Q4 2025 Praxis Precision Medicines Inc Earnings Call

February 19, 2026

Operator: Good day, and thank you for standing by. Welcome to the Praxis Precision Medicines Q4 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 one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one 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.

Speaker #1: Good day, and thank you for standing by. Welcome to the Praxis Precision Medicines fourth quarter and full year 2025 earnings call. At this time, all participants are in listen-only mode.

Speaker #1: 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 *11 on your telephone.

Speaker #1: You will then hear an automated message advising your hand is raised. To withdraw your question, please press *11 again. Please be advised that today's conference is being recorded.

Speaker #1: I would now like to hand the conference over to your speaker today, Dan Ferry, Investor Relations. Please go ahead.

Speaker #2: Good morning, and welcome to the Praxis Precision Medicines, 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.

Dan Ferry: Good morning, and welcome to the Praxis Precision Medicines 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.

Speaker #2: 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.

Speaker #2: 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 obligated to do so.

Speaker #2: Please defer to Praxis' most recent filings with the Securities and Exchange Commission for discussion of certain risks and uncertainties associated with the company's business.

Dan Ferry: Please refer to Praxis' most recent filings with the Securities and Exchange Commission for a 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 Steven Petrou, President of Research and Development, and Megan Sniecinski, Chief Operating Officer. With that, it's my pleasure to turn the call over to Marcio.

Speaker #2: Joining us on today's call are Marcio De'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 Petrou, President of Research and Development; and Megan, Chief Operating Officer.

Speaker #2: With that, it's my pleasure to turn the call over to Marcio.

Speaker #3: 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.

Marcio Souza: Thank you, Dan. Good morning, and thank you for joining the Praxis Q4 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 events across our portfolio, with positive readouts and FDA interactions for ulixacaltamide, relutrigine, and vormatrigine, as well as accelerated development plan for elsunersen. Standing here today, we deliver on our goal to submit 2 NDAs, one for ulixacaltamide in essential tremor and one for relutrigine in SCN2A and SCN8A DEEs. 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 POWER1 for vormatrigine in focal epilepsy and the elsunersen EMBRAVE data.

Speaker #3: It was marked with the breadth of significant clinical achievements and regulatory advance across our portfolio. We positively doubt, and that the interactions for Elixir CosMice, Relutrogene, and Vermetrogene, as well as accelerated development plan for all the nursing.

Speaker #3: Standing here today, we deliver on our goal to submit two NDAs, one for Elixir CosMice in essential tremor and one for Relutrogene in SCN2A and 8A DEs.

Speaker #3: Just like 2025, the 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 PowerOne for Vermetrogene in focal epilepsy.

Speaker #3: In the all the nursing in brave data. In the second half of the year, we expect to complete enrollment for PowerQ. The MO trial for Relutrogene in broad DEs is expected to serve as the base of an SNDA by next year.

Marcio Souza: In the second half of the year, we expect to complete enrollment for POWER2. The EMBOLD trial for relutrigine in broader DEEs is expected to serve as the basis of an sNDA 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 deep dive a little bit on each one of the clinical programs. Now focusing on ulixacaltamide. Last October, we reported the positive top-line results from the Essential3 program, with both studies delivering clinically meaningful and statistically significant results. Study 1 met its primary and all key secondary endpoints, with ulixacaltamide showing meaningful improvements in the MADR-11, in the rate of disease progression, PGI, and CGI.

Speaker #3: 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 in yet another transformational year, bringing innovative treatment to patients with CNS disorders.

Speaker #3: Let me now deep dive a little bit on each one of the clinical programs. Now, focusing on Elixir CosMice. Last October, we reported the positive top-line results from the Essential Tree program, with both studies delivering clinically meaningful and statistically significant results.

Speaker #3: Study one 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.

Speaker #3: Study two 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.

Marcio Souza: Study two also met its pre-specified primary endpoints, with ulixacaltamide 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 ulixacaltamide, 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 ulixacaltamide are well underway.

Speaker #3: Based on these positive data, and the fact that there is no other specific therapy delivering such results as Elixir CosMice, we were granted breakthrough designation by the FDA in December.

Speaker #3: 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.

Speaker #3: Now, as we move towards expecting an approval in the near future, our preparations for the commercial launch for Elixir CosMice are 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 of therapy, or an addressable population as we call it.

Marcio Souza: 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. 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 ulixacaltamide when available in the future. We believe ulixacaltamide has a peak potential of over $10 billion annually.

Speaker #3: 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 Elixir CosMice when available in the future.

Speaker #3: You will believe Elixir CosMice has a big potential of over $10 billion annually. Given the size of the population, the strength of the clinical data, the opportunity for responsible pricing that recognizes 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.

Marcio Souza: Given the size of the population, the strength of the clinical data, the opportunity for a responsible price, and the recognized 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 AAN, we also share additional data from the Essential3 studies in multiple presentations. We look forward to interacting with our core audience in Chicago next quarter and share the exciting data from the Essential3 program. Moving on to our epilepsy programs. We start the 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.

Speaker #3: At AN, we also share additional data from the Essential Tree studies. In multiple presentations, we look forward to interacting with our core audience in Chicago next quarter and sharing the exciting data from the Essential Tree program.

Speaker #3: Moving on to our epilepsy programs. We started this discussion with our Relutrogene program in developmental and epileptic encephalopathies. A group of severe epilepsies characterized by developmental delays with early-onsets for which there are limited to no currently approved treatments.

Speaker #3: In December, at the annual meeting of the American Epilepsy Society, we presented data from the BOLD study in SCN2A and 8A DEs. We delivered overwhelming efficacy.

Marcio Souza: In December, at the annual meeting of the American Epilepsy Society, we presented data from the EMBOLD study in SCN2A and SCN8A DEEs. We delivered overwhelming efficacy, with relutrigine treatment leading to a clinically meaningful and statistically significant change in seizure and associated developmental endpoints, like disruptive behavior, alertness, and communication. Beyond the impressive overall results, the effect of relutrigine was rapid, durable, and continued to deepen with time. Given the strong efficacy results and the favorable safety profile underscoring 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 Disease Designation, making it eligible for the Pediatric Review Voucher program upon approval. The initial addressable population for relutrigine for SCN2A and SCN8A DEEs is roughly 10,000 patients in the US.

Speaker #3: With Relutrogene treatments leading to a clinically meaningful and statistically significant change in seizure and associated developmental endpoints like disruptive behavior, alertness, and communication. Beyond the impressive overall results, the effect of Relutrogene was rapid, durable, and continued to deepen with time.

Speaker #3: Given the strong efficacy results and the favorable safety profile, as well as scoring Relutrogene as best-in-class potential in alignment with the FDA, we have submitted the NDA earlier this year.

Speaker #3: It's worth mentioning that Relutrogene has rare pediatric drug designation, making it eligible for the pediatric review voucher program upon approval. The initial addressable population for Relutrogene for SCN2A and 8A DEs is roughly 10,000 patients in the US.

Speaker #3: However, there are currently over 200,000 patients with DE for which we believe Relutrogene could offer benefits. The ongoing MO study is assessing Relutrogene in the broader DE population.

Marcio Souza: However, there are currently over 200,000 patients with DEE, for which we believe relutrigine could offer benefits. The ongoing EMERALD study is assessing relutrigine in the broader DEE population, and we're on track to complete enrollments in this study this year. If the NDA in SCN2A and SCN8A we just submitted is approved and the EMERALD study is positive, we expect to submit a supplemental NDA for the treatment of broad DEEs by 2027. We believe the full potential of relutrigine in DEE space could be as large as $5 billion in annual revenue. Similarly to the effort for ulixacaltamide in essential tremor, we have initiated pre-launch activities, including key hires and building sufficient inventory for a successful expected launch for relutrigine. Our team has been accelerating the efforts to ensure patients have access to this potential first disease-modifying treatment for SCN2A and SCN8A.

Speaker #3: We are on track to complete enrollments in this study this year. If the NDA in SCN2A and 8A that we just submitted is approved, and the MO study is positive, we expect to submit a supplemental NDA for the treatment of broad DEs by 2027.

Speaker #3: We believe the full potential of Relutrogene in the DE space could be as large as $5 billion in annual revenue. Similarly to the efforts for Elixir CosMice in essential tremor, we have initiated pre-launch activities, including key hires and building sufficient inventory for a successful expected launch of Relutrogene.

Speaker #3: 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 vermathrogene.

Marcio Souza: Moving on to vormatrigine. Our comprehensive development program for vormatrigine, a next-generation, functionally selective small molecule in development as a once-daily treatment for adults with common epilepsies. At the December AES meeting, we shared the full data from our RADIANT Phase 2 study, where vormatrigine demonstrated its best-in-class potential in patients with focal onset seizures. Vormatrigine had fast-acting efficacy, with 58% of patients achieving at least 50% reduction in seizures at week 1, without the need for titration. This effect continues to increase, with patients who proceed to the OLE, achieving 100% median weekly seizure reduction at week 9, which was sustained through week 16. Additionally, we saw that vormatrigine 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 vormatrigine in the next 12 to 18 months.

Speaker #3: Our comprehensive energy program for vermathrogene, a next-generation functionally selective small molecule, is in development as a once-daily treatment for adults with common epilepsies. At the December AS meeting, we shared the full data from our RADIANT Phase II study, where vermathrogene demonstrated its best-in-disease potential in patients with focal onset seizures.

Speaker #3: Vermathrogene had fast-acting efficacy with 58% of patients achieving at least 50% reduction in seizures at week one. We doubt the need for titration. This effect continues to increase with patients who proceed to the OLE were achieving 100% median weekly seizure reduction at week nine, which was sustained through week 16.

Speaker #3: Additionally, we saw that vermathrogene improved efficacy on top of other common antiseizure medications, patients were taking. We are on track for multiple readouts from the pivotal studies for vermathrogene in the next 12 to 18 months.

Speaker #3: The next clinical update will be for PRAX-222, 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.

Marcio Souza: The next clinical update will be for POWER1, our study in focal onset seizures, which exceeded its original enrollment targets. We expect to share the top-line results in Q2 of this year. The second Phase 3 study, POWER2, has been enrolling 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 vormatrigine. We're on track to initiate the POWER3 study, which will evaluate vormatrigine as a monotherapy in the first half of this year as well. Altogether, it's a very robust registrational program that we believe will demonstrate vormatrigine'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.

Speaker #3: The second phase III study, Power 2, has been enrolling patients and we anticipate enrollments to be completed by the end of the year. Those two studies is successful.

Speaker #3: We'll serve as the base of a new drug application for vermathrogene. While I was on track to initiate the Power 3 study, we will evaluate vermathrogene as a monotherapy in the first half of this year as well.

Speaker #3: Altogether, this is a very robust registration program that we believe will demonstrate vermathrogene'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.

Marcio Souza: Turning on to our fourth program in the clinic, elsunersen. Elsunsersen is being developed for the treatment of gain-of-function SCN2A DS, a rare genetic epilepsy characterized by early onset seizures and very detrimental developmental impacts. This past December, we had a favorable meeting with the FDA, where the agency agreed to update the EMBRAVE3 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 this study and expect it to be completed later this year, with a potential NDA for elsunersen next year. While EMBRAVE3 is enrolling, we have some additional data from the EMBRAVE Study, Part A, our phase 1, 2 study evaluating the safety and efficacy of elsunersen versus sham procedure.

