Ladies and gentlemen, thank you for standing by. My name is Krista, and I'll be your conference operator today. At this time, I would like to welcome you to the Rapport Therapeutics Conference Call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during that time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, again press star one. Thank you. I would now like to turn the conference over to Julie DiCarlo. Julie, please go ahead. Thank you, Operator. Joining us on the call today from Rapport are Chief Executive Officer Abe Ceesay, Chief Financial Officer Troy Ignelzi, and Chief Medical Officer Jeff Sevigny. During this call, management will make forward-looking statements, including statements related to its phase II-A trial of RAP-219, as well as timing of additional data from the study, the company's development plans, and the potential commercial opportunity for RAP-219. Our actual results and timing of events could differ materially from those anticipated in such forward-looking statements as a result of risk and uncertainty. Factors that could cause these results to be different from these statements include factors of the company that the company describes in its securities filings, including its annual report on Form 10-K and quarterly reports on Form 10-Q. Rapport undertakes no duty or obligation to update any forward-looking statements as a result of new information, future events, or changes in its expectations. Our call will begin this morning with Abe providing context for the phase II-A trial results. Jeff will then walk through details of the results, after which we'll have a Q&A session during which you'll be able to ask questions. Abe will then make brief closing remarks. With that, I turn the call over to Abe Ceesay, Chief Executive Officer of Rapport. Abe? Thank you, Julie. Good morning, everyone, and thank you for joining our conference call. Today truly marks a great day and promise for patients. We're thrilled to walk through the results from our phase II-A trial of RAP-219 in focal onset seizures. As you've seen in our press release this morning, RAP-219 greatly exceeded expectations on all efficacy measures, including a 78% reduction in clinical seizure frequency and a 24% seizure freedom rate. RAP-219 was also generally well tolerated. We believe the results, coupled with the other differentiating properties of RAP-219, are the beginnings of a potentially best-in-class profile for an anti-seizure medication. Before we jump into our data this morning, I wanted to quickly remind everyone how we got here and of the basis for our belief in RAP-219. The left image on this slide shows RAP-219's robust clinical activity in the gold standard focal onset seizure model of efficacy in animals, the corneal kindling model. The red line shows that even at the highest dose, RAP-219 did not cause rotor rod failures, leading to a differentiated therapeutic index. The human PET image on the right clearly shows that TARP γ-8 is highly expressed in the neocortex and the mesial temporal lobe, precisely the areas where focal seizures originate or propagate. Focal epilepsy is a large market with continued significant unmet need. Despite the fact that there are over 30 approved medications, up to 40% of patients continue to have seizures, and this has not meaningfully changed in over 40 years. The need is driven by the significant limitations associated with currently approved anti-seizure medications, including limited efficacy, tolerability issues, potential for serious adverse events, and complicated administration profiles. We believe that RAP-219 delivers against these unmet needs and has the potential to transform the treatment landscape in FOS. There is a long history of successful brands in FOS, including several blockbuster drugs. Based on these clinical results and with its emerging profile, we believe RAP-219 has the potential to be a multi-billion dollar commercial opportunity subject to its approval. First, we have robust efficacy data from our initial phase II-A trial. Second, the drug continues to demonstrate a highly favorable tolerability profile. Third, RAP-219's ease of use supports widespread adoption among epileptologists and neurologists, given its once-daily dosing, low risk of drug-drug interactions, ability to combine with other medications in support of rational polypharmacy, and long half-life, which has the potential to reduce the risk of breakthrough seizures. Finally, RAP-219 offers a clinical profile that could be highly competitive in the future focal onset seizure market, both as an initial oral formulation and ultimately as a long-acting injectable. An LAI would be the first of its kind in FOS and has the potential to transform the treatment landscape for patients while significantly expanding the commercial opportunity and extending the IP runway. I'll now hand the conference call over to Jeff, our Chief Medical Officer, to walk you through the data. Thank you, Abe. With the guidance of epilepsy experts like Dr. French, the team designed an innovative and scientifically robust study to test RAP-219's effect on epileptiform and clinical seizure activity. To accomplish this, the study enrolled drug-resistant FOS patients who've had an implanted RNS system. The RNS system is a medical device approved as a treatment for epilepsy and consists of two probes