Q3 2024 Praxis Precision Medicines Inc Earnings Call
Good day and thank you for standing by. Welcome to the Practice Precision Medicines.
3rd quarter, 2024 corporate update.
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After the Speaker's presentation, there will be a question and answer session.
Good morning and welcome to the practice Precision Medicine's 3rd quarter 2021 for our financial results and business that they contact call.
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Speaker Change: Q and a call today, our Marshal, Susan, President and Chief Executive Officer at Practice in Tim Kelly, Chief Financial Officer. After providing updates on our key programs, there will be a brief question in your session. With that, to my pleasure to turn the call over to Marshal.
Marshal: Thank you, good morning, and welcome to the practice of Stuttgart Quarters, when the 24 conference call.
Marshal: The Special Court will remain later focused on advancing our pipeline as we gear off for next year to have 4th-throggling registration, totaling to a substantial multi-pidied dollar opportunity.
Marshal: The film's three studies in essential drama essential three for lead-projected music saccouts mine, continues for a rest while.
Marshal: We have confirmed all aspects of the internet and I was in an out-of-date implants to have the results in Q1 2025
Marshal: This studies are well-powered and controlled for success.
Marshal: because there's a range of outcomes for each study as well as the internet and the incoming months. We decided that we only share enough data on timing for both studies one and thirty two once we have evaluated the recommendations on the internet and review board for the internet.
Marshal: In Q3, we're very excited to report the positive top line results for another 515 R pipeline, we're letter G.
Marshal: In the face to Enbowl's trial in Sian 2A and Sian 8A G.
Marshal: In the Fishing Patient Study, Reload for Engineering, Demonstrating in practice for the 6th Potent Reduction in Motor Seasors vs. Plot Seaball.
Marshal: with one third of the patients achieving unprecedented seizure free status.
Marshal: Based on those results, we initiated a second Restration of Cohars of the Envolved Study, which has already started screening patients just weeks after completion of the prior Cohars.
Marshal: In common at Blacks is, where messaging previously known as Braccia 628, is a starting out of the gate's trunk in all areas of our comprehensive energy clinical program.
Marshal: The innovative observatory study and power, a first of its kind, in collaboration with the AppLapSystatic Consortium, launched in the third quarter.
Marshal: In the short period of time, attracted the interest of over a thousand patients will register in the study.
Marshal: We expect the key learnings for empower to impact the entire energy problem.
Marshal: The Phase 2 Regents and the Phase 2 3 Power One Trials are on track for topline results next year
Marshal: Rounding out our report for you, as a nurse and begin those impatience in Brazil in the second quarter for the embrace study. And we continue to engage with regulatory agencies in the Europe and in the US to finalize the development plans in S.Y. and 2A gain of function patients.
Marshal: With our strong balance, we continue to be fully funded as we pursue our visions that ever precision therapies for patients with CMS disorders.
Marshal: Let me now focus some more on New Lecture.
Marshal: A Renovative Essentials with Product Minitude is the biggest and most comprehensive product conducted today.
Marshal: We began recruiting for the two phase two stages just about one year ago and have seen tens of thousands of patients interested in participating
Marshal: This vibrant participation highlights the significance and metmete for the millions of patients with a central tremor in their physicians and caregivers who are seeking a therapy that will allow patients to perform daily activities without impairments.
Marshal: The needs for treatment and essential framework continues to be more defined as we advanced this program. In a survey we conducted with over 400 patients.
Marshal: 7% of the respondents said they do not see over their E.C. symptoms or manage with current streetbats.
Marshal: In a separate survey, we conducted with a hundred and fifty-three in physicians. They shared that 85% of their visits with its patients are focused on looking for treatments.
Marshal: Clearly, there is an incredible need here and we look forward to shortly completing the essential three studies with the GoFBringing an option to the markets.
Marshal: As a quick refresher, the essential three problems have to use the most annual stage three studies being run concurrently.
Marshal: 31 is at 12 weeks to arm placebo controlled parlor group study, and 32 is at 12 weeks randomized with dry state.
Marshal: Both studies use a primary assessment that change in the modified activities of daily living. And they are both running entirely decentralized and in the patient's home rather than at clinical sites.
