Praxis Precision Medicines, Inc.

and thank you for standing by. Welcome to the Praxis Precision Medicine's fourth quarter and full year 2025 earnings call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Dan Ferry, Investor Relations. Please go ahead.

Good morning, and welcome to the Praxis Precision Medicine's fourth quarter and full year 2025 Financial Results and Business Update conference call. This call is being webcast live and can be accessed on the Investor section of 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, clinical development timelines, and financial projections. While these forward-looking statements represent Praxis 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 an obligation to do so. Please refer to Praxis' most recent filings of the Securities and Exchange Commission for discussion of certain risks and uncertainties associated with the company's business. Joining us on today's call are Marcio Souza, President and Chief Executive Officer of Praxis, and Tim Kelly, our Chief Financial Officer. After updates on our key programs, we'll move to a brief Q&A session where Marcio and Tim will be joined by Steve Petro, President of Research and Development, and Megan Snezinski, Chief Operating Officer. With that, It's my pleasure to turn the call over to Marcio.

Thank you, Dan. Good morning, and thank you for joining the PRAXIS fourth quarter 2025 conference call. Let me start by saying that 2025 was a remarkable year for PRAXIS. It was marked with the breadth of significant clinical achievements and regulatory advance across our portfolio. With positive redoubts and FDA interactions for elixir-cosmides, relutrigine, and vermotrigine, as well as accelerated development plan for Alzheimer's. Standing here today, we deliver on our goal to submit two NDAs, one for elixir-calcimide in essential tremor and one for elutridine in SCN2A and 8A DEs. Just like 2025, this year will continue to enhance our clinical portfolio and mark our transformation into a commercial company. Next quarter, We expect to have the top-line results for Power 1 for vomatogenin in focal epilepsy and the Alzheimer's in BRAVE data. In the second half of the year, we expect to complete enrollment for Power 2. The ML trial for litrogenin in broad disease is expected to serve as the base of an SMDA by next year. And those are only a fraction of the deliverables expected in the next 12 months. We have the drugs, the people, and the capital to deliver yet another transformational year, bringing innovative treatment to patients with CNS disorders. Let me now just dive a little bit on each one of the clinical programs. Now, focusing on ULIX Account My. Last October, we reported the positive top-line results from the Essential Tree Program, with both studies delivering clinically meaningful and statistically significant results. Study 1 met its primary and all key secondary endpoints, with Elixir showing meaningful improvements in the MADR11, in the rate of disease progress, PGI, and CGI. Study 2 also met its pre-specified primary endpoints, with Elixir demonstrating a superior maintenance of effects during the randomized withdrawal phase. This was the first time an investigational therapy designed specifically for patients with ET showed positive results in a comprehensive clinical program. Based on this positive data and the fact that there is no other specific therapy delivering such results as ulexacultamides, we were granted breakthrough designation by the FDA in December. Had a very productive pre-NDA meeting also in December with the FDA and worked diligently to prepare the NDA submission. We have recently completed the NDA submission to the FDA. Now, as we move towards expecting an approval in the near future, our preparations for the commercial launch for ElixirCult might be well underway. We estimate that more than 7 million people in the United States live with essential tremor, with about 2 million of them being in immediate need for therapy or an addressable population, as we call. And we're excited about the opportunity to deliver a therapy that can meaningfully improve their daily lives. As we interact with more neurologists in this space, we continue to hear this is a drug that meets a large unmet need in their practice, and their interest continues to improve towards the potential use of ulexacultamide when available in the future. We believe ulexacultamide has a peak potential of over $10 billion annually. Given the size of the population, the strength of the clinical data, the opportunity for responsible pricing that recognize the value of the drug, we have been building our commercial organization infrastructure, including key hires and core aspects of the pre-launch plan, including preparing a comprehensive medical education campaign, which we plan to launch at the upcoming American Academy of Neurology annual meeting in April. At AN, we also share additional data from the Essential 3 studies in multiple presentations. We look forward to interacting with our core audience in Chicago next quarter and share the exciting data from the Essential 3 program. Moving on to our epilepsy programs. We started this discussion with our relutrigine program in developmental and epileptic encephalopathies. a group of severe epilepsies characterized by developmental delays with early onset for which there are limited to no currently approved treatments. In December, at the annual meeting of the American Epilepsy Society, we presented data from the EMBOLD study in SN2A and 