Speaker #3: Turning on to our fourth program in the clinic, as a nurse. As nursing has been developed for the treatment of gain of function SCN2A DEs, a rare genetic epilepsy characterized by early-onset seizures and very detrimental developmental impacts.

Speaker #3: This past December, we have had a favorable meeting with the FDA, where the agents agreed to update the EMBRAVE III registration trial design, simplifying it by converting from the double-blind CHEM control design to a single-arm baseline controlled study, where approximately 30 patients will be enrolled.

Speaker #3: We're quickly enrolling the study and expect it to be completed later this year. With a potential NDA for as a nursing next year. While EMBRAVE III is enrolling, we have some additional data from the EMBRAVE study, Part A, our Phase I, II study evaluating the safety and efficacy of as a nursing versus CHEM procedure.

Speaker #3: 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.

Marcio Souza: The trial is ongoing, and we're on track to report the top-line results from the original 9 patients in the first half of this year. Elsunersen also has rare pediatric drug designation and will qualify for a pediatric review voucher upon approval. Once approved, we believe elsunersen 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 2 NDA submissions, and we're positioned for another catalyst-rich year with multiple readouts of our innovative pipeline. We are planning an R&D Day next quarter to discuss our clinical programs and preclinical programs, and a commercial Day to follow, where we'll highlight our launch strategy, readiness, and more aspects of the launch for ulixacaltamide and relutrigine.

Speaker #3: As a nurse, I also have rare pediatric drug designation and would qualify for a pediatric review voucher upon approval. Once approved, we believe, as a nursing, it has the potential for over $1 billion in annual revenue.

Speaker #3: In summary, 2025 was an 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 readouts of our innovative pipeline.

Speaker #3: 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'll highlight our launch strategy, readiness, and more aspects of the launch for Elixir CosMice and Relutrogene.

Speaker #3: With a very strong balance sheet, we're well capitalized and focused on discipline, execution, to deliver on the preclinical, clinical, and pre-commercial activities this year to come.

Marcio Souza: With a very strong balance sheet, we are well capitalized and focused on discipline of execution to deliver on the preclinical, clinical, and pre-commercial activities this year to come, while unlocking the more than $20 billion opportunities across our comprehensive CNS portfolio. With that, I'll hand over our call to our CFO, Tim Kelly. Tim?

Speaker #3: While unlocking the more than $20 billion opportunities across our comprehensive CNS portfolio. With that, I'll hand over the call to our CFO, Tim Kelly.

Speaker #3: Tim?

Speaker #2: Thanks, Marcia. Good morning, everybody. And thank you for joining today's call. I'll provide a quick summary of our fourth quarter and full year financial results.

Tim Kelly: Thanks, Marcio. Good morning, everybody, and thank you for joining today's call. I'll provide a quick summary of our fourth quarter and full year financial results. 2025 was a year of continued investment into the pipeline while maintaining rigorous financial stewardship. In Q4, operating expenses totaled $97 million, broken down to $77.5 million for R&D and $19.5 million for G&A. That compares to Q4 of 2024, where total operating expenses were $71.4 million, broken down to $56.3 million for R&D and $15.1 million for G&A. For the full year, operating expenses totaled $326 million for 2025, compared to $209 million for 2024.

Speaker #2: 2025 was a year of continued investment into the pipeline, while maintaining rigorous financial stewardship. In Q4, operating expenses totaled $97 million broken down to $77.5 million for R&D and $19.5 million for G&A.

Speaker #2: That compares to Q4 of 2024, where total operating expenses were $71.4 million broken down to $56.3 million for R&D and $15.1 million for G&A.

Speaker #2: For the full year, operating expenses totaled $326 million for 2025, compared to $209 million for 2024. The increase is in both Q4 and full year were driven by an increased spend in our cerebrum and solidus platforms to progress the portfolio, of clinical programs.

Tim Kelly: The increases in both Q4 and full-year were driven by an increased spend in our Cerebrum and thalamus platforms to progress the portfolio of clinical programs. As we go into 2026, we expect to have a significant increase in spend as we invest into our commercial launch activities that Marcio just discussed, as well as continuing to progress the pipeline. We ended Q4 with $926 million in cash, equivalents, and marketable securities, compared to $469 million as of December 31, 2024. This increase to $457 million was primarily due to net proceeds from Praxis October 25 follow-on public offering, and net proceeds from the at-the-market sales of common stock-

Speaker #2: As we go into 2026, we expect to have a significant increase in spend, as we invest in our commercial launch activities that Marcia just discussed, as well as continuing to progress the pipeline.

Speaker #2: We're aiming at Q4 with $926 million in cash, equivalent in marketable securities, compared to $469 million as of December 31, 2024. This increase of $457 million was primarily due to net proceeds from Praxis October 25 follow-on public offering, and net proceeds from the aftermarket sales of common stock, offset by cash used in operations.

Tim Kelly: ... offset by cash used in operations. Our cash position was further strengthened through proceeds from a public offering in January this year, which yielded $621 million. When added to our year-end position, our pro forma cash is approximately $1.5 billion, which is expected to fund operations into 2028. With that, I will pass it back over to you, Marcio.

Speaker #2: Our cash position was further strengthened through proceeds from a public offering in January this year, which yielded $621 million when added to our year-end position, our pro forma cash is approximately $1.5 operations into 2028.

Speaker #2: With that, I will pass it back over to you, Marcia.

Speaker #3: Thank you, Tim. I'm going to now open the call for Q&A. Shannon, would you compile the queue, please?

Marcio Souza: Thank you, Tim. Going to now open the call for Q&A. Shannon, would you compile the queue, please?

Speaker #4: Thank you. As a reminder, to ask a question, please press star when one of your telephone and wait for your name to be announced.

Operator: Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Yasmin Rahimi with Piper Sandler. Your line is now open.

Speaker #4: To withdraw your question, please press star when one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Yasmin Rahimi with Piper Sandler.

Speaker #4: Your line is now open.

Speaker #5: Good morning, team. Congrats to the outstanding timing of the filing. So congrats. Two questions. One directed to Tim and one for Marcia. Tim, if you could maybe walk us through the pre-commercial activities that are going on currently and what the cadence are going to be throughout 2026.

Yasmeen Rahimi: Good morning, team. Congrats to the outstanding timing of the filing. So congrats. 2 questions, one directed to Tim and one for Marcio. Tim, if you could maybe walk us through the pre-commercial activities that are going on currently and what the cadence are going to be throughout 2026. That's very helpful. And then for Marcio, maybe help us understand sort of what additional new data we could, we could be seeing at AAN, and I'll jump back onto the queue for respect to my colleagues to ask questions.

Speaker #5: That's very helpful. And then for Marcia, maybe help us understand sort of what additional new data we could be seeing at AAN and I'll jump back onto the queue for respect to my colleagues to ask questions.

Speaker #3: Yeah. Thanks very much, Yaz. And glad to be talking about what we're doing to prepare for two launches. As you can imagine, we're at the stage now where we're making some key hires and looking to build out the talent for our commercial organization.

Tim Kelly: Yeah, thanks very much, Yas. I'm glad to be talking about what we're doing to prepare for two launches. As you can imagine, we're at the stage now where we're making some key hires and looking to build out the talent for our commercial organization. We've also been focusing on ensuring that we have sufficient inventory for what we expect will be, you know, good, strong launches, and we never want to run out. Be sure that we've got inventory on hand for all scenarios. That's a long lead time activity, so very well at hand to ensure that that's in good shape. And then also looking at for, particularly for ulixacaltamide, helping to improve awareness of the disease. And Marcio, in a moment, will talk about our activities at AAN and all the data we're sharing there.

Speaker #3: We've also been focusing on ensuring that we have sufficient inventory for what we expect will be good, strong launches, and we never want to run out.

Speaker #3: Be sure that we've got inventory on hand for all scenarios. That's a long lead time activity, so very well on hand to ensure that that's in good shape.

Speaker #3: And then also looking out for particularly for Elixir Calcemide, helping to improve awareness of the disease. And Marcia, in a moment, we'll talk about our activities at AAN and all the data we're sharing there.

Speaker #3: We're also looking at that at a time when we can start sharing more about the disease and help patients understand about the innovative therapies we're developing.

Tim Kelly: We're also looking at that at a time when we can start sharing more about the disease and help patients understand about the innovative therapies we're developing.

Speaker #6: Yeah. No, thanks, Tim. Yaz, a lot going on, as you mentioned, right, in terms of making sure that not only the highest quality and NDAs were submitted, as of course was always our priority, but now moving on to making sure those move review with the agency and then on the other side of that, the prescribers really understand or potential prescribers really understand the disease in one hand, which they understand well, but there's obviously a good reminder there.

Marcio Souza: Yeah, no. Thanks, Tim. That's, yeah, there's a lot going on, as you mentioned, right? In terms of making sure that not only the highest quality NDAs were submitted, as of course, was always our priority, but now moving on to making sure it's a smooth review with the agency. And then on the other side of that, the prescribers really understands or potential prescribers really understand the disease in one hand, which they understand well, but there's obviously a good reminder there. And on the other hand, the clinical data for ulixacaltamide, and then relutrigine later in the year as well. In regards to the American Academy of Neurology meeting next quarter, we have about 15 different presentations going on at the meeting. It just speaks about the number of things across the company.

Speaker #6: And then on the other end, the clinical data for Elixir and then Relutrogene later in the year as well. In regards to the American Academy of Neurology, a meeting next quarter we have about 15 different presentations going on at the meeting.

Speaker #6: It's just speaks about the number of things across the company. A number of them are about the essential three program and essential tremor in general.

Marcio Souza: A number of them are about the Essential3 program and essential tremor in general. What we're gonna be doing there, as you will see, and I hope to see you there in Chicago, is oral presentations on the clinical data. AAN actually is very nice for that because the presentations are reasonably long, so we can go into a fair bit of detail on the clinical program, which of course very important for the 13,000 or so neurologists that are our audience. They're gonna be there also to expand the understanding on the overall community of this very strong clinical data sets.

Speaker #6: What we're going to be doing there, as you will see—and I hope to see you there in Chicago—is oral presentations on the clinical data. AAN actually is very nice for that because the presentations are reasonably long.

Speaker #6: So we can go into a fair bit of detail on the clinical program, which of course is very important for the 13,000 or so neurologists that are our audience that are going to be there.

Speaker #6: Also to expand the understanding on the overall community of this very strong clinical data sets. So we're going to be discussing other aspects like the response on the drug and what happens to this patient.

Marcio Souza: So we're gonna be discussing, like, other aspects, like the response on the drug and what happens to these patients, and just how meaningful it is, the combination of all the endpoints, but particularly the primary measure here, that's the MAGL-11. And you're gonna see throughout all the presentations, there are very robust number of new data points. We put a lot out there. So it's not to say that there is any scarcity of data on the Essential3 program, but it is definitely more geared towards the future prescriber here, the neurologist. So incredibly excited, very grateful to the scientific community of AAN to giving us the podium there to present the strong clinical data.

Speaker #6: And just how meaningful it is, the combination of all the endpoints, but particularly the primary measure here that's the MADL-11. And you're going to see throughout all the presentations there are very robust number of new data points.

Speaker #6: We put it a lot out there. So it's not to say that that is any scarcity of data on the essential three program, but there's definitely more geared towards the future prescriber here that is the neurologist.

Speaker #6: So incredibly excited, very grateful to the scientific community of AAN to giving us the podium there to present this strong clinical data.