Marshal: We share on our last quarterly call that we decided to trigger a pre-clans entering analysis on 55 to 75% of the patients have completed the 12 weeks that you want.
Marshal: The analysis will inform us whether we should continue the study throughout completion. If the primary point is max to consider seizing the study or to consider enrolling additional patients to ensure it sufficiently powered for success.
Marshal: Based on the expectation for the sufficient number of patients to complete this study.
Marshal: Cleaning of the data, execution of the statistical testing and analysis by the independent boards in our internal operation.
Marshal: As well as considering the operational impacts in the study completion of 32, we'll be finalizing the training analysis in the first quarter of 2025.
Marshal: Given the range of outcomes, we will not speculate on scenarios or timing for a doubt of 31 and 32. And here we hear from the Internet review boards at which time we will be better informed to provide an update.
Marshal: Regardless, preparations continue to file the NGA as expected in 2025.
Marshal: Now moving on to our highly differentiated Black support for you.
Marshal: We're messaging, previously known as Prost-X8, is a next generation functionally selective small molecule, being developed as a one-stainly oral treatment for adults with epilepsy.
Marshal: We know that treatment options for common epilepsis are lacking in both efficacy and tolerability. And we believe that profile emerging with bromuatrogen, we will provide a high-differentiated, paradigm-shifting way to treat disease.
Marshal: Last quarter, we introduced our broad energy clinical product of a remetraging in focal and geralized graph.
Speaker Change: And I'm glad you shared that the ambitious multi-study goal we aim to achieve our advancing well.
Marshal: and Energy is comprised of four studies aiming to build a strong base of patients for our trial while generating multiple data points over the next 18 months to support the differentiated profile of our messaging.
Marshal: 3 Triangle of Energy are to evaluate the accuracy and safety.
Marshal: The first of this is Radian, an open-labour study that eruptations with either focal or generalized black sea who will receive her mother gene for eight weeks with a state follow-up of two weeks.
Marshal: We have all tracked to the universal top line results in the first half of 2025, which should help us better understand the effectiveness levels of our messaging and its pharmacology in the patient population.
Marshal: The power one in power two studies are 12 weeks phase two three studies in patients with full contact seizures
Marshal: 1. Power 1 is underway and we anticipate stop line riddles towards the ends of 2025.
Marshal: We're slightly stagger the initiation of power to begin recruiting in the first half of 2025.
Marshal: The combined studies are expected in role approximately 500 patients globally.
Marshal: As we consider other areas where a Vermatrogen can play an important role, it's clear that its activities in that 1.7 and 1.8 couple with fast acting pharmacology and safe profile could play an important role in pay management.
Marshal: We're concluding our assessments about the potential role of our Masteraging in Bang and we will be sharing more in the near future.
Marshal: Now turning to our religion, a function is state modulator that is formulated for the gastric use in disease. A group of severe epileptics characterized by developmental delays with early onset.
Marshal: with S.E. and S.E.A. being one of the most severe and refractory forms of these.
Marshal: and we are currently there is no approval to admit.
Marshal: As a reminder, Relatoraging has often and rare perdiacs of designation for these two indications.
Marshal: We're thrilled and humbled to share the umbrella results we have served in face to involve Trioco-Hard's One in its intu-A in 8A less quarter, where we're leveraging the most rate of number of impressive and unprecedented data points.
Marshal: This two-on study was run over 60 weeks with four four-week periods.
Marshal: Patients in the placebo arm were administered placebo for one period and re-lettering for the other three periods.
Marshal: and Niner Depations, All Investigators, Work Away, which bears loss on placebo.
Marshal: Picking Patience completed a study, and Patience had the option to continue to open labor extension after the six weeks.
Marshal: A robust 46% plus you will adjust the reduction in motor seizures over the period of walls of the serves.
Marshal: with 33% are 5 out of 15 patients achieving seizure free status that notably was never seen before in the severe patient population.
Marshal: In addition, we saw this is more fun in fact, noted in the study by both caregivers and clinicians.
Marshal: with Relessaging Leading to Meaningful Improvement in Overall well-being of patients in areas of CISER severity, in intensity, alertness and other important measures.
Marshal: This is also very impressive and encouraging, finding given not only the severity of the disease, but also the lack of improvements in this area with currently available treatments.