that are implanted in regions of the brain with known epileptiform activity. As part of its function, the device continuously monitors, detects, and stores epileptiform activity, including long episodes. Long episodes, which have been previously shown to best correlate with clinical seizures, served as the primary outcome of this study. All patients were required to have had the RNS device implanted at least 15 months prior to screening, and one probe had to be implanted in the mesial temporal lobe, which is where the majority of focal seizures originate. The patient's RNS device settings and background anti-seizure medications had to be stable prior to screening. Patients needed to show evidence of epileptiform and clinical seizure activity, specifically 16 or more long episodes and at least one clinical seizure during the eight-week retrospective review period. Patients meeting these criteria enrolled into a four-week prospective baseline period and then entered an eight-week open-label treatment period, receiving 0.75 mg of RAP-219 for five days, followed by 1.25 mg for the remainder of the treatment period. This dose level achieves a receptor occupancy of approximately 85%, exceeding the target receptor occupancy of 50%- 70% established in the corneal kindling model of epilepsy. Following the eight-week treatment period, patients entered an eight-week follow-up period. There were two primary endpoints, each based on the long episode outcome, one being the proportion of patients with 30% or greater reduction in long episodes and the other being the median percent change in long episodes compared with baseline. Changes in clinical seizures from the prospective baseline were the key secondary outcome, which was similarly analyzed as the proportion of patients with 50% or greater reduction from baseline, as well as the median percent change from baseline. Thirty-eight patients were screened, seven screens failed, and one experienced an AE and was lost to follow-up during the prospective baseline period. Thus, 30 patients entered the eight-week treatment period and were dosed with RAP-219. There were four discontinuations during the treatment period, three attributed to TEAE. Ultimately, 26 patients completed the treatment period. We pre-specified three analyses populations, the first being the safety population, comprised of all 30 patients receiving at least one dose of RAP-219. The next being the mITT population, comprised of the safety population minus two patients who received less than three weeks of RAP-219 and one patient whose RNS settings were inadvertently changed during the treatment period. The sample size of this population was 27, and it was used for the primary endpoint analysis on long episodes. The last being the mITT-CS population, comprised of the mITT population minus two patients who did not have any clinical seizures during the four-week prospective baseline period. The sample size of this population was 25, and it was used for the key secondary analyses on clinical seizures. Based on the baseline characteristics, you'll see that the patients enrolled are highly drug-resistant and representative of those typically enrolled in late-stage studies. On average, these patients had epilepsy for more than 20 years and had an RNS device for 4.6 years. Five patients had one of their RNS probes outside of the mesial temporal lobe. The patients were on a median of three other anti-seizure medications, and in fact, 70% were on three or four anti-seizure medications in addition to the RNS device. The most commonly used anti-seizure medications were lamotrigine, levetiracetam, and cenobamate. As we move to the efficacy analyses, I remind you that the long episode analyses are based on the mITT population, and the clinical seizure analyses are based on the mITT-CS population. All analyses were based on the entire eight-week treatment period. First, I'm delighted to report that the study met both primary endpoints with high statistical significance. Treatment with RAP-219 resulted in a 71% median reduction in long episode frequency from baseline. Turning to the responder analysis on the right, 85.2% of patients achieved a 30% or greater reduction in long episodes. As a reminder, a 30% reduction in long episodes was selected as our responder threshold because it is associated with a clinically meaningful, that is, a 50% or greater reduction in clinical seizures. Nearly the same proportion of patients achieved a 50% or greater reduction in long episodes, and 48.1% of patients achieved a 75% or greater reduction in long episodes. These efficacy data, combined with the greater than 90% concordance between long episodes and electrographic seizures, demonstrate that RAP-219 is having a deep and robust effect on electrographic seizure frequency. I'm even more excited to share the clinical seizure results shown here. Treatment with RAP-219 resulted in a 77.8% median reduction in clinical seizure frequency compared with the prospective baseline. Looking at the responder analysis on the right, 72% of patients achieved a 50% or greater reduction in clinical seizures. This is a threshold that is considered clinically meaningful. 56% of patients achieved a 75% or greater reduction. The third bar on the graph shows the percentage of patients who are 100% responders. 