Q1 2026 Praxis Precision Medicines Inc Earnings Call

May 7, 2026

Speaker #1: Good day, ladies and gentlemen, and thank you for standing by. Welcome to the Praxis Precision Medicines first quarter 2026 financial results conference call. At this time, all participants are in a listen-only mode.

Operator: Good day, ladies and gentlemen, and thank you for standing by. Welcome to the Praxis Precision Medicines' Q1 2026 Financial Results Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question, you will need to press star 1 1 on your telephone keypad. As a reminder, this conference call is being recorded. At this time, I would like to turn the conference over to Mr. Dan Ferry of LifeSci Advisors. Sir, please begin.

Operator: Good day, ladies and gentlemen, and thank you for standing by. Welcome to the Praxis Precision Medicines' Q1 2026 Financial Results Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question, you will need to press star one one on your telephone keypad. As a reminder, this conference call is being recorded. At this time, I would like to turn the conference over to Mr. Dan Ferry of LifeSci Advisors. Sir, please begin.

Speaker #1: After the speaker's presentation, there will be a question-and-answer session. To ask a question, you will need to press star 11 on your telephone keypad.

Speaker #1: As a reminder, this conference call is being recorded. At this time, I would like to turn the conference over to Mr. Dan Ferry of LifeSight Advisors.

Speaker #1: Sir, please begin.

Speaker #2: Good morning, and welcome to Praxis Precision Medicines first quarter 2026 financial results and business update conference call. This call is being webcast live and can be accessed on the investor section of Praxis's website at www.praxismedicines.com.

Dan Ferry: Good morning and welcome to Praxis Precision Medicines' Q1 2026 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 on an obligation to do so. 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.

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's views as of today, they should not be relied upon as representing the company's views in the future. Praxis may update these statements in the future, but is not taking on an obligation to do so.

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

Speaker #2: Joining the call today are Marcio De'Souza, President and Chief Executive Officer of Praxis, and Tim Kelly, Chief Financial Officer. After providing 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 Stanczynski, Chief Operating Officer.

Dan Ferry: Joining the call today are Marcio Souza, President and Chief Executive Officer of Praxis, and Tim Kelly, Chief Financial Officer. After providing updates on our key programs, we'll move to a brief Q&A session where Marcio and Tim will be joined by Steven Petrou, President of Research & Development, and Megan Sniecinski, Chief Operating Officer. With that, it's my pleasure to turn the call over to Marcio.

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

Speaker #3: Thank you, Dan. And good morning, everyone, and thanks for joining Praxis' first quarter 2026 conference call. Building on our remarkable 2025, we have continued executing across our portfolio and our journey to become a commercial company.

Marcio Souza: Thank you, Dan, and good morning, everyone, and thanks for joining Praxis' First Quarter 2026 conference call. Building on a remarkable 2025, we have continued executing across our portfolio in our journey to become a commercial company. With strong momentum building across 4 late-stage assets, representing more than $20 billion in peak sales potential. With the NDAs for ulixacaltamide and relutrigine accepted by the FDA and PDUFA dates set, we're ramping up commercial efforts to support the 2 potential US launch within the next 8 months, while also making significant progress with our other clinical programs. It was incredibly exciting to announce that we have completed recruitment for the EMERALD study in the broad DEE population, with top-line results expected in Q4 of this year, which we expect to support a potential supplemental NDA next year.

Speaker #3: With strong momentum, building across four late-stage assets representing more than $20 billion in peak sales potential. With the NDAs for Elix Account Mid and Relutrogen accepted by the FDA, and PDUFA Date set, we're ramping up commercial efforts to support the two potential US launches within the next eight months.

Speaker #3: While also making significant progress with our other clinical programs. Those incredibly exciting to announce that we have completed recruitment for the Emerald study in the broad DE population.

Speaker #3: With top-line results expected in the fourth quarter of this year. Which we expect to support a potential supplemental NDA next year. We're also on track to report results from our Power One study for Brometrogen later this quarter.

Marcio Souza: We're also on track to report results from our POWER1 study for vormatrigine later this quarter. Also made exciting progress with our solids ASO platform, with the positive results from the EMBRAVE part A showing a disease-modifying effect of elsunersen in SCN2A early onset GE and substantial reduction in monthly seizures, amongst many other results. With key hires made in our commercial organization and a strong financial foundation, we're accelerating the delivery of life-altering treatments to patients with CNS disorders. Let me provide a bit more detail on each one of our programs. Let's just start with ulixacaltamide. The FDA acceptance for ulixacaltamide's NDA marked a meaningful step forward for the 7 million Americans living with essential tremor, who currently have no ET specifically developed treatments approved.

Speaker #3: Also made exciting progress with our solids ASO platform. With the positive results from the Embrace Part A showing a disease-modifying effect of housing nursing in SCN2A early onsets DEs.

Speaker #3: And substantial reduction in monthly seizures amongst many other results. With key hires made in our commercial organization, made strong financial foundation, we're accelerating the delivery of life-altering treatments to patients with CNS disorders.

Speaker #3: Let me provide a bit more detail on each one of our programs. Let's just start a few legs up. The FDA acceptance of our Elixas NDA marked a meaningful step forwards for the $7 million Americans living with essential tremor.

Speaker #3: Who currently have no ET specifically developed treatments approved. We estimate that about 2 million of those people living with ET are in the immediate need for a therapy that can clinically improve their daily lives.

Marcio Souza: We estimate that about 2 million of those people living with ET are in immediate need for a therapy that can clinically improve their daily lives. Representing a potential for over $10 billion in peak sales. To unlock the benefit for patients and the value, we have been diligently preparing for a commercial launch based on the PDUFA date of 29 January next year. The commercial leadership team is in place with our field force planned to be hired and trained in advance of the launch. We continue to expand and build the commercial infrastructure across multiple areas like operations, marketing, access, and compliance. We have also successfully established a distribution network to ensure drug availability at launch at successful levels. Earlier this year, we conducted a very comprehensive observational study with physicians to understand their view of ET and ulixacaltamide.

Speaker #3: Representing a potential for over $10 billion in peak sales. To unlock the benefits for patients and the value, we have been diligently preparing for a commercial launch based on the PDUFA date of January 29 next year.

Speaker #3: The commercial leadership team is in place with our field force planned to be hired and trained in advance of the launch. And we continue to expand and build the commercial infrastructure across multiple areas like operations, marketing, access, and compliance.

Speaker #3: I have also successfully established a distribution network to ensure drug availability at launch a successful levels. Earlier this year, we conducted a very comprehensive observational study with physicians to understand their view of ET and Elix Account Mide.

Speaker #3: We surveyed more than 2,300 US physicians who collectively managed tens of thousands of patients. The results were beyond encouraging. They validated Elix Account Mide profile across efficacy, the breadth of benefits, and tolerability.

Marcio Souza: We surveyed more than 2,300 US physicians who collectively manage tens of thousands of patients. The results were beyond encouraging. They validated ulixacaltamide profile across efficacy, the breadth of benefits, and tolerability, reinforcing the more than $10 billion peak sale potential and the needs for a drug like ulixacaltamide in the markets. Importantly, we also wanted to hear in more detail from patients and conduct a similar work with over 1,300 ET patients, which further validated the agreements between the needs of patients in terms of their functional benefits with the results of the Essential3 program. It's truly exciting to be in a place of such alignment among treating physicians, patients, and the results of our program.

Speaker #3: Reinforcing them more than $10 billion peak sale potential. And the needs for a drug like Elixa in the markets. Importantly, we also wanted to hear in more detail from patients and conducted a similar work with over 1,300 ET patients.

Speaker #3: Which further validated the agreements between the needs of patients in terms of their functional benefits with the results of the essential three program. It's truly exciting to be in a place of such alignment amongst treatment physicians, patients, and the results of our program.

Speaker #3: We're also very pleased with our robust presence at the American Academy of Neurology annual meeting last month. With 15 scientific presentations, including a plenary presentation highlighting the essential three program results which received the AM's abstract of distinction in movement disorder awards.

Marcio Souza: We're also very pleased with our robust presence at the American Academy of Neurology annual meeting last month, with 15 scientific presentations, including a plenary presentation highlighting the Essential3 program results, which received the AAN's Abstract of Distinction in Movement Disorder Awards, which underscore the strong interest and engagements of the medical community. To further enhance our engagement with healthcare professionals, we have launched the Essential To Me disease state campaign. Let's now move to our epilepsy programs. As we shared in March, in another pivotal moment for Praxis and patients, the FDA has accepted with priority review the NDA for relutrigine for seizures associated with SCN2A and SCN8A GE. Those are severe patients affected early in life and where the seizures are intractable from the very beginning. It's important to highlight that if approved, relutrigine would be eligible for a pediatric review voucher.

Speaker #3: Which underscore the strong interest and engagements of the medical community. To further enhance our engagement with healthcare professionals, we have launched the essential to me disease state campaign.

Speaker #3: Let's now move to our epilepsy programs. As we shared in March, in another pivotal moments for Praxis and patients, the FDA has accepted with priority review the NDA for Relutrogen.

Speaker #3: For seizures associated with SCN2A and 8A DE. Those are severe patients affected early in life and where the seizures are intractable from the very beginning.

Speaker #3: It's important to highlight that if approved, Relutrogen would be eligible for a pediatric review voucher. With the PDUFA date of September 27, preparation for launch are moving full steam ahead with continued hiring of commercial roles, building sufficient inventory establishing a comprehensive patient support program, and engaging with payers to ensure timely access upon potential approval.

Marcio Souza: With the PDUFA date of September 27, preparation for launch are moving full steam ahead with continued hiring of commercial roles, building sufficient inventory, establishing a comprehensive patient support program, and engaging with payers to ensure timely access upon potential approval. We remain confident on the clinical potential for relutrigine and the benefits to the broader GE population. With recruitment in EMERALD study now completed in record time, it's clear that patients and investigators share our view. The potential launch in SCN2A and SCN8A will build the foundation. The results of the EMERALD later this year, if positive, will significantly expand the commercial potential for relutrigine by several folds, considering the broad GE population is comprised of over 200,000 patients in the US.

Speaker #3: We remain confident on the clinical potential for Relutrogen and the benefits to the broader DE population. With recruitment in Emerald study now completed, in record time, it's clear that patients and investigators share our view.

Speaker #3: The potential launch in SCN2A and 8A will build the foundation. And the results of the Emerald later this year if positive will significantly expand the commercial potential for Relutrogen by several folds considering the broad DE population is comprised of over 200,000 patients in the United States.

Speaker #3: Let's now talk about Brometrogen. The most potent and selective sodium channel modulator ever developed for the three and a half million people living with epilepsy in the United States.

Marcio Souza: Let's now talk about vormatrigine, the most potent and selective sodium channel modulator ever developed for the 3.5 million people living with epilepsy in the United States. We have three key milestones in the near future for the program. The first is the readouts of the POWER1 phase III study later this quarter. The initiation of the Power Three study, a milestone in the community, using all the exciting features of vormatrigine to deliver on what the majority of the market really needs. Later in the year, the completion of the Power Two phase III study, which is evaluating dose of 20, 30, and 40 milligrams once daily. Enrollment is progressing well, and we're on track to finalize the study this year and report early next year. Let's talk about elsunersen, the first ASO in our platform.

Speaker #3: We have three key milestones in the near future for the program. The first is the readouts of the power one phase three study later this quarter.

Speaker #3: Then the initiation of the power three study a milestone in the community using all the exciting features of Brometrogen to deliver on what the majority of the markets really needs.

Speaker #3: And then later in the year, the completion of the power two phase three study, which is evaluating those of 20, 30, and 40 milligrams once daily.