Marshal: Lastly, Relator Genoa's generally well-tolerated with no drug related series of birth events or those reductions required during the study.
Marshal: This results for first step up with religion as a potential force in best in class treatment.
Marshal: and following the successful proof of concept we initiated screening for a co-harce year of their study which aims to enroll 80 patients and has been receiving interest from physicians and caregivers.
Marshal: Moving this closer to our goal of bringing a potential precision therapy for those severe patients.
Marshal: In addition across all these, which affect nearly 200,000 people in the US, 72% of the patients are currently on a sudden channel block.
Marshal: When we see the data from litrogen which uses a more target approach on the sodium channel mechanism of action, we believe that it's a broader potential for litrogen across all these.
Marshal: With Dettie Mines, we're ready diligently working with the regulatory agencies to finalize the Emerald Study Protocol for all these. We expect to finalize by the end of this quarter and initiate in 2025.
Marshal: We're very excited by both the potential and the progress of our Sergeant General Modulators for Metrogene and Reletra gene and there's a lot more to come in 2025.
Marshal: Running off a clinical epilepsy problem is our fourth ASO, as a nurse. Designed to select a bleak-decrease expression of the AT&T 2 aging and directly started the underlying calls in ODIOM staff's seizures in AT&T 2 AG.
Marshal: [inaudible] Let's go on to review the question.
Marshal: This continues to be an exciting time for practice.
Marshal: and 2024 has been a transformative year.
Marshal: Looking ahead to 2025 have a number of inflection points and you remain the rigorous focus on execution.
Marshal: We look forward to our potential first of many NDA submissions in 2025.
Marshal: With that in mind, let me now turn the call over to our Chief Financial Officer, Tim Kelly.
Marshal: him.
Tim Kelly: Thanks, Marcio. And good morning, everybody. And thank you for joining today's call. I'll provide a quick summary on our third quarter financials.
Tim Kelly: In Q3, our operating expenses were $57.1 million, with $41.9 million of that for R&D, and the remaining $15.3 million for G&A. It reflects an increased amount of clinical activity in our improvement disorder and epilepsy programs.
Tim Kelly: During the third quarter, Prax has spent $27.7 million in operating cash, similar to the second quarter of 2024, and it reflects our focus on working capital.
Tim Kelly: We ended Q3 with $411.2 million in cash, cash equivalents and marketable securities.
Marshal: which compares to $81.3 million of cash at December 31st, 2023, with the increase primarily due to the net proceeds from Praxis' follow-on public offerings earlier this year.
Tim Kelly: Our task supports a runway into 2027, and it includes funding all of the programs that Marcio discussed today through their readouts. Now I'll pass it over to you, Marcio.
Marcio: Thank you, Tim. Now we're going to open the call for our Q&A operator.
Speaker Change: Thank you as a reminder to ask a question please press star 1 1 on your telephone and wait for your name to be announced to withdraw your question please press star 1 1 again one moment for questions
Speaker Change: Our first question comes from Ritu Baral with TD Cowan. You may proceed.
Ritu Baral: Good morning, guys. Thanks for taking the question. A couple of questions on relutrogen.
Ritu Baral: for TEE.
Tim Kelly: Specifically, as you think about the 80 patients in the expanded cohort for 80 patient expanded cohort sufficient for registration.
Tim Kelly: Will the enrollment criteria for that 80 patients be any different than the original 15 patients? And if so,
Tim Kelly: Do you expect it to result in any or prospectively expected to result in any changes to efficacy or safety? And then the 2nd, part of that question is you mentioned that you are seeking alignment with regulators in the 1st half.
Tim Kelly: Can you talk to maybe any more specifics around that timing, how you might expect cohort to change based on feedback and any specifics on what you're asking?
Tim Kelly: on Emerald. Thanks.
Speaker Change: Sounds good. Thanks for the question. So on the first one, for the 80 additional patients that are enrolling on the second cohorts on the study right now, so number one, like there are active patients. So we've been screening those patients in and getting them into the study, which is
Speaker Change: Very good news in our view. The the major difference I would call on this study is actually the start dose for the patient's randomized to drug.
