Abraham Ceesay, CEO, and to his left, Troy Ignelzi, CFO. Welcome, both of you. Thanks, Andrew. As usual, some people may not be as familiar with the Rapport story, so would you mind level setting what you're working on, your overall strategy platform milestones over the next six to 12 months? That could be very helpful. Sure. Rapport, we're a company that is focused on precision neuroscience. Our foundational technology and scientific foundation is based on receptor-associated proteins. We'll talk a little bit more specifically about why receptor-associated proteins are important in terms of a potential drug target in the context of RAP-219. Our lead program, RAP-219, is a program that targets a specific receptor-associated protein associated with the AMPA receptor, which is called TARPγ8. This is a receptor-associated protein with the AMPA receptor that has very specific neuroanatomical distribution, which makes it really an ideal target for our lead indication, focal epilepsy, but also other indications that we're pursuing with this compound. We released last year, in September, really meaningful phase II data for our lead indication in focal onset seizures. We're currently advancing that program into phase III studies, which are truly getting up and running as we speak. In terms of additional milestones, we have recently re-guided to bring in our bipolar mania readout with RAP-219 to the fourth quarter of this year. We're also on track to be able to release our first cut of open label extension data in focal onset seizures with RAP-219 in the fourth quarter of this year. Another program that we're very excited about is the LAI formulation with RAP-219, which we think could be transformational for epilepsy as well as bipolar with RAP-219. We are currently in IND-enabling activities, and look to have that human PK data for the long-acting injectable in 2027. Wonderful. Maybe to start with the focal epilepsy program with RAP-219, congratulations on a really great data set in October of last year. Maybe walk us through big picture, what kind of attributes are we talking about that makes your compound superior to what's out there? Why does this have blockbuster potential? Yeah, I think the best way to understand the potential value of RAP-219, and as you mentioned, Andrew, kind of the blockbuster potential of RAP-219, is really to think about it through the context of what clinicians and patients are looking for in new treatments in focal onset seizures. This is a field that has had over 30 drugs approved and available for the treatment of focal onset seizures, but the patient population continues to have significant unmet need. There's 1.8 million patients in the U.S., and roughly 30%-40% of those patients are treatment-resistant, meaning they're currently managed and treated with multiple anti-seizure medications, but they continue to have breakthrough seizures. What patients and clinicians are looking for, first and foremost, is a novel MOA. An MOA that can be added to polypharmacy and really provide additive efficacy, as well as a drug that is better tolerated. Most all anti-seizure medications that are currently available are interacting with receptors kind of in a ubiquitous nature in the brain. What that is causing is, although you're seeing some level of efficacy, pretty significant tolerability issues associated with those anti-seizure medications. What we see with RAP-219 is given the fact that we are targeting TARPγ8, which is a receptor-associated protein associated with the AMPA receptor that is primarily expressed in forebrain structures, both the mesial temporal lobe as well as the neocortex. We're able to drive efficacy where focal seizures both originate and propagate. By targeting those receptors only in the forebrain, we're able to really mitigate some of those most bothersome AEs that are associated with other anti-seizure medications. What we saw in our phase II results is really unprecedented efficacy. We saw a 77.8% median reduction in clinical seizures. That was accompanied by a meaningful reduction, a 71% reduction in a biomarker that we assessed, which is a long episode, or in the terms of our study, an electrographic seizure. When you look at that efficacy, we also saw a really appealing tolerability profile. The drug also has attributes that are ideal for an anti-seizure medication. It is extremely potent, so that leads to a low dose. It has a 22-day half-life, also has a profile in terms of drug-drug interactions that we don't think will be a culprit, or at risk for a DDI, which is very important as you think about adding it to polypharmacy. QD dosing as well as novel mechanism and no titration, essentially, too. Yes. That's good. After that data set, at AAN this year, in April, you shared some washout data. I think you alluded to it with your 22-day half-life, but maybe speak to the significance. The same patients from the phase II wash out of their drug, and you shared data at AAN. Speak to the significance. What do other drugs maybe show as well? Sure. In our phase II trial design, we had an eight-week treatment period, and then we had an eight-week washout period. What you're alluding to, Andrew, is at the AAN presentation, we are able to share our data from that washout period. What we were really encouraged by is, given the half-life of the drug, which is approximately 22 days, what we saw is really continued efficacy through that washout period, given the fact that drug is still on board, even though these patients come off therapy due to the half-life. Specifically, as I mentioned in our secondary endpoint around clinical seizure reduction, at eight weeks, we saw a 77.8% median reduction in clinical seizures. That actually increased to 90% at week 12. Why is that important? That's really important because when you look forward to our phase III trial and all other phase III trials, those are 12-week treatment durations. This gave us a lot of confidence in terms of the effect that we could potentially see at 12 weeks as we move into phase III. The