Good afternoon, everyone. Thank you so much for joining us. Really pleased to have with us the Rapport team. With me, I have Abe Cisse, Chief Executive Officer, and Troy Ignell, the Chief Financial Officer. To start here, Abe, Rapport's about to initiate its first pivotal program following positive proof-of-concept data in focal-onset epilepsy. In this context, can you lay out the company's key priorities and catalysts over the next 12 to 18 months?

Sure. So, thank you, Salvian, for having us here today. So, as a reminder, we released our phase two data in September of 25, and it was phenomenal data. You know, we were very encouraged by that data with RAP219 and focal onset seizures. That data was really marked by what we saw was pretty much unprecedented results in terms of seizure reduction, roughly a 78% median reduction in seizure frequency. That data puts us in a great position where we're now actively enrolling our Phase III studies, so we're able to really accelerate the start of those studies. In addition to that, we are currently wrapping up our Phase II study in bipolar mania, also with RAP219. And we have brought in the guidance for the readout of that trial from the first half of 27 into the fourth quarter of this year. And then as we think about really furthering kind of the clinical utility of RAP219, we're also moving forward into primary generalized tonic-clonic seizures, which is the next largest form of seizures next to focal onset seizures. That trial will start in 27, and then we're also looking to expand the profile of RAP219 with a long-acting injectable. We're currently in IND-enabling activities for that program and look to initiate that PK study in 27 as well.

With regard to the Phase 3 program epilepsy here and focal onset seizures, can you provide an update on the current status of site activation and patient screening for the program?

Yeah, so we are currently activating sites as we speak. This is a large global trial that is across many continents, and the study is a rolling site activation. So we'll be continuing to bring sites on board over the coming months. We're also currently enrolling patients. So we feel really good about what we see thus far. Now, as I mentioned, these are large trials. They're global trials. And what we've seen in terms of other sponsors is that there's really two ends of the spectrum. One in the Xenon program that took a long time to enroll, but ultimately they did a great job with their program. And then we've seen some other sponsors that are on kind of the shorter end of the spectrum. As we've kind of laid out our program in terms of overall enrollment, we think we can deliver data faster than Xenon, but quite frankly we don't want to be on that short side because we think that really could impact trial quality.

One other thing maybe to add to that, we did sign a partnership with Tenacia. Tenacia is a main company that focuses specifically on CNS in China. They have rights to commercialization in China. but they'll also be part of our global Phase III patient accumulation. So we think that's going to help us as well with the overall recruitment time at this trial executed efficiently, but with the quality that Abe referred to.

And what percentage of your overall trial size will come out of the China site?

Yeah, we haven't guided to that. We think it's going to be kind of an appreciable percentage of overall patients, but we haven't guided to that. And quite frankly, we'll be really kind of monitoring trial quality across all of our sites. So that will be a key aspect of seeing what the overall total patient volume is coming from sites in China.

And that'll be fine in terms of a regulatory pathway with?

Yeah, we do. We think it's going to be fine. And, you know, I think it's been, you know, somewhat overlooked or underappreciated that these focal onset seizure trials are global. You're going to far-reaching countries, you know, in Eastern Europe, as an example. So the FDA has been very open to making sure that they understand that these data are being accumulated across many countries, and we don't see any issues with one of those countries being China. Yeah.

Given the Phase 2A data shared in September demonstrated about a 78% reduction in clinical seizures and a 24% seizure freedom rate, how do these metrics inform your confidence and the powering of the registrational Phase 3 trial?

Yeah, I'll talk about it in two aspects exactly how you framed it. One is confidence and then talk a little bit about the power of a study because I think those are two interrelated yet separate concepts. In terms of confidence, it gave us a lot of confidence going into phase three in two regards. First is if you just look at the base study. As you mentioned, we had a 78.7% reduction in clinical seizure frequency. But what was really important in our study is we also had an objective biomarker. that really corroborates that. So when we look at that data, coupled with a 24% seizure freedom rate, which is really one of the highest levels of seizure freedom that has been seen in recent trials, and also is really not impacted by a placebo rate, that gave us a lot of confidence, again, corroborated by that objective biomarker that we could replicate and really see those types of results in phase three. The second aspect that we were really bullish about is what we saw in our AAN release, which was the eight-week washout period that was part of our trial. So it was an eight-week treatment period and an eight-week washout period. And what we now understand about RAP219 is it has a 22-day half-life. So in that washout period, although patients were off drug, there were sterile therapeutic concentrations of drug on board, and we saw that seizure reduction go from that roughly 80% range up to a 90% reduction in clinical seizure frequency. And when you look at what a phase three trial, the endpoints are at 12 weeks. So now we see even further deepening of a response. So we feel really confident going into phase three. Now, that doesn't exactly translate into the powering of a study, because when you think about powering of a study, you want to be conservative. So we have taken kind of that traditional powering of other programs into the study. But the other reason for that is when you think about an indication like focal onset seizures, there is a level of safety exposures that you need to accumulate. So by being a little bit more conservative on the powering, that ensures a higher probability of success, but it will also allow us to accumulate those safety exposures that are going to be required for registration.

