motor incomplete spinal cord injury? No. There is no reason. It's the same mechanism of action with CSPGs that affects individuals with thoracic and lumbar and the small number that have sacral injuries. I anticipate down the road that very quickly after approval, that we will be targeting other levels of spinal cord injury very, very rapidly after approval. In the context of that, obviously, there is the potential to envision additional studies alongside or succeeding RESTORE, for example, in people with paraplegia, in people who have the acute tetraplegia manifestation that you mentioned earlier. Can you just give us a sense, maybe a hint of how NervGen is thinking about tackling these additional patient populations from drug development, clinical trials, timing standpoint? Yeah. We're not publicly putting out right now how we're going to be doing that or when we're going to be doing that, I think it's just an absolute natural progression, Ram, that we will be going into those areas as rapidly as possible. Look, our mission is to improve the lives of individuals with spinal cord injuries, not just cervical spinal cord injury. Our goal is to really make this drug available for every single individual that has had a spinal cord injury to improve their life and improve their functional outcome. Also, I think it's worth mentioning the unlimited recruitment window that, correct me if I'm wrong, I believe you're going to be using in the context of the RESTORE trial. In other words, you're not placing a restriction on the timing with which the original injury occurred as a prerequisite for enrollment into the study. Maybe you could elaborate a little bit on this, the thinking behind it, and ultimately assuming positive results from the RESTORE trial and potential registration of NVG-291, how this could conceivably impact the commercial trajectory of the drug. And maybe I misunderstood this, but we are enrolling individuals from 1 to 10 years out from their injury. There is some gating of this. We don't go below 1 year because there's still some natural, from a natural history standpoint, individuals from 6 to 12 months can still have some spontaneous improvement. We want to make sure that individuals in this chronic SCI study don't really have the ability to have any spontaneous natural improvement to remove that out of the equation. Listen, from a standpoint of not gating this, yes, we're using 10 years as a cutoff at this point in time, but that doesn't mean someone that's healthy with a chronic tetraplegia who's 12, 15, 20 years out and is good health, there's no reason that they would not be able to use this drug. As I stated earlier, in chronic spinal cord injury, the longer you are from the injury, the more sprouting there is of neurons to regenerate. We feel that we'll have a benefit in those individuals as well. I think, for our audience's edification, essentially what I'm driving at here is there is no need for NVG-291 to be deployed within 0 or 24 or 72 hours of the original injury taking place. This is a chronic SCI paradigm. You are defining the cutoff at 1 year, but in all likelihood, and I'm asking here your opinion as a physician, if this drug were available commercially, I think it would be very unlikely for practitioners to restrict its use to patients who were at most 10 years out from their SCI, or conversely, patients who had to be at least 1 year from their original injury. Ultimately, if the drug worked, I think it would be deployed as frequently, as widely as possible. I agree with you, Ram. Look, and I will answer this as a physician, and you've been in this industry a long time, and I have as well, just as a practicing physician. When you have a drug that comes on the market, it starts to be used in beyond the confines of what the clinical trial was. The clinical trial defines the subset of population that you want to focus on. Our goal is to get a drug to market and to get it to individuals as efficiently and rapidly as possible. I don't foresee any gating factors of it being used earlier or later beyond the timeframe of 1 to 10 years after its approval. I think this also leads us logically to two other aspects. The first clearly is, now that you've segmented for us the number of patients, how this dovetails into the potential pricing and pharmacoeconomic considerations. Sure That might be at play here. I think it would be particularly helpful for our audience, Adam, if you could highlight first and foremost the lifetime estimated cost of caring for patients with chronic SCI, including the cost to the U.S. healthcare system along with the lost productivity cost, and then maybe contextualize this within the precedent case reference points that exist of other drugs that were recently approved to treat hitherto unaddressable, debilitating neurological conditions that involved significant functional impairment. Although I would venture to say that spinal cord injury is probably among the worst, if not the worst, of these kinds of conditions. Ram, from a per individual or I don't usually call spinal cord injury individuals patients, but on a per individual basis, spinal cord injury is probably the most, if not the most expensive condition that we take care of in the United States. I'm only going to talk in U.S. here. It is about from a cost per patient, it can be up to $6 million. Really depends on the level of the injury, but if you take a cervical spinal cord individual, it's up to $6 million over their lifetime, plus lost work, which is potentially $2 million. You're looking at a lifetime cost for up to $8 million for an individual. That's massive when you consider that there's roughly 320,000 individuals affected with spinal cord injury in the United States. From a healthcare standpoint, it's a $58 billion hit to the U.S. healthcare system, and again, that's for 320,000 individuals. That is a very large per individual hit. Yeah, one of the most expensive conditions that exist out there. If you are looking for broader frame of other indications, you could look at SMA, you could look at SPINRAZA, Zolgensma, MS therapies. An MS therapy could run $50,000-$100,000 annually. Zolgensma is a one-time treatment that's around $2 million-$2.1 million. SPINRAZA for SMA is about $750,000 in year one. These are in the broader CNS landscape. Obviously, there are no direct competitors in the spinal cord injury landscape that we can compare prices to. You mentioned obviously that there are no drugs in the spinal cord injury domain that you can compare pricing to, and I certainly don't want to give the impression that one can compare apples to oranges, right? Right. Here I'm really talking about medical devices. You briefly mentioned earlier this medical device called ARC-EX, which has been approved. I think it would be helpful for our audience if you could elucidate the manner in which ARC-EX is being deployed, the way in which it's regarded by practitioners, and the key functional metrics by which its impact, or lack thereof, in spinal cord injury is quantitated. Because from my understanding, it's a medical device, it's not a drug. There are specific aspects of its benefits to SCI patients that seem to have very little to do with what NervGen is pursuing with NVG-291. Like, for example, its impact on stabilization of blood pressure. Maybe you could help elaborate on that. Yeah, I want to make a statement that this is not a head-to-head comparison or anything that I'm going to say about ARC-EX is a comparison of our drug to theirs. Like you said, it's apples to oranges. You're dealing with a device, not a drug. Obviously, with NVG-291, it's a systemic therapeutic agent. We're having a global systemic impact on the drug, whereas a device, especially what ARC-EX is doing, it's a transcutaneous stimulation of nerves, and especially the one on the cervical spinal cord area to drive function in the hand. When it's activated, it creates an impulse, an electrical impulse to improve hand function, and they measured that by GRASSP also, and that's how they were approved. Listen, when that device is turned on, it's effective. I don't believe that the effect is a permanent effect. It must be activated for it to be going on. From a competition standpoint for ARC-EX, almost all physiatrists or physical therapy locations, they use some form of transcutaneous stimulation. I know this because when I go meet with some of these institutions that are really KOLs, they want to pair our drug with their stimulation. Obviously from an NVG-291 standpoint, the big difference that we have, other than the fact that we are globally affecting them, is that we are enabling neurons to regenerate. A stimulation external device can only work with the number of neurons that are available. NVG-291, from what we can tell by the improvement in function that we see in the clinical trials, by just virtue of deduction, we are recruiting additional neurons. that would benefit an electrical stimulation, whether it's transcutaneous like with the ARC-EX or in using these physical therapy locations. I know that we have limited time at this point, but I definitely wanted to run through several other aspects that are very important. Firstly, I think it would be helpful to summarize where the company currently is from an operational runway perspective. Sure. how this dovetails with the projected cost, both per patient and as a whole, of the RESTORE trial, as well as what you expect the projected cost to be to move NVG-291 from where it is now to a potential NDA filing. In particular, I think, Adam, it would be helpful for our audience to gain an understanding of just how cost-effective and capital-efficient the path to market for a drug like NVG-291 is, given the fact that it's not anticipated that there will be meaningful, significant, spontaneous recoveries in a placebo patient, given the fact that there is no available standard of care from a pharmacotherapeutic standpoint, and given the fact that in the discussions with the FDA, the agency has proven amenable to the design of a single registrational study. I'll remind our audience that a lot of times in indications where there are existing available pharmacotherapies, two well-controlled randomized controlled trials need to be conducted in order to satisfy the requirements, the prerequisites for approval. That is not the case here. Also that the parameters of the RESTORE trial dovetail very closely with the parameters that were used to evaluate NVG-291's impact in the CONNECT trial. There is a clear congruence, which also provides both risk mitigation from the perspective of the assurance of a future positive outcome, but also efficiency with regard to right-sizing the clinical trial itself in a pivotal context. Ram, listen, I agree with everything that you just said. Listen, we are a very cost-effective company, and that's the way I run businesses. We are very capital-efficient. This