Tim Kelly: So starting on the previous study was at half a milligram per kilogram per day and this one is one milligram per kilogram per day. So it's straight up into the one we believe to be the most efficacious.
Speaker Change: So I believe the impact is going to be on that, it's just a fact.
Speaker Change: or faster may I say effect in terms of like separation and a deeper effect possibly maintain or even expanding the number of seizure-free days and number of patients there. No real major like
Tim Kelly: Change on the inclusion criteria. So from a patient population perspective, we're not expecting to see a different one here.
Tim Kelly: and then on the, on the timing for, for Emerald.
Speaker Change: So we do have a protocol. We are aligning on specifics there. I would say it's a little bit more, maybe traditional, is what I would call. We're expecting to run like a parallel group, a one to one, 12 weeks.
Speaker Change: What you are aligning is really the inclusion of those patients.
Speaker Change: So our view and our position right now.
Speaker Change: is everything kind of typically defined.
Speaker Change: Unknown Patients with, with G, independently of their general typical, like, geology.
Speaker Change: and for as long as they have no sensitivity to the mechanism number one and to seizure burden that are consistent with what we believe we can play a high impact that should be sufficient.
Speaker Change: So just double-checking like a number of like small details in terms of how to randomize and size and things like that which should be done by by the very end of the year and then we're going to be able to operationalize by the very beginning of next year.
Speaker Change: got it so I want to clarify you are going to genotype these patients but all they need to have is a genetic mechanism that's rational that is right okay got it thank you oh thank you
Speaker Change: Thank you.
Speaker Change: Our next question comes from Yasmin Rahimi with Piper Sandler. You may proceed.
Yasmin Rahimi: Good morning, team. Thank you so much for all the thoughtful comments. A few questions on the interim analysis. I think investors were just wondering,
Yasmin Rahimi: I think the interim was expected to happen end of year, maybe just some color around why it got a little bit moved into 1Q2025.
Yasmin Rahimi: and then it appears based on the remarks you've made that we're studying to will not read out before the interim or at the interim will get an insight about one and two. I just want to make sure just to get in. If you could just walk us through sort of the.
Yasmin Rahimi: Disclosures around both of the studies that could be helpful.
Yasmin Rahimi: And then last question is, I think you guys noted that upon the outcome of the data and you would reinitiate a Parkinson's disease program in 2025.
Speaker Change: Unknown Speaker Could you maybe comment on like the success in AT with moving on to Parkinson's or what would that be a phase 2 study, phase 3 study, any color around that would be helpful and I'll jump back into the queue.
Speaker Change: Sounds good, Thad. Thanks, yeah. So we'll start on the in-trend, right? So I'll start by saying we're very confident on the execution for the in-trend.
Yasmin Rahimi: I like every aspect that our monitoring and every discussion just increase our confidence on a successful like execution.
Yasmin Rahimi: Of course, it is biased towards our success to begin with.
Yasmin Rahimi: and for making sure we wrapped up the program live.
Speaker Change: is to deliver a successful program that we can file an NDA and can be incredibly clear the efficacy, the safety of eucalyptomide hydrochlorate for this patient.
Speaker Change: When you look into that, there was a number of things that were either bumping up in terms of availability of IDMC members, their ability to conduct the analysis, cleaning up the data, and I'll argue the most important factor here is the influence on study tubes.
Yasmin Rahimi: That is the second part of your question.
Speaker Change: All right. In the eventuality, which is quite a possibility, that the entering and outings work exactly as we expect, so very positive.
Yasmin Rahimi: We wanted to make sure the result of Study 2 is about the same time to shortly thereafter, number one. But two, that there is no influence, and by influence I mean negative influence on Study 2 results.
Speaker Change: So when you're looking into as a program, it made sense for us to make this, which in our view is a small and slight change.
Speaker Change: that is safeguarding the overall, like, positive results in our view of the combined studies, right, Study 1, Study 2, each combination.
Speaker Change: and the package for, for the NGA.
Speaker Change: So that is the main rationale on our end. Everything is progressing brilliantly so far.
Speaker Change: that on the, on the Parkinson's disease study, I think that as our content grows into the outcome.