other aspect of this that you mentioned, Andrew, is the half-life. Most other anti-seizure medications have very short half-lives, and that's a huge risk for patients living with focal onset seizures. One of the biggest fears for patients, their caregivers, as well as clinicians, is a missed dose. A missed dose in this patient population has the risk of breakthrough seizures. Breakthrough seizures have the risk of significant morbidity, and in some cases, mortality. When you look at a drug that has the type of coverage that we have with a 22-day half-life, that's a big benefit for patients. No one would ever encourage missing a dose, but the reality is that happens in a chronic condition, and having that extended half-life could really provide a lot of protection for patients. Right. Maybe it gives you also some confidence in your LAI program, which we can touch on a little bit later, too. Yes. Yeah. Those same patients then now go back to being treated. I think there are 27 patients in the washout. How many have actually went back to the open label extension, where you'll share data in Q4? We have an open label extension that was available for these patients that were involved in our phase II study. That open label extension had a gap period. Patients did not directly roll over into the open label extension study, and that was really due to us just enabling the open label extension due to long-term tox that has now obviously been completed. Patients are enrolling into that open label extension study. We haven't guided specifically on how many patients have enrolled, and that continues to occur. What we can say is we're really encouraged by what we're seeing in that enrollment. Those patients are actively enrolling. They're going to be reinitiated on RAP-219, and we expect to be able to share an initial cut of that data in the fourth quarter. We look at this data really primarily from a safety perspective. We think that that is the most informative as we think about this data set, the fact that patients will have longer exposures on RAP-219. That's very important as clinicians really think about the profile of novel anti-seizure medications to understand long-term safety. Understood on safety. Is it fair to assume, sure, there is a gap period, but they resume, that efficacy could be similar to what you saw in the original eight weeks of 78%? Should we expect that or not necessarily? Yeah. It's hard to say right now, and we're not setting expectations around efficacy for a couple reasons. The first is that these patients did have a gap period. We know that through that gap period, things in their medical history could have changed as well as their background anti-seizure medications could have changed. The patients are re-baselined going into that open label extension period. We will have a new baseline period. We will be able to derive efficacy from this study. It's just not going to be a direct comparison to what we saw in that initial eight-week treatment period. Right. There will be some efficacy information, but it's hard to compare one-to-one just given the nature, again, of how these patients ultimately came into the open label extension period. Okay, great. I guess one more is the open label extension. Do you think it could be three or six months of follow-up? Secondly, it's just the existing patients. There are no de novo patients, to be clear, in this open label extension. Yes. I think your timeframe is kind of directionally right, in terms of the level of exposures that patients will have going into that fourth quarter data release. Yes, this initial open label extension study will just be the patients from the 201 study, our phase II study. Now we are opening other open label extension studies associated with our phase III program. There will be open label extension study for patients in our two phase III studies, our FOCUS 1 and FOCUS 2 study that will be able to enroll into an open label extension study. There's another part of that open label extension study that will also capture de novo patients that ultimately will be able to allow us to achieve our appropriate safety exposures. Great. Speaking of the phase III FOCUS 1, based on clinical trials, I think start a dose or a site maybe started up in late May. Anyway, it's starting up now basically. Yes, it is in earnest. As we speak, those sites are being initiated, and we're actively looking to screen patients as well. Right. As we think about phase II to phase III translation, how much do you think efficacy that you saw in phase II could degrade from the 78% at week eight? I know you mentioned now we have a week 12 more treatment. How are you thinking about absolute efficacy for the drug by week 12 in these trials, as well as how placebo might perform and what kind of placebo-adjusted separation are you thinking? Yeah. Yeah. We look at the phase II study, and we believe that it is highly translatable going into phase III, in terms of efficacy. We believe that the way that we ran the phase II study and given the fact that all clinical seizure reduction is corroborated by a highly objective biomarker, really gives us a lot of conviction in terms of the efficacy that we can see in phase III. As we think about the results for phase III, we are not necessarily taking a discount in efficacy for phase III. Now, I want to be really clear on that versus how one may think about powering a phase III study. What the phase III studies don't do is we did not power the study based on the results and the treatment effect that we saw in phase II. There's a couple of reasons for doing that. One is, I think in drug development, you always want to be thoughtful about the powering of your phase III studies. The second is, as you think about an indication like focal onset seizures, there is the requirement for a safety database. We want to be, one, thoughtful about the powering the study, and then two, also having sample sizes that allow us to fulfill those safety exposures. As we think about the powering and overall separation from placebo, very