Speaker #4: Thank you. Our next question comes from the line of Ritu Baral with TD Cowen. Your line is now open.

Operator: Thank you. Our next question comes from the line of Ritu Baral with TD Cowen. Your line is now open.

Speaker #7: Hi, guys. This is Athena Chen-An for Ritu. Thanks for taking the question. I have another one on Elixir. You previously indicated that the label may include alternative titration schedules.

[Analyst] (TD Cowen): Hi, guys. This is Athena Chin on for Ritu. Thanks for taking the question. I have another one on ulixacaltamide. You previously indicated that the label may include alternative titration schedules. What is the status on this? And, are you currently running additional studies to support this? If the label doesn't include these schedules, how will you be educating and guiding prescribers upon launch? And then I have another follow-up.

Athena Chin: Hi, guys. This is Athena Chin on for Ritu. Thanks for taking the question. I have another one on ulixacaltamide. You previously indicated that the label may include alternative titration schedules. What is the status on this? And, are you currently running additional studies to support this? If the label doesn't include these schedules, how will you be educating and guiding prescribers upon launch? And then I have another follow-up.

Speaker #7: What is the status on this? And are you currently running additional studies to support this? If the label doesn't include these schedules, how will you be educating and guiding prescribers upon launch?

Speaker #7: And then I have another follow-up.

Speaker #6: Yeah. Thanks, Athena. So maybe I'll break it down, if I may. Your question is in two parts, right? So, with being—discussing since you asked about education—and surprisingly, I would say there's very little education needed here, with being presenting the data for advisory boards, for consultation meetings, to a number of key opinion leaders in the country, very top key opinion leaders.

Marcio Souza: Yeah. Thanks, Athena. So maybe I'll break it down, if I may, your questions in two parts, right? So we've been discussing since you asked about education, and surprisingly, I would say there's very little education needed here. We've been presenting the data for advisor boards, for consultation meetings, to a number of key opinion leaders in the country, very top key opinion leaders. And it is very clear that they see this is incredibly robust and very, very easy to deal with the potential tolerability for a subset of patients here that we know might have that. Now, going back to the matter of the label, as we previously discussed. We propose not only submitted proposed label to the FDA, not only the standards titration that was done in the clinical study, right?

Speaker #6: And it's very clear that they see this incredibly robust and very, very easy to deal with the potential tolerability for a subset of patients here that we know might have that.

Speaker #6: Now, going back to the matter of the label, as we previously discussed, we propose not only submitting the proposed label to the FDA, not only the standards titration that was done in the clinical study, right?

Speaker #6: So seven days 20 milligrams, seven days at 40, and then seven days at stay stable dose of 60. But also an alternative that we discussed with the FDA.

Marcio Souza: So 7 days, 20mg, 7 days at 40, and then 7 days at, at a stable dose of 60. But also an alternative that we discussed with the FDA. I think as we move forward, as you continue to engage with the agents here, that it's now their view has to prevail in terms of what's the final label is going to be. So it would be pretentious of us to say what's going to happen there. But it came on the heels of discussions with them and alignment. The agents was incredibly clear with us that they did not expect us to conduct clinical studies pre-approval on this regard. So as we always respect the opinion of the FDA and the guidance they give, of course, we're not doing.

Speaker #6: I think as we move forward, as you continue to engage with the agents here, it's now their view has to prevail in terms of what's the final label is going to be.

Speaker #6: So it would be potential to us to say what's going to happen there. But it came in the heels of discussions with them and alignments.

Speaker #6: The agents were incredibly clear with us that they did not expect us to conduct clinical studies pre-approval on this regard. So as we always respect the opinion of the FDA and the guidance they give, of course, we're not doing I believe and now that's my interpretation.

Marcio Souza: I believe, and now that's my interpretation, that is because this is really not a safety issue, right? This- that is, some tolerability that happens on a subset of patients. It's very quick, it resolves very quickly, and the efficacy, most importantly, is very strong. So when you put from a benefit-risk perspective, that is both our interest, the prescriber's interest, and the agent's mandates, that is all maintained quite nicely. But we're going to see how this, this progress, during the review, and we're very enthusiastic about the ability to have serving not only, the 70% or so of patients that stay and do really well, but, hopefully, 100% of the patients that, try this drug.

Speaker #6: That is because this is really not a safety issue, right? That is some tolerability that happens on a subset of patients. It's very quick.

Speaker #6: It resolves very quickly. And the efficacy, most importantly, is very strong. So when you put, from a benefit-risk perspective—that is both our interest, the prescriber's interest, and the agency's mandates—that is all maintained quite nicely.

Speaker #6: We're going to see how this progresses during the review. And we're very enthusiastic about the ability to have serving not only the 70% or so of patients that stay and do really well, but hopefully 100% of the patients that try this drug.

Speaker #7: Got it. And as to the commercial prep for both Relutrogene and Elixir, how much capital allocation should we be thinking about between the two programs?

[Analyst] (TD Cowen): Got it. And as to the commercial prep for both relutrigine and ulixacaltamide, how much capital allocation should we be thinking about between the two programs?

Athena Chin: Got it. And as to the commercial prep for both relutrigine and ulixacaltamide, how much capital allocation should we be thinking about between the two programs?

Tim Kelly: You know, I think in terms of allocation, you can imagine that with ulixacaltamide being a much broader market, we will be probably, you know, putting more of the allocation there. I think we're looking at, as I said, the disease awareness campaign, probably a bigger field for us as we get into that part of the, the work as well. The inventory build is going to be a bit bigger. So we want to be sure, go back to the old line, you only get one chance to launch a drug, and we want to be sure we're investing appropriately for a great launch. I think with the relutrigine, when we look at that market, particularly focused initially on the SCN2A and SCN8A population, it is a bit more focused. So, there's a lot of disease awareness for us to be doing there.

Speaker #6: I think in terms of allocation, you can imagine that with Elixir being a much broader market, we will be probably putting more of the allocation there.

Speaker #6: I think we're looking at, as I said, the disease awareness campaign, probably a bigger field for us as we get into that part of the work as well, the inventory build is going to be a bit bigger.

Speaker #6: So we want to be sure that I go back to the old line, you only get one chance to launch a drug. And we want to be sure we're investing appropriately for a great launch.

Speaker #6: I think with the Relutrogene, when we look at that market, particularly focused initially on the 2A and 8A population, it is a bit more focused.

Speaker #6: So there's a lot of disease awareness for us to be doing there. It's a more focused effort, though, with those physicians. But we want to be laying the groundwork for the indication expansion that we hope will come in 2027 with the Emerald study.

Tim Kelly: It's a more focused effort, though, with those physicians, but we want to be laying the groundwork for the indication expansion that we hope will come in 2027, with the EMERALD study. So it's a bit of a strategic move in how we will do the commercial prep for relutrigine also.

Speaker #6: So it's a bit of a strategic move on how we will do the commercial prep for Relutrogene also.

Speaker #7: Got it. Thank you. I'll hop back in the queue.

[Analyst] (TD Cowen): Got it. Thank you. I'll hop back in the queue.

Athena Chin: Got it. Thank you. I'll hop back in the queue.

Speaker #4: Thank you.

Marcio Souza: Thank you.

Speaker #6: Thanks, Athena.

Tim Kelly: Thanks, Tiana.

Operator: Our next question comes from the line of Yatin Suneja with Guggenheim. Your line is now open.

Speaker #4: Our next question comes from the line of Yatnam Simea with Guggenheim. Your line is now open.

Yatin Suneja: Hey, guys. Thank you for taking my questions. I have two questions. With regard to the POWER3 study, can you just articulate to us how will that study help you move towards the frontline setting or to, in FOS? So that's one. And then the second question is around the review timeline. So, I think, Marcio, it'll be good if you can address the review timeline for both the NDAs. So we do get questions from investors in terms of priority review or not. So it will be good to sort of address it today. Thank you.

Speaker #8: Hey, guys. Thank you for taking my questions. I have two questions. With regard to the Power-3 study, can you just articulate to us how will that study help you move towards the frontline setting or to an FOS?

Speaker #8: So that's one. And then the second question is around the review timeline. So we at MRC will be good if you can address the review timeline for both the NDAs.

Speaker #8: We do get questions from investors in terms of priority review or not, so we'll be good to sort of address it today. Thank you.

Speaker #6: Yeah, thanks. Thanks, Yatnam. So, starting with Power-3, right? So just a reminder on what we are trying to accomplish here. So, Power-1 is the first study here towards registration for bometogene, reading out—as we just narrowed here in Q2. The study enrolls a fair bit more than the original 230 patients that were planned.

Marcio Souza: Yeah. Thanks. Thanks, Yatin. The, so starting with POWER3, right? So just, just a reminder on what we are trying to accomplish here. So POWER1, as the, like, first, study here for, towards registration for vormatrigine, reading out as we just narrowed here in Q2. The study enrolls a fair bit more than the original 230 patients that were planned. So very, very happy with how enthusiastic the investigators were on enrolling patients on this study, particularly like when you consider comparatively how well this study enrolls, right? POWER2, as we're enrolling quite nicely right now as well, would be the second registrational. But when you look into the markets, and it's something quite interesting, what this goes on in focal onset seizures.

Speaker #6: So very, very happy with how enthusiastic the investigators were on enrolling patients on this study, particularly when you consider comparatively how well this is studying roles, right?

Speaker #6: Power-2, as we're enrolling quite nicely right now as well, would be the second registrational. But when you look into the markets, and it's something quite interesting, what this goes on and focus on fat seizures.

Speaker #6: You do have I would say a part of this market that is the more refractory patients or going to even argue hyper-refractory being super treated, multiple ASMs, really struggling for years and years, possibly decades, here.

Marcio Souza: You do have, I would say, a part of this market that is the more refractory patients or going to even argue hyperrefractory, being super treated, multiple ASMs, really struggling for years and years, possibly decades, here. And that's where most of drug developments and most of what the level four epilepsy centers, the key opinion leaders in epilepsy have been focusing. But when you go to the rest of the market, and it's probably the physicians would call the rest because it's the majority of the markets. [The rest] are the patients that are 70, 80% of the patients with focal onset seizures; they still can't thrive, they still can't carry on with their lives. There's all sorts of restrictions because they're having, like, breakthrough seizures, from time to time, and they're really not doing well. That market has stayed untapped until now.

Speaker #6: And that's where most of drug developments and most of what the level four epilepsy centers the key opinion leaders in epilepsy have been focusing.

Speaker #6: But when you go to the rest of the market, and it's probably a little facetious to call rest because it's the majority of the markets, right?

Speaker #6: The patients that are 70, 80 percent of the patients with focal onset seizures, they still can't thrive. They still can't carry on with their lives.

Speaker #6: There's all sorts of restrictions because they're re having breakthrough seizures from time to time, and they really are not doing well. That market has stayed untapped until now.

Marcio Souza: So speaking with those physicians and people who treat significant number of patients, right, which it is a different subset of the ones we're looking. The needs there is for a drug that they can trust and understand how to remove the treatments, so they can be confident, and they are very enthusiastic about vormatrigine for that matter. So, we've been in consultation with them for finalizing this design. We're getting this off the ground very soon. We thought today was the day to reinforce and celebrate submitting two NDAs, so we're gonna be talking about that more in the near future. But what it does to the drug, while not required for registration, right? This is not a requirement, as is the ever-evolving requirement for registration in the United States, as we are seeing this week. So we're very excited about what's to come.