Speaker Change: Unessential framework, we need to really be ready to the expansion right by time is an incredibly important Asset on this business. We want to make sure that
Speaker Change: the unindicational value for ourselves, for potential strategics, and so on and so forth.
Speaker Change: I guess off the ground we had I've got some feedback from the FDA last time in terms of what they would like to see on a PG study so we have a very good idea
Speaker Change: to design a phase two or three study in Parkinson's that would significantly advance this program as well. So we're just restarting that in terms of the planning, so we are ready at that time to kick off and restart.
Speaker Change: portfolio of indications and polylexa instead of just one.
Speaker Change: Great. Thank you. And I'll jump back in the queue.
Speaker Change: Thank you.
Speaker Change: Our next question comes from June Lee with Truist Securities. He may proceed.
June Lee: Oh, thanks for the update, guys. Just a quick clarification. Will you be including Lennox-Gastaut in the broader DEE study? Because there's really no genetic basis for Lennox-Gastaut, and you seem to want to stick to syndic epilepsy based on your response to V2 squared.
Speaker Change: question, and I have a follow up.
Speaker Change: Sounds good. We will include LGS patients on this. We will attempt to the answer again to read to you before. We are providing an attempt to collect as much genotype information as sometimes.
Speaker Change: As you know, they're going to be
Speaker Change: Unknown Speaker Cannot typically define clinically defined and not have like a final diagnose there. But we believe that as these patients are right now and looking to actually data on the literature on claims data for projects, it's one of the highest use of the actual funding channel mechanism.
Speaker Change: with one of the highest issues in terms of tolerability, which we think is a sweet spot for our drugs. So yes, we will be doing, but at the same time, that is part of this entire discussion about inclusion criteria and measuring in the discussion we're having right now.
Speaker Change: Great. So it's a true DE study. Great. You know, for the interim analysis for essential program.
Speaker Change: I just wanted to clarify that your
Speaker Change: When you sit and refer to interim analysis, you're referring to the study one interim. So your randomized withdrawal trial top line will depend on the interim from the parallel comparator trial. Is that correct? And then is yeah.
Speaker Change: Yeah, so and then number part two, is that is there or is there no inferiority analysis baked into that interim analysis?
Speaker Change: Yeah, so the interim analysis is on study one only, as you mentioned, right? We don't believe that would be necessary or appropriate for an interim non-study two.
Speaker Change: The
Speaker Change: Basically, there's an alignment in terms of like database lot planning between the multiple events that we're talking here. So that is, could be somewhat of an influence because those studies are recruited on quality template, right? As you know, from the same pool of patients and they are randomized today study.
Speaker Change: So that's why that could be some influence or depending on the outcome of the internal as well.
Speaker Change: We will be reading out study two, of course, shortly thereafter on the intranet. That is an easier, one could argue, study to monitor based on, like, event rates and things like that. So quite bullish about that to begin with.
Speaker Change: What was the second part of your question about the inferiority, or sorry, so that is...
Speaker Change: a futility margin on the on the lower end of the conditional power as it is standards
Speaker Change: on the intranet.
Speaker Change: which should be considered that is a stop for overwhelming advocacy as well. New World wanted to balance all of that, of course, from an information production perspective and from a spending perspective and the overall execution to drive towards a successful outcome.
Speaker Change: Right, and then last question, you know, as we look to the, you know, very likely approval of from in January, it's actually impressive that it even works at all, because it only targets 1 of the 3 voltage gated sodium channels in the nervous system. So, it's.
Speaker Change: Actually, interesting that you're advanced looking at your, your formal teaching in pain as well, which targets 2 out of 3 pain receptors or not receptors, but voltage channels, any anecdotal evidence of pain reduction from your phase 1 or any other.
Speaker Change: Yeah, so we're super excited about this as well. We've been looking for a while. It's not something that made sense from a priority execution capital allocation beforehand for us, but now we believe it does.
Speaker Change: We do have a very strong preclinical evidence on in pain models and in general, like a very potent inhibitor of one seven and one eight, as you know,
Speaker Change: That mechanism and the duality of the mechanism is quite important in pain generally acute and subchronic and chronic
Speaker Change: We thought that, yep, we're excited with what we're seeing, and we think that what's most appropriate for us is just to finalize everything, look into it from a competitive standpoint.