24% percent of patients were seizure-free during the full treatment period of weeks one through eight. This is also a good time to mention that all five of the patients who had one probe outside the mesial temporal lobe were clinical seizure responders. These clinical results, corroborated by the objective electrographic results from the RNS system, provided great confidence on the therapeutic potential of RAP-219. RAP-219 was generally well tolerated. The most common TEAEs were dizziness, headache, and fatigue. Overall, most TEAEs were mild, with the remainder being moderate. There were no severe or serious AEs or clinically significant laboratory vital signs or ECG abnormality. Three or 10% of patients discontinued due to a TEAE. One patient had a grade one worsening of pre-existing memory impairment, one patient had a grade one panic attack, and one patient had a grade two worsening of pre-existing anxiety. Finally, I would point out that rage or aggression was not observed in this study. To summarize, RAP-219 demonstrated a statistically significant reduction in both long episodes and clinical seizures and was generally well tolerated. The emerging profile of RAP-219, including its once-daily dosing, low risk of drug-drug interactions, and long half-life, which could reduce the incidence of breakthrough seizures in the setting of missed doses, speaks to the potential for RAP-219 to be a transformative treatment for patients subject to approval. Regarding the next steps, we plan to meet with the FDA for an end-of-phase II meeting in the fourth quarter of this year, and we believe we are enabled and well positioned to initiate the phase III program in the third quarter of 2026. With that, I'll turn the call back over to Abe. Thank you, Jeff. As a reminder, RAP-219 represents a pipeline and a product opportunity. We believe these data further reduce risk in our development efforts in focal onset seizure registrational trials and the ongoing phase II trial in bipolar mania. We'll provide an update later this year on our plan and timeline for RAP-219 in DPNP. Additionally, we continue our development work of an LAI formulation of RAP-219. Nonadherence to prescribed anti-seizure medications is up to 50% and can present a significant issue in optimizing treatment for patients and lead to potential breakthrough seizures. We believe an LAI formulation has the potential to improve patient adherence and, based on feedback from the community, to expand the potential clinical utility across all of RAP-219's indications. We continue to be excited about the potential of our discovery programs, α6 in chronic pain and α9α10 in hearing disorders. Our work continues towards nominating development candidates for both. Today's results put in motion a number of anticipated meaningful catalysts for Rapport over the next two years, which are represented on this slide. Most importantly, we are well positioned to initiate two phase III trials in focal onset seizures with RAP-219 in the third quarter of 2026. From a financial perspective, we ended Q2 2025 with $260 million in cash and cash equivalents, which we expect to be sufficient to fund our operations through the end of 2026. A blockbuster anti-seizure medication has to deliver robust efficacy, competitive tolerability, and be easy to administer, driving broad utilization by both epileptologists and neurologists. We believe RAP-219 has this potential. Based on these clinical results and with its emerging profile, we believe RAP-219 could represent a multi-billion dollar commercial opportunity subject to its approval. With that, we'll open up the call for Q&A. Operator? Thank you. We will now begin the question and answer session. If you would like to ask a question, please press star one on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star one again. We ask that you do limit yourself to one question and one follow-up. Your first question comes from Salveen Richter with Goldman Sachs. Please go ahead. Good morning. Congratulations on the data. How are you thinking about translatability to a phase III study, particularly in the context of the baseline characteristics and seizure freedom rate? As you think of the placebo factors that play into that? Sure. Thank you, Salveen, so much for your question. I'll just tee this up, and then I'll let Jeff share some more details. I think looking at the overall study design as well as the baseline characteristics that we observed in this trial, we feel about as good as one can going into phase III. We think that the patients are highly representative of those patients that are going to be enrolled in registrational trials. Importantly, when you look at the baseline seizure frequency of 10, we think that is highly representative of overall disease burden that is usually observed in phase III trials. Jeff, specifically, you could just touch on placebo rates that are typically observed in phase III trials and maybe also how we handle that in terms of statistical analysis as well. Yeah, sure. There's a long history of phase III trials in epilepsy, and there's a well-established placebo rate that's observed in phase III. That rate's approximately 20%. That includes more recent phase II and phase III studies. In our statistical analysis, that's what we assumed. That's what our outright hypothesis was, and that's what we used. We feel like these results