Speaker #6: So, speaking with those physicians and people who treat a significant number of patients, right—which is a different subset from the ones we're looking at—the need there is for a drug that they can trust and understand how to remove the treatments so they can be confident, and they are very enthusiastic about bometrogene for that matter.

Speaker #6: So we've been in consultation with them for finalizing this design. We're getting this off the ground very soon. We thought today was the day to reinforce and celebrate submitting to NDAs.

Speaker #6: So we're going to be talking about that more in the near future. But what it does to the drug while not required for registration, right?

Speaker #6: This is not a requirement. As is the ever-evolving requirement for registration in the United States, as we are seeing this week, so very excited about what's to come.

Speaker #6: But it is something we can see as moving to first-line potentially this drug in the future, which is from a serving patients is what we all should be aiming for.

Marcio Souza: But it is something we can see as moving to first line, potentially, this drug in the future, which is from a serving patients, is what we all should be aiming for. We're just in a very privileged position that bumetanide might be the drug that allows patients and physicians to do that. On your second question about the review timelines, you can imagine that the decisions we have to make are multiple folds, right? So one, obviously, the timing of the submissions is now in the past. The second is the entire understanding and relationship and workload and so forth with the agency. Good reminder here that while DN one or Division of Neurology one and two are two different divisions, there's a lot of shared resource.

Speaker #6: We're just in a very privileged position that bometrogene might be the drug that allows patients and physicians to do that. On your second question about the review timelines, you can imagine that the decisions you have to make are multiple faults, right?

Speaker #6: So one, obviously, the timing of the submission is now in the past. The second is the entire understanding and relationship and workload and so forth with the agency.

Speaker #6: Good reminder here that while the N1 or Division of Neurology 1 and 2 are two different divisions, there's a lot of shared resource. We have two NDAs at the same time with them.

Marcio Souza: We're having two NDAs at the same time with them. Very obviously, relutrigine is easier, I'm gonna say, not because it's easier from a clinical or anything like that, it's just much, much less data, by single study, rare indication, and that by itself, from a workload perspective, is smaller. So we decided to request a priority review for that application. But we decided not to request for ulixacaltamide for multiple reasons, right? Those that I just mentioned, but there's a broader business reason, about the time of the launch and the maximization of the revenues over time for this drug, particularly around PIC, particularly around payer and overall dynamics of discounting, and so on, that happens year later in the launch.

Speaker #6: Very obviously, Relutrogene is easier. I'm going to say not because it's easier from a clinical or anything like that—it's just much, much less data, right?

Speaker #6: Single study, rare indication—and that by itself, from a workload perspective, is smaller. So we decided to request priority review for that application. But we decided not to request for Alexa CultMite for multiple reasons, right?

Speaker #6: Those that I just mentioned, but there's a broader business reason about the time of the launch and the maximization of the revenues over time for this drug, particularly around PIC, particularly around payer and overall dynamics of discounting and so on that happens year later in the launch.

Marcio Souza: So on a drug that can be and will be as big as ulixacaltamide, we can't, like, pick up the dollars and forget about the millions on this one. So I think we need to be, and we were very focused strategically on the overall value here.

Speaker #6: So on a drug that can be and will be as big as Alexa CultMite, we can't pick up the dollars and forget about the millions.

Speaker #6: On this one. So I think we need to be and we were very focused strategically on the overall value here.

[Analyst] (TD Cowen): Very good. Thank you so much.

Athena Chin: Very good. Thank you so much.

Speaker #8: Very good. Thank you so much.

Speaker #6: Of course.

Marcio Souza: Of course.

Operator: Thank you. Our next question comes from the line of Joon Lee with Truist Securities. Your line is now open.

Speaker #9: Thank you. Our next question comes from the line of June Lee with Truist Securities. Your line is now open.

Speaker #10: Hey, guys. Congrats on all the progress, and thanks for taking our questions. I just want to clarify the response from the prior question that you just answered.

Joon Lee: Hey, guys, congrats on all the progress, and thanks for taking our questions. Just wanted to clarify the response from the prior question that you just answered. So you mentioned business reasons for not asking for priority review for ulixacaltamide in ET. Just to clarify, is that because asking for standard review as opposed to priority review would result in almost a year delay in being forced to negotiate under IRA? That's question number one. Question number two, you know, looking forward to your presentations at AAN, can we expect any long-term follow-up data? The reason I ask is long-term efficacy came up as a key point for payer KOs regarding reauthorization of ulixacaltamide in ET. And the last question is, you know, in the past, you've telegraphed around $50,000 list price for ulixacaltamide.

Speaker #10: So you mentioned business reasons for not asking for priority review for Alexa CultMite and ET. Just to clarify, is that because asking for standard review as opposed to priority review would result in almost a year delay in being forced to negotiate under IRA?

Speaker #10: That's question number one. Question number two, looking forward to your presentations at AAN, can we expect any long-term follow-up data? The reason I ask is long-term efficacy came up as a key point for our payer KOLs regarding reauthorization of Alexa and ET.

Speaker #10: And the last question is, in the past, you telegraphed around $50,000 list price for Alexa CultMite. Is that still the case? And can you help us understand your thought process behind the pricing strategy?

Joon Lee: Is that still the case? And can you help us understand your thought process behind the pricing strategy? Thank you.

Speaker #10: Thank you. Yeah. June, I think we are you're on the right direction there, right, in terms of when you're looking at and we're forecasting this drug.

Marcio Souza: Yeah. June, I think we are—you're in the right direction there, right? In terms of what we are looking at and we're forecasting this drug. Of course, there are multiple dynamics, and you just named some of them, right? Like what payers and reauthorization and like potential step edits, and you name it. But, the Inflation Reduction Act and the dynamics of the act right now is important consideration as well as a very important consideration. This is a heavily, Medicare Part D, population, so we want to make sure we're both responsible on how we're launching, we're also maximizing and giving the proper value for the drug. And that includes looking to the life cycle of evolution of the current iteration of the act, when it impacts, when it kicks in. I believe that's where you're going there.

Speaker #10: Of course, there are multiple dynamics and you just named some of them, right? Like what payers and reauthorization and potential step edits, and you name it.

Speaker #10: But the inflation reduction act and the dynamics of the acts right now are important considerations as well as a very important consideration. This is a heavily Medicare Part D population so we want to make sure we're both responsible on how we're launching.

Speaker #10: We're also maximizing and giving the proper value for the drug. And that includes looking to the life cycle of evolution of the current iteration of the acts when it impacts when it kicks in.

Speaker #10: I believe that's what you're going there. That is a pretty big difference in value, depending on when that negotiation happens. And it was a key consideration.

Marcio Souza: There is a pretty big difference in value, depending on when that negotiation happens. It was a key consideration on our filing strategy. The second, on the data to be presented, I think multiple follow, yes, we're always, like, gonna be presenting more and more data to reinforce the short-term and long-term value of ulixacaltamide in essential tremor. One point we believe there is still room to explore here is really how strong the data is. I know you recently spoke to some payers and, like, payer groups, and they... If I understand correctly, they agree with how strong this data is and how high the potential for this drug is.

Speaker #10: On our filing strategy. The second on the data to be presented I think multiple fault, yes, we're always going to be presenting more and more data to reinforce the short-term and long-term value of Alexa CultMite in essential tremor.

Speaker #10: One point we believe there's still room to explore here is really how strong the data is. I know you recently spoke to some payers and payer groups and if I understand correctly, they agree with how strong this data is and how high the potential for this drug is.

Speaker #10: But it's what is the understanding is not clear yet in the markets because we haven't put this data out there. It's just how deep the effect is on a very large proportion of patients.

Marcio Souza: But what is the understanding is not clear yet in the market because we haven't put this data out there, is just how deep the effect is on a very large proportion of patients. And when you look into drugs, it's not one size fits all. So we want to make sure that gets reinforced, it gets holistically reviewed. While we're very excited about having our principal investigators presenting this data to their peers, they've been thrilled with the execution, with the results, and I think now is the time to let them take the stage, and present this data as key opinion leaders in the field. So stay tuned. I know we're trying to cover a lot in this call, but stay tuned for, for April. I'm sure we're gonna be pleased.

Speaker #10: And when you're looking to drugs, it's not one size fits all. So we want to make sure that gets reinforced, that gets holistically reviewed, while we're very excited about having our principal investigators presenting this data to their peers.

Speaker #10: They being thrilled with the execution, with the results, and I think now is the time to let them take the stage. And present this data as key opinion leaders in the field.

Speaker #10: So stay tuned. I know we're trying to cover a lot in this call, but stay tuned for April or I'm sure we're going to be pleased.

Speaker #8: Thank you so much, guys. Looking forward.

David Hoang: ... Thank you so much, guys. Looking forward.

David Hoang: Thank you so much, guys. Looking forward.

Speaker #9: Thank you.

Operator: Thank you.

Speaker #10: All right. Thank you.

Marcio Souza: Thank you.

Speaker #9: Our next question comes from the line of Andrew Say with Jefferies. Your line is now open.

Operator: Our next question comes from the line of Andrew Sey with Jefferies. Your line is now open.

Speaker #11: Hey, good morning. Congrats on all the progress. Appreciate the updates. Maybe shifting to Relutrogene, actually. You're pursuing this broader label, the Emerald Study, for all DEE.

Andrew Tsai: Hey, good morning. Congrats on all the progress. Appreciate the updates. Maybe, actually, shifting to relutrigine. You're pursuing this broader label, the EMERALD study, for all DEE. So how many different DEE patients in the phase 3 does the FDA want to give you a broad label, and how many different DEEs have you enrolled so far? And secondly, for that study, as we think about what you want to see, is it fair that you might be expecting efficacy to be similar or even stronger than what you saw in SCN2A and SCN8A? And maybe explain why. Thanks.

Speaker #11: So how many different DEE patients in the phase three does the FDA want to give you a broad label? And how many different DEEs have you enrolled so far?

Speaker #11: And secondly, for that study, as we think about what you want to see, is it fair that you might be expecting efficacy to be similar or even stronger than what you saw in SCN2AAA and maybe explain why?

Speaker #11: Thanks.

Speaker #10: Yeah. Thanks. Thanks, Andrew. So if you're looking to Emerald right now, right, let me separate a couple of things there. So one, as I mentioned in the remarks and then Tim mentioned as well in one of the answers, the goal here at this point in time is to get that SNDA by next year.

Marcio Souza: Yeah. Thanks. Thanks, Andrew. So if you look into EMERALD right now, right, let me separate a couple of things there. So one, as I mentioned in the remarks, and then Tim mentioned as well in one of the, the answers, the, the goal here, at this point in time, is to get that sNDA by next year. And it should give you the confidence on what's happening on the study, right now. Really incredible interest, incredible enthusiasm, and engagement from the physicians that are referring to the sites or participating in sites, in this study. We took a very basic approach, right? If you go and you look into the most recent definition of these, like Dr. Scheffer's recently published around this, and really going back to the basics, right?

Speaker #10: And it should give you the confidence on what's happening on the study. Right now, really incredible interests, incredible enthusiasm, and engagement from the physician that are referring to the sites or participating in the sites.

Speaker #10: And this study. We took a very basic approach, right? If you go and you look into the most recent definition of DEEs, Dr. Schaffer's recently published around this, and really going back to the basics, right?

Speaker #10: What is a developmental epileptic encephalopathy? What are the drivers? What should we be treated? And Relutrogen sits on that junction of really helping the broadest population at least hypothetically right now since we're going to have to see the results in DEE.