Speaker Change: As well, make sure that we'll be competitive and then talk about our plan early in the year with all of you.
Speaker Change: Thanks for all your answers. Of course. Thank you.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Francois Brizois with Oppenheimer. You may proceed.
Francois Brizois: Hi, thanks for the questions and thanks for kind of going through the potential scenarios here and the complexity and the dependence between or the the impact of study one on study two so but in terms of you know what to share on the interim is it you know could it go into data or that's actually a really good case scenario where we stop the study because things are working out or is it more
Francois Brizois: You know, can we be assured that the actual top line of study one will be after study two that might come short after the interim look, just any, any help there understanding the timeline of the top line versus the interim for study one.
Francois Brizois: Yeah, sounds good. Thank you. So the
Speaker Change: like, I think the scenario is like, if I think about bootcamps here, so one, as you mentioned, like the potential to to stop like for overall efficacy, that obviously is not the base case. Well, let's just play that out.
Francois Brizois: and then both studies would be having the results at the same time, right? Like study one and study two at that point in time, which obviously would be quite positive, complete package, and so on.
Francois Brizois: I think that is now an opportunity as well to increase the size of StudyOne.
Francois Brizois: And on that case, the conversation will be having as we're moving study one forward, we're increasing the size. And for study two, we should have the results like very quickly as well. So that's when it dissociates.
Francois Brizois: that you, that is the highest.
Speaker Change: Unknown Speaker A priority probability that will happen is on that just because the range of the conditional power is the largest or the widest.
Speaker Change: on that song.
Speaker Change: So I think that's the two I would say we should plan the most around.
Francois Brizois: with the first one having the highest impact right in terms of like operationally making sure ready to like wrap it up the the other two studies and so on. So that's what we one of the considerations and how how it looks when you're being ready for for the intern.
Speaker Change: Okay, thank you. And then on the DE commercial front, there's a lot of different ways to look at this market. Can you help us understand, you know, U.S., ex-U.S., how you think about the commercial potential here? Yeah, the vast majority of the business, and I would say from a dollar value perspective, is in the United States.
Francois Brizois: Our modeling shows around 70%
Francois Brizois: in the U.S. and then the about 30% outside of the U.S.
Francois Brizois: for FIC. We're talking about a
Francois Brizois: multi-billion dollar pick here in G.E.s, right? We just completed yet like another refinements of the epidemiology in the U.S. and looking into the utilization of the mechanism, limitations, and so on. And it's a little bit shy of 200,000 patients.
Francois Brizois: In the one hour.
Francois Brizois: when you consider that even relatively small market share.
Francois Brizois: gets to quite important figures in terms of like the potential big revenue and then the outside of the U.S. becomes a little bit more I'm going to call opportunistic from a business perspective. Obviously important to have access to patients as well.
Francois Brizois: but not as important to get the drug off the ground and get quite meaningful revenue. So about two-thirds in the US, one-third outside of the US, that's how we'll be modeling.
Speaker Change: Thank you. Thank you.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Yad and Sinesh with Guggenheim. You may proceed.
Speaker Change: Hey guys, thank you for taking my question. Just a couple for me as well. Mostly on the ET side, could you provide us where you are at least on the enrollment front and how many patients have been enrolled in study one and two if you could?
Speaker Change: And then, you know, we understand this in time, could you also.
Speaker Change: talk about and maybe put some numbers around the possible sample size adjustment ranges.
Speaker Change: Based on the pre-specified plan, like how long would that take at the maximum if you decide to increase the size and let's say you go with the maximum number of patients that are allowed, how long?
Speaker Change: okay?
Francois Brizois: Yeah.
Speaker Change: Absolutely. So I'll give as much as we feel that we could give right now in order like to preserve the optionality for us. So the current status state I would say of patients, right, the way we look into is not on the top of the screening but on patients being randomized per week.
Speaker Change: So when you look into what we can maintain constantly is anywhere between 20 and 30 patients per week randomized.
Speaker Change: Neopatient.
Speaker Change: So, so if you fast forward to potential scenario here, so I'm going to use like two scenarios, right? An increase of a hundred, an increase of two hundred patients, you can see that that could be achieved in like anywhere between like three to six weeks.