similar to what contemporary studies have done, whether you look at the Xenon program or previous programs, that kind of separation from placebo, our powering is somewhat similar to that. I see. Maybe around 15 or 20% or something placebo- adjusted delta. Yeah. Yeah. In that range. Okay, thank you. The two trials, FOCUS 1 and FOCUS 2, technically have, I think, different dosing. Yep levels. For the studies to succeed, do both dose levels in each study need to hit stat sig versus placebo, or can the top dose only beat placebo stat sig and you're good to go kind of thing? Yeah. Couple things prior to just addressing the question directly, I want to just provide some context. The first question is why? Why have we chose multiple doses in phase III? We think that given the profile of the drug, it is really a differentiating factor for us to bring forward multiple doses that could be efficacious from a prescriber's perspective. That is information that we've received from the community, and we think bringing forward multiple doses as you think about ultimate prescribing information could be highly valuable. When we designed the studies, we looked at three doses that based on our understanding of the PK of the drug, insights from our phase II study will really provide shots at efficacy across three dose levels. In one study, we have what is called mid-high, and then the other study, we have low-mid. From a statistical standpoint, really everything is anchored around that mid dose because that is the common dose across two studies. Really that is where the anchor point is. We have had dialogue with the FDA through our end of phase II, and we feel confident that the design of these studies will really give us a shot to have a successful study based on that mid dose, then followed by the high dose, and then following from a statistical priority, the low dose. Oh, super helpful. In terms of data timing, I know there's no guidance, but can you give us a bookend of other recent studies? You mentioned Xenon. I can think of Praxis, which reported some data earlier this week. Yes. There's Biohaven. I guess, point being, Praxis and Biohaven was pretty fast. Xenon was on the slower end. Yes. Remind us how many years it took those studies, and where do you think you could fall? Yeah. You've laid out the spectrum, Andrew. On the long end, you have Xenon's program. Now, I want to just say, I think the Xenon team has done a remarkable job and did a remarkable job in their development program. The reality is, when they started that development program, it was one of the most challenging times to do focal onset seizure studies, both in terms of the competition for recruitment, but also you had COVID and other dynamics. That's one end of the spectrum. The other end of the spectrum is some other sponsors that you had mentioned, which have either guided to or delivered data in a much more rapid fashion. As we look at the landscape, quite frankly, we do not want to be on either end of that spectrum. We don't want to be as aggressive as certain sponsors. When we look at overall trial conduct and ultimately how we believe a program should be run, we think that going too rapid really starts to have an impact on patient quality in terms of enrollment. Also, we think that there's certain things that are tailwinds for us that won't make our program as long as Xenon. What we have mapped out is roughly a three-year timeline to data. What I can say is, we'll continue to monitor our enrollment, and I think give us a year into this program or so, we'll be in a much better place to really put a more finer line on the delivery of data. Yes. Great. Thank you. Maybe shifting a little bit to the LAI program where there's phase I data in 2027. Bigger picture, which epilepsy drugs have an LAI formulation? How does it boost the appeal of RAP-219 if you did have one successfully in the real world? Why is this important? Thank you. There are currently no available long-acting injectables for focal onset seizures or epilepsy. We believe, and this is supported by the feedback that we receive from the community, that a long-acting injectable would be transformational for patients. Going back again to the comment that I made around the fear of missing a dose for patients, clinicians, as well as their caregivers. A long-acting injectable would really be a solution for that. It would be a real differentiating aspect for RAP-219 as you think about the overall profile of the drug. The drug has some inherent qualities that make it amenable to a long-acting injectable, which other anti-seizure medications don't. One, low solubility, two is the inherent half-life of the drug, and then three is the potency. All three of those aspects really allow this drug and RAP-219 to be the only anti-seizure medication that really has a straightforward path to a long-acting injectable. The other dynamic that we think is somewhat underappreciated is how that would change the overall market dynamics for RAP-219 as a commercial asset. The reality is, in order to be able to access a long-acting injectable, you would first have to be exposed to the oral formulation. We think that that will really drive uptake and share to RAP-219. The second is, as you think about the terminal value of RAP-219, it's a complete game changer. What a long-acting injectable formulation does is roughly extend the IP runway for the asset for another decade. As we think about a $2+ billion market opportunity on the oral formulation alone, that really markedly changes the overall terminal value of the asset as well. Got it. Phase I data, again, in 2027. Will this be in healthy volunteers, and what exactly do you want to see in the phase I data set? Is it higher receptor occupancy for a long duration? I don't know. Yeah. Really what we're looking at in this first phase I study is PK. That's really what you're looking to confirm. We already know RO and concentration relationship based on our oral formulation. Really what we're looking for here in this initial study is to really