Speaker #3: Enrollment is progressing well in our own track to finalize the study this year and reports early next year. Lastly, let's talk about LG Nursing, the first ASO in our platform.

Speaker #3: As nursing also has a rare pediatric drug designation. And it's being developed for the treatment of early seizure onset patients with SCN2A mutations. We have recently reported the results of Embrave part A, which enrolls nine children aged 2 to 12 through randomized 3 to 1 to LG Nursing or SHAM over 24 weeks.

Marcio Souza: elsunersen also has a rare pediatric drug designation and is being developed for the treatment of early seizure onset patients with SCN2A mutations. We have recently reported the results of EMBRAVE Part A, which enrolled 9 children aged 2 to 12 to randomize 3 to 1 to elsunersen or sham over 24 weeks. We're thrilled with the impressive 77% placebo-adjusted reduction in monthly seizures and the disease-modifying components seen across multiple domains in those patients while maintaining the generally safe and well-tolerated profile. The overall data from both the EMBRAVE program, open-label extension, and emergency use program globally highlight durable seizure reduction and meaningful global gains, which further underscore the transformational potential of this drug. In conclusion, we're off to a great start for momentum continuing to accelerate across our clinical portfolio. Preparations for commercial launch of ulixacaltamide or relutrigine well underway. The completion of the EMERALD study enrollments.

Marcio Souza: Elsunersen also has a rare pediatric drug designation and is being developed for the treatment of early seizure onset patients with SCN2A mutations. We have recently reported the results of EMBRAVE Part A, which enrolled 9 children aged 2 to 12 to randomize 3 to 1 to elsunersen or sham over 24 weeks. We're thrilled with the impressive 77% placebo-adjusted reduction in monthly seizures and the disease-modifying components seen across multiple domains in those patients while maintaining the generally safe and well-tolerated profile. The overall data from both the EMBRAVE program, open-label extension, and emergency use program globally highlight durable seizure reduction and meaningful global gains, which further underscore the transformational potential of this drug. In conclusion, we're off to a great start for momentum continuing to accelerate across our clinical portfolio. Preparations for commercial launch of ulixacaltamide or relutrigine well underway. The completion of the EMERALD study enrollments.

Speaker #3: We're thrilled with the impressive 77% placebo-adjusted reduction in monthly seizures, and the disease-modifying components seen across multiple domains in those patients. While maintaining the generally safe and well-tolerated profile.

Speaker #3: The overall data from both the Embrave program, open label extension, and emergency use program globally highlight durable seizure reduction and meaningful global gains. Which further underscore the transformational potentials of this drug.

Speaker #3: In conclusion, we're off to a great start for momentum continuing to accelerate across our clinical portfolio preparations for commercial launch of Elix Account Mide and Relutrogen well underway, the completion of the Emerald study enrollments, power one top line readout coming up, and many other achievements to come.

Marcio Souza: POWER1 top-line readout coming up, many other achievements to come. Backed by a strong balance sheet and a long multi-layer IP portfolio across the programs, we're focused on rigorous execution and driving progress across our innovative first and best-in-class portfolio of CNS therapies. I'll hand over the call to our CFO, Tim Kelly. Tim?

Speaker #3: Backed by a strong balance sheet, and a long multi-layer IP portfolio across the programs, we're focused on rigorous execution and driving progress across our innovative first and best-in-class portfolio of CNS therapies.

Speaker #3: And I'll hand over the call to our CFO, Tim Kelly. Tim, thank you, Marcio. Good morning, everybody. And thank you for joining today's call.

Tim Kelly: Thank you, Marcio. Good morning, everybody. Thank you for joining today's call. I'll provide a quick summary of our Q1 financials. In Q1, our operating expenses were approximately $106 million, with $78 million of that for R&D and the remaining $28 million for SG&A, driven by ramping activities and hiring related to commercial launch preparations. During the Q1, Praxis spent $86 million in operating cash, compared to $53 million in Q1 2025, reflecting greater clinical trial activity, headcount growth, and commercial launch preparations. As of 31 March 2026, Praxis had $1.4 billion in cash equivalents, and marketable securities, compared to $926 million as of 31 December 2025.

Speaker #3: I'll provide a quick summary of our first quarter financials. In Q1, our operating expenses were approximately $106 million, with $78 million of that for R&D, and the remaining $28 million for SG&A, driven by ramping activities and hiring related to commercial launch preparations.

Speaker #3: During the first quarter, Praxis spent $86 million in operating cash, compared to $53 million in the first quarter of 2025, reflecting greater clinical trial activity, headcount growth, and commercial launch preparations.

Speaker #3: As of March 31st, 2026, Praxis had $1.4 billion in cash, cash equivalents in marketable securities, compared to $926 million as of December 31st, 2025.

Speaker #3: This increase of approximately $474 million was primarily attributable to net proceeds from Praxis' January 2026 follow-on public offering and interest income on marketable securities, partially offset by the previously mentioned cash used in operations.

Tim Kelly: This increase of approximately $474 million was primarily attributable to net proceeds from Praxis' January 2026 follow-on public offering and interest income on marketable securities, partially offset by the previously mentioned cash used in operations. The company's cash equivalents, and marketable securities as of 31 March 2026, are expected to fund operations into 2028. With that, I will hand the call back to Marcio.

Speaker #3: The company's cash, cash equivalents, and marketable securities as of March 31st, 2026, are expected to fund operations into 2028. With that, I will hand the call back to Marcio.

Speaker #1: Thank you, Tim. Appreciate the review. I'm going to now move to a Q&A. Howard, maybe you can compile the queue for us.

Marcio Souza: Thank you, Tim. Appreciate the review. We're going to now move to a Q&A. Howard, maybe you can compile the queue for us.

Speaker #3: Ladies and gentlemen, if you have a question or comment at this time, please press star 11 on your telephone keypad. If your question has been answered or you wish to remove yourself from the queue, simply press star 11 again.

Operator: Our first question or comment comes from the line of Yasmeen Rahimi from Piper Sandler. Your line is now open.

Speaker #3: Again, if you have a question or comment at this time, please press star 11 on your telephone keypad. Please stand by while we compile the Q&A roster.

Speaker #3: Our first Yasmin Rahimi from Piper Sandler. Your line is now open.

Operator: Our first question or comment comes from the line of Yasmeen Rahimi from Piper Sandler. Your line is now open.

Yasmeen Rahimi: Good morning, team. Thank you so much for all the great updates. Maybe also congrats on EMERALD bringing to the finish line enrollment and data in Q4 as it's an important readout this year. Maybe remind us, right, what is the data that we have to support relutrigine working in a broader DEE population, both across preclinical and clinical data? Also, what do you see on a blinded basis across safety and efficacy that continues to give you confidence on a high success in the EMERALD study? I'll jump back in the queue.

Speaker #4: Good morning, Tim. Thank you so much for all the great updates. Maybe also congrats on Emerald bringing to the finish line enrollment and data in four queue as it's an important readout this year.

Speaker #4: Maybe remind us, right, what is the data that we have to support Relutrogen working in a broader DE population both across preclinical and clinical data?

Speaker #4: And then also, what do you see on a blinded basis across safety and efficacy that continues to give you confidence on a high success in the Emerald study?

Speaker #4: And I'll jump back in the queue.

Speaker #1: Sounds good. Thanks, Yas. I'll take a step back here and maybe talk a little bit about the genesis of going to the broad DE population, right?

Marcio Souza: Sounds good. Thanks. Thanks, Yas. I'll take a step back here and maybe talk a little bit about the genesis of going to the broad DEE population, right? When you look into seizure activities, particularly on those intractable conditions like DEEs, we know full well just how difficult those patients are to control. Also know that when they can have at least some partial control for the most part, it's because there is a way to inhibit or block, better modulate their sodium channel activities. Like, you simply cannot have seizure activity without participation of those channels.

Speaker #1: When you look into seizure activities particularly on those intractable conditions like DEs, we know full well just how difficult those patients are to control.

Speaker #1: Also know that when they can have at least some partial control, for the most part, is because there is a way to inhibit or block better modelates their sodium channel.

Speaker #1: Activities like you simply cannot have seizure activity without participation of those channels. So when we work conducting the in both program for SCN2A and HA, the number one question we're getting from physicians back then is like, "When are you going to expand this beyond this?" So we'll take that in mind in terms of the overall clinical proof of concepts, their idea, and the needs that we're seeing.

Marcio Souza: When we were conducting the EMBOLD program for SCN2A, the number one question we're getting from physicians back then is like, When are you going to expand this beyond this? We'll take that in mind in terms of the overall clinical proof of concepts, their idea and the needs that we're seeing. We had to slow down a little bit and do a lot of work. You might have seen, and it's available in our website, a fair bit of the work in terms of different animal models, which are incredibly predictable in epilepsy.

Speaker #1: But we had to slow down a little bit and do a lot of work. And you might have seen, and it's available in our websites, a fair bit of the work in terms of different animal models which are incredibly predictable in epilepsy.

Speaker #1: On understanding whether or not this there was a good scientific rationale on top of the electrophysiology rationale, on top of the molecular rationale, to go to this.

Marcio Souza: on understanding whether or not there was a good scientific rationale on top of the epilepsy etiology rationale, on top of the molecular rationale to go to this. The last part, we had to make sure that the FDA was in agreement that we could study in this population, right? Safety is paramount, making sure that we're actually understanding the populations we're in. When we checked all those boxes, we're able to initiate the study. I think what is incredible, I would say, is just the level of interest. Right? If you look into ourselves, if you look into other studies in DEE before, if you look into competitive, and I'm going to put that very loosely, the awards, the studies that are going right now, there was no interest on those others.

Marcio Souza: On understanding whether or not there was a good scientific rationale on top of the epilepsy etiology rationale, on top of the molecular rationale to go to this. The last part, we had to make sure that the FDA was in agreement that we could study in this population, right? Safety is paramount, making sure that we're actually understanding the populations we're in. When we checked all those boxes, we're able to initiate the study. I think what is incredible, I would say, is just the level of interest. Right? If you look into ourselves, if you look into other studies in DEE before, if you look into competitive, and I'm going to put that very loosely, the awards, the studies that are going right now, there was no interest on those others.

Speaker #1: And then the last part we had to make sure that the FDA was in agreement that we could study in this population, right? Safety experiment, making sure that we actually understanding the populations we're in.

Speaker #1: So when we checked all those boxes, we're able to initiate the study. I think what is incredible I would say is just the level of interest.

Speaker #1: All right? If you look into our cells, if you look into other studies, indeed before if you look into competitive and I'm going to put that very loosely the words studies that are going right now, there was no interest on those others.

Marcio Souza: It's kind of pretty obvious by the pace of enrollments that is happening with us and with others out there. The number one reason why is, like, physicians are very confident on the availability here just like we are. Gave us, of course, this extra ability to move the things forward. If I can turn to the business for a second, right? We are in the business of helping patients, but at the same time, the only way to continue to helping them is by continuing to generate, like, proper positive returns to invest in the future. The actual expansion towards GE, broad GE is, like, 20-fold what it is the initial application for SCN2A and SCN8A, which is incredibly important. The second part makes not only scientific sense, but it's a tremendous upside in terms of the potential of this drug.

Speaker #1: It's kind of pretty obvious by the pace of enrollments that is happening with us and with others out there. And the number one reason why is like physicians are very confident on the ability here, just like we are.

Speaker #1: So gave us, of course, this extra ability to move the things forwards. But if I can turn to the business for a second, right?

Speaker #1: We are in the business of helping patients, but at the same time, the only way to continue to helping them is by continuing to generate proper positive returns to invest in the future.