are well above that 20% and well above what's been reported by other studies. I would also point out that the seizure freedom rate was 24%, and generally speaking, seizure freedom over eight weeks does not have any placebo response. We believe that that's a very strong metric to weigh the effects of the drug. In terms of translatability, I also want to point out a couple of things that are really important to understand, and that is the biological target is highly expressed in the neocortex and in the mesial temporal lobe. These are precisely the areas of the brain where focal onset seizures originate. We strongly believe that these results will be translatable to a broader population. Thank you. Your next question comes from the line of Andrew Tsai with Jefferies. Please go ahead. Hey, good morning. Congrats on the very strong data set as well. My first question is around the overall profile of RAP-219. I think a differentiating feature in anti-seizure medications in general is the ability to have rapid efficacy. Did you see rapid action within the first couple of weeks? Can you confirm if efficacy does trend better over time, such that the week eight efficacy data point is the strongest across the entire eight-week study? Is it fair to assume we can see the kinetics later at AES this year? Thank you. Jeff. Thank you for that question. The primary analysis was done over the course of weeks one through eight. We have also looked at weeks one through four versus five through eight. I can tell you that the results are generally the same when you compare across those two time points. We haven't performed any formal statistical analysis on the kinetics of onset, but looking at the long episodes, at least visually, it is clear that the onset is within days of taking the drug for the first time. In terms of presentation, we plan to present these data at AES this year. There probably will not be much more than what's presented here. There's quite a bit of statistical analysis that is still ongoing. We, of course, will plan to present additional data in 2026. Thanks. In the safety AE tables, can you provide any color around the 10% rate of falls? If you expect that rate to be the same or consistent in the next pivotal phase III studies, that would be helpful. Thanks. Yeah. What I can say is that falls were not related to things like dizziness, ataxia, balance disorder, or gait disorder. Two of them occurred in the setting of seizures, and one was related to tripping on the patient's dog. I don't believe that this is considered a high rate relative to other anti-seizure medications. It's hard to know to what extent this will translate into phase III. Other than mechanistically, we don't necessarily feel it's directly related to dizziness or gait disorder. Thanks. Congrats again. Thank you, Andrew. Your next question comes from the line of Joseph Thom with TD Cowen. Please go ahead. Hi there. Good morning. Thank you for taking my questions, and congrats on the excellent outcome. Obviously, pretty strong responses across the board. Did you see any change in response based on the type of background therapy that the patients were taking? Maybe second, just related to the initiation of the phase III program, can you kind of walk us through the steps that need to occur before you can kick off that registrational program? Anything gated related to CMC or TOX, or is it mostly just kind of getting sites up and going and finalizing details with the FDA? Thank you. Thank you for that question. We have not formally analyzed the effects of these background anti-seizure medications, but I can tell you, in looking at the data, there does not appear to be any modification based on one's background anti-seizure medication usage. That is, the effect is robust and not dependent on whether the number of and what types of background anti-seizure medications were being used. In terms of next steps, we believe we are fully enabled to start our phase III program. Of course, our first step is to have a meeting with the FDA for an end-of-phase II meeting to confirm that they believe that as well. There are no other gating studies or things that we need to do apart from a meeting with the FDA and the usual things that are required in order to start operationally to start a phase III study. Great. Congrats again. Thanks, Joe. Thank you, Joe. Your next question comes from the line of Paul Matteis with Stifel. Please go ahead. Hey, good morning. Thank you so much for taking my question. Congrats on the data. I guess as it relates to the phase III program, can you talk about your guys' preparedness to execute this program in a timely manner? There's been discussion in the FOS space that studies can take a long time to conduct, that it's not a trivial thing for a patient to get into a study and make commitments to not changing underlying medications, like all sorts of things like that. Maybe just talk about your strategy here. If you have any loose thoughts on what's a good benchmark for how long the phase III program will take to conduct. Thank you. Yeah, great. Thanks for the question, Paul. Given my experience in this space, I think you have to kind of take a step back and think about the broader macro picture as it relates to operationalizing and ultimately executing these phase III trials. There are a couple of things that