Praxis Precision Medicines, Inc.

Good day and thank you for standing by. Welcome to the Praxis Precision Medicine's third quarter 2024 corporate update. At this time, all participants are in a listen-only mode. Please be advised that today's conference is being recorded. After the speaker's presentation, there will be a question and answer session. To ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. I would now like to hand the conference over to your speaker today. Dan Ferry from LifeSci.

Good morning, and welcome to the Praxis Precision Medicine's third quarter 2024 financial results and business update conference call. This call is being webcast live and can be accessed on the investor section of the Praxis website at www.praxismedicines.com. Please note that remarks made during this call may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These may include statements about the company's future expectations and plans, critical development timelines, and financial projections. While these forward-looking statements represent Praxis's views as of today, they should not be relied upon as representing the company's views in the future. Praxis may update these statements in the future, but is not taking on an obligation to do so. Please refer to Praxis's most recent filings with the Securities and Exchange Commission for discussion of certain risks and uncertainties associated with the company's business. Joining the call today are Marcio Souza, President and Chief Executive Officer of Praxis, and Tim Kelly, Chief Financial Officer. After providing updates on our key programs, there will be a brief question and answer session. With that, it's my pleasure to turn the call over to Marcio.

Thank you. Good morning, and welcome to the Praxis Third Quarter 2024 conference call. This past quarter, we remain laser-focused on advancing our pipeline. as we gear up for next year to have four programs in registration, totaling to a substantial multi-billion dollar opportunity. The Phase 3 study in Essential Tremor, Essential 3, for our lead program, ULIX Account Mine, continues to progress well. We have confirmed all aspects of the internal analysis and are now updating the plans to have the results in Q1 2025. Both studies are well-powered and controlled for success. Because there's a range of outcomes for each study, as well as the interim analysis in the coming months, we decided that we will only share an update on timing for both Study 1 and Study 2 once we have evaluated the recommendation from the Interim Review Board for the interim analysis. In Q3, we're very excited to report the positive top-line results for another asset in our pipeline, relutrigine. in the Phase II NBALDS trial in SCN2A and SCN8A DEs. In the 15-patient study, relutrigine demonstrated an impressive 46% reduction in motor seizures versus placebo, with one-third of the patients achieving an unprecedented seizure-free status. Based on those results, we initiated a second registrational cohort of the NBALDS study, which has already started screening patients just weeks after completion of the prior cohorts. In common epilepsies, Bormetrogen, previously known as Praxis 628, is starting out of the gate strong in all areas of our comprehensive energy clinical program. The innovative observational study Empower, a first of its kind, in collaboration with the Epilepsy Study Consortium, launched in the third quarter. And in this short period of time, attracted the interest of over 1,000 patients who registered in the study. We expect the key learnings from EMPOWER to impact the entire energy program. The Phase II RADIANTS and the Phase II to EMPOWER-1 trials are on track for top-line results next year. Rounding out our portfolio, Elze and Ursyn begin those in patients in Brazil in the second quarter for the EMBRAVE study. and we continue to engage with regulatory agencies in Europe and in the U.S. to finalize the development plans in SCN2A gain-of-function patients. With our strong balance sheet, we continue to be fully funded as we pursue our vision to deliver precision therapies for patients with CNS disorders. Let me now focus some more on Ulexa. Our innovative Essential 3 program in ET is the biggest and most comprehensive program conducted today. We began recruiting for the two Phase 3 studies just about one year ago and have seen tens of thousands of patients interested in participating. This vibrant participation highlights the significant unmet needs for the millions of patients with essential tremor in their physicians and caregivers who are seeking a therapy that will allow patients to perform daily activities without impairments. The needs for treatment in essential tremor continues to be more defined as we advance this program. In a survey we conducted with over 400 patients, Up to 77% of the respondents said they do not feel their ETC symptoms are managed with current treatments. In a separate survey we conducted with 150 treating physicians, they shared that 85% of their visits with ETC patients are focused on looking for treatments. Clearly, there is an incredible need here, and we look forward to shortly completing the Essential Treats Study with the goal of bringing an option to the market. As a quick refresher, the Essential 3 program has two simultaneous Phase 3 studies being run concurrently. Study 1 is a 12-week two-arm placebo-controlled parallel group study, and Study 2 is a 12-week randomized withdrawal study. Both studies use as primary assessments the change in the modified activities of daily living, and they are both run entirely decentralized as in the patient's home rather than at a clinical site. We share in our last quarterly call that we decided to trigger a pre-planned interim analysis when 50 to 75% of the patients have completed the 12-week study one. The analysis will inform us whether we should continue the study throughout completion, if the primary endpoint is matched to consider ceasing the study, or to consider enrolling additional patients to ensure it's sufficiently powered for success. Based on the expectation for the sufficient number of patients to complete the study, cleaning of the data, execution of the statistical testing, and analysis by independent