Marcio Souza: -to invest in the future. The actual expansion towards GE, broad GE is, like, 20-fold what it is the initial application for SCN2A and SCN8A, which is incredibly important. The second part makes not only scientific sense, but it's a tremendous upside in terms of the potential-

Speaker #1: The actual expansion towards DE, broad DE, it's like 20-fold what it is the initial application for SCN2 and HA. It's incredibly important. But the second part makes not only scientific sense, but it's a tremendous upside in terms of the potential of this drug.

Marcio Souza: of this drug. Lastly, I know we kept, like, piling catalysts throughout the year. You guys might be tired of us having so many readouts, but we thought it was very important to get that, like, shortly thereafter to really, with a fresh, hopefully approval at that point in time, it gives the FDA a lot of flexibility to actually look into just the additional data and potentially even qualify to certain accelerated mechanisms that have been available. All in all, we see it as a tremendous and maybe the key updates today that we're giving in terms of value inflection for investors.

Speaker #1: And then lastly, I know we keep piling catalysts throughout the year. You guys might be tired of us having so many readouts. But we thought it was very important to get that shortly thereafter to really with a fresh, hopefully approval at that point in time, it gives the FDA a lot of flexibility to actually look into just the additional data and potentially even qualify to certain accelerated mechanisms that have been available.

Marcio Souza: Lastly, I know we kept, like, piling catalysts throughout the year. You guys might be tired of us having so many readouts, but we thought it was very important to get that, like, shortly thereafter to really, with a fresh, hopefully approval at that point in time, it gives the FDA a lot of flexibility to actually look into just the additional data and potentially even qualify to certain accelerated mechanisms that have been available. All in all, we see it as a tremendous and maybe the key updates today that we're giving in terms of value inflection for investors.

Speaker #1: So on and off, we see there's a tremendous and maybe DE key updates today that we're giving in terms of value inflection for investors.

Speaker #4: Thank you so much.

Yasmeen Rahimi: Thank you so much.

Speaker #1: Thank you.

Marcio Souza: Thank you.

Speaker #3: Thank you. Our next question or comment comes from the line of Ritu Baral from TD Cowen. Your line is now open.

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

Speaker #4: Good morning, guys. Thanks for taking the question. A lot of client questions just around the upcoming PRAX-222 readout and what our expectations should be. How do you, knowing the baseline and knowing the relative baseline of other competitive therapies, how should investors—how should we be looking at placebo-adjusted seizure reduction, the safety profile, and then how might that data then frame the PRAX-222 to N3 studies, given the different doses in those studies and the different dosing paradigms?

Ritu Baral: Good morning, guys. Thanks for taking the question. A lot of client questions just around the upcoming power readout and what our expectations should be. Knowing, knowing the baseline and knowing the relative baseline of other competitive therapies, how should we be looking at placebo-adjusted seizure reduction, the safety profile, and then how might that data then frame the Power Two and Three studies given the different doses in those studies and the different dosing paradigms?

Speaker #1: Yeah. Great. Great set of questions there, Ritu. So I think let's just start with the baseline that that's what you mentioned, right? So we if you look historically, at least in recent history, baseline for full-concept seizures in the refractory population so one, two, three ASMs and you know the drill there on the other criteria.

Marcio Souza: Yeah. Great, great set of questions there, Ritu. Well, I think let's just start with the baseline, that that's what you mentioned, right? If you look historically, at least in recent history, baseline for focal seizures in the refractory population, so 1 to 3 ASMs, and you know the drill there on the other criteria, being hovering around like 9 to 11, 12 countable seizures on the previous 28 days, right? And I think we're probably a little higher than that, a tiny bit here for POWER1, which was kind of what we're aiming for, right? We knew these patients are fairly refractory. We're very confident about the drug.

Speaker #1: Being roving around like 9 to 11, 12 countable seizures on the previous 28 days, right? And I think we're probably a little higher than that a tiny bit here.

Speaker #1: For power one, which was kind of where we were aiming for, right? We knew these patients are fairly refractory or very confident about the drug.

Speaker #1: We wanted as well to make sure that once we established there, and very clear efficacy as we expect, allow us to move incredibly quickly as well towards the ultimate goal of this drug that's being widely available for any patient with full-concept seizures and in the future other types of seizures as well.

Marcio Souza: We wanted as well to make sure that once we establish there, and very clear efficacy as we expect, allow us to move incredibly quickly as well towards the ultimate goal of this drug as being widely available for any patient with focal seizures and in the future, other types of seizures as well. That brings to a second part of your question, that is the expectations. I think that it's always dangerous to talk about expectations and setting bars, artificial bars, this late in the game in terms of like, literally like weeks, I would say, before our readouts.

Speaker #1: That brings to a second part of your question that is the expectations. And I think that it's always dangerous to talk about expectations and setting bars artificial bars this late in the game in terms of literally like weeks I would say before our readouts.

Speaker #1: But we've been fairly consistent on the expectation here throughout the years is number one, as the severity increase, I think this is one of the few areas and you've got to be very excited about science that the new drugs still deliver a lot.

Marcio Souza: We've been fairly consistent on the expectation here throughout the years is, number one, as the severities increase, I think this is one of the few areas, and you've got to be very excited about science, that the new drugs still deliver a lot. We just see that recently with another program. We expect to see the same like here, drug delivered despite, like, being piling up on a lot of, a lot of other drugs for all the years in a higher baseline, so more severity. We historically been giving that kind of a baseline, sorry, adjusted by placebo around 30% or so, as quite meaningful because when we talk to physicians, when you look into the actual prescription pattern, that seems to be a number that lands incredibly well.

Speaker #1: And we just see that recently with another program we expect to see the same like here drug delivered despite being piling up on a lot of other drugs throughout the years in a higher baseline.

Speaker #1: So more severity and we historically been giving that kind of not baseline, sorry, adjusted by placebo around 30% or so as quite meaningful because when we talk to physicians, when you look into the actual prescription pattern, that seems to be a number that lends incredibly well.

Speaker #1: And then the last part is safety, right? As you mentioned, and we're very confident about the safety profile of this drug—both what we've seen in a blinded base on POWER 1, but also what we are seeing on a blinded base on POWER 2. That was the very last topic you mentioned.

Marcio Souza: The last part is safety, right? As you mentioned. We're very confident about the safety profile of this drug, both what we're seeing in a blinded base on POWER1, but also what we are seeing on a blinded base Power Two. That was the very last topic you mentioned. Fairly comprehensively, I think we're excited about the upcoming readouts. Another cards to flip, another program to hopefully accelerate to bring to patients. Power Two is going really well. As you saw as well in the press release, we re-reiterated finalizing the study by the end of the year and reading out early next year.

Speaker #1: So fairly comprehensively I think we're excited about the upcoming readouts another cards to flip another program to hopefully accelerate to bring to patients and power two is going really well.

Speaker #1: So as you saw as well in the press release, we reiterated finalizing the study by the end of the year and reading out early next year.

Speaker #1: So on and on to think about a potential third or fourth drug or potential third submission of an NDA or fourth if you account for this NDA in 12 months is no joke.

Marcio Souza: All in all, to think about a potential of third or fourth drug, or potential third submission of an NDA or fourth if accounts for this NDA in 12 months is no joke, and we are very, very proud of that.

Speaker #1: And we are very, very proud of that.

Speaker #4: Given that baseline, what about seizure-free Marcio? Last question. I promise.

Ritu Baral: Given that baseline, what about seizure-free, Marcio? Last question, I promise.

Speaker #1: Yeah. No, no. He's nicked in one there. I think again, we should unblind it. I do feel the number one thing is really to make sure you have very solid reduction.

Marcio Souza: Yeah. No, no. Like there's Nick then one there, huh? Like I think again, we should unblind it. I do feel the number one thing is really to make sure we have very solid reduction, but of course we want to see seizure freedom here as well. It's important. It's something we saw on the RADIANT data, right? That when you treat patients longer, like by week 10, 12, their median seizure gets to 100%, the reduction. Of course, we want to see the more we treat, the longer we treat patients, a very deepening of effect. That's what start we're seeing. I'll leave it like that, but we're excited with the overall profile.

Speaker #1: But of course, we want to see seizure freedom here as well. It's important. It's something we saw on the radiance data that when you treat patients longer, like by week 10, 12, they are median seizure gets to 100s.

Speaker #1: The percents, the reduction. So of course, we want to see the more we treat the longer we treat patients a very deepening of effect.

Speaker #1: That's what, historically, we're seeing. And I'll leave it like that. But we're excited with the overall profile. Of course.

Ritu Baral: Thank you.

Marcio Souza: Of course.

Speaker #3: Thank you. Our next question or comment comes from the line of Tiago Fauth from Raymond James. Your line is now open.

Operator: Thank you. Our next question or comment comes from the line of Thiago Faust from Raymond James. Your line is now open.

Operator: Thank you. Our next question or comment comes from the line of Tiago Fauth from Raymond James. Your line is now open.

Speaker #5: Great. Thanks so much for taking the question. I had just one quick one on Ulixa. It's mostly related to the communication plan to the street on the regulatory interactions.

Thiago Faust: Great. Thanks so much for taking the question. I had just one quick one on ulixacaltamide, and it is also related to the communication plan to the street on the regulatory interactions. It is still a huge area of focus with investors. I am curious, what is the level of detail that the street can expect on around mid-cycle review, label and discussion, CMC inspection scheduling or anything related to that? Thank you.

Tiago Fauth: Great. Thanks so much for taking the question. I had just one quick one on ulixacaltamide, and it is also related to the communication plan to the street on the regulatory interactions. It is still a huge area of focus with investors. I am curious, what is the level of detail that the street can expect on around mid-cycle review, label and discussion, CMC inspection scheduling or anything related to that? Thank you.

Speaker #5: Still a huge area of focus with investors. So I'm curious, what's the level of detail that the street can expect on around mid-cycle review, labeling discussion, CMC inspection scheduling, or anything related to that?

Speaker #5: Thank you.

Speaker #1: Thanks. Thanks, Tiago. So maybe again, I'll take another step back here as well, right? So we of course being communicated by the FDA when the expected mid-cycle meetings are going to happen for both programs.

Marcio Souza: Thanks. Thanks, Thiago. Maybe again, I'll take another step back here as well, right? We are, of course, being communicated by the FDA when the expected mid-cycle meetings are gonna happen for both programs, their communication pattern with us when label negotiation is gonna expected to be started and completed, the entire cycle. We have very good visibility from the agency's goals and from the conversations with us in relation to that. Also can tell you that throughout this process, I think a very good shift, I would say on the FDA is just their ability to really try to keep communicating with the companies throughout the process.

Marcio Souza: Thanks. Thanks, Tiago. Maybe again, I'll take another step back here as well, right? We are, of course, being communicated by the FDA when the expected mid-cycle meetings are gonna happen for both programs, their communication pattern with us when label negotiation is gonna expected to be started and completed, the entire cycle. We have very good visibility from the agency's goals and from the conversations with us in relation to that. Also can tell you that throughout this process, I think a very good shift, I would say on the FDA is just their ability to really try to keep communicating with the companies throughout the process.

Speaker #1: They are communication pattern with us. When label negotiation is going to expect it to be started and completed. The entire cycle. So we have very good visibility from the agencies goals and from the conversations with us in relation to that.

Speaker #1: Although I can tell you that throughout this process, I think a very good shift I would say on the FDA is just the ability to really try to keep communicating with the companies throughout the process.

Speaker #1: And we are seeing that in both programs. Which gives us I'm going to be cautiously optimistic here about a good level of comfort on how the process is moving on both drugs.