Marcio Souza: What is a developmental epileptic encephalopathy? What are the drivers? Like, why should we be treated? And relutrigine sits, like, on that junction of really helping the broadest population, at least hypothetically right now, since we're going to have to see the results in DEE. So we took the approach of phenotypically defined versus genotypically defined these patients for this study. What I can tell you right now, without saying too much, is that it is a very diverse group of patients that we have on the study. Both enrolled studies and patients in screening, they are very diverse, not completely unexpected or unexpected at all.

Speaker #10: So we took the approach of phenotypically define versus genotypically define these patients for this study. What I can tell you right now without saying too much is that it is a very diverse group of patients.

Speaker #10: That we have on this study. Both enrolled studies and patients in screening that are very diverse. Not completely unexpected or unexpected at all. And when we position and we discuss this study with the agency and I can never speak on their behalf, but I tell you our interpretation, is that the idea here is to treat the disease is not to treat the cause of the disease.

Marcio Souza: When we position and we discuss this study with the agency, and I can never speak on their behalf, but I tell you, our interpretation is that the idea here is to treat the disease, is not to treat the cause of the disease. Would be pretentious to any of us to try to do that. And the understanding is that you cannot have a seizure without participation of sodium channel in the neurons, and therefore, this is like omnipresence type of mechanism that we can use. So that is the definition right now. There is no subgroups, or there are no quotas for different, if I may, for different etiologies. So we're really looking into, like, an overall effect.

Speaker #10: We'll be pretentious to any of us to try to do that. And the understanding is that you cannot have a seizure without participation of sudden channel in the neurons.

Speaker #10: And therefore, this is omnipresent type of mechanism that we can use. So that is the definition right now that is no subgroups or there are no quotas for different if I may, for different etiologies.

Speaker #10: So we're really looking into an overall effect. When you go back to the last part of your question, and what you expect here, we need to go back to translation.

Marcio Souza: When you go back to the last part of your question and what to expect here, we need to go back to translation. We need to go back to the preclinical data since we do not have the clinical data yet. And when you go back there, and we look into all different models that we tested, all the fundamental electrophysiology and basic biology of the channel deposition, the physical density of the channels in a critical juncture in the neurons, what we see is like quite overwhelming preclinical efficacy. So when we had that before on SCN2A, on the different models with SCN8A, on the allergenic model, I think the way we're looking into that is, like, those are very good translational models.

Speaker #10: We need to go back to the preclinical data. Since we do not have the clinical data yet. And when you go back there, and we look into all different models that we tested, all the fundamental electrophysiology and basic biology of the channel deposition, the physical density of the channels in a critical juncture in the neurons, what we see is quite overwhelming preclinical efficacy.

Speaker #10: So when we had that before, on SCN2A, on the different models, with SCN8A on the allogeneic model, I think the way we're looking into that is those are very good translational models.

Speaker #10: Now we have clinical data on those indications that translated well, so we expect to translate well as well. I think it would be a little bit too early to guide on how well that translation would be.

Marcio Souza: Now we have clinical data on those indications that translated well, so we expect to translate well as well. I think it would be a little bit too early to guide on how well the translation would be, but you've got to remember, from an overall DEE perspective, there is basically nothing for these patients as well. So while I'm incredibly excited about showing results, maybe the same may be better than we're seeing on SCN2A and SCN8A, it's absolutely not needed to deliver a very fundamental change on the way these patients are treated right now. But as I said in the past, we're going to see this soon enough. So we're just going to keep our heads down, executing on EMERALD, and soon enough, we're going to be discussing, hopefully significant benefit for patients on that population.

Speaker #10: But you got to remember from an overall DEE perspective, that is basically nothing for this patient as well. So while I'm incredibly excited about showing results, maybe the same, maybe better than what we're seeing on 2A and 8A, it's absolutely not needed to deliver a very fundamental change on the way these patients are treated right now.

Speaker #10: But as I said in the past, we're going to see this soon enough. So we're just going to keep our heads down executing on Emeralds.

Speaker #10: And soon enough, we're going to be discussing, hopefully, significant benefit for patients in that population.

Speaker #11: Makes sense. Thank you.

Andrew Tsai: Makes sense. Thank you.

Speaker #10: You bet.

Marcio Souza: You bet.

Speaker #9: Our next question comes from the line of Douglas Sow with HC Wainwright. Your line is now open. Douglas, your line is open. Please check your mute button.

Operator: Our next question comes from the line of Douglas Tsao with HC Wainwright. Your line is now open. Douglas, your line is open. Please check your mute button.

Speaker #10: Oh, sorry about that. I was on mute. Marcio, maybe it's a little bit of a follow-up on that last question. In terms of Relutrogene, and then I have a follow-up from Atrogene.

Douglas Tsao: Oh, sorry about that. I was on mute. Marcio, maybe it's a little bit of a follow-up on that last question in terms of relutrigine, and then I have a follow-up on vormatrigine. But just sort of when you anticipate utilization, do you see sort of utility across the. It sounds like you see utility across the DEE, the entire DEE spectrum, and even in indications where there are sort of ASOs or sort of more targeted therapies being developed, and arguably sort of relutrigine will sort of become a workhorse used, you know, regardless of what other therapies may also be deployed for particular patient populations. Thank you.

Speaker #10: But just sort of when you anticipate utilization, do you see sort of utility across the it sounds like you see utility across the entire D spectrum.

Speaker #10: And even in indications where there are sort of ASOs or sort of more targeted therapies being developed, and arguably sort of Relutrogene will sort of become a workhorse used regardless of what other therapies may also be deployed for a particular patient population.

Speaker #10: Thank you. Yeah. No, that's a very good question though. The workhorse probably I wouldn't use that term, but I'm glad you did. Because I think that's one way to look into a drug like in a toolbox like Relutrogene.

Marcio Souza: ... Yeah, no, that's a very good question, though. Yeah, the workhorse, probably I wouldn't use that term, but I'm glad you did, because I think that's one way to look into a drug like, in a toolbox, like relutrigine, where physicians would have that available that they don't have right now, right? They have to ask too many questions, too many tries. Like, unfortunately, a lot of those patients don't have that time to keep trying and optimizing. And quite importantly, like there's what? 20, 25 drugs that are normally tried in this population. Virtually none of them have been tried, and officially, like with randomized studies, properly developed in pediatric populations or in adolescents or in early adults here.

Speaker #10: Where physicians would have that available that they don't have right now. They have to ask too many questions too many tries. Unfortunately, a lot of those patients don't have that time to keep trying and optimizing and quite importantly, there's what, 20, 25 drugs that are normally tried in this population.

Speaker #10: Virtually none of them have been tried and officially with randomized studies properly developed in pediatric populations or in adolescents or early adults here. So we never talk about that other side of label use that we really don't know what you're doing.

Marcio Souza: So we never talk about that other side of, of label use, that we really don't know what you're doing, on those populations. So what we hear a lot from physicians here globally is that certainty of the drug that's being rationally developed for this indication. So there's a lot of enthusiasm there. Now, to think that this is a silver bullet, would be, like, completely absurd. There is not such a thing as a silver bullet in medicine. I think we all wish there was, but there isn't. So we do see this as a kind of an overall background therapy for some patients. Ideally, would be monotherapy. For other patients, they're gonna continue in other drugs. You mentioned ASO, particularly. I think ASOs are getting consolidated as kind of the second workhorse.

Speaker #10: On those populations. So what we hear a lot from physicians here globally is that certainty of the drug that's being rationally developed for this indication.

Speaker #10: So there's a lot of enthusiasm there now. To think that this is a silver bullet would be completely absurd. That is not such a thing as a silver bullet in medicine.

Speaker #10: I think we all wish there was. But there isn't. So we do see this as a kind of an overall background therapy for some patients ideally would be monotherapy.

Speaker #10: For other patients, they're going to continue in other drugs. You mentioned ASOs particularly. I think ASOs are getting consolidated as kind of the second workhorse.

Speaker #10: I think we're finally beyond some of the dreams we had about other modalities on gene therapy. And really understanding that that's a very, very good mechanism.

Marcio Souza: I think we're finally beyond some of the dreams we had about other modalities, on gene therapy, and really understanding that that's a very, very good mechanism. So combinations between ASOs, for example, and others, and relutrigine, we expect to be the norm, right? We look forward for the moments where these discussions are about how the use is happening versus all these hypotheticals, because these patients don't have a lot of time, and really excited about helping them.

Speaker #10: So combinations between ASOs, for example, and others and Relutrogene we expect to be the norm. We look forward for the moments where this discussions are about how they use is happening.

Speaker #10: Versus all these hypotheticals, because these patients don't have a lot of time, and I'm really excited about helping them. Okay. Great, Marcio. That's really helpful.

Douglas Tsao: Okay. Great, Marcio. That's really helpful. And then just on vormatrigine, I'm just curious, in the RADIANT study, as patients go sort of past that, the initial point and we're in the open label extension, I'm just curious, have you gotten data or seen data of patients who are withdrawing some of their background meds, sort of a little bit of a preview or look, if you will, into the, the POWER3 study? And in particular, patients who are maybe able to pull off, you know, sort of some of the more problematic, you know, sort of efficacious, but perhaps more sort of less tolerable drugs like cenobamate or carbamazepine, et cetera. Thank you.

Speaker #10: And then just for Atrogene, I'm just curious. In the radiant study, as patients go sort of past that, the initial point and we're in the open label extension, I'm just curious.

Speaker #10: Have you gotten data or seen data of patients who are withdrawing some of their background meds sort of a little bit of a preview or look if you will into the power three study?

Speaker #10: And in particular, patients who are maybe able to pull off sort of some of the more problematic sort of efficacious, but perhaps more sort of less tolerable drugs like Sinovamide or Carbamazepine, etc.

Speaker #10: Thank you. Yeah. We're seeing across the boards reduction, elimination, removal of background therapies as patients continue to have experience on the open label. With Vermatrogene, physicians are very excited about that possibility, and I would say patients are more excited about that.

Marcio Souza: Yeah. We're seeing across the board reduction, elimination, removal of background therapies as patients continue to have experience on the open label with vormatrigine. Physicians are very excited about that possibility, and I would say patients are more excited about that. As you can imagine, of course, efficacy is king here, right? But the queen is safety for these patients, and it is very hard for them to daily operate as humans when they are, like, on all those medications. So it's always a very important. It's not only that, right? I think one of the drugs you just mentioned has just been, like, put on a new warning for drug-induced liver injury.

Speaker #10: As you can imagine, of course, efficacy is king here. But the queen is safety. For these patients and it is very hard for them to daily operate as humans when they are on all those medications.

Speaker #10: So it's always a very important it's not only that, right? I think one of the drugs you just mentioned has just been put on a new warning for drug-induced liver injury.

Marcio Souza: So you got to think about the long-term impacts of these drugs, and being vormatrigine, at least so far, like, so clean, it's quite important for these patients as well. So we're seeing more and more enthusiasm. Of course, every time you remove a drug, the first question you need to ask is: What happens to the primary measure? What happens to seizures? And I'm very happy to preliminarily report that we're seeing exactly what we were expecting to, right? It's maintenance of seizure control while really not being necessary to use. I believe you asked this from a clinical perspective, but I'm gonna jump into here into the commercial perspective.

Speaker #10: So you got to think about the long-term impacts of this drugs. And being Vermatrogene at least so far so clean it's quite important for these patients as well.

