Okay. Yes. Thank you. You're all set. Forward that, please. Great. Thank you. Yep. Welcome, everybody. My name is Tyler Van Buren, and I'm welcoming you to the 44th JP Morgan Healthcare Conference. Our next presentation is Rapport Therapeutics, and I would like to invite the CEO, Abraham Ceesay, for his presentation. Thank you. Thank you, Ty, and thank you to the JP Morgan team, and good morning to everybody. Great opportunity today to share our updates here at Rapport Therapeutics. 2025 was a real foundational year for the company. We're entering 2026 in a very, very strong way, and we look forward to sharing those updates with you. Today, I will be making some forward-looking statements during the presentation, so just a regular disclaimer around that. We'd like to really start with the vision of Rapport Therapeutics. This is a company that was created to build the leading precision neuroscience company. We realize that precision is somewhat of a loosely used term in our industry. Also, it can be loosely used in neuroscience. But we do think that we are a unique company in the fact of our foundational scientific technology, which are receptor-associated proteins that we believe will bring precision to life for neuroscience. This is a company that was created through a collaboration between Third Rock and J&J to form Rapport Therapeutics. In terms of the company creation effort, we were able to bring several members of the J&J team that were working on our lead program as well as our discovery pipeline. So our institutional knowledge around our programs is significant here at Rapport. Receptor-associated proteins really allow us to build compounds that we think are highly specific for a broad set of neuroscience indications. We also believe that this differentiated pharmacology can lead to more effective therapies for a broad set of neuroscience indications, but also therapies that are better tolerated. Our lead program, which we'll spend the majority of our discussion on today, is RAP-219. RAP-219 is a novel forebrain-restricted TARP gamma-8 AMPA modulator program. We released robust phase two data in focal onset seizures in September of 2025, and we're rapidly progressing that program into pivotal studies in an accelerated fashion starting in the second quarter of this year. We're a very well-financed company. At the close of September 30th, 2025, we had roughly around $513 million on the balance sheet, which provides us cash runway into the second half of 2029. So if we think about the opportunity that we have here at Rapport, we believe we're solving a widely understood yet very vexing challenge as it relates to conventional CNS drugs. Conventional CNS drugs are oftentimes ubiquitous in nature, meaning they are interacting with receptors throughout the brain and sometimes the body that often are delivering efficacy but are not well tolerated by patients. As you think about the opportunity with receptor-associated proteins, we believe that we have the opportunity to create more specific compounds, small molecules for a whole host of neurological conditions. The first way that that is materialized is through the approach that we are using with our lead program, RAP-219, and that is targeting a specific receptor-associated protein that allows our program to be very precise. So in the case of our lead program, RAP-219 targets a receptor-associated protein associated with the AMPA receptor, TARP gamma-8, which allows this compound to be forebrain-restricted, only target AMPA receptors in areas such as the mesial temporal lobe as well as the neocortex. By doing that, we believe we can deliver efficacy, and we'll talk a little bit about those observations for our proof of concept study, and sparing the hindbrain, we can really mitigate some of the most bothersome tolerability issues that patients face. The other way that receptor-associated protein science shows up in terms of the work that we are doing at Rapport is through some of our discovery efforts. By leveraging receptor-associated proteins, we're able to uncover novel targets and really allow drug development and discovery efforts in areas that were previously or targets that were previously undruggable, and we'll share a little bit about our progress there and some of the programs in our discovery pipeline, so let's take a moment to just review our pipeline. This is a robust pipeline, a pipeline that is anchored by RAP-219, our lead program from a clinical perspective, but also supported by a well-enabled late-stage discovery platform as well, so RAP-219, our strategy has always been to really interrogate this biology and approach a pipeline in a product type of strategy. Our lead indication is focal onset seizures. As I mentioned, we had our proof of concept data that we released in September of 2025. We see this as best-in-class data, and we just are coming off the heels of a positive interaction with the FDA late last year that now allows us to accelerate this program into pivotal studies that will start in the second quarter of this year. We also recently announced our expansion of the epilepsy portfolio into primary generalized tonic-clonic seizures, or PGTCS. This is the next most prevalent form of epilepsy next to focal onset seizures. Given the robust data that we saw in the phase 2 study, as well as the preclinical models that really support RAP-219 and primary generalized tonic-clonic