Marcio Souza: We are seeing that in both programs, which gives us, I'm gonna be cautiously optimistic here about a good level of comfort on how the process is moving on both drugs. Having said that, I think it would not be appropriate for us to give play-by-play. At the mid-cycle, I think the expectation are in our end is that they're gonna be like no major concerns, like keep reviewing, keep finalizing, crossing the T's and dotting the I's. If that's the case, I think we should expect very little from us. Of course, if something meaningful happens on those meetings, either on the view of like maybe they want to see something or the opposite, they are moving faster and maybe they want to accelerate things.

Speaker #1: Having said that, I think you would not be appropriate for us to give play-by-play. And at the mid-cycle, I think the expectation or in our end is that they're going to be like no major concerns like keep reviewing, keep finalizing, crossing the T's and dotting the I's.

Speaker #1: And if that's the case, I think we should expect very little from us. Of course, if something meaningful happens on those meetings, either on the view of maybe they want to see something or the opposite.

Speaker #1: They are moving faster and maybe they want to accelerate things. I think it would be appropriate for us to have a discussion. But we need to get to that point with both applications to be able to have a discussion.

Marcio Souza: I think it would be appropriate for us to have a discussion, but we need to get to that point with both applications to be able to have a discussion. I know you asked EULEX, but I want to make sure our equally loved child gets some attention here with relutrigine.

Speaker #1: I know you asked Ulixa whether I want to make sure our equally loved child gets some attention here with related to.

Thiago Faust: Fair, fair enough. Fair enough. Thank you so much.

Tiago Fauth: Fair, fair enough. Fair enough. Thank you so much.

Speaker #5: Fair enough. Fair enough. Thank you so much.

Speaker #1: Of course.

Marcio Souza: Of course.

Speaker #3: Thank you. Our next question or comment comes from the line of François Brizois from LifeSide Capital. Your line is open.

Operator: Thank you. Our next question or comment comes from the line of François Brisebois from LifeSci Capital. Your line is open.

Speaker #5: Hey, thanks for the question and congrats on the emerald recruitment there. I was just wondering, maybe if you can help us understand, obviously, the patient population size is quite different between 2A and 8A.

François Brisebois: Hey, thanks for the question, and congrats on the EMERALD recruitment there. I was just wondering maybe if you can help us understand. Obviously, the patient population size is quite different between 2A and 8A and then going to broad. I was just wondering on the broad side, how different are these patients? My question is geared towards expectations. Is it, you know, that the 2A and 8A are so severe that if we look at that data that kinda sets these, you know, artificial bars or whatnot on expectations for the broad DEEs? Is that a dangerous game based on maybe the heterogeneity of the patients? Just a little more understanding on who are you going after with these broad DEEs.

Speaker #5: And then going to broad. But I was just wondering on the broad side, how different are these patients? And my question is geared towards expectations.

Speaker #5: Is it that the 2A and 8A are so severe that if we look at that data, that kind of sets these artificial bars or whatnot on expectations for the broad DEs?

Speaker #5: Or is that a dangerous game based on maybe the heterogeneity of the patients? Just a little more understanding on who are you going after with these broad DEs?

Speaker #1: Yeah. And thanks, Frank. I'll split that question in two parts, right? So one, it is kind of insane to think this way but it is the reality of the markets, right?

Marcio Souza: Yeah. I'll thanks, François. I'll split that question in 2 parts, right? One, it is kind of insane to think this way, but it is the reality of the markets, right? When you go to these patients and to the physicians and we understand their clinical course and just how the disease is a downward slope, it only gets worse over time, for those patients, unfortunately, leading to all sorts of complications and SUDEP, and so on. It is very clear that any improvements would be the bar, meaning, stat sig is the bar for this, for the EMERALD study, right?

Speaker #1: When you go to this patients and to the physicians and we understand their clinical course and just how the disease is a downward slope.

Speaker #1: It only gets worse over time. For those patients, unfortunately, leading to all sorts of complications and suit that and so on. It is very clear that A, improvements.

Speaker #1: Any improvements would be the bar. Meaning stat cig is the bar for this for the emerald study, right? Of course, we want to deliver the best possible results for those patients.

Marcio Souza: Of course, we want to deliver the best possible results for those patients, but I also think we have to be very careful about setting up the bars and as I said, in relation to the previous study with POWER1 on Rich's question. Here we are in a situation that is a very large market, but that is nothing. It's kind of the end of the line, right? If you think about these patients and throughout the time we expect to give them a lot. I think for this study, we need to be happy if we see statistical significance as we expect to and some improvements. Now, to go to the other side of the questions like how heterogeneous is this population? Our recruitment strategy was very clear.

Speaker #1: But also I think we have to be very careful about setting up the bars. And as I said, in relation to the previous study with power one on reduced question.

Speaker #1: So here we are in a situation that is a very large market. But that is nothing. It's kind of the end of the line, right?

Speaker #1: If you think about the patients and throughout the times we expect to give them a lot. But I think for this study, we need to be happy if we see statistical significance as we expect to.

Speaker #1: And some improvements. Now, if you go to the other side of the questions like how heterogeneous is this population? Our recruitment strategy was very clear, right?

Marcio Souza: It was, we want these patients to be diagnosed with DEE, so that's very serious, has to be early, has to have a developmental impact together with seizure onsets and a number of countable seizures at baseline. Having said that, we wanted the most diverse group of patients possible because that's what we're going after. That's what no other drug can do right now. We accomplished that. By definition, one could argue that SCN2A and SCN8A are harder to treat, but this is more heterogeneous to treat. If you can see, like, even half, I would say what we're seeing on enrolled would be. It's even hard to imagine how big of a market that would be. If we see just stabilization and improvements on these patients, that would be incredibly meaningful.

Speaker #1: Was we want these patients to be diagnosed with DEs. So that's very serious. Has to be early. Has to have a developmental impact to get her with seizure onsets.

Speaker #1: And a number of countable seizures at baseline. Having said that, we want the most diverse group of patients possible because that's what we're going after.

Speaker #1: That's what no other drug can do right now. And we accomplish that. By definition, one could argue that 2A and 8A are harder to treat.

Speaker #1: But this is more heterogeneous to treat. So if you can see even half, I would say, well, what are we seeing on emerald would be just don't even it's even hard to imagine how big of a markets that would be but if we see just stabilization and improvements on these patients, that would be incredibly meaningful.

Speaker #1: So on setting it up, what is meant to be a really major opportunity for all of us.

Marcio Souza: On setting it up, what is meant to be a really major opportunity for all of us.

Speaker #5: Maybe if I could sneak in. On AN, you obviously, I think the plan area was packed. About 8,000 people attending. And so can you just talk about your interactions with neurologists and movement disorder specialists?

François Brisebois: Maybe if I could sneak in. On AAN, I think the plenary was packed. It's like about 8,000 people attending. Can you just talk about your interactions with neurologists and movement disorder specialists? Does that trigger any interest for ex-US? Can you share what you guys are thinking on the ex-US stage for ulixacaltamide?

Speaker #5: Does that trigger any interest for XUS? Can you share what you guys are thinking on the XUS stage for Ulixa Caltimine?

Speaker #1: Yeah. Thanks for reminding us. I'll say that I think we got so excited and so wanting to move forward as always that sometimes don't stop.

Marcio Souza: Thanks for reminding us of things that I think we get so excited and so wanting to move forward as always that sometimes don't stop, slow down, and smell the roses. Being on that plenary at AAN in Chicago a couple weeks back and with, like, about 8,000 physicians attending, being the first one recognized as the most important clinical study presented at the meeting. It was very emotional for some of us, for me, certainly. The cool part, the most cool part was actually the number of people who came afterwards to us and wanting us to go to their practice with our medical affairs team and present to the entire practice and for them to start thinking and so on. It just reinforced the part.

Speaker #1: Slow down and smell the roses. Yeah. Being on that planetary, at AN in Chicago, a couple of weeks back and with about 8,000 physicians attending, being the first one, recognizes the most important clinical study presented at the meeting.

Speaker #1: It was very emotional for some of us. For me, certainly. But the cool parts and the most cool parts was actually the number of people who came afterwards.

Speaker #1: To us. And one thing was to go to their practice with our medical affairs team and present to the entire practice. And for them to start thinking and so on.

Speaker #1: So it's just reinforced the bar. Now, that is a huge interest on XUS. As you can imagine, we believe to be very clear, this is first and foremost a US opportunity right now.

Marcio Souza: Now, there is a huge interest on ex-US, as you can imagine. We believe, and to be very clear, this is first and foremost a US opportunity right now. We're putting our heads down, and we're executing in the US. There are multiple implications of current policies in the United States, particularly the pricing policies, that I would say don't excite us too much on explore split strategies for outside of the US. We wouldn't put at risk the US business. This is something that someone has to do globally. Of course, we're planning to eventually get there, but we're not really too excited about splitting the geographies with anyone else.

Speaker #1: We're putting our heads down. And we're executing the US. There are multiple implications of current policies. In the United States, particularly the pricing policies.

Speaker #1: That I would say don't excite us too much on explore split strategies for outside of the US. We would then put a risk the US business.

Speaker #1: So this is something that someone has to do globally. And of course, we're planning to eventually get there. But we're not really too excited about splitting the geographies with anyone else.

Speaker #5: Thank you.

François Brisebois: Thank you.

Speaker #6: Thank you. Our next question or comment comes from the line of Yateen Suneha from Guggenheim. Your line is now open.

Operator: Thank you.

Marcio Souza: Yeah.

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

Speaker #7: Hey, guys. Can you hear me?

Yatin Suneja: Hey, guys. Can you hear me?

Speaker #1: Yep.

Marcio Souza: Yep.

François Brisebois: Yep.

Speaker #7: Okay. Perfect. Hey, guys. Congrats. Very nice update. Maybe two questions for me. Marci, you addressed the expectations for power ones. The follow-up question I have there is that at least in power one, we're going to get data on the 30 milligram QD dose.

Yatin Suneja: Perfect. Hey, guys. Congrats. Very nice update. Maybe two questions from me. Marcio, you addressed the expectations for Power One. The follow-up question I have there is that at least in Power One, we're gonna get data on the 30-milligram QD dose. Could you maybe talk about the potential to capture additional efficacy with the 40-milligram in Power Two? Just love to hear from you. How should we think about the 30 and the 40s, if there is any potential there? You know, a broader question on the commercial side. Obviously, you are undertaking two big launches in the next, let's say, 6 months or so. Could you talk about the manufacturing, supply chain, all of that stuff? Where do you stand there? Thank you so much.

Speaker #7: So could you maybe talk about the potential to capture additional efficacy with the 40 milligram in power two? Just love to hear from you.

Speaker #7: How should we think about the 30 and the 40s if there is any potential there? And then a broader question on the commercial side.

Speaker #7: I mean, obviously, you are taking undertaking two big launches in the next, let's say, six months or so. So could you talk about the manufacturing, supply chain, all of that stuff?

Speaker #7: Where do you stand there? Thank you so much.

Marcio Souza: No, of course, Yatin. Maybe even starting with that, right? We imagine when we're planning these launches, we're like, Okay, what is likely to happen? That's how we set our base and how we set, like, the financial expectations, and you see in our forward-looking statements and overall, what you're saying there. We go and we talk to the market, and we're like, starts to be maybe we're a little conservative on some of those. What if we're wrong on the upper side of that? What if we are wrong by several folds on the upper side of that? That's how we have to plan supply in our view. That's what we've been doing, right?

Speaker #1: Yeah. Of course. Yeah. Maybe even starting with that, right? So we imagine when we're planning this launches, we're like, "Okay. What is likely to happen?" And that's how we set the our base and how we set the financial expectations.

Speaker #1: And you see in our forward-looking statements and overall what you're saying there. And then we go and we talk to the market. And we're like, "Starts to be maybe we're a little conservative on some of those." And what if we're wrong on the upper sides of that?