Francois Brizois: of Condemnation. Of course you need 12 weeks after that to completion of a study but it is very fast in terms of accruing new patients to today's study if needed.
Speaker Change: Thank you. Of course.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Douglas Tsao with H.G. Wainwright. You may proceed.
Douglas Tsao: Hi, good morning. Thanks for taking the questions. Just to confirm, Marcia, what you just said, so I think you indicated 30 patients. Is that enrolled and randomized or is that simply enrolled into the study in the scenario that you expand?
Speaker Change: the patient population for essential 30.
Speaker Change: Yeah, so that is what we, very, very comfortable from our like pace of randomization that we can achieve very, I'll say, relatively easily. I'm not going to say easily because there's a lot that goes on on this.
Speaker Change: randomized patients in a given week.
Speaker Change: Okay.
Speaker Change: Okay, great. That's helpful. And then just
Speaker Change: If you could provide a little more color in terms of moving from oxygen into these pain indications and
Speaker Change: what type of work you're going to be doing.
Speaker Change: or need to do before coming out with a more sort of.
Speaker Change: Expanse or sort of coming forward with the with the full development plan.
Speaker Change: Unknown Speaker
Speaker Change: So, so we're, we're working and I'll say thanks for others working on this space, right? There's a, there's a lot that's been done on the last few years. I hear as well. And when you're looking to.
Speaker Change: What is important for us are a couple of things, right? So one is the pharmacology itself, right? Like, can we have the release of, like, can you get to C-Max and to relationships with C-Max, like, quickly enough?
Speaker Change: For certain types of pain, what is the ideal types of pain?
Speaker Change: What is our confidence in terms of preclinically?
Speaker Change: and potentially early clinical data, biomarker data, et cetera, that could get us to a point that we're incredibly confident, as we were in that last week, for when we, like, move into a focal to have a similar package, I would say.
Speaker Change: and and then like really understanding things back to what we're talking about here, and I think differently from other things being developed.
Speaker Change: both central and peripheral aspects of the disease so
Speaker Change: How much more can we expect from this mechanism? Once again, ideal education, ideal study to show that and costing that study and things like that. So that's the works being done literally as we speak.
Speaker Change: a lot more to be finalized between now and the end of the year and I think we're going to be in a very good position early in the year to showcase that to all of you.
Speaker Change: Okay, great. And then just one more on Elson Erson. I think with last quarter, you indicated that the first patient was being enrolled in sort of a global registration study. But I think today you indicated that there
Speaker Change: Sort of being added to in brave and I just want to understand if there's been any change
Speaker Change: as you think forward about the Global Registration Program for that drug.
Speaker Change: Yeah, so now that that's a very important aspect as well though. So the way we've been looking into Alzheimer's is about twofold here. So one
Speaker Change: We consider it to be important to explore, particularly the safety at different exposure levels.
Speaker Change: And that's a lot of what's being done in Brazil right now on the second cohort is
Speaker Change: I want you to really randomize like patient or to drug or placebo or to drug or sham on that case.
Speaker Change: we're exploring a range of those that are actually increasing the dose on those patients. We're doing all the other assessments as well, as you can imagine. So it was important for us to actually keep that separated from what we believe to be a very good long-term efficacious exposure dose, that is the one milligram.
Speaker Change: for months for for the global study. We have very good alignments already in general what is needed there, but we do have still a meeting pending this year with the FDA on finalizing.
Speaker Change: which was likely changed on their end on the our expectations from from when the meeting will appear so nothing problematic there but it's Kevin
Speaker Change: Kind of drove the fact that we need just a little bit more time to make sure we have confidence on the final throttle call so we can initiate it. So that is the bottom line for that one.
Speaker Change: Okay, so with the patients being
Speaker Change: Unknown Speaker studied in Brazil now, are you, you're looking at some additional doses. And if the result, I mean, is there a scenario, I know you've been very confident in the one milligram.
Speaker Change: for kick dose. I mean, is there a chance that if results warrant that you would potentially will get higher doses in the US and European registrational studies?
Speaker Change: Yeah, we must follow the science, right? So what we've seen so far on the patients in the U.S. which are continuing taking the drug and on the patient in Europe and in Australia that actually took higher dose.