seizures, we feel like this is a natural step as we think about the clinical utility of the compound in epilepsy. The next area that we're focused on is bipolar mania. Bipolar mania has some clinical precedence where anti-seizure medications are often used to treat bipolar mania, as well as some biological relevance that I'll touch on that we believe we have a real opportunity to transform how bipolar mania is treated. This trial is currently rolling a proof of concept study, and we expect that data in the first half of 2027, and then finally, we have the opportunity to develop a long-acting injectable formulation for RAP-219. This would be the first long-acting injectable of its kind in epilepsy, truly transformational for patients, and also provides a really nice IP runway extension as we think about the franchise of RAP-219. Finally, we have our discovery platform, which at this time is focused on nicotinic receptors, two late-stage programs, alpha-6 beta-4 for chronic pain and migraine, as well as alpha-9, alpha-10 for vestibular disorders. For alpha-6 beta-4, we're really excited to say that we have nominated our development candidate for alpha-6 beta-4. We're entering IND-enabling studies, and should be in a position in 2026 to update on the timing of getting that program into the clinic, so as we think about the opportunity for RAP-219, we see an opportunity that is really emerging that is allowing RAP-219 to potentially address several indications that have significant unmet need, but also have large patient populations and significant market opportunity. Focal onset seizures, roughly 1.8 million patients, approximately $15 billion market opportunity. Primary generalized tonic-clonic seizures, around 800,000 patients, a $7 billion market opportunity. Bipolar mania, 1.5 million patients, $40 billion market opportunity. And then, as I mentioned, the long-acting injectable that surrounds all of these indications that we think will increase the clinical utility of RAP-219, but really provide significant durable revenue, significantly past standard LOE timeframes. So I'd like to transition and spend a little bit of time on focal epilepsy, the unmet need, as well as the data that supports RAP-219 as a best-in-class therapy potentially for this indication. So as I mentioned, focal epilepsy, there's roughly 1.8 million patients in the U.S. living with focal onset seizures. Importantly, this patient population has pretty high unmet need. 30%-40% of these patients are what we call treatment-resistant or refractory. This means that these patients are currently being treated with anti-seizure medications, but they continue to have breakthrough seizures. That, as I mentioned, is roughly a $15 billion market opportunity, and there's significant limitations with the current treatments that are available to these patients. First is limited efficacy. Although there's over 25 approved medications for these patients, the reality is not many new mechanisms of action have been introduced to treat this condition. So we think RAP-219 has a great potential to bring a novel MOA that can really provide breakthrough efficacy. In addition to limited efficacy, many anti-seizure medications, if not all anti-seizure medications, have significant tolerability issues. Tolerability issues such as sedation, somnolence, gait impairment really have a debilitating impact on patients' quality of life. Given the targeting of RAP-219, we believe we can mitigate some of those tolerability issues. There's risks of potential serious adverse events, the risk of breakthrough seizures with missing a dose, as well as very complicated dosing and administration profiles. RAP-219 is a compound that is really designed to really target the biology that is critical to treat focal onset seizures. On the left-hand side of this slide, what you see is just an image of the brain, and what's highlighted are the areas that are most important in terms of antagonizing receptors as you think about where focal seizures both originate and propagate, and that's in areas of the mesial temporal lobe as well as the cerebral cortex. Importantly, on the right-hand side, you can see the distribution of this target, TARP gamma-8. And what we know about this target is it is enriched and expressed exactly in the areas of the brain that are critical as you think about interrupting your seizures and really controlling seizures. On the top of the PET images, you can see that what is highlighted is the broad expression of TARP gamma-8 in the areas of the neocortex as well as the mesial temporal lobe. And on the bottom, what you can see is there's not much expression, if any, in the areas of the hindbrain. And that's important because if you can avoid interacting with receptors in the hindbrain, that gives you the opportunity to potentially mitigate those most bothersome AEs, things such as somnolence, sedation, as well as gait impairment. So as I mentioned, we're on the heels of some very promising phase 2A proof of concept data. I'd like to take a moment just to walk through the study design and then walk through the study results, both efficacy as well as safety. The phase 2A trial design was a truly innovative design. This was a design that we at Rapport and our team at Rapport created in collaboration with some of the top thought leaders in the epilepsy community. This design specifically enrolled refractory focal epilepsy