8AGEs. We delivered overwhelming efficacy. with relutrigine treatments leading to a clinically meaningful and statistically significant change in seizure and associated developmental endpoints, like disruptive behavior, alertness, and communication. Beyond impressive overall results, the effect of relutrigine was rapid, durable, and continued to deepen with time. Given the strong efficacy results and the favorable test profile, and the scoring relutrigine best in class potential, in alignment with the FDA, we have submitted the NDA earlier this year. It's worth mentioning that relutrigine has rare pediatric drug designation, making it eligible for the Pediatric Review Voucher Program upon approval. The initial addressable population for relutrigine for SCN2A and HAGs is roughly 10,000 patients in the US. However, there are currently over 200,000 patients for which we believe relutrigine could offer benefits. The ongoing NREL study is assessing relutrigine in the broader GE population and we're on track to complete enrollments in this study this year. If the NDA in SCN 2A and 8A we just submitted is approved, and the annual study is positive, we expect to submit a supplemental NDA for the treatment of broad DEs by 2027. We believe the full potential for literature in the DE space could be as large as $5 billion in annual revenue. Similarly to the efforts for ulexacultamide in essential tremor, we have initiated pre-launch activities, including key hires and building sufficient inventory for a successful expected launch for erythrogene. Our team has been accelerating the efforts to ensure patients have access to this potential first disease-modifying treatment for SCN2A and SCN8A. Moving on to vermatrogene. Our comprehensive energy program for vermatrogen, a next-generation functionally selective small molecule in development as a once-a-day treatment for adults with common epilepsies. At the December AF meeting, we shared the full data from our RADIANT Phase II study, where vermatrogen demonstrated its best in disease potential in patients with focal onset seizures. Vermatrogen had fast-acting efficacy with 58% of patients achieving at least 50% reduction in seizures at week one without the need for titration. This effect continues to increase with patients who proceeded to the RLE were achieving 100% median weekly seizure reduction at week nine, which was sustained through week 16. Additionally, we saw that vermatrogen improved efficacy on top of other common anti-seizure medications patients were taking. We are on track for multiple readouts from the pivotal studies for vermatrogen on the next 12 to 18 months. The next clinical update will be for Power 1, our study in focal onset seizures, which exceeded its original enrollment targets. We expect to share the top line results in the second quarter of this year. The second phase three study, PowerQ, has been rolling patients and we anticipate enrollments to be completed by the end of the year. Those two studies, if successful, will serve as the base of a new drug application for Fumatrogene. We're also on track to initiate the Power3 study, which will evaluate vermatrogen as a monotherapy in the first half of this year as well. Altogether, this is a very robust registrational program that we believe will demonstrate vermatrogen's potential to address the significant unmet needs of approximately 3 million people in the United States suffering from common epilepsies. potential to achieve over $4 billion in annual revenue. Turning on to our fourth program in the clinic, as a nursing. As nursing is being developed for the treatment of gain-of-function HCN2AEDs, a rare genetic epilepsy characterized by early-onset seizures and very detrimental developmental impacts. This past December, we have had a favorable meeting with the FDA, where the agents agreed to update the EMBRAVE-3 registration trial design, simplifying it by converting from the double-blind sham control design to a single-arm, baseline-controlled study, where approximately 30 patients will be enrolled. We are quickly enrolling the study and expect it to be completed later this year, with a potential NDA for all the nursing next year. While EMBRAVE-3 is enrolling, we have some additional data from the EMBRAVE study, Part A, or Phase 1-2 study evaluating the safety and efficacy of osinersin versus sham procedure. The trial is ongoing and we're on track to report the top-line results from the original nine patients in the first half of this year. Azunosa also has rare pediatric drug designation and would qualify for a pediatric review voucher upon approval. Once approved, we believe Azunosa has the potential for over $1 billion in annual revenue. In summary, 2025 was a year of major portfolio advancements as we enter our pre-commercial phase. We started 2026 strong with two NDA submissions, and we're positioned for another catalyst-rich year with multiple redoubts of our innovative pipeline. We're planning an R&D day next quarter to discuss our clinical programs and preclinical programs, and a commercial day to follow, where we highlight our launch strategy, readiness, and more aspects of the launch for Ulexacultimide and relitrigine. With a very strong balance sheet, we're well capitalized and focused on discipline of execution to deliver on the preclinical, clinical, and precommercial activities this year to come, while unlocking the more than $20 billion opportunities across our comprehensive CNS portfolio. With that, I'll hand over a call to our CFO, Tim Kelly.