One thing to add on the probability of success, because there's been discussion about it recently, over the last 50 years, nine out of every 10 drugs that had good phase two data, robust phase two data, also had robust phase three data. So it's a very predictable therapeutic area to begin with, but adding the patients on and we think even adds more credibility to the opportunity for rapport.

What generally happens to the one out of ten that doesn't make it, that doesn't translate?

Yeah, the ones that there's really been about three, and those, it's pretty clear. One is when you look at their Phase II results, they have not been definitive in terms of a very clear efficacy signal. That has been really kind of the major outlier.

Given the Phase II study was conducted in a highly refractory population with an implanted RNS device, speak to your confidence or just your view on the ability of this data to translate to a broader FOS population in the Phase III.

Yeah, so when you look at the demographics of the patients that were enrolled in our study, really the only difference is that they had this RNS device. When you look at their demographics outside of that, they look like a typical focal onset seizure patient. If anything, these patients were probably a little bit more refractory. In our study, 70% of patients were on three to four anti-seizure medications. That is in addition to the device. So you can really think about them being on four to five treatments for their epilepsy. So we think it was a highly refractory patient population where we saw these very robust results. So we think that data will translate well, again, because we're seeing all of the seizure reduction that is corroborated by that biomarker. The other question we get around this patient population is that this patient population, in terms of where their foci was for their seizure onset zone, was in the mesial temporal lobe. They had to have that confirmed and defined. But the reality is that's representative of the entire FOS patient population. The majority of patients have their foci in the mesial temporal lobe. If they don't, the majority of the seizures outside of that are starting in the neocortex. That's exactly where TARP gamma-8, the target of RAP219, is expressed. So we think that the representation in the broader FOS population will definitely be there.

And what additional insights do you expect to glean from the Oakland label extension data in the fourth quarter, particularly around durability and dose optimization?

Yes. So, all patients that were in the 2-on-1 study completers had the opportunity to roll over into an open-label extension study. One of the important aspects here is to just think about the nature of this study. We were working on some long-term tox data to enable the open-label extension study. The importance of that is that patients weren't able to roll directly into the open-label extension study. So the first in the phase two study, there was an eight-week treatment period, an eight-week washout period where they were washed out of drug, and then they had a gap of time before they were able to roll into the open-label extension. So from an efficacy standpoint, they are re-baselined. We will be measuring efficacy, but we won't be able to make the comparison back to the baseline data from the phase two treatment period. It just won't be, you just can't really do that in a very clean way because of that gap in time. So we will measure efficacy, but primarily we're looking at this study for safety reasons. And that's usually the most important aspect, especially in epilepsy, to really understand kind of long-term safety exposure as you think about open-label extension. And we're actively enrolling that study. We're really encouraged with what we're seeing in terms of the available patients and those patients rolling into the open-label extension study. We'll release that data or the first cut of that data in the fourth quarter of this year. And we think in the range of kind of three to six months exposure is what we're going to be able to evaluate.

And given the open-label nature of the Phase 2A, talk to how you're managing for placebo response in the Phase 3.

Yeah. So, you know, one of the things in the Phase 2 study is that, yes, it was open-label, but we think that this washout period from the study really helps clarify any potential perceived placebo effect. Because remember, these patients were washed off drug. They had no idea what the half-life of the drug was. And if one were to believe in a placebo effect in this study, what you would see is a really rapid return to baseline in the patients in the Phase II study. We didn't see that. We didn't see that because there was still drug on board given the 22-day half-life. And then when you really follow those patients for that second eight weeks, what you do see is this really nice PK to PD relationship. So as concentrations are starting to wear off, you are starting to see the return of both the electrographic biomarker and long episodes as well as clinical seizures. So we feel that confident in the results that we saw in phase two. Now for phase three, when you're really thinking about managing placebo, there are a couple things that you want to do from a clinical trial conduct standpoint, a protocol standpoint. One is you really want to make sure that the patients you're enrolling really are focal onset patients and have a really well-defined baseline. So we are doing, we think, the right things there to ensure that we're capturing the right patients, adjudicating the right patients, and the right patients are enrolling in the And then the second aspect is really seizure capture throughout the study. And that really comes down to the e-diaries and really making sure that patients are trained really well on how to capture their seizures. And these are really the things that we believe were done by Xenon as well. And we also employ the work of the Epilepsy Study Consortium to really help us along that path as well.