patients, the same type of patients that will be enrolled in our registrational trials. But the difference with this patient population is they had an implantable device, a device by the name of the RNS System manufactured by a company by NeuroPace. The RNS System is approved as a therapeutic device, but in the case of our trial, the RNS System was really leveraged for its diagnostic capability that measures a highly objective biomarker that is strongly associated with clinical seizures, and that's referred to as a long episode. Just briefly reviewing this trial design, this trial design leveraged a pretty lengthy pretreatment period, an eight-week retrospective baseline period followed by a four-week prospective baseline period. Patients were then enrolled or then transitioned to an eight-week treatment period. It was an open-label study, and they were treated with 0.75 milligrams of RAP-219 for five days and then 1.25 milligrams for the remaining of the treatment period. There also was an eight-week follow-up period or a washout period of RAP-219. The data that I will be sharing today is focused on the treatment period. We will be releasing the full data set that will include the washout period in the second quarter of this year. The primary endpoints for this study were the long episode, and you should think of a long episode as an electrographic seizure. So this is the epileptiform activity and the electrographic seizure that precedes a clinical seizure. So this objective biomarker allows us to, at the epileptiform activity level, really detect changes with RAP-219 and also allows us to correlate that to the reduction that we see in clinical seizures, which was the key secondary endpoint. So just a quick review of the patient disposition of the study population. 38 patients were assessed for eligibility. We ended up dosing 30 patients, so eight were excluded and did not meet eligibility criteria. And then 26 patients completed treatment. What we will review are three different pre-specified analysis populations. The first is the safety population, which is the 30 patients. The MITT population for long episode efficacy, which is the electrographic endpoint of 27, and then the MITTCS population, which is a population of 25, and that is the modified intent to treat population for clinical seizures. The reason that it goes from 27- 25 is that two patients did not have clinical seizures in their prospective baseline period, so those patients, from a denominator standpoint, there was really nothing to measure as you think about the efficacy of clinical seizures. We should say that those patients that did not have clinical seizures in the prospective baseline period also did not have clinical seizures in the eight-week treatment period, and I mentioned all of these populations were pre-specified. So if you look at the demographics and the baseline characteristics of this patient population, what we're really encouraged by is that these patients are highly representative of the focal onset seizure patients that ultimately will be enrolled in phase three trials. If you look at the demographics of these patients in terms of the time they've lived with focal onset seizures, the number of anti-seizure medications, the number of clinical seizures they had at baseline, it's highly representative of those that have been enrolled in preceding trials, as well as the patients that will ultimately be enrolled in our phase three trials. If anything, these patients probably are a bit more severe, and that's highlighted by the fact that roughly 70% of patients were on at least three or four background anti-seizure medications. And then when you look at the background anti-seizure medications that these patients were on, lamotrigine, levetiracetam, cenobamate, these are really the most powerful agents that are used to treat patients, and these patients continue to have breakthrough seizures. So I'd like to spend first a moment on the primary endpoints. We're extremely excited about this data. This data exceeded our expectations as well as the expectations in the community. So what you're seeing on this slide is representation of the primary endpoint, which was the reduction of long episodes. And you should consider these as electrographic seizures. And you can see that that's noted on the bottom of the slide, that 92% of these long episodes were deemed as electrographic seizures by independent epileptologist reviewers. So on the left-hand side, what you're seeing is the median% reduction of long episodes of 71%. Our threshold for success was to see a 30% reduction in long episodes, so this far exceeded our expectations, and then on the right-hand side, you can see various cuts of a responder analysis, and as I said, our threshold was 30%, and the reason our threshold was 30% is through our analysis as well as other published data that 30% reduction in long episodes is associated with the clinically meaningful threshold of 50% reduction in clinical seizures, so to see 85% of patients achieve that threshold is significantly meaningful. On this slide, what we're showing is clinical seizure reduction, and this is, again, very impressive data and really shows the potential of RAP-219 for focal onset seizures. On the left-hand side, you're seeing the percent change, the median percent change reduction in clinical seizures, and we observed a 77.8% reduction in clinical seizures. On