boards, and our internal operations, as well as considering the operational impacts in the study completion of study two, we'll be finalizing the interim analysis in the first quarter of 2025. Given the range of outcomes, we will not speculate on scenarios or timing for readouts of study one and study two until we hear from the interim review boards at which time we'll be better informed to provide an update. Regardless, preparations continue to file the NDA as expected in 2025. Now moving on to our highly differentiated epilepsy portfolio. Vermotrigine, previously known as Prax-628, is a next-generation, functionally selective small molecule being developed as a once-daily oral treatment for adults with epilepsy. We know that treatment options for common epilepsies are lacking in both efficacy and tolerability, and we believe the profile emerging with vermotrigine will provide a highly differentiated, paradigm-shifting way to treat this disease. Last quarter, we introduced our broad energy clinical program for vermetrogene in focal and generalized epilepsy. And I'm glad to share that the ambitious multi-study goal we aim to achieve are advancing well. Energy is comprised of four studies aiming to build a strong base of patients for our trial while generating multiple data points over the next 18 months to support the differentiated profile of vermetrogene. Three trials of NRG are to evaluate the efficacy and safety. The first of this is RADIANCE, an open-label study that enroll patients with either focal or generalized epilepsy who receive Ormetragyne for eight weeks with a safe follow-up of two weeks. We are on track to deliver on top-line results in the first half of 2025. which should help us better understand the effectiveness levels of ermetrogene and its pharmacology in the patient population. The Power 1 and Power 2 studies are 12-week Phase 2-3 studies in patients with focal onset seizures. Power 1 is underway, and we anticipate stop-line results towards the end of 2025. We will slightly stagger the initiation of Power2 to begin recruiting in the first half of 2025. The combined studies are expected to enroll approximately 500 patients globally. As we consider other areas where vermatrogen can play an important role, it's clear that it's activity in F1.7 and F1.8. coupled with fast-acting pharmacology and safe profile, could play an important role in pain management. We are concluding our assessments about the potential role of Ormetrogen in pain, and we will be sharing more in the near future. Now turning to our Reletrogen, a functioning state modulator that is formulated for pediatric use in DEs, a group of severe epilepsies characterized by developmental delays with early onset. with SCN2A and SN8A being one of the most severe and refractory forms of these. And where currently there is no approved treatment. As a reminder, relitrogen has orphan and rare pediatric designation for these two indications. We're thrilled and humbled to share the unparalleled results we observed in phase two and bulk trial cohort one in SN2A and 8A last quarter, where relitrigine demonstrated a number of impressive and unprecedented data points. This two-arm study was run over 16 weeks with four four-week periods. Patients in the placebo arm were administered placebo for one period and relitrigine for the other three periods. and neither the patients or investigators were aware which period was on placebo. Fifteen patients completed a study, and patients had the option to continue to an open-label extension after the 16 weeks. A robust 46% placebo-adjusted reduction in motor seizures over the period was observed. with 33% or 5 out of 15 patients achieving seizure-free status that notably was never seen before in the severe patient population. In addition, we saw a disease-modifying impact noted in the study by both caregivers and clinicians, with resurgent leading to meaningful improvement in overall well-being of patients in areas of seizure severity and intensity, alertness, and other important measures. This is also very impressive and encouraging finding, given not only the severity of the disease, but also the lack of improvement in these areas with currently available treatments. Lastly, relitrogen was generally well-tolerated with no drug-related series of adverse events or dose reductions required during the study. These results further set up relitrogen as the potential first and best in class treatments. And following the successful proof of concept, we initiated screening for cohort two of the study, which aims to enroll 80 patients and has been receiving interest from physicians and caregivers, moving us closer to our goal of bringing a potential precision therapy for those severe patients. In addition, across all of these, which affected nearly 200,000 people in the U.S., 70% to 80% of the patients are currently on a sodium channel block. When we see the data from litrigine, which used a more targeted approach on the sodium channel mechanism of action, we believe there is a broader potential for litrigine across all GEs. With that in mind, we're already diligently working with the regulatory agencies to finalize the Emerald Study Protocol for all GEs. We expect to finalize by the end of this quarter and initiate in 2025. We're very excited by both the potential and the progress of our sodium channel modulators, vermetrogene and reletrogene, and there's a lot more to come in 2025. Rounding out our clinical epilepsy program is our first ASO, Elzinersen, designed to selectively decrease expression of the SCN2A gene and directly target the underlying cause in early onset seizures in SCN2A DE. Last quarter, we continued part A of the EMBRAVE protocol in Brazil. This part of the study will provide important control data, examine the safety and effectiveness of Elzinersen in a very severe disease population. This continues to be an exciting time for Praxis, and 2024 has been a transformative year. Looking ahead to 2025, we have a number of inflection points, and we remain the rigorous focus on execution. We look forward to our potential first of many NDA submissions in 2025. With that in mind, let me now turn the call over to our Chief Financial Officer, Tim Kelly.