study, the RESTORE study, it's going to enroll 150 individuals. It will run for a little bit over a year, and we anticipate the study cost is about CAD 50 million. As far as we are very much aligned as a single registrational study at this point in time, that's what we're anticipating. I think the bar here to get approval is very low. We've had very strong results with the GRASSP quantitative prehension results that we saw at both 12 and 16 weeks. When we take these results to KOLs, they are thoroughly impressed with the functional improvement that these individuals are seeing. It's far in excess of what they ever thought that they would see. That's the good news here. Where we are right now is we are pouring all of our efforts into getting the phase III RESTORE study up and running by mid-2026. We are currently performing site selections. We have drug supply that is ready to go. We've engaged a CRO. We are on track to start this summer. Just remind us, as of the end of 2025, how much cash the company had and what the operational runway currently is with the resources that you possess. From a runway standpoint, we have funded 20% of the trial to date. We will be exploring multiple avenues to support the program, including non-dilutive as well as traditional financing options for the clinical trial, Ram. With respect to ultimately the timing of potential submission and regulatory approval, just remind us at this juncture which designations NVG-291 has from the FDA, and if you anticipate, particularly given the high unmet nature of the medical need, potential priority review upon acceptance of the filing. Yeah. Here's where we stand. We're going to start this summer. We anticipate that we will end enrollment in early second half 2027, data readout in first half of 2028, with NDA submission in the second half of 2028. I think, getting to your efficiency of the company, single registrational study. We are a well-powered study, saw very good results in the phase I-B/IIa study. There's no competition. We don't see that we won't hit this benchmark again in the RESTORE study. We feel very confidently going into this phase III study right now. With regard to the manufacturing of the product itself, this is a peptide, right? Yes. Maybe just elucidate for us how simple, straightforward, and amenable to scale up the manufacturing process is, and where you currently stand in that context as you look ahead to potential preparation for commercialization. I also want to emphasize to our audience, given the size of the target market here, given the fact that it is clearly a specialty indication managed by specialist prescribers in very well-identified centers of excellence, this is clearly an indication that would be amenable to self-commercialization just from a strategic. Yes optionality standpoint if you decided to go that route. Yeah. Listen, Ram, we have every intention of continuing to take this drug forward. From a commercialization standpoint or actually a manufacturing scalability standpoint, we have invested heavily over the last couple of years as far as manufacturing. The process that we have is readily scalable for a commercial start in a couple of years. We have enough drug for both this study and additional studies that we will be doing in the future. That is not an issue at all. Can you confirm that the drug is currently manufacturable at gram or kilogram scale? Oh, yes. Kilogram scale. Correct. Okay. Before we close, I just want to mention that this is a technology platform. NVG-291 is not the only arrow you have in your proverbial quiver. There is a backup molecule, NVG-300, which is based on the same fundamental understanding of CSPG biology. I think it would be helpful to just enumerate very briefly before we close what you intend to do with NVG-300, how you're thinking about essentially separating and distinguishing the indications that you effectively target with NVG-291 versus NVG-300, and what the timing might be of entry of NVG-300 into the clinic. Sure. As I stated earlier, and I say this many times, we are not just a spinal cord injury company. We are a neurotrauma company, and we're a neurodegenerative company. Because in areas where there is an upregulation of chondroitin sulfate proteoglycans, such as in stroke, such as in traumatic brain injury or traumatic hearing loss or peripheral nerve injury or MS or ALS, we feel very strongly that this drug will be effective in creating new connections. We are internally discussing right now what our next indication is, and we are discussing whether that will be a target of NVG-291 or a target of NVG-300. Those are discussions that we're having internally, and we will use it in, I would say, just from a standpoint of what is the most effective use of each molecule for each indication. They're very closely structurally related, correct? Can you just remind us what the differences are between 291 and 300 from a structural standpoint? We have not put that out public yet, they both target CSPGs. Okay. I think we're out of time. We're going to have to leave it there. Adam, clearly a very, very interesting company. As you mentioned, a cost-effective, capital-efficient, and risk-mitigated approach to drug development in SCI, an area of very high unmet medical need. Thank you so much for walking us through the salient features of the NervGen story, and thank you to our audience for their attention. Ram, thank you very much. I really appreciate your time.