Speaker #10: So we're seeing more and more enthusiasm. Of course, every time you remove a drug, the first question you need to ask is, what happens to the primary measure?

Speaker #10: What happens to seizures? And I'm very happy to preliminarily report that we're seeing exactly what we were expecting to, right? Maintenance of seizure control.

Speaker #10: While it’s really not necessary to use, what I believe you asked is from a clinical perspective. But I’m going to jump in here from a commercial perspective.

Speaker #10: As you believe the value proposition of by the very first time on a drug that you can sequentially reduce the use of other drugs is very different than a drug that you just throw on the top, get used for a little bit, and maybe removes.

Marcio Souza: As you believe, the value proposition of, by the very first time on a drug, that you can sequentially reduce the use of other drugs, is very different than a drug that you just throw on the top, get used for a little bit, and maybe removes. So very excited. I think we're gonna have more data and more discussions to talk about that, as when we have the POWER1 results as well and, and giving an overall program updates.

Speaker #10: So very excited. I think we're going to have more data and more discussions to talk about that. As when we have the power one results as well and giving an overall program updates.

Speaker #10: Okay. Great. That's super helpful and congrats with the progress. Thank you.

Douglas Tsao: Okay, great. That's super helpful, and congrats on the progress.

Marcio Souza: Thank you.

Speaker #1: Our next question comes from the line of François Brisbos with LifeSci Capital. Your line is now open.

Operator: Our next question comes from the line of Francois Brisebois with Life Sci Capital. Your line is now open.

Speaker #11: Hi. Thanks for taking the questions and congrats on all the progress. It's quite a 2025 for you guys. So maybe on ELSA nursing, there's a lot to touch on, but I don't think much has been touched on this one.

François Brisebois: Hi, thanks for taking the questions, and congrats on all the progress. It's quite a 2025 for you guys. So maybe on elsunersen, there's a lot to touch on, but I don't think much has been touched on this one. Can you help us? You know, EMBRAVE data is coming soon, so just maybe set expectations there a little bit. And I think there's so much going on with the company that maybe help us understand why it's so important that the, you know, the update on just having a single arm comparison for EMBRAVE3 and what that means.

Speaker #11: Can you help us embrace data is coming soon? So just maybe set expectations there a little bit. And I think there's so much going on with the company that maybe help us understand why it's so important that the update on just having a single-arm comparison for Embrace 3 and what that means.

Speaker #10: Yeah. So thanks for that, Frank. So ELSA as we call ELSA nursing is definitely sometimes gets the backseat on this question. So I appreciate what we see in a sense, right, what linking your questions to those questions.

Marcio Souza: Yeah. So, thanks for that, Frankie. So elsunersen, or as we call it, like, elsunersen, it's like, it definitely sometimes gets the backseat on these questions, so I appreciate. We see in a sense, right, linking your questions to all questions, this is like an ecosystem. All these drugs are all going to be used, they're going to be different cases, use one more and the other less or combinations, and you name it, in the future. So we have this cohort right now, 9 patients, 3 to 1, randomized, to sham or drug. Our intention there was to continue to understand the safety, the efficacy, the PK, of this drug.

Speaker #10: This is like an ecosystem or these drugs are all going to be used they're going to be different case on use one more and the other less or combinations and you name it in the future.

Speaker #10: So we have this cohort right now, nine patients, three, two, one, randomized to sham or drug. Our intention there was to continue to understand the safety, the efficacy, the we're very excited because every time you have control data, independently or even open label data, independently of the number of patients is yet another opportunity for us to understand the drug impacts.

Marcio Souza: But we're very excited, because every time you have control data independently or even open label data, independently of the number of patients, is yet another opportunity for us to understand the drug impacts. We know, the study went really well, with these patients, like did really well from a safety perspective. Since then, we can monitor, like, generally, which is not a given, right, in any given disease. And we believe that it can be quite informative. The FDA left the door open for us on the discussions we had about the overall value of the datasets on the overall program, right? So we, we wanted to make sure we are, we're very respectful, and we were mindful of that, but it can have a very high value depending on the results here, in the next few months.

Speaker #10: We know they study went really well with these patients like did really well from a safety perspective since then we can monitor generally, which is not a given, right, in any given disease.

Speaker #10: And we believe that it can be quite informative—the FDA left the door open for us on the discussions we had about the overall value of the data sets on the overall program, right?

Speaker #10: So we wanted to make sure we're very respectful and we're mindful of that, but it can have a very high value depending on the results.

Speaker #10: Here in the next few months. Now, when you look into that, we're very pleased, and it's likely a surprise that the agents were really pushing us to actually get Embrace 3 to be controlled on baseline. I think they're definitely putting their money where their mouth is in terms of accelerating drug development for drugs with a high potential translatability, plausible mechanism, and this drug fits right in all of that.

Marcio Souza: Now, when you look into the-- we're very pleased and likely surprised that the agency was really pushing us to actually get EMBRAVE3 to be controlled on baseline. I think they're definitely putting their money where their mouth is in terms of accelerating drug development for drugs with a high potential translatability, plausible mechanism, and this drug fits right in all of that. We did switch the study globally to a single arm with the patients randomizing-- well, I guess not randomizing, now they're dosing on the study. And it's been like a great experience with all the PIs and all the patients globally.

Speaker #10: We did switch the study globally to a single arm within patients randomized—well, I guess not randomizing; now they're dosing on the study. It's been a great experience with all the PIs and all the patients globally.

Speaker #10: So a little bit longer on the timelines, not really long on biotech years, but long for us since there's a lot going on. But we do expect to be done with this study this year as well.

Marcio Souza: So a little bit longer on the timelines, not really long on biotech years, but long for us since there's a lot going on. But we do expect to be done with this study this year as well, which would potentially get another, yet another NDA, in the near future. Very different positioning, as you can imagine, commercially, very complementary to the relutrigine efforts. They are doing the same prescriber population, overall same patient population, so you can see how synergistic this can be on the overall life cycle of the company.

Speaker #10: Which would potentially get another yet another NDA in the near future. Very different positioning as you can imagine commercially very complementary to the Rilutrogen efforts they were doing same prescriber population overall same patient population.

Speaker #10: So you can see how synergistic this can be on the overall life cycle of the company. No, that's very helpful. And then on you looked at calcimide I don't think you mentioned anything about XUS efforts.

François Brisebois: No, that's, that's very helpful. And then on ulixacaltamide, I don't think you mentioned anything about ex-US efforts. I was just wondering, such a big market here, I assume ET is everywhere else. Any thoughts there that you can share? And then the launch, obviously, without priority review, this is maybe a little premature, but you've had so many trials and, you know, so many patients on this. I'm just wondering, in terms of line of sight, you know, in terms of a launch trajectory off the bat, do we know where these patients are? Or, you know, any color there would be helpful.

Speaker #10: I was just wondering such a big market here. I assume ET is everywhere else. Any thoughts there that you can share? And then the launch obviously without priority review this is maybe a little premature, but you've had so many trials and so many patients on this.

Speaker #10: I'm just wondering in terms of line of sight in terms of a launch trajectory off the bat. Do we know where these patients are or any color there would be helpful?

Speaker #10: Yeah. Yeah. Absolutely. So maybe the easiest part of the question here absolutely no. Where these patients are I think we have daily motivation as patients keep calling our IR line, keep sending us messages and keep reminding us to keep pushing that they're waiting it's quite motivating for me and for the rest of the team to keep moving there.

Marcio Souza: Yeah, yeah, absolutely. So, maybe the easiest part of the question, we absolutely know where these patients are. I think we have daily motivation, as patients keep calling our IR line, keep sending us messages, and keep reminding us to keep pushing, that they are waiting. It's quite motivating for me and for the rest of the team to keep moving there. And just like the millions of patients that we have mapped to prescribers in the US. That in a sense, I think it answers the second question or the first question that I'm answering second. While there is huge unmet need outside of the US, and we appreciate that, and we are very compassionate in relation to that, the focus of the company has to be in the US right now.

Speaker #10: And just like the millions of patients that we have mapped to prescribers in the U.S., that in a sense, I think, answers the second question or the first question that I'm answering second.

Speaker #10: While that is huge on that needle side of the US and we appreciate that and we are very compassionate in relation to that the focus of the company has to be in the US right now.

Marcio Souza: We were laser focused on making sure the highest possible quality NDA was submitted. Now we are laser focused that the highest possible quality launch is done for this. When looking to the magnitudes of this, this launch, I think you would be ill-conceived and intended for us to get distracted at this point in time with other geographies. So very good trajectory, very good number of patients, as you can imagine, an open label extension right now, which would expect it would transition right away to commercial. Other pools of patients that we believe are going to be right before, and then just the spontaneous demands that we are seeing piling up on top of our database already for the launch.

Speaker #10: We were laser focused on making sure the highest possible quality NDA was submitted. Now, we are laser focused on ensuring that the highest possible quality launch is done for this.

Speaker #10: And when looking to the magnitudes of this launch I think it would be you conceived and intended for us to get distracted at this point in time with other geographies.

Speaker #10: So very good trajectory. Very good number of patients as you can imagine on open label extension right now which would expect it would transition right away to commercial.

Speaker #10: Other pools of patients that we believe are going to be right before and then just the spontaneous demands that we are seeing piling up on top of our database already for the launch.

Speaker #10: So I don't want to get over our skis here but this is definitely trending towards a successful launch. Excellent. Thank you, Mr. Ferry.

Marcio Souza: I don't want to get over our skis here, but this is definitely trending towards a successful launch.

François Brisebois: Excellent. Thank you, Francois.

Operator: Thank you. Our next question comes from the line of Ami Fadia with Needham and Company. Your line is now open.

Speaker #1: Thank you. Our next question comes from the line of Amy Fadia with Needham and Company. Your line is now open.

Speaker #11: Good morning. Thanks for taking my question and congratulations on the submissions both the submissions this month. My question is on vometrazine and regarding how what you assumed for your peak revenue potential particularly regarding utilization in first line and if you could provide some color on how you see utilization in earlier lines of therapy impacting persistency of patients and duration of treatment and how will the power program help you build the clinical data that supports or provides some color on how long patients stay on treatment as they get treated with vometrazine in earlier lines of therapy?

Ami Fadia: Good morning. Thanks for taking my question, and congratulations on the submissions, both the submissions this month. My question is on vormatrigine and regarding what you assumed for your peak revenue potential, particularly regarding utilization in first line. And if you could provide some color on how you see utilization in earlier lines of therapy impacting persistency of patients and duration of treatment, and how will the POWER program, you know, help you build the clinical data that supports or provides some color on how long patients stay on treatment as they get treated with vormatrigine in early lines of therapy? Thank you.

Speaker #11: Thank you.

Speaker #10: No, thanks. Thanks, Amy. So, the retention we are seeing right now, as an early indicator of what you are asking, is incredibly high.

Marcio Souza: No, thanks. Thanks, Ami. The, so the retention we are seeing right now, right, as an early indicator of what you are asking is, it's incredibly high. And once we talk about POWER1 results, we're gonna be able to talk about that as well. Patients not only participate in these studies, but really staying on the long run. So that gives us an early flavor of how retention in overall commercial is going to be. And of course, they are staying on drug differently from other drugs and different from other trials because they are having benefits, and because they're having a safe experience with this drug. The way we currently forecast the movements between third line, second line, first line is actually very responsible, I would say.

