Conference Transcript - PRAX 2026-05-12

Operator

I'm very pleased to have with us here Megan Snizinski from Praxis who's going to run through a presentation. Megan?

Megan Sniecinski, COO

Thank you. Hi, good afternoon. I'm Megan Snizinski, the Chief Operating Officer at Praxis. Building on a remarkable 2025, we've continued executing across our portfolio in our journey to become a commercial company and we're gaining momentum across all of our four late-stage assets. These are our forward-looking statements. Everything we do at Praxis comes back to one thing, accelerating the delivery of life-altering therapies for patients suffering from CNS disorders, many of whom have been waiting for decades. Looking at our near-term horizon, what's ahead for us this year sets us up well to deliver on this mission. I want to use our time today to share more about what's happening across each of our programs, what we're excited about, and what lies ahead for the company. Our broad pipeline has several near-term catalysts, and we're heads down executing to deliver on them. Our ULIXA NDA and Essential Tremor is under review with a PDUFA date late January 2027. And ahead of that, we have our NDA for relutrogene under priority review with a PDUFA date in late September. At our earnings call last week, we also announced that recruitment was complete for our Emerald study in broader DEEs, with top-line results reading out in the fourth quarter of this And looking to vermatrogene, we have our Power I Phase III study read out this quarter. and we'll be initiating the power three monotherapy study a milestone this community is has been waiting for using all of the existing exciting features of the rheumatogene profile to deliver on what patients need and then later in the year we'll complete the power two phase three study enrollments progressing well and we're on track to finalize it later this year and report early next year. And looking at ELSA-NURSEN, we recently reported results from our EMBRAVE Part A study. And EMBRAVE 3 is now enrolling and expected to complete in 2027, serving as the registrational trial for our NDA filing. We're building towards four first and best-in-class CNS therapies over the next two years, representing more than $20 billion in peak sales potential. Our cash position of $1.4 billion at the end of March positions us well with a runway into 2028, putting us beyond the launch of relutrogene and Ulexa, and giving us the resources we need to continue executing and creating value for patients. Let me start with Ulexacaltamide and essential tremor, a disease that's been completely neglected for decades and where we're about to change everything. Essential tremor is one of the most common movement disorders affecting 7 million Americans. And yet there has never been a single FDA approved therapy specifically for this disease. ET patients struggle to write their name, to eat with a spoon, have a hard time even pouring a glass of water to drink. And these are not minor inconveniences. These are devastating daily losses. And we estimate approximately 2 million patients are seeking treatment and seeking a therapy that can meaningfully improve their daily function. This represents about a 10 billion in peak sales opportunity in the US alone. Our Essential 3 program was comprised of two phase three studies, a placebo-controlled parallel group design, and then a randomized withdrawal study design with a very unique design feature that allowed study allocation and treatment allocation to be fully blinded between participants, study staff, and investigators. At AAN last month, the Essential 3 program was awarded the Abstract of Distinction in Movement Disorders, a very meaningful recognition for a study at the Most Important Neurology Congress in the U.S. During the plenary presentation, we showed the baseline disability of the trial participants, which mirrors what's seen in clinical practice. What stands out is that over 90% of participants reported worsening in the last three months. And this speaks to the progressive aspect of the disease. And then in the data on the chart you see here, you can see the extent of significant disability across everyday activities that these patients experience. Essential tremor impacts all aspects of functioning. With the unmet needs so high, we are thrilled Essential 3 is the first successful Phase 3 program for a drug in essential tremor. Both Phase 3 studies were positive with clinically significant and statistically significant results across both primary and secondary endpoints. And then on safety and tolerability, we saw no drug-related SAEs, and the treatment emergent AEs were mild, occurred early during titration, and resolved. And what physicians tell us is that they feel very comfortable managing these side effects in the context of proactive patient counseling. At AAN last month, we also shared further data supporting the rapid, deep, and consistent drug effect. we observed across activities of daily living and other outcome measures. Patient reported and clinician assessed outcomes all move in the same direction, and it's this kind of consistency that really builds physicians' confidence. When we look at the extent of response in our combined analyses, we see remarkable gains in functioning. These results were statistically significant at all responder thresholds, And this real robust data represents true functional gains for patients. And to have nearly half of the patients regaining four points is remarkable. And that's why we're seeing strong interest and engagement from the medical community. Earlier this year, we conducted a very comprehensive observational study with physicians to understand their view of essential tremor and elixacaltamide. We surveyed over 2,000 physicians in the U.S. who collectively manage over 40,000 ET patients, and the results were