the right-hand side, you're seeing various cut points for responder analyses, 50% being that first clinically meaningful responder threshold where we saw 72% of patients achieve that, 75% response threshold with 56% of patients. Then importantly, seizure freedom was achieved in 24% of patients. We should say that the study was not designed to detect statistical significance in clinical seizures, but given the effect size that was observed, we hit a statistical significance for all of these various endpoints. The 24% clinical seizure freedom rate is one of the most impressive clinical seizure rates that has been observed with anti-seizure medications. Importantly, clinical seizure freedom does not really succumb to a placebo rate. Historically, in trials, you see a placebo rate of 0%- 2%. We think that this is really a highly objective endpoint as you observe this data in an open-label fashion. And also, we use the most conservative measure of clinical seizure freedom, truly from day one to 56 or weeks one through eight as you consider that 24% seizure freedom rate. So from a tolerability standpoint, the drug was well tolerated. On this slide, you can see that the majority of adverse events were mild to moderate in nature. We did not observe any serious adverse events. We report on the eight treatment-emergent adverse events that are reported or observed in greater than 10% of patients. Those included dizziness, headache, fatigue, fall, nausea, and somnolence, very similar to what you observe in anti-seizure medication trials. On the right-hand side of the slide, you can see that we did observe a 10% discontinuation rate, again, one that we think bodes very well for this compound and is also consistent with the target biology. This is a low discontinuation rate as you consider other anti-seizure medications. So as we look at this profile for RAP-219, we see a truly best-in-class therapy emerging for RAP-219, one that's supported by best-in-class efficacy, a drug that is generally well tolerated and consistent with the precision biology. We see an ease of use given the compound's characteristics, once-daily dosing, the ability to add to polypharmacy with the lack of drug-drug interactions, and a long half-life. As I mentioned, we're also looking at a long-acting injectable that we think would be transformational for these patients and really be able to expand the clinical utility of RAP-219. We just completed a set of market research with over 100 epileptologists and neurologists that confirmed this best-in-class profile. And really, what we have seen is a desire to utilize RAP-219 very early in the treatment algorithm that has translated into a greater than $2 billion market opportunity in FOS alone. So given that data, given the strong alignment that we have achieved with the FDA, we're in a position to accelerate our program into the registrational studies. So we will be running two parallel registrational trials. The construct here is presented. These are very traditional trials leveraging clinical seizure reduction endpoints captured by eDiaries. So really, nothing novel in this design and very similar to the designs that have been utilized for preceding trials. Specifically, there will be an eight-week pretreatment period, a 14-week treatment period, which will consist of anywhere from one to two weeks of titration leading to all patients receiving at least a 12-week treatment period and then an eight-week post-treatment period. On the back end of this study, there will be the opportunity for patients to enroll into an open-label extension study. We'll be assessing three doses in these studies: 1.25 milligrams, 0.75 milligrams, and 0.25 milligrams. Importantly, all of these doses achieve receptor occupancy that we are very confident delivers efficacy. Our target receptor occupancy is 50%-70%. Our 0.25 dose, we believe, will achieve 50% receptor occupancy. And 0.75 and 1.25, we believe, are achieving roughly 80%-85% receptor occupancy. So we're really confident in the dose selection. And we also believe that this dose selection could potentially lead to labeling that provides a lot of flexibility for clinicians as they think about the best way to be able to treat patients with focal onset seizures. We also are, as I mentioned, moving this program forward into primary generalized tonic-clonic seizures. This is based on the robust data that we did see in the phase 2 study, but also some preclinical data that supports the activity of this compound in generalized seizures. This is a market that has very similar unmet need, around 800,000 patients. But what you can recognize here is that, again, 30%-40% of patients continue to be treatment-resistant and have limited treatment options. So we see this as roughly another $500 million opportunity as we think about the overall opportunity with RAP-219. From an LAI perspective, RAP-219 is positioned extremely well to develop the first long-acting injectable for epilepsy. It has very unique characteristics and really the three hallmark characteristics that you would want to see in a compound for a long-acting injectable. First is a low dose, really defined by the compound's potency. And you can see it has really picomolar affinity for the target. It's a very, very potent compound, low clearance with an inherent 8- 14-day half-life, and then low solubility, so we're excited to say that we have nominated the candidate