Speaker #1: And then what if you're wrong by several folds on the upper side of that? And that's how we have to plan supply in our view.

Speaker #1: And that's what we've been doing, right? We're blessed to for Ulixa, for example, to have dual like two completely independent drug substance manufacturers. They are being rock and rolling.

Marcio Souza: We're blessed to, for ulixacaltamide, for example, to have dual, like two complete independence drug substance manufacturers. They are being rock and rolling, make drug for us to have inventory. We're talking about metric tons of drugs here of ulixacaltamide, just to give you an idea of scale. This is not like a small scale in general. It's like a very large scale. We're also quite happy with the fact that the process is relatively, I'm gonna say, in the grand scheme of things, simple. We're being able to align that with the FDA before the submission. We're good there. relutrigine, of course, the scale is smaller for SCN2A and SCN8A, but it's not small for GEs.

Speaker #1: Drug for us to have inventory. We're talking about metric tons of drugs here of Ulixa just to give you an idea of scale. This is not a small scale in general.

Speaker #1: It's like a very large scale. And we're also quite happy with the fact that the process is relatively I'm going to say the grand scheme of things simple.

Speaker #1: And we've been able to align that with the FTA before the submission. So we're good there. Relutrigene, of course, they scale is smaller for 2N8A.

Speaker #1: But it's not small. For DEs, so we're thinking about that as well. And we prepare for that for the launch to very different distribution strategies, as you can imagine, right?

Marcio Souza: So we're thinking about that as well, and we pre-prepare for that for the launch to very different distribution strategies, as you can imagine. Right? A much more full white glove, like 1-on-1 interactions all the way to the point of use with the riluzole. And we're building like that. Then on the ulixacaltamide, we want to do a 1-to-1 as well, but of course, there's a little bit less downstream here. Both inventory and management of the patient taking the drug are quite sorted out. If I go back to your POWER1, Power Two interrelatedness question, 20, 30 milligrams POWER1, well, we believe we're gonna see very, very strong results there. It does beg the question, is that even more to come?

Speaker #1: It's like a much more full wide glove, like one-on-one interactions, all the way to the point of use with the Relutrigene and we're building like that.

Speaker #1: And then on the Ulixa, we want to do a one-to-one as well. But of course, there's a little bit less downstream here. So both inventory and management of the patient taking the drug have been quite sorted out.

Speaker #1: If I go back to a power one, power two interrelatedness question, 20, 30 milligrams power one believe we're going to see very, very strong results there.

Speaker #1: But does beg the question, is that even more to come? So if you're looking to recent history, very, very recent history, right? What we're seeing is companies dabbling with the issue of even a little bit more drug and you trip the wire and then the drug becomes completely useless from a clinical practice perspective.

Marcio Souza: If you look into recent history, very, very recent history, right? What we're seeing is companies dabbling with the issue of even a little bit more drug, and you trip the wire, and then the drug becomes completely useless from a clinical practice perspective. We saw that in our results a few weeks back, when there are two dose, and the top dose cannot be used at all by patients, despite delivering a little bit more efficacy on paper. That is not the case here, right? We know that that is not that limitation with vormatrigine. When you think about the unmet need of patients in the 3.5 million, not the 30,000 that maybe others are going after. That is the real market we're going after. It requires to understand the heterogeneity of all those patients.

Speaker #1: We saw that in a results a few weeks back when there are two doses and the top dose cannot be used at all by patients.

Speaker #1: Just by delivering a little bit more efficacy. On paper. But that is not the case here, right? We know that that is not that limitation with formatrogen.

Speaker #1: So when you think about the youth may need of patients and the three and a half million, not the 30,000 that may be others are going after, that is the real market we're going after.

Speaker #1: And it requires to understand the heterogeneity of all those patients. That's why having the ability to deliver meaningful either a 20, a 30, a 40, you name it, is so important.

Marcio Souza: That's why having the ability to deliver meaningful, either 20, 30 or 40, you name it, is so important. Not to create expectations that it could be even better, but of course, by definition, it could be even better there on Power Two. We'll get there soon and we're gonna be able to review it. I hope I answered your questions.

Speaker #1: So not to create expectations that it could be even better, but of course, by definition, it could be even better there on power two.

Speaker #1: So we'll get there soon. And we're going to be able to review it. I hope I answered your questions.

Speaker #5: Very helpful. Thank you so much.

Yatin Suneja: Very helpful. Thank you so much.

Speaker #6: Thank you. Our next question or comment comes from the line of Kembe's Yazdi from BTIG. Your line is now open.

Operator: Thank you. Our next question or comment comes from the line of Kambiz Yazdi from BTIG. Your line is now open.

Speaker #8: Morning, team. Thank you so much for the questions. Three for me. On Ulixa, with the Essential to Me disease education campaign launched in April, can you give us a sense for the early response from healthcare providers and how you think this initiative is going to translate into kind of the top of the patient funnel heading into the PDUFA?

Kambiz Yazdi: Morning, team. Thank you so much for the questions. Three for me. On ulixacaltamide, with the Essential To Me disease education campaign launched in April, can you give us a sense for the early response from healthcare providers and how you think this initiative is going to translate into kind of the top-of-patient funnel heading into the PDUFA? Maybe briefly on relutrigine. I know you touched base on it, Marcio Souza, how were you able to enroll EMERALD so rapidly compared to competitors in the DEE space? Lastly, on vormatrigine, you commented a little bit about blinded Power One, Power Two safety. How are you handling investigators' set option to reduce dose of background medication in Power One relative to the RADIANT study? Thank you so much.

Speaker #8: Maybe briefly on Relutrigene. I know you touched base on it, Marcio, but how were you able to enroll Emerald so rapidly compared to competitors in the DEE space?

Speaker #8: And lastly, on verumatrogen. You commented a little bit about blinded POWER 1, POWER 2 safety. How are you handling investigators' option to reduce dose of background medication in POWER 1 relative to the RADIANT study?

Speaker #8: Thank you so much.

Speaker #1: Sounds good. I'll try to tackle all of them so I can move on. So essential to me, was something we developed with patients and the way they see themselves.

Marcio Souza: Sounds good. I'll try to tackle all of them, so we can move on. Essential To Me was something we developed with patients and the way they see themselves. I think once the reaction from the providers are being fantastic. Like, people really love it. They see their patients. It reminds them to act. We're very happy with this. It will and it's already doing it like a great job on building further our database pre-launch to understand really who would be kind of the first in line here, both on the providers and on the patient. I'm gonna give more of an update there next quarter as well. On the how did you enroll EMERALD, right?

Speaker #1: And I think once the reaction from the providers are being fantastic. People really love it. They see their patients. It reminds them to act and so we're very happy with this.

Speaker #1: It will, and it's already doing it, a great job on building further our database pre-launch to understand really who would be kind of the first in line here, both on the providers and on the patient.

Speaker #1: We're going to give more of an update there next quarter as well. On the how they're doing role Emerald, right? I would say to go back in time and people would ask and maybe I'm going to be criticized by this comment, but I'm going to give it a try.

Marcio Souza: I would say to go back in time, people would ask and maybe I'm gonna be criticized by this comment, but I'm gonna give it a try. Who'd ask Jordan how the hell he could be Jordan, right? He would go back to the court and would train and would understand the shots that worked and the ones that didn't, and he wouldn't take any win as a win, but as an opportunity to the next win, to work. I think we're never gonna be as good as Jordan was, but I think we're pretty serious about every single day asking ourselves how can we do better because these patients need us. We're pretty good as well on actually getting sites that have a large number of patients and therefore have the ability to enroll.

Speaker #1: Who'd ask Jordan how the hell he could be Jordan, right? So it would go back to the court and would strain and would understand the shots that worked and the ones that didn't.

Speaker #1: And it wouldn't take any win as a win but as an opportunity to the next win. To work and I think we're never going to be as good as Jordan was, but I think we're pretty serious about every single day asking ourselves, how can we do better?

Speaker #1: Because this patient needs us. And we're pretty good as well on actually getting sites that have a large number of patients and therefore have the ability to enroll and they understand us from the beginning, right?

Marcio Souza: They understand us from the beginning, right? Meaning they understand that our expectations is highest quality first and foremost, but also high speeds in terms of you don't sit on queries or don't sit on eligibility form. You don't sit on a meeting that's gonna happen next week. You need us, we're there immediately. I think our team is just, if I were to say fantastic, they would be beyond fantastic on doing all of this 'cause everyone is here for one single reason, is to help these patients. That's as simple as that. I think there was a last question that I actually forgot now.

Speaker #1: Meaning they understand that our expectations is highest quality first and foremost. But also high speeds in terms of you don't sit on queries. We don't sit on eligibility form.

Speaker #1: You don't sit on a meeting that's going to happen next week. You need us. We're there immediately. And I think our team is just if I were to say fantastic, they would beyond fantastic.

Speaker #1: On doing all of this. Because everyone is here for one single reason is to help this patient. So that's as simple as that. And I think that was a last question that I actually forgot now.

Speaker #5: Yes. Just briefly, on vermatrogen, you talked a little bit about blinded power one, power two.

Kambiz Yazdi: Yes. Just briefly, on vormatrigine, you talked a little bit about blinded POWER1, Power Two.

Speaker #1: Got it.

Marcio Souza: Got it.

Kambiz Yazdi: Tolerability. How are you handling the investigator option to reduce dose and background in POWER1 relative to what was observed in RADIANT? Thank you so much.

Speaker #5: Tolerability. How are you handling the investigator option to reduce dose and background in power one relative to what was observed in radiant? Thank you so much.

Kambiz Yazdi: Tolerability. How are you handling the investigator option to reduce dose and background in POWER1 relative to what was observed in RADIANT? Thank you so much.

Speaker #1: Yeah, yeah. Absolutely. So what we learned from radiants, right, we got a both pragmatic and programmatic reduction system in power one. One must be very confident on what the investigational drug does to allow for the background to be reduced.

Marcio Souza: Yeah. Yeah. Absolutely. What we learned from RADIANT, right, we got like a pragmatic, both pragmatic and programmatic reduction system in Power One. One must be very constant on what the investigational drug does to allow for the background to be reduced. Others reduce the investigational drug, as you know, 'cause they don't trust the drug so much. Not our case. We allow that to happen. I will tell you it happens sparsely, which obviously is very important. But I think was very effective as well. It's the same algorithm for Power Two. I think physicians are very happy with how it's done. It's very safely done. Also very logical, the way it's done.

Speaker #1: Others reduce the investigational drug, as you know, because they don't trust the drug so much. Not our case. So we allow that to happen.

Speaker #1: I'll tell you, it happens partly with obviously very important. But I think what's very effective as well is the same algorithm for power two.

Speaker #1: I think physicians are very happy with how it's done. It's very safely done. Also very logical. The way it's done and it considers the fact that the background sometimes on placebo creates circumstances as well, which is required.

Marcio Souza: It considers the fact that the background sometimes on placebo creates like circumstance as well, which is required. It keeps the blinds, keeps the integrity, but at the same time, manages the study in general. Super happy with that as well.

Speaker #1: So keeps the blinds, keeps the integrity, but at the same time manages the study in general. So super happy with that as well.

Speaker #5: Thank you so much.

Dan Ferry: Thank you so much.

Kambiz Yazdi: Thank you so much.

Speaker #1: You bet.

Marcio Souza: You bet.

Speaker #6: Thank you. Our next question or comment comes from the line of Amir Fadia from Needham and Company. Your line is now open.