I think are important drivers in efficiency. First is the competitive context and how many ongoing trials are occurring at these global sites as you think about recruiting patients. We think we'll be well positioned there, just given the fact that some of those trials will either be wrapping up or out of the market by the time we initiate our trials. The second is the profile of the drug, and I think that is really critical as you think about both investigator interest as well as patient interest. A drug that is once daily dosed, has limited drug-drug interactions, and has history in the space, i.e., has done a previous study and investigators really understand the drug well, which would be the case for RAP-219, I think bodes very well for executing a trial, meaning you're not narrowing the top of the funnel and you have to exclude a bunch of patients that are on other medications that may have drug-drug interactions. The last piece is being very thoughtful about how we think about country selection and site selection. We have an excellent team here at Rapport from both clinical operations and clinical development space. This is a team that has been actively working in the space for a while. We think that we're really well positioned there. We're not in a place right now where we can guide the actual length of the trial. That will be work we'll continue to do as we prepare. As I said, from a macro perspective, we feel about as good as we can given those dynamics and the profile of the drug. Thanks, Abe. One last question. Are two phase IIIs here enough for you to meet ICH guidelines, assuming that is the goal or the need to meet ICH guidelines? If not, how might you plan on meeting that FDA requirement? We are obviously evaluating that. I think what you're referring to here, Paul, is ICH guidelines as it relates to safety exposures. We are evaluating that. We do feel that two phase IIIs, as well as additional exposures through phase I pharmacology studies and long-term extension, as well as looking at de novo exposures, will be sufficient for us to meet ICH guidelines. Great. Thanks and congrats again. Thank you. Your next question comes from the line of Jason Butler with JMP. Please go ahead. Hi. Thanks for taking the questions and congrats on the results. Can you just discuss how these results, in your mind, translate into your confidence in the bipolar trial that's ongoing and what preclinical data or mechanistic rationale there is for the drug in bipolar disorder? Secondly, on the long-acting injectable, have you generated preclinical data yet that supports a viable profile, or when can we expect to see preclinical data ahead of the clinical PK guidance you've given? Thanks. Yeah, great. Thank you, Jason. If you don't mind, I'm going to answer your second question first, and then we'll go back to your first question. In terms of our LAI development efforts, we feel confident in terms of our early formulation work. From a feasibility standpoint, the team has done a lot of preclinical work to get us really moving in the right direction in terms of having a viable LAI formulation. In terms of expectations and when we would be prepared to have data externally, we're really anchoring to that milestone, which was reflected on the slide of 2027, where we would see our initial PK results. One of the things that we'll be really thoughtful about is just making sure that that is, from a cadence perspective, put in development at the right time as we think about getting our phase III program off the ground as well as any other NDA or registration-enabling phase I studies that we may do. We feel we're in a really good position based on the early feasibility work. In terms of bipolar, I'll just provide a perspective, and then I'll ask Jeff to make some comments too. You know, bipolar inherently is a more challenging indication given the fact that there really are no preclinical models that are highly suggestive of efficacy in bipolar mania. What we should note is that KOLs, if they point to any model, often look at the corneal kindling model as being a point of preclinical data that could be relevant for bipolar mania. I think we obviously, at the beginning of this development effort in bipolar mania, took that data, as well as the fact that we know that anti-seizure medications have been effective in this indication. We took both of those into account as we think about the potential in bipolar mania. I think for this study, one of the things that we're very encouraged by is the fact that we know we're having robust target engagement and the drug is also well tolerated. We think that the dose that we're bringing forward in bipolar mania is one that gives us the best chance of success. We know now, coming off of these results, that we're having pharmacologic activity at this RO. We're feeling pretty confident about continuing to execute that study and looking forward to data at the beginning of 2027 as well. Jeff, if you want to share anything else from a bipolar perspective. Yeah, it's important just to underscore the demonstration of target engagement, of target pharmacology. The basis of the thesis is the understanding that the glutaminergic system is contributing to acute bipolar mania. This drug, through this mechanism, attenuates the glutaminergic pathway. Finally, I would say the area of the brain