One other thing to point back to on the phase two was the seizure freedom rate. That gives us a lot of confidence in the path forward, too, because regardless of placebo, you don't see that significant of a reduction in seizure freedom even in a placebo arm ever. It's usually around 2%, and we were at 25%. We were at 20% at 12 weeks, and that was with eight weeks on drug and four weeks without the drug being administered. So the seizure freedom rate is also a pretty directional piece of data.

And you recently revised the estimated half-life of the drug from 14 days to 22 days. So in that context and the long-acting injectable, just touch on the clinical and strategic rationale for developing a long-acting injectable and what we should expect to learn from the human PK data next year.

So first is there's never been a long-acting injectable for epilepsy patients. And when we talk to the community, the feedback that we get from the community and the words that we hear are transformational for patients. Patients living with various forms of epilepsy, both for the patient, their caregivers, as well as the clinician, one of the biggest concerns is about missing a dose because many anti-seizure medications have very short half-lives. You miss a dose and you have the risk of a breakthrough seizure, which has high morbidity, but in some cases actually mortality. So one of the reasons we're looking forward to this long-acting injectable, and the primary reason, is we think it could be transformational for patients. Then when you look at the value side of the equation, we think that it could completely change the way that RAP219 is looked at as an asset in the market. The first is to access a long-acting injectable, you first step through an oral therapy. So we think that that will ultimately drive uptake of the oral formulation of RAP219 in order for patients to be able to access that long-acting injectable formulation. The second piece is what it does for the terminal value of the asset. So what we see is the potential to extend the IP runway pretty significantly into the late 2040s with the first formulation. and any formulation we do beyond that would be additive. So when you think about a program that has a multi-billion dollar sales potential and you're able to extend that for potentially another decade in terms of IP runway, that really changes the terminal value of the program as well.

And how does it play out in a patient if the patient becomes refractory to the drug?

Yeah, so that's the strategy when you look at an LAI. formulation and how it's introduced. The first thing that the clinician would most likely do is start the patient on an oral formulation. So they would want that a good probably month or so under their belt to ensure that the patient is deriving efficacy from the therapy, but also able to tolerate it. So moving into an LAI, you would want to be confident that really all I'm switching is the formulation, and I've already confirmed that the patient is achieving efficacy and can tolerate the drug. And that's usually the way the LAIs are introduced. Not only are they introduced that way in clinical practice, but they're also often delayed in terms of their introduction to the market. So roughly anywhere from two to four years after the launch of the oral formulation is when you're going to see an LAI introduced to the market.

And can you speak to the regulatory strategy, both in the U.S. and globally?

Yeah, so the first step for us from P.K., and that's the data that we'll have in 27, that information, we'll have some discussions with the FDA around how to move this program forward. So we don't have yet an understanding on, you know, do we just need to do, you know, a bridging type of study or would we need to do a full efficacy study with the LAI? You've seen approaches across both paths, and we'll just have to have that dialogue with the FDA once we have some PK results. Got it.

We're going to see top-line Phase II bipolar mania data in the fourth quarter. Just help us understand the bar for success here.

So there's reasons to believe in RAP219 and bipolar. Inherently, it is a more challenging indication in terms of preclinical to clinical translation. than epilepsy, but it's one based on a whole host of reasons thinking about the role of glutamate in bipolar, really the areas of the brain that one believes is really a culprit in terms of the excitability in bipolar mania, and then analogs of other ASMs that have been shown to be effective in bipolar mania. When you look at results in bipolar mania trials and you look at both antipsychotics as well as anti-seizure medications, what you see is a range of anywhere from a four-point to a six-point improvement in the YMRS on a placebo-adjusted basis. So we've powered the study to detect a four-point change. What's important here is when you look at the efficacy is to look at the totality of the profile in bipolar mania. The reality is, is even if you achieve, say, a six-point placebo-adjusted difference in the YMRS, the primary endpoint, the reality of those therapies is that many of those therapies are not well-tolerated. So you think about antipsychotics as an example. They're sedating, extrapyramidal symptoms, weight gain. What all that leads to is patients have a very low adherence. So we think we have the ability to not only deliver that efficacy, but also carry forward the tolerability profile that we saw in epilepsy, which is non-sedating, no impact on gait, as well as no weight gain, and non-dopaminergic, which we think would be a highly differentiated profile.

How much risk do you think there is in terms of this indication playing out via the data?

Yeah. As I said, it is a lower probability of success indication. And at the same time, we look at the value of the company right now, and we don't think that there's a lot of value built in in bipolar as well. So we see that it could be, you know, significant upside for the asset and for the company overall. You know, the reality is if we saw a positive result in bipolar, you know, we're talking about, you know, multi-billion dollar market opportunity, not only in epilepsy, but an additional multi-billion dollar opportunity in bipolar. But as I said, it's a lower probability of success indication, just given the fact that there is not a lot of preclinical to clinical translation that exists in bipolar.