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

[Analyst] (Needham & Company): hi, this is Purna on for Ami. Thank you for taking our question. For focal onset epilepsy, are there any first-to-market dynamics you see if Xenon’s product is first to market? Our KOL checks have been overwhelmingly positive for vormatrigine, but just wanted to understand if there are any other factors that may have an impact here. Also, have you had any early discussions with payers on what data you may need to generate to support earlier line use? Thank you.

Speaker #9: Hi. This is Poona on for Ami. Thank you for taking our question. For focus on epilepsy, are there any first-to-market dynamics you see if Xenon's product is first-to-market?

Speaker #9: Our KOL checks have been overwhelmingly positive for vermatrogen, but just wanted to understand if there are any other factors that may have an impact here.

Speaker #9: And also, have you had any early discussions with payers on what data you may need to generate to support earlier line use? Thank you.

Speaker #1: Yeah. So I think what you're looking to the overall market, right? And we did a lot of work on this. It's very sad in a sense that when you go outside of the very small number of patients that are treated at level four epilepsy centers and you go to a much larger market outside of that, these patients are failing at very high proportions.

Marcio Souza: Yeah. I think when you look into the overall market, right? We did a lot of work on this. It's very sad in a sense that when you go outside of the very small number of patients that are treated at level 4 epilepsy centers, and you go to a much larger market outside of that, these patients are failing at very high proportions. They are, like, switching medications, like they're adding on top of that, and so on. I said this before, I don't believe there is a 1 winner game here that if we had 10 other drugs in focal onset seizures, that would be needed, right? What we have right now is completely inadequate.

Speaker #1: They are switching medications. They're adding on top of that and so on. So I said this before. I don't believe that is one winner game here that if we had 10 other drugs in focus on seizures, it would be needed, right?

Speaker #1: What we have right now is completely inadequate. Having said that, the biggest complication for all the years is when you get a drug and you really can't allow the physician to have flexibility to tailor for their patients' needs.

Marcio Souza: Having said that, the biggest complication for all the years is when you get, like, a drug and you really can't, like, allow the physician to have flexibility to tailor it for their patients' needs. I think what we're seeing with vormatrigine is that it gives a lot of flexibility in terms of what can be done, as we just discussed, on the previous question, for example. It's not the case for other potential competitors here. Also pretty confident about our overall pace, right? Like being a few months behind, remind all of you, we were way more than several months behind the other DEE study not that long ago. Now we are reading out soon when the other study is not even reading out until late next year.

Speaker #1: And I think what we've seen with vermatrogen is that it gives a lot of flexibility in terms of what can be done. As we just discussed, on the previous question, for example, and it's not the case for other potential competitors here.

Speaker #1: But also pretty confident about our overall pace like being a few months behind remind all of you we were way more than several months behind the other DE study not that long ago.

Speaker #1: And now we are really now soon and the other study is not even reading out until late next year. So I'm not sure if a few months is really a first mover advantage.

Marcio Souza: I'm not sure if a few months is really a first-mover advantage, and I don't believe there was ever a mechanistic sodium channel, a modulator removed from the market. There certainly was for the other mechanism that you mentioned, and all the safe signals are showing up there as well. I think the physicians we talked to are happy on having more options, but cautious about things that they've seen before not happening too well or working so well for patients on the safety side. We'll play that. We'll play full court press on the market, and I have no doubt we're gonna win.

Speaker #1: And I don't believe there was ever a mechanistic surgeon channel modulator removed from the markets. But there certainly was for the other mechanism that you mentioned.

Speaker #1: And all the safe signals are showing up there as well. So I think the physicians we talked to are happy on having more options.

Speaker #1: But cautious about things that they've seen before not happening too well or working so well for patients on the safety sides. So we'll play that.

Speaker #1: We'll play full card press on the markets and I have no doubt it's going to win.

Speaker #9: Got it. That makes a lot of sense. Thank you.

[Analyst] (Needham & Company): Got it. That makes a lot of sense. Thank you.

Speaker #6: Thank you. Our next question or comment comes from the line of Andrew Sy from Jefferies. Mr. Sy, your line is now open.

Operator: Thank you. Our next question or comment comes from the line of Andrew Tsai from Jefferies. Mr. Tsai, your line is now open.

Speaker #8: Hi. Good morning. Appreciate all the updates. I know we've talked a lot about Emerald study. I did have one small pointed question about it.

Andrew Tsai: Hi. Good morning. Appreciate all the updates. I know we've talked a lot about EMERALD Study. I did have one small pointed question about it. When you guys shared the 2 AAN data, 53% placebo-adjusted reduction overall, curious if you saw a consistent seizure reduction in both or each of the 2 DEE subgroups. Maybe that can give investors confidence you'll see robust and consistent efficacy across broader DEE subgroups. You know, would it be possible to share the seizure reduction in both subgroups? For ET, appreciate all the AAN analyses and so forth. You know, maybe based on your ongoing work on a friendlier titration schedule, ultimately, should this be approved, what kind of compliance rate do you expect to see in the real world?

Speaker #8: When you guys shared the 2AAA data 53th percent placebo-adjusted reduction overall, I'm curious if you saw a consistent seizure reduction in both or each of the two DEE subgroups.

Speaker #8: Maybe that can give investors confidence that you'll see robust and consistent efficacy across broader DE subgroup. So would it be possible to share the seizure reduction in both subgroups?

Speaker #8: And then for ET, appreciate all the AAN analyses and so forth. And maybe based on your ongoing work on a friendlier titration schedule, ultimately should this be approved, what kind of compliance rate do you expect to see in the real world?

Andrew Tsai: How long do you think Bulexa responders could be on the drug for? Thank you.

Speaker #8: How long do you think elixir responders could be on the drug for? Thank you.

Andrew Tsai: How long do you think Bulexa responders could be on the drug for? Thank you.

Speaker #1: Yeah. No. Thanks, Andrew. Maybe I will start with ET and then we can move back to 2A and 8A on involves and in general.

Marcio Souza: Yeah. No. Thanks. Thanks, Andrew. Maybe I'll start with ET and then we can move back to AAN and in both, and in general. When you ask physicians, right, and, we had a number of advisory boards and this insanely large, like, overall observational study, we asked them on how they would manage and what the expectation is. And I think the positive surprise for us was just, like, how comfortable they were on managing what we know to be a tolerability concern that happens on the first few days and first few weeks of this drug, right? We're going into this launch fully aware of that being the single most important driver of retention of patients in the long run.

Speaker #1: So when you ask physicians, right, and we had a number of advisory boards and this insanely large overall observational study, we asked them on how they would manage and what the expectation is.

Speaker #1: And I think the positive surprise for us was just like how comfortable they were on managing what we know to be a tolerability concern that happens on the first few days and first few weeks of this drug, right?

Speaker #1: We're going into this launch fully aware of that being the single most important driver of retention of patients in the long run. And they're incredibly comfortable.

Marcio Souza: And they're incredibly comfortable, and were actually telling us the things that we thought they could do in terms of, like, calling these patients and then advising them better and so on and so forth. So very comfortable with that. Now, how does that translate to overall retention over time, and financials? There are two approach here that we can take. One is saying what are the things we're thinking about, and that is your classical oral chronic therapy compliance and retention. Starts anywhere there on the 60% to 80%, right? That just overall numbers out there. Then what is the minimum to sustain the forecasts we put in front of you all to be over $10 billion? That number is way smaller. I'm not saying the number will be smaller.

Speaker #1: And we're actually telling us the things that we thought they could do in terms of calling these patients, and then advising them better, and so on and so forth.

Speaker #1: So very comfortable with that. Now, how does that translate to overall retention, over time, and financials? There are two approaches here that we can take.

Speaker #1: One is saying what are the things we're thinking about and that is your classical oral chronic therapy compliance and retention. So starts anywhere there on the 60s to 80 percent, right, that just overall numbers out there.

Speaker #1: And then what is the minimum to sustain the forecasts we put in front of you all to be over $10 billion? And that number is way smaller.

Speaker #1: So I'm not saying the number will be smaller. I'm saying we're going to have to believe on something to go into a forecast. And we don't need to believe a lot.

Marcio Souza: I'm saying we're gonna have to believe on something to go into a forecast, and we don't need to believe a lot to go to 10 billion plus. That gives us insane comfort. We also have hundreds of patients in the safe database, as you know, that have been on this drug for 6 months, 1 year, 2 years. That gives us a very good indicator on how persistent all these patients are. On the second question is very actually appropriate to be asked right now the results on SCN2A. Despite the fact that the manifestations in the elapsed physiology and the overall clinical manifestation of Nav1.2 deregulations and Nav1.6 deregulations are very different.

Marcio Souza: I'm saying we're gonna have to believe on something to go into a forecast, and we don't need to believe a lot to go to 10+ billion. That gives us insane comfort. We also have hundreds of patients in the safe database, as you know, that have been on this drug for 6 months, 1 year, 2 years. That gives us a very good indicator on how persistent all these patients are. On the second question is very actually appropriate to be asked right now the results on SCN2A. Despite the fact that the manifestations in the elapsed physiology and the overall clinical manifestation of Nav1.2 deregulations and Nav1.6 deregulations are very different.

Speaker #1: To go to $10 billion plus. And that gives us insane comforts. We also have hundreds, hundreds of patients in the safe database as you know that have been on this drug for six months, one year, two years.

Speaker #1: So that gives us a very good indicator on how persistent all these patients are. On the second question is very actually appropriate to be asked right now, the results on 2A and 8A, despite the fact that the manifestations and the elastic physiology and the overall clinical manifestation of NAV1.2 deregulations and NAV1.6 deregulations are very different.

Speaker #1: The results are quite similar. And very good in terms of the overall reduction, developmental gains, and seizure freedom. So it gives us insane comforts that it is so similar across 2A and 8A as well.

Marcio Souza: The results are quite similar, like, and very good in terms of the overall reduction, developmental gains, and seizure freedom. It gives us insane comfort that it is so similar across SCN2A as well. Very good points. Thanks for reminding us to make the highlights.

Speaker #1: Very good points. Thanks for reminding us to make the highlights.

Speaker #8: Thank you. As always.

Andrew Tsai: Thank you, as always.

Speaker #1: Of course.

Marcio Souza: Of course.

Speaker #6: Thank you. Our next question or comment comes from the line of David Hong from Deutsche Bank. Mr. Hong, your line is open.

Operator: Thank you. Our next question or comment comes from the line of David Hong from Deutsche Bank. Mr. Hong, your line is open.

Speaker #10: Hey, great. Thanks for taking my question. So I just had a couple here. Maybe back to Vermatragen in focal epilepsy across Tower 1 and Tower 2.

David Hong: Oh, great. Thanks for taking my questions. I just had a couple here. Maybe back to vormatrigine in focal epilepsy across POWER1 and Power Two. I know you're looking at 3 doses, 20, 30, 40 mg. How many of those doses would you like to actually take to market? What do you think would be, you know, the best number for commercial viability? In terms of the Power Three study, the monotherapy study that you also intend to conduct, could you talk a little bit about how that fits into your broader plans for vormatrigine? Why aren't other sponsors pursuing monotherapy studies like that? Thanks a lot.

Speaker #10: I know you're looking at three doses. 20, 30, 40 megs. How many of those doses would you like to actually take to market? And what do you think would be the best number for commercial viability?

Speaker #10: And then in terms of the Power 3 study, the monotherapy study that you also intend to conduct, could you talk a little bit about how that fits into your broader plans for Vermatragen?

Speaker #10: And why aren't other sponsors pursuing monotherapy studies like that? Thanks a lot.

Speaker #1: Thanks. No, thanks so much for the question, Dave. So 2030, 40, when you started at 24 Power 1 and the thought is like normally people start if you go to the public documents for other sponsors, for example, everyone's going to be like, "How close to the MES is it 50?