that is most affected or thought to be most affected in bipolar mania is, in fact, the mesial temporal lobe, the amygdalar, and hippocampal regions, exactly the areas where RAP-219 targets. Great. Thanks for taking the questions and congrats again. Thanks, Jason. Thanks, Jason. Your next question comes from the line of Justin Walsh with Jones Trading. Please go ahead. Hi. Thanks for taking the question. Given the emerging profile we're seeing here, do you see RAP-219 combining more favorably with some ASMs versus others? Yeah, I think Jeff's addressed that. Right now, what we're seeing is no distinction in terms of efficacy with any background anti-seizure medication mix, which we think is highly favorable as you think about, ultimately, what the community and the market is looking for. They're looking to be able to add on a novel MOA within rational polypharmacy, really to drive additional efficacy. That, coupled with the fact that we believe there's low to no risk of drug-drug interactions, I think puts us in a very favorable position. Great. Thanks for taking the question. Your next question comes from the line of Li Chen with H.C. Wainwright. Please go ahead. Hi everyone. This is Li Chen for Dr. Tao. Thanks for taking our questions and congratulations. Maybe one for me is, can you please talk about the level of the physician feedback and how they anticipate the use of RAP-219 in the clinic if approved? Maybe the second question is, what's your thought on exploring additional dosing regimens in phase III so that you have more comprehensive dosing information for physicians to choose from? Thank you very much. Thank you for the question. In terms of physician feedback, maybe I can talk about both physician feedback prior to these results and then some of the anecdotal feedback we've got based on these results. Prior to the results, I think there was great belief in RAP-219. It's a novel MOA. It's a drug, again, that has a profile in terms of its administration, once daily dosing, long half-life, no DDIs, or low potential for DDIs. That was very appealing. I think the feedback that we received, both through our market research as well as conversations within the community, is that this would be a drug that would have a high potential to be added on in the refractory setting, but also as they thought about getting comfortable with the drug, being able to move up the treatment algorithm. I think based on these results, that profile has only grown in terms of its positive reception. All of those criteria that I walked through have remained consistent. I think what these results show and what we've heard is really the potential for a best-in-class opportunity. That's the feedback that we have heard. The ability to deliver efficacy at this degree and maintain that safety profile, I think, has the community really encouraged. What we see is really a multi-billion dollar type of opportunity here. If you were to look at what drugs really cross that threshold in terms of true blockbusters, they're drugs that are able to be utilized both by the epileptologist and neurologist. To do that, you need a profile that the general neurologist feels very comfortable using and adding without a lot of concern or consideration for drug-drug interaction, dosing other drugs, adjusting the dose of other drugs, as well as the potential for a serious adverse event. We feel like the data that we've produced, plus what we know about this drug, really fits that profile. That's where we really see this drug stacking up as a drug that really can achieve that broad utilization both across general neurologists and epileptologists. In terms of dosing, we feel that we have a dose as we think about moving it forward into phase III studies. Jeff said we're fully enabled, but I'll let Jeff share a little bit more as to how we will kind of evaluate dosing strategy going into phase III. Yeah. As Abe says, we have a dose, I think, that's been established by this study. We also have a great understanding of receptor occupancy in this dose that we used for our KDP target. There may be some latitude to have more than one dose. I don't want to get into phase III specifics. It's a bit premature, but we have put together what I think will be a great protocol. Once we review it with the FDA and get feedback, we can share further information. Great. That was our last question. I really want to thank everybody for joining the call, and I'll just make some closing comments here. RAP-219 was designed to maximize efficacy while reducing typical CNS adverse events. Today's results bear witness to that design and offer hope to a range of underserved patient populations who could be helped by this new class of drugs. We would like to sincerely thank all the patients and investigators involved in our ongoing study. Without their contribution, these results would not be possible. We would also like to thank NeuroPace and our CRO partners for their close collaboration through this study. Lastly, I want to sincerely thank all of our outstanding team members here at Rapport who designed and executed so well this very thoughtful study. We look forward to updating you on further progress in the coming year. Thank you again for everybody joining today. This concludes today's conference call. Thank you for your participation, and you may now disconnect.