Great. And you also talked about your other programs here. Can we walk us through the strategy with the rest of the pipeline?

Sure. So, you know, we built this company to really be a fully integrated leading precision neuroscience company. And as part of the founding of the company was to really apply receptor-associated protein science across other ion channels and other areas where our discovery team really believed that by getting to either subunits or specific receptor-associated proteins, we ultimately can drive efficacy while dialing out tolerability. So our first approach there beyond RAP219 and targeting the AMPA receptor and TARP gamma-8 being the receptor-associated protein was to look at nicotinic receptors and specifically look at a nicotinic receptor that has some history as well as a level of genetic, as well as clinical validation for being a really interesting target for pain, and that is the alpha-6 receptor, nicotinic receptor. There was a historic program here, one that showed a lot of promise, but unfortunately, given the fact that it was a pan-nicotinic agonist, really had some tolerability liabilities. What we believe through receptor-associated protein science, we've been able to identify the subunit that is really driving analgesia, and that is our alpha-6-beta-4 program. That program is currently in IND-enabling activities, and based on that, we should be in the clinic next year. We also have another nicotinic program, alpha-9, alpha-10, that is targeting vestibular disorders, and what I can say is we're actively working on several other programs that we continue to make some progress on, and as those programs progress, we think we're going to be in a great position to bring those into the clinic as well.

Troy, remind us of your current cash runway here and how you plan to prioritize capital allocation between the Phase III FOS trials and then the primary generalized tonic clonic seizure study that's planned to start in the first half next year.

Yeah, we've got enough cash to get into the second half of 2029. And while we haven't given guidance externally on our timeline for the FOS Phase 3 program, we think it's sufficient to get to the end of that trial. Also in that period, as you mentioned, we will start the PGTCS next year, but we'll have the bipolar mania trial that we'll read out, and we'll also have the long-acting injectable Phase 1 PK results that we think provide opportunities for catalysts for the company along the way.

And what is the read-through from FOS mechanistically to PGTCS?

Yeah, so we think that the translation is high. One is the robust results that we saw in the FOS trial and the level of seizure reduction that we're able to see. The second is when you think about, again, the expression of TARP gamma-8, Although primary generalized tonic-clonic seizures generalize in nature, i.e. the name, the origination point and the propagation point overlaps really nice with where TARP gamma-8 is expressed. So we think that the anatomy is right, the target is right. And then there are models that are pretty informative of primary generalized tonic-clonic seizures, one of them being the PTZ model, which we saw really robust results with RAP-209 and other gamma-8 TARP compounds.

Great. Maybe a last question here, one on commercialization. So, we've seen cases where we've had really good clinical data, but the market opportunity hasn't played out commercially. You know, I guess, help us understand what's played out with some of these companies, but how you ensure that you have this nice read-through here to your peak sales opportunity or your actual resulting peak sales?

I think there's a couple things to think about here. First is to really ground on what the market is looking for for a novel anti-seizure medication. The first is a novel MOA. That's first and foremost. This is a treatment paradigm of polypharmacy. So when clinicians look to add on a new anti-seizure medication into polypharmacy, they want a novel mechanism of action, one that can provide that additive efficacy. The second is they want a drug that is well-tolerated, and most importantly, a drug that is not going to exacerbate the most bothersome adverse events that are associated with the ASMs that they're on, primarily sedation as well as gait impairment. And then the last is a compound that can be broadly utilized. So one that doesn't have drug-drug interactions has a pretty straightforward dosing and administration profile. And why that's most important is because having that type of profile allows not only the epileptologist to be comfortable using it, but most importantly, the general neurologist. Without that profile, the patient exposures execute a multi-billion dollar asset. And that's where you look at a drug like Xcopri, as an example, that had really strong efficacy results. But when you look at the rest of the profile, tolerability, dosing administration, what you see with Xcopri is it's really only being used by the epileptologist. It's still on track to be a billion-dollar drug, but the challenge for that drug will always be if you don't have general neurologist utilization, your ability to get to multi-billion-dollar utilization is just challenging. We just completed a set of market research with over 100 epileptologists and neurologists. In that market research, we had RTPP, we had the Xenon TPP, and we were really encouraged with what we saw. First, we saw that RAP219, both in the context of currently available ASMs as well as novel ASMs, was seen as a best-in-class profile. We saw broad utilization and a desire for broad utilization across general neurologists as well as epileptologists. And really interestingly, we saw a desire to use RAP219 as early as first line. That's really unheard of for a novel agent in terms of epilepsy and anti-seizure medications. Now, we don't believe we're going to see first-line utilization because patients will step through generics, but seeing second-line utilization just completely changed the trajectory of what we could see in overall utilization and top-line sales.

Great. Well, with that, thank you so much. Really appreciate the time today.

Thank you, Savi. Appreciate it.