Marcio Souza: Thanks. No, thanks so much for the question, Dave. 20, 30, 40, when you start it at 20 for Power One, the thought is like, normally people start if you go to the public documents for like other sponsors, for example, everyone's gonna be like, how close to the MES TC50 can I get when you translate that to humans? I'm gonna be pretty close to that because I cannot go much higher. We can go much higher here. We're like, where do we start that the drug's gonna be clearly effective, right? Where do we end for now when we believe that's kind of the maximum efficacy? I think that's the blue cones that you're seeing.

Speaker #1: Can I guess when you translate that to humans?" And I'm going to be pretty close to that because they can all go much higher.

Speaker #1: We can go much higher here. So we're like where do we start the drugs are going to be clearly effective, right? So that's where it started at.

Speaker #1: And where do we end for now when we believe that it's kind of the maximum of efficacy? And I think that's the bookends that you're seeing.

Marcio Souza: A, a pretty big feedback from the thousands of neurologists that treats these patients is flexibility important for them as they're going through different patient types and different comorbid conditions. We intend to bring all of those to the market because we believe that gives the highest flexibility positions and our largest ability to obtain and keep market share, right? Power Three is a different animal. Power Three requires the profile for vormatrigine. The answer to your question, why others are not doing it, is because they cannot, right? You need to be able to use the drug as monotherapy. Now there's steps towards monotherapy, right? It's not an immediate reduction to monotherapy. It has to be done pretty safely, pretty thoughtfully.

Speaker #1: But a pretty big feedback from the thousands of neurologists that treat these patients is flexibility is important for them. As they're going through different patient types and different comorbid conditions.

Speaker #1: And so we intend to bring all of those to the market because we believe that gives the highest flexibility to physicians and our largest ability to obtain and keep market share, right?

Speaker #1: Power 3 is a different animal. Power 3 requires the profile of Vermatragen. So the answer to your question, why others are not doing it, is because they cannot.

Speaker #1: Right? Because you would be able to you need to be able to use the drug as monotherapy. Now, there are steps towards monotherapy, right?

Speaker #1: It's not an immediate reduction to monotherapy. It has to be done pretty safely, pretty thoughtfully. But the patients fail because they can't be on one mechanism.

Marcio Souza: The patients fail because they can't be on one mechanism. The only mechanism that can, if tolerated, as we believe here for vormatrigine, can truly stop any seizures is by acting on the IFs and by modulating these channels. We're the only ones that do that right now. Like everything else is upstream of the mechanism. That's why the confidence when you have a drug like vormatrigine, as I said in my prepared remarks, this is the most potent and most selective ever developed. We have this data publicly available for anyone to scrutinize. That is the confidence there.

Speaker #1: The only mechanism that can if tolerated, as we believe here, Vermatragen can truly stop any seizures is by acting on the IS and by modulating these channels.

Speaker #1: And we're the only ones that do that right now. Everything else is upstream of that mechanism. So that's why the confidence when you have a drug like Vermatragen, as I said on my prepared remarks, this is the most potent and most selective ever developed.

Speaker #1: So we have this data publicly available for anyone to scrutinize. So that is the confidence there. What it does is to move from what has been in a little bit, a little bit of the definition of insanity on how these drugs are developed to get more and more severe patients.

Marcio Souza: What it does is to move from what has been in a little bit of the definition of insanity on how these drugs are developed to get more and more severe patients, smaller pools of patients, and they no longer represent the broader markets on those refractory studies. You're never really addressing the true market, the true needs that are those patients who are struggling to go back to work, struggling to stay driving, struggling to have concentration. Significant number of patients with epilepsy go into disability costs themselves and the healthcare system and the Social Security system. Insane amount of resource because the drugs they were put in are compounding the issue with the condition.

Speaker #1: Smaller pools of patients and they no longer represent the broader markets on those refractory studies. And you're never really addressing the true markets, the true manese that are those patients who are struggling to go back to work, struggling to stay driving, struggling to have concentration.

Speaker #1: Significant number of patients with epilepsy go into disability. They cost themselves and the healthcare system and the social security system. Insane amount of resource.

Speaker #1: Because the drugs they were put in are compounding the issue with the condition. And I think we have an obligation as a company with such potent, such interesting drug to go there and change and revolutionize, as we say, the treatments of epilepsy.

Marcio Souza: I think we have a obligation as a company with such a potent, such a interesting drug to go there and change and revolutionize, as we say, the treatments of epilepsy. That is the long answer to the question.

Speaker #1: That is the long answer to the question.

Speaker #10: Thanks a lot.

David Hong: Thanks a lot.

Speaker #1: You bet.

Marcio Souza: You bet.

Speaker #6: Thank you. Our next question or comment comes from the line of Jay Olson. Oh, I'm sorry. Olson Jay from OPCO. Your line is now open.

Operator: Thank you. Our next question or comment comes from the line of Jay Olson. Oh, I'm sorry. Olson Jay from Oppenheimer. Your line is now open.

Speaker #1: Oh, hi. Thanks for taking the question. I'm glad all the progress. This is a challenge on the line for Jay. Maybe a couple from us.

[Analyst] (Oppenheimer): Oh, hi. Thanks for taking the question and congrats on all the progress. This is Chang on the line for Jay. Maybe a couple from us. First on the ulixacaltamide commercialization. Just curious about with the feedback from AAN, and market research you conducted, kind of what do you view as the most important driver of adoption? Then, I think at AAN you also presented some data on building channel model later in pain. I'm just also curious about related thinking around this opportunity and if there's anything we should expect in the near term. Thank you.

Speaker #1: First, I'm the OLIX commercialization. Just curious about what the feedback from A and the market research you conducted was. Kind of, what do you view as the most important driver of adoption?

Speaker #1: And then I think at A and you also presented some data on certain channel modulator in pain. So I'm just also curious about your latest thinking around this opportunity and if there's anything we should expect in the near term.

Speaker #1: Thank you. Yeah, yeah. Of course. Thanks, Shane. So the most important thing for physicians, right, when you rank and as I mentioned before, and I appreciate you bringing up the question, it was very extensive testing and really understanding the details from them.

Marcio Souza: Yeah, yeah, of course. Thanks, Chang. The most important thing for physicians, right, when you rank, and as I mentioned before, and I appreciate you bringing up the question, was very extensive testing and really understanding the details from them. There are a number of things they really like. They really like the fact that they never had something targeted for essential tremors. Having something that the most fundamental mechanism is T-type calcium modulation, and now they have something for that, or soon they're gonna have something for that. The second that was actually a little bit surprising to all of us. They absolutely love the fact that in 2 weeks, for the majority of the patients, you have the ability to have a conversation with the patients, and they really have an effect.

Marcio Souza: Thanks, Chang. The most important thing for physicians, right, when you rank, and as I mentioned before, and I appreciate you bringing up the question, was very extensive testing and really understanding the details from them. There are a number of things they really like. They really like the fact that they never had something targeted for essential tremors. Having something that the most fundamental mechanism is T-type calcium modulation, and now they have something for that, or soon they're gonna have something for that. The second that was actually a little bit surprising to all of us. They absolutely love the fact that in 2 weeks, for the majority of the patients, you have the ability to have a conversation with the patients, and they really have an effect.

Speaker #1: And there are a number of things they really like. They really like the fact that they never had something targeted for essential tremors. So having something that fundamentally the most fundamental mechanism is to type calcium modulation.

Speaker #1: And now they have something for that or soon they're going to have something for that. The second was actually a little bit surprising to all of us.

Speaker #1: They absolutely love the fact that in two weeks for the majority of the patients, you have the ability to have a conversation with the patients and they really have an effect.

Speaker #1: They just don't have that right now in a sustainable manner. They like the fact that we tested the durability of effects on study two.

Marcio Souza: They just don't have that right now in a sustainable manner. They like the fact that we tested the durability of effects on study 2. I would say all those things together, there are many others, really, are gonna be key drivers of adoption. As I mentioned on one of the previous call about like inventory and building, if anything, they're giving us indications they're gonna prescribe to way more patients than we originally thought there. The second part of your question about our pain program. Well, I think we've been, as you can imagine, right, we're a CNS company. We need to look into areas of science that make sense for us based on our technology on one end. On another end, we do have a fair bit of things that are moving forward.

Speaker #1: And I would say all those things together, there are many others really are going to be key drivers of adoption. And as I mentioned on one of the previous call about inventory and building if anything, they're giving us indications they're going to prescribe to way more patients than we originally thought there.

Speaker #1: And then the second part of your question about our pain program, well, I think we've been, as you can imagine, right, we're a CNS company.

Speaker #1: We need to look into areas of science that make sense for us based on our technology. On one end, on another end, we do have a fair bit of things that are moving forwards.

Speaker #1: As we discussed today, many more catalysts to come. So we've been taking a measured approach in terms of exploring a number of other areas in science that our molecules and our platforms can play a significant role.

Marcio Souza: As we discussed today, many more catalysts to come. We've been taking a measured approach in terms of exploring a number of other areas in science that our molecules and our platforms can play a significant role. At AAN, we did present some of the work we've been doing in pain. You will hear more from us in the future about how we are advancing quite significantly on that regard as well.

Speaker #1: And at AN, we did present some of the work we've been doing in pain. And you will hear more from us in the future about how we are advancing quite significantly on that regard as well.

Speaker #10: Got it. Thank you so much.

[Analyst] (Oppenheimer): Got it. Thank you so much.

Speaker #1: You bet.

Marcio Souza: You bet.

Speaker #6: Thank you. Our next question or comment comes from the line of Douglas Sal from HC Wayne Rapp. Your line is now open.

Operator: Thank you. Our next question or comment comes from the line of Douglas Tsao from H.C. Wainwright. Your line is now open.

Speaker #11: Hi. Good morning. Thanks for taking the question. Hello. Can you hear me? Sorry about that. Marcio, just starting with Emerald, I'm just curious congrats on completion of enrollment.

Douglas Tsao: Hi. Good morning. Thanks for taking the question. Hello, can you hear me?

Marcio Souza: Yes, we can, Doug.

Douglas Tsao: Sorry about that. You know, Marcio, just starting with EMERALD, I am just curious. Congrats on completion of enrollment. Obviously, demand was very strong. I am just curious if you have insight in terms of the subsets of patients that you received, and were there any particular disease where you saw very strong demand to reflect sort of the magnitude of unmet need? Because obviously, for so many of these, there is no approved therapy, and physicians are just basically trying to figure it out as they go along using sort of off-label ASMs.

Speaker #11: Obviously, demand was very strong. I'm just curious if you have insight in terms of the subsets of patients that you received, and were there any particular Ds where you saw very strong demand to reflect sort of the magnitude of unmet need?

Speaker #11: Because obviously, for so many of these, there's no approved therapy. And physicians are just basically trying to figure it out as they go along using sort of off-label ASMs.

Speaker #1: Yeah. Doug, I'm going to be honest. When we went to the sites and we talked to physicians, we presented a protocol maybe what I haven't said in the call so far is we disappointed a lot of physicians by telling them, "No, no, no.

Marcio Souza: Yeah. Doug, I'm gonna be honest, like, when we went to the sites and we talked to physicians, we presented a protocol. Maybe what I haven't said in the call so far is we disappointed a lot of physicians by telling them, No, no, you gotta stop. You can't enroll more patients on this study. They really got there pretty fast because exactly, and it seems like you have a deep understanding of this, exactly what you just said. There is so many patients out there that there is very little or nothing they can do. Even patients who have other drugs technically approved, but they failed already, right? They try to have some optimal response.

Speaker #1: You got to stop. You can't enroll more patients." On this study, we really got there pretty fast because the exactly and seems like you have a deep understanding of this exactly what you just said.