for long-acting injectable formulation. We're moving that into IND-enabling studies and expect our first human PK data with the LAI in 2027. I'd like to touch a little bit on bipolar mania, another large market, as I mentioned, 1.5 million patients in the United States living with bipolar mania. It's a $40 billion market opportunity. The limitations of standard of care are very similar to what's happening with epilepsy patients. The drugs that are available for these patients have significant tolerability issues. They have limited efficacy. There's potential for serious adverse events, and given that constellation of issues, there is low adherence for these compounds. Interestingly, when you look at the standard of care, some of the most widely used medications for bipolar mania patients are anticonvulsants or anti-seizure medications. So there is a level of clinical precedence for using anti-seizure medications to treat this disorder. And some of these have labeled indications for bipolar mania as well as maintenance. There's also a real strong biological rationale to support why we believe in RAP-219 and bipolar mania. Bipolar mania is characterized by increased glutamate levels and hypermetabolism in the cortical limbic networks. We know that glutamate signaling is primarily mediated by AMPA receptors. And what we understand about RAP-219, it is a very powerful negative allosteric modulator for the AMPA receptor and really decreasing glutamate trafficking. So we feel like the biology really supports RAP-219 here. Also, when you look at some of the most widely used therapies, lithium valproate as well as lamotrigine that are approved therapies for bipolar act in part by attenuating glutamatergic transmission as well, so we feel like the program is well positioned here, and we're in active enrollment of this study, encouraged with enrollment, and as I mentioned, expect data in the first half of 2027, so when you really combine this opportunity with RAP-219, we see a significant market opportunity emerging, one that is a multi-billion-dollar market opportunity across various forms of epilepsy, both focal onset seizures as well as primary generalized tonic-clonic seizures as well as bipolar, and then as we think about the long-acting injectable, we think that that can be applied across all indications that we're seeking, but also gives the potential for durable revenue well beyond traditional LOE. I mentioned at the beginning of the discussion our discovery platform. Our discovery platform is focused on leveraging receptor-associated protein science. This was core to the foundation of the company that we were not just a single-asset company, but we were a company that could build a self-sustaining and regenerative pipeline in neuroscience. We're excited, as I mentioned earlier, to announce that we have nominated our first development candidate coming from our discovery pipeline. And this is the Alpha-6 beta-4 program. This is a program that has strong genetic validation as well as a level of clinical validation for areas of chronic pain, primarily neuropathic pain. Specifically, there was a long-standing effort in pharma around this target, the Alpha-6 target. Abbott, before they became AbbVie, had some very promising data with this mechanism, ABT-594. This was a pan-nicotinic agonist targeting the Alpha-6 receptor. Unfortunately, given the fact that it was not a specific compound, although it showed very promising efficacy in neuropathic pain, it was limited by its tolerability. Our scientists at Rapport have uncovered what we believe is the subunit of the Alpha-6 sensory neuron that one is driving analgesia, and if you can be specific to that subunit, can also dial out the tolerability. That is the Beta-4 component of that, so we have a first-in-class compound that we have nominated for a DC. We're moving this into IND-enabling activities and look forward to getting this program in the clinic. Given this program, we have prioritized Alpha-6 beta-4 in our pain strategy as well as migraine. We have some really promising data in migraine for Alpha-6 beta-4 as well. One of the things that we updated coming into the meeting is we were looking at RAP-219 in diabetic peripheral neuropathic pain. That program was put on clinical hold by the FDA, but we were able to get that program off of clinical hold coming to the end of the year of 2025 so that IND is no longer on clinical hold. Given the promise and what we believe is the best asset to move forward in pain and the best target to really interrogate in pain, we have prioritized the Alpha-6 program and will no longer be pursuing RAP-219 in diabetic peripheral neuropathic pain. As you look forward for the next 12- 24 months here at Rapport, we believe we have a very catalyst-rich calendar over the course of 2026 and 2027. In 2026, we have a couple of key data sets that we will be releasing. First is the full data set in the second quarter of this year that will incorporate the eight-week follow-up period with those top-line results from our phase 2 study. In that, we'll be able to really confirm the PK profile of RAP-219 during the washout period. And leveraging that objective biomarker, we'll be able to understand when electrographic activity as well as clinical seizures start to arise for patients. In addition, patients that were involved in the phase 2 proof of concept study have the ability to enroll into an