have proof of formulation. The fact that we have a formulation that can achieve that PK profile, and then you're also looking at certain aspects of the LAI that you want to ensure meet certain safety criteria. Looking at injection site reactions as an example, and also looking at the profile of the PK to ensure that you don't have a burst profile or any other PK profile that might make you have to go back to the drawing board on formulation. What we can say is based on the inherent qualities of RAP-219, as I've already mentioned, and as well as our previous formulation work, we're really confident with what we see. That human PK data would be the next de-risking event. Got it. What kind of dosing frequency are we talking about? Yeah. Is it every month or is it every six months? Yeah. Our first formulation is looking at an every monthly profile. What we're currently working on and will continue to work on are extended profiles beyond the monthly. Got it. After the phase I, let's just say you liked what you saw, what would be the next steps? Do you actually go to phase II or can you jump to phase III? How does this work? That's still undefined, and we'd have to have those conversations with the agency. There's been multiple long-acting injectables in other disease areas. There's a little bit of variability based on the disease area. Once we have those human PK results, we'll talk to the agency, and we'll figure out what that path looks like in terms of including that as part of an sNDA with the RAP-219 oral formulation, which would be the base of the NDA. Got it. Okay. Shifting to other programs you're pursuing with the same drug, PGTCS, which is primary generalized tonic-clonic seizures, you're starting a phase III in 2027. Any color when data could be, and maybe confidence why you want to pursue this indication? Yeah. The confidence really was driven by our results that we saw in our phase II study in FOS. As you think about this seizure type, there's a lot of reasons to believe, both based on our preclinical experience in certain animal models, as well as the distribution of the target, and then also as you look at the phase II results in FOS, to really believe that this drug could have an impact in primary generalized tonic-clonic seizures. The reason that we're starting this program as early as we are is that these trials do take longer to recruit. It's just a harder patient population to recruit. It is also the second largest form of epilepsy behind focal onset seizures and has a very similar profile in terms of the unmet need, with roughly 30%-40% of those patients also being refractory. Our belief here is, given the length and time it takes to recruit these studies, we wanted to get going on this program earlier, because we think having that labeled indication as close to our indication in FOS would be another differentiating factor and really just expand the clinical utility of RAP-219. Perfect. In the meantime, as we wait for these programs to evolve, you also have a bipolar phase II to hit a readout in Q4, also for the same asset. It is a placebo-controlled readout I think will be meaningful. Bottom line, when I think bipolar mania, I think antipsychotics. Remind us what the antipsychotics show on the Young Mania Score. Is that the bar to beat here? Yes. A program that we're excited about, one that I think everyone is aware that neuropsych indications, quite frankly, have a lower probability of success versus a condition like epilepsy, just given the fact that there is low preclinical to clinical translation. There's many reasons to believe in this experiment with RAP-219 based on what we know about bipolar mania, the role of glutamate, the distribution of the target, and why RAP-219 could be a really interesting mechanism and compound here. In terms of the current standard of care, you mentioned atypical antipsychotics. There are other anti-seizure medications that have been approved in bipolar mania, both in terms of acute mania as well as maintenance therapy. The true efficacy measure is the YMRS, the Young Mania Rating Scale. When you look at approved drugs, there's anywhere from a 4-7-point placebo-adjusted difference. We have powered our studies to detect a four-point change. When you think about really that four to seven-point range, what's important is to think about the totality of the picture of the drug. These current treatments that are available for bipolar mania may deliver some level of efficacy. The reality is the tolerability profile is really not ideal for patients living with bipolar. When you think about atypical antipsychotics, you have EPS symptoms, you have weight gain, and other issues. What we see with RAP-219 is the ability to have a mechanism that drives efficacy but is non-dopaminergic and does not produce sedation or some of those EPS symptoms. Right. Maybe one more question in the last minute is just, personally, I think looking at the safety could be important, too. Long story short, FYCOMPA, another AMPA, does have a black box for aggression behavior and so forth. Is it fair, would you agree that this fourth quarter readout could be a double whammy in terms of it could also help you de-risk further that you do not have that kind of signal that FYCOMPA might show kind of thing? We would agree that we think that this fourth quarter readout with bipolar is going to be informative in two forms, as you mentioned. One is having an efficacious drug in bipolar mania would really increase the opportunity with RAP-219. Regardless of the efficacy readout, we're going to have another 125 patients that are exposed to RAP-219. These are acutely manic patients. Having that level of safety data in addition to the data that we've already produced across all of our phase I studies, our phase II study, as well as the open label extension study, we think is going to be a really robust safety data set. Okay. I think that's all the time we have. Thank you for walking us through your story, and congratulations on all the progress. Thanks, Andrew. Thank you, everyone.