beyond encouraging. They validated ULIXA's profile across efficacy, the breadth of benefits, as well as the tolerability profile. It's clear ULIXA addresses a need physicians have felt for decades. The pent-up demand is real and reinforces the $10 billion peak sales I mentioned earlier, and also demonstrates the real need for a drug like Elixir in the market. We also surveyed almost 1,300 patients, and the activities they told us were impacted most are exactly the activities where Essential 3 showed benefit. it. It's truly exciting to be at a place where there is such alignment between the physicians, the patients, and the results of our program. We're full steam ahead on our commercialization and build. We have our leadership in place, and the field force hiring is on track for completion well ahead of the launch, where we want to have the field teams in place and trained well in advance of our PDUFA date, and we continue to expand and build the commercial infrastructure across all commercial areas. We've also successfully established a distribution network to ensure drug availability at launch and sufficient levels, and we continue to engage with the healthcare professionals, including launching the Essential to Me disease state awareness campaign last month at AAN. Now turning to vermatigine, our common epilepsy program. Vermatigine is the most potent and selective sodium channel modulator ever developed in epilepsy. With over 3 million patients affected by this disease, we see a third, over a third, are changing their medications each year, and nearly two-thirds have to be on two or more anti-seizure medications the patients are simply cycling through treatment options that don't work well enough and and they deserve better and this represents the differentiation where matrigine can bring to patients and it goes well beyond just the efficacy it's once daily dosing no food requirements fast acting no titration and minimal ddi risk and these are the features that physicians and patients have been asking for we know physicians need more good drugs for their patients and vermatrigine represents that real differentiation and we're positioning it for broad foundational use in the treatment paradigm at aas in december we presented the full data from our radiant study where vermatrigine demonstrated best in disease potential in focal onset seizures. Vormatrigine has fast-acting efficacy without the need for titration, and the effect continues to increase with more treatment time. Additionally, we saw that Vormatrigine improved efficacy on top of other common anti-seizure medications that patients were taking. As I mentioned earlier, there are three key milestones in the near future for this program. the first is the readout of power one study this quarter and power three is set to generate data in the context of monotherapy treatment which the majority of the market really needs and enrollment is progressing well in our second phase three study power two and we're on track to finalize that this year and read out early next in our dee programs we have two complementary assets that together have the potential to address real need in epileptic encephalopathies. Relutrogene stands to become the first approved therapy specifically for SCN2A and SCN8A DEEs. Severe childhood epilepsies where seizures can begin in the first weeks of life and where nothing works for these children our clinical profile is ideal it's once daily no titration is needed and a pediatric friendly formulation that can be given orally and it's designed for families caring for severely ill pediatric patients the embold study was stopped early at interim where we delivered overwhelming efficacy and we saw relutrogene treatment leading to a clinically meaningful and statistically significant change in seizure frequency and associated developmental endpoints like disruptive behavior alertness and communication beyond these impressive results the effect of relutrogene was rapid durable and continued to deepen with time and the strong efficacy results and a favorable safety profile really underscore relutrogene's best in class potential. Looking at DEEs broadly, you simply cannot have seizure activity without participation of the sodium channels. Across all DEEs, regardless of the underlying genetic etiology, Hyperactive sodium channels are in the pathway, and relutrogene addresses that common mechanism. The current USDEE market is over 200,000 patients, approximately 20 times the initial 2A and 8A population. If Emerald is positive, this becomes one of the largest rare disease commercial opportunities we know of. We shared last week that recruitment of Emerald is complete in record time, and it's clear caregivers, patients, and investigators share our view of the potential of relutigine. Our top-line readout for Emerald will be the fourth quarter of this year. We build the foundation with the potential launch of 2A and 8A, and the results of Emerald later this year, if positive, will significantly expand the commercial potential for rilutrigine by several fold. Lastly, let's talk about Elsinurson, the first ASO in our platform. We recently presented exciting results from our Part A study, and we're thrilled with the impressive seizure reduction, as well as disease-modifying components that we saw. The overall data from the EMBRAVE program and OPAL label extension, as well as our emergency access program, really set up the potential for this to be a transformational drug in DEEs. So in conclusion, we are off to a great start with momentum across all of our clinical profiles programs. We're on track for our commercial launches in both relutrogene and Ulexa. And when we're backed by a strong balance sheet and a broad IP portfolio across our programs, we continue to be focused on our execution and delivering innovative therapies for CNS. Thank you.