open-label extension study. We're actively enrolling that study. And we look to present by the end of 2026 additional data from that open-label extension study, so really the first cut of that data. As you look forward for 2027, we're on track in the studies enrolling very well. The bipolar study in the first half of 2027 will probably be in a position in the spring of this year to guide on a very specific timeline for that data as we see more enrollment come through. We look to initiate our trial in primary generalized tonic-clonic seizures and also look to have our initial PK data from the long-acting injectable formulation. In addition to this, we will be updating on our catalyst for the Alpha-6 beta-4 program. As I mentioned, that program is currently in IND-enabling work, and we're hopeful that that program will be entering the clinic in 2027, so with that, I'd like to thank everyone for their attention, and I'll turn it over to Tyler for Q&A. Thank you very much. All right. Just before Q&A, I want to invite Troy, the CFO, and Jeff, the CMO, to the panel. Thank you for that wonderful presentation. Do we have any questions from the audience? Okay. Well, I'll start it off here. So one question that's been on my mind is when you think of RAP-219's phase two A FOS data, how do you compare that to other drugs in epilepsy that are in development right now? Jeff, do you want to take that? Yeah. Great question. And one always has to be careful about comparing results from studies across studies, of course. But I mean, the phase two results are really unprecedented in terms of efficacy. And the tolerability profile is very favorable. Of course, it's an open-label study, but it gives us great hope that it could be one of the first-in-class, leader-in-class for a new ASM with a new mechanism of action and a drug that has no DDIs, that has a long half-life, which is great for physicians and patients in case they miss a drug over one or two days. So it has a great profile, a great efficacy readout. Again, I think it's unprecedented and a very favorable safety and tolerability profile. Great. And sort of following up on that, what would you need to see in phase three for this to be the next Keppra? Certainly, replication of phase 2 would be, I mean, again, still unprecedented. In terms of efficacy, anything above 50%, I think would be 50% non-placebo adjusted, would be considered a leader in efficacy and far superior than Keppra, in fact. I mean, one of the reasons Keppra is so widely used is it's very easy for physicians to use and to start patients. It's the usability of the drug. So we think the drug has those attributes. And so far, it has far superior efficacy. Okay. Thank you for that. And I mean, one thing you touched on is this long-acting injectable, and it will be the first in epilepsy. How do you expect the community? How do you think the community is going to think about that? Yeah, so as you think about a long-acting injectable, usually LAI formulation is presented roughly two to three years after the oral formulation is launched, and the reason for that is you want physicians as well as patients to be able to experience the oral formulation of a drug, and then once they have experience with that, being able to transition and allow for the option of a long-acting injectable. So the way that we see this working in practice is that patients are able to achieve a level of efficacy, ensure that they're tolerating the oral formulation, and then being able to transition to a long-acting injectable. When we think about the long-acting injectable in terms of dosing timelines, our initial presentation, we're targeting roughly a monthly depot of RAP-219, and we think, and what we hear from the community is, again, this would just be transformational for patients. One of the biggest fears for patients as well as their caregivers is the potential for a missed dose of a drug. The potential for a breakthrough seizure not only leads to morbidity, but in some cases, mortality. And having a drug on board in an LAI formulation would really help mitigate that risk. Thank you. I don't want to take up all of the space here. Do we have any questions from the audience? Okay. Well, thank you. I'll keep going on then. So another question. Oh, okay. Sure. Thank you. The question is maybe more color around the formulation technology of the long-acting platform. For example, give us some maybe guideline around the half-life of the formulation or estimated kind of range. Yeah. So when you think about the long-acting injectable formulation, as I mentioned in my prepared remarks, there's some inherent characteristics of RAP-219 that make this amenable to a long-acting injectable. So it has low solubility, it has low clearance, so a built-in half-life, long half-life in the oral formulation, which is anywhere from eight to 14 days. So as you think about the LAI formulation, we have to formulate it from a suspension standpoint, but there's not much complexity that comes with that formulation, just given the inherent characteristics of the compound. The way that we have approached this and the team has approached this is to really be thoughtful about this formulation. We want to be using previously utilized excipients and solvents. So there's long-term talks that have already been established. And we think that we have a pretty straightforward pathway here. We want to see the PK that.