Speaker #1: That is so many patients out there that is very little or nothing they can do. Even patients who have other drugs technically approved, but they failed already, right?

Speaker #1: Or they tried to have suboptimal response. So it is very broad. We have both phenotype and genotype of patients we got here, and it is within what we expected.

Marcio Souza: It is very broad, the both phenotype and genotype of patients we got here, and it is within what we expected. Unfortunately, and maybe this is a mea culpa, an apology, we couldn't get all the patients that wanted to be on this study on this study. I think our promise is if the drug works, we're gonna get the drug to them in the near future. Really, really happy on everything and all the dynamics here.

Speaker #1: And unfortunately, and maybe this is a mea culpa and apology, we couldn't get all the patients that wanted to be on this study. On this study, but I think our promise is if the drug works, we're going to get the drug to them.

Speaker #1: In the near future. So really, really happy on everything and all the dynamics here.

Speaker #10: Okay. Great. And if I can, on a follow-up in terms for vermatrogen, just with power one, I'm just curious, do you have any insight in terms of the discontinuation rate so far?

Douglas Tsao: Okay, great. If I can, on a follow-up in terms for vormatrigine, just with POWER1, I'm just curious, do you have any insight in terms of the discontinuation rate so far? Obviously, I think in RADIANT, there were some discontinuations. We certainly heard from clinicians that, you know, they sort of had patients who maybe dropped out, who if they would have provided some additional counseling, just given the robustness ultimately of the drug, it would maybe sort of encourage them to stay in. Additionally, given the fact that you sort of titrate up in POWER1, you know, if we're seeing any evidence that that is having an effect. Thank you.

Speaker #10: Because obviously, I think in Radiant, there were some discontinuations, but we certainly heard from clinicians that they sort of had patients who maybe dropped out who would have provided some additional counseling just given the robustness.

Speaker #10: Ultimately, of the drug, it would have maybe sort of encouraged them to stay in. As long as additionally, given the fact that you sort of titrate up in power one, if we're seeing any evidence that that is having an effect.

Speaker #10: Thank you.

Speaker #1: Yeah, absolutely. So pretty happy with how it got reduced. I would say the overall discontinuation here in terms of the historical with the program.

Marcio Souza: Yeah, absolutely. We're pretty happy with how it got reduced. I would say the overall discontinuation here in terms of the historical with the program, I think some of the points you mentioned, right? People get more experience with the studies and so on. They get more comfortable in managing. So I'll say I think we're very comfortable with that. I think we're very comfortable with the new benchmark as well when you consider like drugs people are excited about have like 22% to 25% discontinuation with further 25% dose reduction on the top dose, that's definitely not what we are seeing. We think we are very competitive here, considering, like, recent competitive events. Okay, great. Thank you so much. Of course.

Speaker #1: I think some of the points you mentioned, right, people get more experience with these studies and so on. They get more comfortable managing. So I'll say I think we're very comfortable with that.

Speaker #1: I think we're very comfortable with the new benchmark as well when you consider drugs people are excited about have 22 to 25 percent discontinuation, with further 25 percent dose reduction on the top dose.

Speaker #1: That's definitely not what we are seeing. So we think we are very, very competitive here considering recent competitive events.

Speaker #10: Okay. Great. Thank you so much.

Speaker #1: Of course.

Speaker #6: Thank you. Our next question or comment comes to the line of Daniel Brill from Trua Securities. Your line is now open.

Operator: Thank you. Our next question or comment comes from the line of Danielle Brill from Truist Securities. Your line is now open.

Speaker #12: Hi. Tyler here for Danielle. Thanks so much for taking our questions. My question is regarding the total addressable market in essential tremor. So up to 7 million patients have essential tremor, but you've recently said that there are approximately 1 million actively seeking treatment.

[Analyst] (Truist Securities): Hi, Tyler here for Danielle. Thanks so much for taking our questions. My question's regarding the total addressable market in essential tremor. Up to 7 million patients have essential tremor, but you've recently said that there are approximately 1 million actively seeking treatment. What's this gap between the predicted prevalent population and the seeking treatment? With that, is education still needed in the field for more accurate diagnosis? Do higher volume academic centers typically have that more accurate diagnosis?

Speaker #12: So what's this gap between the predicted prevalent population and the seeking treatment? And with that, is education still needed in the field for more accurate diagnosis?

Speaker #12: And do higher volume academic centers typically have that more accurate diagnosis?

Speaker #1: Yeah. So there's about 2 to 2 and a half million patients right now either who are being treated and seen a physician at this moment or just done it and are sitting on the sidelines.

Marcio Souza: Yeah. There's about, like, 2 to 2.5 million patients right now, either who are being, like, treated and seeing a physician at this moment or just done it and are sitting on the side. When you go from 7 to, let's say, 2 to 3, it is a drop, but it's not unheard of. I would say there are many reasons here. It is not a misdiagnosed problem, and I want to clarify that. This is mostly like something they know, and they either not speaking publicly or disclosing or discussing because they know there's a stigma. There's the facts. I think we just saw this week, Susan Collins speaking about her diagnosis of essential tremor in defense of people attacking that she might not be fit, which obviously is absurd, right?

Speaker #1: So when you go from 7 to, let's say, 2 to 3, it is a drop, but it's not unheard of. I would say there are many, many reasons here.

Speaker #1: It is not a misdiagnosed problem. And I want to clarify that. So and this is mostly something they know and they either not speaking publicly or disclosing or discussing because they know there's this stigma.

Speaker #1: There's the facts. I think we just saw this week Senator Collins speaking about her diagnosis of essential tremor in defense of people attacking that she might not be fit, which obviously is absurd, right, because this is a progressive disease only of movements, for example.

Marcio Souza: Because this is a progressive disease only of movements, for example, but people are afraid of talking about things like that. It is a disease that for the most part, runs in the family, so people are aware. It is a combination of 2 factors. One is the progress, so it's how quickly and how far the disease patients are. We call that the level of disability, and that's what gives us about 2 million. The other is society sometimes not being too ready for someone to raise their hands and say they have a condition. I think the last one is one, you have 2 or 3 family members and a physician tells the first one, There's nothing I can do right now 'cause there's no good alternatives available. You disengage the other family members.

Speaker #1: But people are afraid of talking about things like that. It is a disease that for the most part runs in the family. So people are aware it is a combination of two factors.

Speaker #1: One is the progress. So it's how quickly and how far the disease patients are. We call that the level of disability. And that's what gives us about 3 million.

Speaker #1: And the other is society. Sometimes not being too ready for someone to raise their hands and say they have a condition. And I think the last one is one you have two or three family members and a physician tells the first one there's nothing I can do right now because there's no good alternatives available.

Speaker #1: You disengage the other family members. If you look at my upcoming to the market, hopefully soon, that all those dynamics change, right? So we bring this to the forefront.

Marcio Souza: With ulixacaltamide coming to the market, hopefully soon, all those dynamics change, right? We bring this to the forefront. One of the reasons why our campaign is called Essential To Me, because it's really what is essential for them, for the patients. That's what we want to awaken on that.

Speaker #1: One of the reasons why our campaigns called essential to me because it's really what is essential for that for the patients. That's what we want to awaken on that.

Speaker #12: Thanks so much.

[Analyst] (Truist Securities): Thanks so much.

Speaker #1: Of course.

Marcio Souza: Of course.

Speaker #6: Thank you. Our next question or comment comes from the line of Brian Scorni from Bayard. Your line is now open.

Operator: Thank you. Our next question or comment comes from the line of Brian Skorney from Baird. Your line is now open.

Speaker #13: Hey, good morning, team. Thanks for putting me in here. You've alluded to the opportunity to develop the Ulexa and the role of T-type calcium channel antagonists and indications beyond ET.

Brian Skorney: Hey, good morning, team. Thanks for fitting me in here. You've alluded to the opportunity to develop Ulixa and the role of T-type calcium channel antagonists and indications beyond ET. Obviously, your plate's pretty full with two NDA reviews and running another few pivotal studies, so maybe it's a little bit on the back burner. Just wondering if you had any updated thoughts on the exploration of other indications where Ulixa could have an impact, and if there's any timeframe you can provide where we might hear an update on that.

Speaker #13: Obviously, you're pretty full with 2NDA reviews and running another few pivotal studies. So maybe it's a little bit on the back burner, but just wondering if you had any updated thoughts on the exploration of other indications where Ulexa could have an impact and if there's any timeframe you can provide where we might hear an update on that.

Speaker #1: Yeah. Brian, we did select two other indications. We're going to be going through. We're just going through the last, I would say, checking everything here, taking a time.

Marcio Souza: Yes. Brian, we did select two other indications we're gonna be going through. We're just going through the last, I'll say, checking everything here, taking the time and making sure that we can discuss a little bit more publicly. We're discussing the format of that as well, if it's an R&D day or if it's maybe a series of calls and experts with us. Tonight's just for bits, and we're gonna be able to talk about that. We are very excited, both scientifically, patient-side, and market potential for either of those indications.

Speaker #1: And making sure that we can discuss a little bit more publicly. We're discussing the format of that as well, if it's an R&D day or if it's maybe a series of calls and experts with us.

Speaker #1: So sit tight just for a bit, and you're going to be able to talk about that. We are very excited, both scientifically, patient side, and market potential for either of those indications.

Speaker #13: Great. Thanks for the update.

Brian Skorney: Great. Thanks for the update.

Speaker #1: Thank you.

Marcio Souza: Thank you.

Speaker #6: Thank you. I'm afraid that's all the time we have for Q&A at this time. I would like to turn the conference back over to Mr. Mar, ECO Souza, for any closing remarks.

Operator: Thank you. I'm afraid that's all the time we have for Q&A at this time. I would like to turn the conference back over to Mr. Marcio Souza for any closing remarks.

Speaker #1: So thank you very much, everyone. I'm sorry for the questions we couldn't take on today's call. I think we're running a little bit ahead here.

Marcio Souza: Thank you very much, everyone. I'm sorry for the questions we couldn't take on today's call. I think we're running a little bit ahead here. Incredibly exciting way to start the year, right? As you think back on the last 12 months, so much happened in really moving the needle for so many patients. Yet another study they were finalizing, making sure that we flip the card, make sure that if there is a benefit, we're gonna get that as quickly as possible. This year already with EMBRAVE part A being positive, EMBRAVE3 recruiting really well. EMERALD coming up, Power One coming up, Power Two coming up. New indications as Brian just asked. We're full steam ahead. The focus is very clear.

Speaker #1: Incredibly exciting way to start the year, right, as you think back on the last 12 months. So much happened. In really moving the needle for so many patients.

Speaker #1: Yet another study that were finalizing making sure that we flip the card, make sure that if there is a benefit, we're going to get that as quickly as possible.

Speaker #1: This year already, we've embraced part A being positive, embraced three recruiting really well, Emerald coming up, part one coming up, part two coming up, new indications as Brian just asked.

Speaker #1: So we're fully seen ahead. The focus is very clear. It's to deliver as much value for everyone, including our shareholders. And we promise you we'll have our heads down on the execution here, getting everything done thanks for the interest and we're going to be talking soon.

Marcio Souza: It's to deliver as much value for everyone, including our shareholders. We promise you, we'll have our heads down on the execution here, getting everything done. Thanks for the interest, we're gonna be talking soon.

Speaker #14: Ladies and gentlemen, thank you for participating in today's conference. This concludes the program. You may now disconnect. Everyone have a wonderful day. Speaker standby.

Operator: Ladies and gentlemen, thank you for participating in today's conference. This concludes the program. You may now disconnect. Everyone, have a wonderful day. Speakers stand by.