Speaker #10: And once we talk about power one results we're going to be able to talk about that as well. Patients not only participating on the studies but really staying on the long run.

Speaker #10: So that gives us an early flavor of how retention and overall commercially is going to be. And of course, they are staying on drug.

Speaker #10: Differently from other drugs and different from other trials because they are having a benefits and because they're having a safe experience with this drug.

Speaker #10: The way we currently forecast the movements between third line, second line, first line is actually very responsible, I would say. So we're not looking for this at day one of launch.

Marcio Souza: So we're not looking for this at day one of launch. We're not even looking to this at year one at launch. We know it takes time for these things to happen. We know that the overall penetration is not like the highest, but when you look into our peak revenue right around $4 billion or so in overall, like, you can imagine that we couldn't just be hyper penetrating the first line, because otherwise this would be much, much higher than what we have right now. So there is a huge potential there for upsides, as you can imagine. But at the same time, there are many firsts that happened for us in the last few years. And I think we're always very responsible to say what we knew and what we didn't.

Speaker #10: We're not even looking to this at year one. At launch we know it takes time for these things to happen. We know that the overall penetration is not like the highest but when you look into our peak revenue right around four billion dollars or so in overall you can't imagine that we couldn't just be hyper penetrating the first line because otherwise this would be much, much higher than what we have right now.

Speaker #10: So that is a huge potential there for upsides as you can imagine. But at the same time, as we there are many firsts that happen for us, right, in the last few years.

Speaker #10: And I think we're always very responsible to say what we knew and what we didn't. And I think what we know right now is that there's incredible interest from utilizing this drug.

Marcio Souza: And I think what we know right now is that there's incredible interest on utilizing this drug. What we don't know is the dynamic of that. So we are really keeping, I would say, very tempered our enthusiasm in terms of how the penetration is gonna be there, and that's reflected on our conservative to, realistic, one could call peak revenue right now.

Speaker #10: What we don't know is the dynamic of that. So we are really keeping I would say very tempered our enthusiasm in terms of how the penetration is going to be there and that's reflected on our conservative to realistic one could call peak revenue right now.

Speaker #1: Thank you.

Ami Fadia: Thank you.

Speaker #2: Thank you.

Operator: Thank you.

Speaker #1: Our next question comes from the line of Brian Scorni with Baird. Your line is now open.

Marcio Souza: You bet.

Operator: Our next question comes from the line of Brian Skorney with Baird. Your line is now open.

Speaker #12: Hey, good morning, everyone. Thank you for taking my question. I guess we'll get some guidance on NDA acceptance, but I wanted to just get your preliminary thoughts on if the review division has given any indication on an advisory committee for either REL-104 or riluzole. I mean, it seems that AdComms are getting more rare under this current iteration of the FDA.

Brian Skorney: Hey, good morning, everyone. Thank you for taking my question. I guess we'll get some guidance on NDA acceptance, but wanted to just get your preliminary thoughts on if the review division has given any indication on an advisory committee for either relutrigine or ulixacaltamide. I mean, it seems that AdComs are getting more rare under this current iteration of the FDA. And relutrigine's mechanism seems pretty straightforward with the data. It probably wouldn't require one, but thoughts on ulixacaltamide in particular.

Speaker #12: And religion's mechanism seems pretty straightforward with the data. I probably wouldn't require one but thoughts on Eulixa in particular.

Speaker #10: Yeah. No indication whatsoever at this point in time. One wouldn't expect much of an indication before day sixes and day 74 interactions with the agency.

Marcio Souza: Yeah. No, no indication whatsoever at this point in time. One wouldn't expect much of an indication before day 60s and day 74 interactions with the agency, but there's no indication right now, Brian.

Speaker #10: But there's no indication right now, Brian.

Speaker #2: Great. Thank you.

Brian Skorney: Great. Thank you.

Speaker #1: Thank you. Our next question comes from the line of Jay Olson with Oppenheimer. Your line is now open.

Operator: Thank you. Our next question comes from the line of Jay Olson with Oppenheimer. Your line is now open.

Speaker #13: Oh, hey, congrats on all the progress and thank you for taking our question. As you plan your pre-launch activities for both Eulixa and Relutrigene, can you talk about the potential synergies you can leverage between these two launches and then eventually how those synergies could help set up your future launches of vometrazine and Elsa Nursing?

Jay Olson: Oh, hey, congrats on all the progress, and thank you for taking our question. As you plan your pre-launch activities for both ulixacaltamide and relutrigine, can you talk about the potential synergies you can leverage between these two launches? And then eventually, how those synergies could help set up your future launches of vormatrigine and elsunersen. Thank you.

Speaker #13: Thank you.

Speaker #10: Yeah, certainly. So from a I'll take from the borrowing side, right, from an infrastructure perspective, back office perspective, lots of synergy. And how things are set up and we've been doing a lot of that on the backgrounds like how the systems are set up and so on.

Marcio Souza: Yeah, certainly. So from a-- I'll take from the borrowing side, right? From an infrastructure perspective, back office perspective, lots of synergy, and how things are set up, and we've been doing a lot of that in the background, like how the systems are set up and so on. Until not that far in the past, we were actually considering a lot more synergy in the fields as well, and on the approach to the markets. Because we believed before the EMBOLD's positive results last year, that we'd have a little bit more time with relutrigine, so we'd be able to leverage that. And that changed a lot once we are now really launching two drugs in about the same time.

Speaker #10: Until not that far in the past, we were actually considering a lot more synergy in the fields as well and on the approach to the markets because we believed, before the Inboards positive results last year, that we would have a little bit more.

Speaker #1: Our time with with our liturgy . So we'd be able to leverage that and that changed a lot . Once we are now really launching to drugs in about the same time .

Speaker #1: While that is a very significant overlap , I'm going to call zip codes , right ? Like we hospitals that have or clinics that have very high overlap of patients with and GS , our focal , we don't believe that it's prudent right now to take any distractions or taking a go to market strategy for both for individually for these and individually for essential tremor to maximize each one of them .

Marcio Souza: While there is a very significant overlap in, I'm gonna call it ZIP codes, right? Like with hospitals that have or clinics that have very high overlap of patients with ET and GEs or focal, we don't believe that it's prudent right now to take any distractions, so we're taking a go-to-market strategy for both, for individually, for GE, and individually for essential tremor to maximize each one of them. Now, since your question extrapolated to the future, Jay, when you're looking to, like, focal onset seizures, for example, generalized seizures, you name it, other things that might come in the future, there is very, very high overlap between prescribers for the majority of the epilepsy patients today, and the majority of the essential tremors today in the markets.

Speaker #1: Now , since your question extrapolated to the future J , when you look into like focal onset seizures , for example , generalized seizures , you name it , other things that might come in the future that is very , very high overlap between prescribers for the majority of the epilepsy patients today and the majority of the essential tremors today in the markets .

Speaker #1: So you can see how a praxis presence might be beneficial at that point in time . Now we are talking maybe 2 or 3 years from now and that's going to be maximizing that .

Marcio Souza: So you can see how a practice presence might be beneficial at that point in time. Now, we are talking maybe 2 or 3 years from now, and that we're going to be maximizing that. Now, let me bring back to, like, 60 days or so from now, when we're going to be in Chicago with all these prescribers, all right? If we were to count the universe of prescribers coming to the annual meeting of the Academy of Neurology, we're talking about over 70% of the prescriptions for ET and focal in the US are present at that meeting. So there is a natural overlap here. We're just gonna be maximizing that overlap more a few years from now than a few months from now.

Speaker #1: Now , let me bring back to like 60 days or so from now , when we're going to be in Chicago with all this prescribers .

Speaker #1: Right . If if we were to count the universe of prescribers coming to the annual meeting of the Academy of Neurology , we're talking about over 70% of the prescriptions for ET and Focal in the US are present at that meeting .

Speaker #1: So that is a natural overlap here . We're just going to be maximizing that overlap more a few years from now than a few months from now

Speaker #2: That's great .

Speaker #3: Thank you . Congrats again .

Justin Walsh: Great. Thank you. Congrats again.

Jay Olson: Great. Thank you. Congrats again.

Speaker #2: Thanks .

Speaker #1: Thank you .

Marcio Souza: Thank you.

Speaker #4: Our next question comes from the line of Kambiz Yazdi with BTIG. Your line is now open.

Operator: Our next question comes from the line of Kambiz Yazdi with BTIG. Your line is now open.

Speaker #5: Morning , guys . Congrats on the NDA submissions . Three questions on my end . First , can you provide an update on the essential Tremor patient database ?

Kambiz Yazdi: Morning, guys. Congrats on the NDA submissions. Three questions on my end. First, can you provide an update on the essential tremor patient database? How is that already validated the size of the ET market? Second, the FDA's default position is that one adequate and well-controlled study, combined with confirmatory evidence, will serve as the basis of market authorization of novel products. How do you think about that with regards to vormatrigine and FOS? And then, my third and final question is, how should we think about the timing of the relutrigine EMERALD top line? Would an interim analysis be a possibility for EMERALD? Thank you so much.

Speaker #5: How is that already validated ? Validated the size of the market ? Second , the FDA's default position is that one adequate and well controlled study combined with confirmatory evidence will serve as the basis of marketing authorization of novel products .

Speaker #5: How do you think about that ? With regards to vermouth and Foss ? And then my third and final question is how should we think about the timing of Emerald top line ?

Speaker #5: Would an interim analysis be a possibility for Emerald ? Thank you so much .

Speaker #1: Thanks , Gavin . By try to go through for your questions here . If I understood them correctly . Right . So on .

Marcio Souza: Thanks, Kambiz. I try to go through your questions here if I understood them correctly. Right, so on – and I think I missed the very first one, so I might ask you to repeat which one was on ET.

Speaker #1: And I think I missed the very first one . So I might ask you to repeat that . Which one was on ET ?

Speaker #5: Yeah , the first one was can you provide an update on your essential tremor patient database ? How is that already validated ? The size of the ET market .

Kambiz Yazdi: Yeah, the first one was, can you provide an update on your essential tremor patient database?

Marcio Souza: Oh, yes, the database.

Kambiz Yazdi: How is that already validated the size of the ET market?

Speaker #1: Yeah . So we continue to validate and grow . And I think we intentionally didn't talk about this today . Since now we are moving from the clinical focus one to the commercial focus efforts .

Marcio Souza: Yeah, so we continue to both validate and grow. And I think we intentionally didn't talk about this, today, since now we are moving from the clinical focus one to the commercial focus, effort, and I'm gonna give, like, a larger update at our commercial day, in the near future there. So I'm gonna keep you holding your breath a little bit, in relation to that. I'm gonna go to the EMERALD and then go back to the second question. So of course, there is always an opportunity for the interim. It's not a current plan for EMERALD's, and the reason why it's not a current plan is really the pace of enrollments in EMERALD right now.

Speaker #1: And we're going to give like a larger update at our commercial day in the near future there . So I'm going to keep you holding your breath a little bit in relation to that .

Speaker #1: I'm going to going to go to the Emerald and then go back to to the second question . So of course , there is always an opportunity for , for it's not the current plan for emeralds .

Speaker #1: And the reason why it's not a current plan is really the pace of enrollments in Emerald right now . I think we've been realistic slash conservative about the timelines today , but but that is really a very fast pace of enrollment that might not allow for that .

