Praxis Precision Medicines, Inc.

Good day. Thank you for standing by. Welcome to the Practice Physician Medicine second quarter 2024 Corporate Update Conference 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 1-1 on your telephone. You will then hear an automatic message advising your hand is raised. Please note that today's conference is being recorded. I will now hand the conference over to your speaker host, Daniel Ferry. Please go ahead.

Good morning, and welcome to Praxis Precision Medicine's second quarter 2024 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. This call is also being recorded. 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'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 a discussion of certain risks and uncertainties associated with the company's business. Leading the call today will be Marcio Sousa, President and Chief Executive Officer of Praxis. Tim Kelly, Chief Financial Officer, will also be joining Marcio. 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 second quarter 2024 conference call. PRAXIS is driven by our mission to dare for more as we discuss throughout the call today. We have organized today's call to provide you with a comprehensive update on recent progress on upcoming milestones for our key clinical programs. I'm very proud of the significant progress we have made so far this year. We set PRAXIS in a position to have up to four programs in our registration phase by 2025. We continue to successfully drive our lead clinical program, ulexacultamide, towards registration, including the execution of our Pivotal Essential III trials in essential tremor, which expect the top-line results later this year. Additionally, following the positive VPR results in PRAC 628, we have designed a comprehensive clinical program, including three interventional studies in epilepsy patients and a first-of-kind observational study in collaboration with the Epilepsy Study Consortium. We look forward to building on the encouraging preclinical and clinical data generated to date with top-line results from the first efficacy study expected in the first half of next year. Switching to the upcoming redoubt this quarter, we remain on track to report top-line results for the Phase II and both studies of relitrogen, or Prax562, in pediatric patients with developmental and epileptic encephalopathies. We're very excited about the upcoming readouts and the potential of relitrogen in SCN2A and 8A. We also look forward to exploring this pipeline and molecule opportunity across a broad range of indications. With our strong cash position, we're fully funded throughout several key readouts, which will continue to position Praxis at the forefront of precision medicine for CNS disorders. Let me now spend a few more minutes on Ulexa. The unmet need for ET patients is undeniable, with millions of patients in the U.S. in need of a therapeutic option that allows them to perform daily activities without the impairment created by the condition. With such a large market opportunity, the ET landscape has been ready for innovation. Ulexacultamide is a unique and highly selective small molecule inhibitor of T-type calcium channels designed to block abnormal neuronal burst firings. which should lead, as you've seen, and you're going to be looking into the new study, to improvements of ET symptoms in patients. It has been only a short nine months since we started the biggest and most comprehensive ET program conducted to date with Essential 3, comprised of two simultaneous Phase 3 studies, including a 12-week parallel design and a 12-week randomized withdrawal one. Essential 3 incorporates a decentralized design to reduce patient burden, which has been working super well, together with stratification of key parameters to maintain balance across groups, and the implementation of a very comprehensive screening protocol to ensure suitable patients participate in the study. We knew going in Essential 3 that the proper endpoint had to be the MA-DL11, as we discussed previously. And also the importance of putting in place the controls to minimize variability and placebo effect. And that was all done. While we're confident about the design and the execution of the program, we're also cognizant of being the first in a space like essential tremor. And the responsibilities that are bestowed upon us to leave no rock unturned in order to maximize the provenance of success of ELIXA. With all of this in mind, We built in from the very beginning of the study, from the onset, a planned interim analysis for the parallel group study, or study one in the Essential 3 program. We have discussed this plan with the FDA, and we intend to complete the analysis in Q4 2024. The base assumption we've been using, and we're going to continue to use at this point in time, is that we would read out the study shortly thereafter. The strong participation we are seeing in Essential 3 continues to highlight the significant termed needs for new therapies in essential tremor, and we really look forward to fulfilling these needs and filing our plans NDA next year. I'll now move to our highly differentiated deplepsy portfolio, beginning with PRAC628. As a reminder, PRAC628 is a next-generation, functionally selected small molecule from our CERBRO platform. 628 is currently being developed as a once-a-day oral treatment for adults with epilepsy. Building up these strong results into date with 628, both preclinically and clinically, we have started a comprehensive late-stage program in epilepsy, and we call this program ENERGY. 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 BRAC628. We're very excited to be collaborating with the Epilepsy Study Consortium in a first-in-kind initiative to characterize a very large group of epileptic patients and, amongst other things, assess the appropriateness of participation in clinical studies. This initiative is conducted under a clinical protocol called Empower, which is expected to be up and running this quarter and to be active during the entire development program for PRAC 628. RADIAN is the first of three planned efficacy and safety studies we expect to start in the coming months. RADIAN will enroll patients with either focal or generalized epilepsy who receive 628 for eight weeks. Site engagement and recruitment initiatives are underway, and we plan to enroll up to 50 patients and expect top-line results in the first half of 2025. Radiance is expected to provide important safety, PK, and efficacy information about sex weight, and we're really looking forward to it. Power 1 and 2 are our 12-week Phase 2-3 studies in patients with focal onset seizures. Power 1 is expected to start enrolling later this year, with results expected by the second half of 2025. We expect Power 2 to be initiated in the first half of next year, which we believe, together with Power 1, will generate a robust efficacy package for PRAX-X2H. With that, I'll now like to turn to our relutrigine program for GEs, which are a group of severe epilepsy characterized by developmental delays with early onset. Relutrigine is a first-in-class small molecule and preferentially inhibits persistent sorting occurrence which has been shown to be quite a key driver in uncontrolled seizures in multiple GEs. The preclinical and clinical data we reviewed before for relutrigine supports a differentiated profile in GEs, particularly those without any effective NSAID traits available today. We look forward to the top-line results from our proof-of-concept study and BALDS this quarter. We have been particularly humbled by the severity of the patients in the study and the urgent needs they bring to the table for better therapies. At the time of the readout, we expect to be able to share the efficacy and safety of the placebo control part of the study, as well as available data from the long-term extension portion, as appropriate. We believe relutrigine has potential as a best-in-class option serving as a backbone therapy across multiple DE indications, and really look forward to discuss that further with you all in the near future. Finally, I'd like to turn to Alzheimer's or PRAX222, our ASO designed to selectively decrease expression of SCN2A genes and directly target the underlying cause of early onset seizures in SCN2A DE. In the second quarter of this year, we initiated the first arm of the global registration study for Alzheimer's in Brazil, which is expected to be followed shortly by the expansion of the program in Europe and in the U.S. later this year. This study builds on the very encouraging data from part one of INBRAVE, where patients achieving significantly seizure reduction and significantly increase in seizure-free days while being generally safe and well-tolerated. As we take all of the updates together, we anticipate all four programs to rapidly advance throughout late stage development with multiple regulatory filings expected in the next few years, which is incredibly exciting. With that, let me now turn the call over to our Chief Financial Officer, Tim Kelly. Tim?