Marcio Souza: I think we're being realistic, conservative about the timelines today, but that is really a very fast pace of enrollment that might not allow for that. And then on the last one on how we think about generation of evidence vis-a-vis the commissioner, like New England Journal of Medicine yesterday publication, we applaud it. I think it can be and will be. I have the ultimate trust on this, on our country, that's gonna be used responsibly. And we believe that in drugs where very clearly, like epilepsy, very clearly, the second study was not that necessary in the past. Those are good case studies and tests for the future. We could not possibly be trying to guide you today that that's gonna be the standard for our drugs.

Speaker #1: And then on the last one , on how we think about generation of evidence vis a vis the commissioner , like new England Journal of Medicine yesterday publication , we we applauded .

Speaker #1: I think it can be and will be I have viewed mates trust on this on our country . That's going to be used responsibly and and we believe that in drugs where very clearly like epilepsy , very clearly .

Speaker #1: The second study was not necessary in the past , those are good case studies . And tests for for the future . We could not possibly be trying to guide you today that that is to be the standard for our drugs .

Speaker #1: There is a lot of water that needs to go under that bridge , but we are enthusiastic about what that can help , can do for drug development and for practice , particularly in the near future .

Marcio Souza: There is a lot of water that needs to go under that bridge, but we are enthusiastic about what that can do for drug development and for Praxis, particularly in the near future. So stay tuned.

Speaker #1: So stay tuned .

Speaker #5: Thank you .

Kambiz Yazdi: Thank you.

Speaker #4: Our next question comes from the line of Justin Walsh with JonesTrading. Your line is now open.

Operator: Our next question comes from the line of Justin Walsh with Jones Trading. Your line is now open.

Speaker #6: Hi . Thanks for taking the question with your clinical successes . Have you been seeing increased attention paid to your cerebrum platform and related to that , can you remind us how both cerebrum and solidus are differentiated and their ability to select quality candidates for your pipeline ?

Justin Walsh: Hi, thanks for taking the question. With your clinical successes, have you been seeing increased attention paid to your Cerebrum platform? And related to that, can you remind us how both Cerebrum and Solidus are differentiated in their ability to select quality candidates for your pipeline?

Speaker #1: Yeah , yeah , absolutely . We do . As you can imagine , that is I think just like a renaissance , maybe I would say on understanding that the best mechanism to address a lot of this disease is through antisense oligonucleotides .

Marcio Souza: Yeah, yeah, absolutely. We do. As you can imagine, that is, I think, Justin, like a renaissance, maybe I would say, on understanding that the best mechanism to address a lot of these diseases is through antisense oligonucleotides. So we're seeing a lot of interest across the board actually. On this, you're gonna hear more in the near future about how we're gonna maximize it. I also believe that there's a different way. We talked about standards today, I talked about plausible mechanism today. There are different things there to maximize. We always follow two pillars, right? The biology, when you're and what is the best way to address, and then the business on the other side. Without business, biology is irrelevant. Without biology, business is irrelevant.

Speaker #1: So we're seeing a lot of interest across the board , actually on this . We're going to hear more in the near future about how we're going to maximize .

Speaker #1: I also believe that there's a different way we talked about standards today . I talked about plausible mechanism today . There are different things there to to maximize .

Speaker #1: We always follow two pillars , right ? The biology when you're and what is the best way to address . And then the business on the other side without business biology is irrelevant .

Speaker #1: Without biology , business is irrelevant . So I think we try to to do both of them . And that's why we're here today discussing the successes and the future success .

Marcio Souza: So I think we try to do both of them, and that's why we're here today discussing the successes and the future success. So I think that is stay tuned, but there's gonna be a lot more on that platform as well.

Speaker #1: So I think that is stay tuned . But there are going to be a lot more on that platform as well

Speaker #4: Thank you. Our next question comes from the line of David Hwang with Deutsche Bank. Your line is now open.

Operator: Thank you. Our next question comes from the line of David Huang with Deutsche Bank. Your line is now open.

Speaker #7: Hi there . Thanks for taking my question . So maybe first one on Elixir Calcium , an essential tremor . Could you just discuss a little bit about the distribution of the prescriber base , how well do you understand , you know , whether these prescribers will be based in , let's say , academic centers versus community ?

David Hoang: Hi there. Thanks for taking my question. So maybe first one on ulixacaltamide and essential tremor. Could you just discuss a little bit about the distribution of the prescriber base? How, how well do you understand, you know, whether these prescribers will be based in, let's say, academic centers versus community? Is this a product that would be prescribed by, you know, general neurologists broadly? And then one on vormatrigine. As we think about the evolving landscape in focal epilepsy, there's several potassium channel-focused therapies that are in late-stage development and potentially coming to market soon. How do you think vormatrigine fits in amongst those products? And what, and what would docs look at when selecting a therapy? Thanks a lot.

Speaker #7: Is this a product that would be prescribed by general neurologists broadly ? And then won on dermatology , as we think about the evolving landscape in focal epilepsy , there's several potassium channels , focused therapies that are in late stage development and potentially coming to market soon .

Speaker #7: How do you think Eugene fits in amongst those products , and what would docs look at when selecting a therapy ? Thanks a lot .

Speaker #1: Thanks, Dave. The distribution... And I would say the distribution of patients and the distribution of drug, and the prescribing patterns, are very well understood.

Marcio Souza: ... Thanks, Dave. The distribution, and I'll say the distribution of patients and the distribution of drug and the, the prescribing pattern is very well understood. I think we've been talking about that for a bit. That was one of the very first functions and knowledge that we built in the company. I would arrogantly tell you that we, we have an exquisite understanding on this, and each one of the physicians that have cases in the US right now, is the majority of them, the vast majority are general neurologists, and they're very eager and willing to, to engage with us. I think on Vorma and the competitive landscape, this was not and never gonna be a zero-sum game. We welcome, we are cheering for the next readouts on the space coming up soon.

Speaker #1: I think we've been talking about that for a bit . That was one of the very first functions and knowledge that we built in the company .

Speaker #1: I would arrogantly tell you that we have an exquisite understanding on this , and each one of the physicians that have case in the US right now is the majority of them , the vast majority , general neurologists .

Speaker #1: And they're very eager and willing to to engage with us . I think , on Varma and the competitive landscape , this was not and never going to be a zero sum game .

Speaker #1: We welcome . We are cheering for the next readouts on this space coming up soon . And we believe that that is really is in the best interest of patients that are multiple positive .

Marcio Souza: And we believe that that is really in the best interest of patients, that there are multiple positive readouts and drugs, and we can use them. And we just see the path to first line only happens with vormatrigine. So, competitively welcome, gonna have some competition on the refractory patients on the third line, but there's no competition on the earlier lines. Yeah. Thanks for the question.

Speaker #1: Readouts and drugs. We can use them, and we just see the path to first line only happens with gene—so, competitively.

Speaker #1: Welcome . Going to have some competition on the refractory patients on the third line . But there's no competition on the other lines .

Speaker #1: There. Thanks for your question.

Speaker #4: Thank you . Our next question comes from the line of Ben Burnett with Wells Fargo . Your line is now open .

Operator: Thank you. Our next question comes from the line of Ben Burnett with Wells Fargo. Your line is now open.

Speaker #6: Great . Thank you so much . I want to come back to an earlier question on elixir . And just the potential to explore titrating patients .

Ben Burnett: Great. Thank you so much. I want to come back to an earlier question on ulixacaltamide, and just the potential to explore titrating patients. I think the-- you mentioned an alternative titration protocol. I guess, curious if you could give us a little more color on this, and I guess would this alternative titration protocol start patients at a lower dose? And then secondly, you also talked about standard review for ulixacaltamide, and I think you walked through a couple sort of business reasons for that. But it feels like it also would give you some time to maybe iron out a titration protocol, and is-- was that also a consideration?

Speaker #6: I think you mentioned an alternative titration protocol . I guess . Curious if you could give us a little more color on this .

Speaker #6: And I guess would this alternative titration protocol start patients at a lower dose ? And then secondly , you also talked about standard review for elixir , and I think you walked through a couple sort of business reasons for that .

Speaker #6: But it feels like it also would give you some time to maybe iron out a titration protocol, and was that also a consideration?

Speaker #1: Yeah . Thanks , Ben . The no , there was not a consideration actually , I would say that was not an important consideration .

Marcio Souza: Yeah. Thanks, Ben. No, that was not a consideration actually, well, I'll say that was not an important consideration. Of course, it's always up to the FDA if they want to discuss more. We had a very robust discussion about that topic with the agents before. It was very good to see that this is not a major concern, but there's obviously an interest from us and from them when there is an efficacious drug that we try to actually expose and get the maximal amount of patients. That is the idea. It is not a lower dose, right? It's starting at 20mg. It's just staying at 20mg for longer.

Speaker #1: Of course it's always up to the FDA if they want to discuss more . We had a very robust discussion about that topic with the agency before it was very good to see that , that this is not a major concern .

Speaker #1: But there's obviously an interest from us . And from them when there is an efficacious drug that we try to actually expose and get the maximum amount of patients , that is the idea .

Speaker #1: It is not a lower dose , right ? It's starting at 20mg . It's just staying at 20mg for longer , because what we see here is what looks like it's really just a few days that they stay longer , or that dose that tends to subside .

Marcio Souza: Cause, what we see here, is what looks like, it is really just a few days that they stay longer on that dose that tends to subside the side effects, and then they have the opportunity to have the effects. So that's the, that's the idea there. I think, of course, there is thousands of things that can come up in conversations with the agency, but, that was not, one of them that we are planning as a main conversation for sure.

Speaker #1: The side effects . And then they have the opportunity to have the effects . So that's the that's the idea . There . I think .

Speaker #1: Of course , that is thousands of things that can come up in conversations with the agency . But that was not one of them that we were planning as a main conversation for sure

Speaker #4: Thank you . I would now like to turn the call back over to Marcio De'Souza for closing remarks .

Operator: Thank you. I would now like to turn the call back over to Marcio Souza for closing remarks.

Speaker #2: Yeah .

Marcio Souza: Yeah. Oh, thank you, everyone. I think we ran a little bit even over the allotted time, so I appreciate you all hanging in with us here. All the enthusiasm shared by all the analysts and our shareholders. Can't say how much I appreciate, and all of us here at Praxis appreciates the patients that participate in all the studies, that continue to engage with us. As we are here, very humbly, submitting two NDAs, which I don't believe has ever been done by a company in our stage on the same quarter.

Speaker #1: Well , thank you everyone . I think we run a little bit even over the allotted time . So I appreciate you all hanging in with us here on the enthusiasm shared by all the analysts and our shareholders can say how much I appreciate .

Speaker #1: And all of us here at Praxis appreciate the patience of those who participate in all the studies and continue to engage with us. We are here very humbly submitting to NDAs, which I don't believe has ever been done by a company at our stage.

Speaker #1: On the same quarter , the real motivation for everyone that works like days and nights on the last several years . But particularly in the last few months , has been the fact that if someone , as we say outside of the door , that we don't know they need these drugs , so just going to dedicate this moment to all of them and thank them for participating in our studies , I'll looking forward to interact with all of you soon .

Marcio Souza: The real motivation for everyone that worked, like, days and nights, on the last several years, but particularly in the last few months, has been the fact that there is someone, as we say, outside of the door, that we don't know; they need these drugs. So, just gonna dedicate these moments to all of them and thank them for participating in our studies. So, looking forward to interact with all of you soon, and thanks for tuning in.

Speaker #1: And thanks for tuning in.

Operator: This concludes today's conference. Thank you for your participation. You may now disconnect.

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