Speaker Change: then in the wild.
Speaker Change: It's not meaningfully different in terms of to your control gains on like development milestones and and things like that now We've got to remain open to to the possibility that yes, it's going to be meaningfully different and meaningfully faster, whatever and if that's the case
Speaker Change: We would be in a position to complement the global study either in its open label phase, right after the control phase, or even in a different cohort if that is warranted. So we'll be driven by the results that we see here.
Speaker Change: but the timeline in terms of like the original four patients that are going to be those there are perfectly aligned with the enrollment timeline we have for the global studies. So it shouldn't be a conflict in terms of how to get to the best possible results for those patients.
Speaker Change: Okay, great. Thank you very much.
Speaker Change: Thank you.
Speaker Change: Our next question comes from can be jazzy with Jeffrey's you may proceed.
Kennen MacKay: Morning team, a couple of questions for me.
Speaker Change: The placebo response was pretty well controlled in the central 1 essential 3 has a more innovated centralized design. What steps have you taken to control people response and study 1 in a central 3.
Speaker Change: And then as a 2nd kind of set of questions, maybe on for matching, what has sodium channel blockers demonstrated historically in seizures.
Speaker Change: And what would a registrational program consist of in generalized epilepsy?
Speaker Change: Thank you.
Kennen MacKay: Sure.
Speaker Change: Thanks, Kevin. So placebo was already pretty well controlled, as you said, on attention one.
Kennen MacKay: when you're looking to essential three, there was one aspect that that we wanted to add to further control that. So, so what are we seeing it?
Kennen MacKay: There is a, I'll say slight, but important change on patients that are less stable at baseline. And what I mean by that is
Kennen MacKay: there were pre-screening assessments or sorry a pre-rhythmization assessment on study on essential one in a baseline assessment so when you look into those patients that vary more in between those
Kennen MacKay: they tended to be a little bit higher on placebo. Now, the study was, again, at the end of the day, it's going to be like four times smaller than...
Kennen MacKay: Essential 3. So we wanted to ask the question whether or not the influence is going to be similar, right? So we chose to actually add maximum variability parameter between those visits and to formally have M visits.
Kennen MacKay: the pre-randomization ones.
Kennen MacKay: We believe, because...
Kennen MacKay: You can monitor patients for all the study and we know how long it takes for the drug to start working that we're very successful on on controlling that on on making sure that.
Kennen MacKay: the patients that are similar to what we want from E1, right? We don't want to depart from the cohorts.
Kennen MacKay: Unknown Speaker 0.0.0.0 Unknown Speaker 0.0.0.0
Kennen MacKay: And then on the second question on generalized by the primary or not.
Kennen MacKay: It's mixed, the results, historically.
Kennen MacKay: and I think partially because that isn't really being
Kennen MacKay: a faulty channel blocker that is very selective.
Kennen MacKay: and that really works on as the neurons are like firing a lot and expanding a lot in terms of like the
Kennen MacKay: loss of control, I'm going to call on the on the action potentials that can really block the pathological events, but not the physiological for this patient.
Kennen MacKay: that is a very good evidence with more selective or partially more selective.
Kennen MacKay: Drugs. So we are, interestingly enough, I would say anecdotally, the conversations that we've been having, like a lot of the conversations that get off the ground and get excited,
Kennen MacKay: A lot of people are equally or more excited, actually, about the generalized loss. It was a little bit surprising to me.
Kennen MacKay: that there is so much excitement on Generalized with Rheumatology and I believe it's because there is a huge unmet need there and obviously those seizures are incredibly important.
Kennen MacKay: as well what they have been from a severity and potential impact and in terms of fatality as well for this patient so
Kennen MacKay: We're going to see soon enough, I would say, from Radiance, what kind of impacts we can have there. And Radiance is going to serve as a kind of springboard for us.
Kennen MacKay: Design, what I would expect to be a registrational phase study for for generalized as well.
Speaker Change: Great. Thank you.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Ami Fadio with Needham, you may proceed.
Ami Fadio: Hi, good morning. Thanks for all the updates. A couple of quick questions for me. Firstly, on Alexa, can you comment on the enrollment and what percent of patients have completed randomization relative to the target enrollment for the two studies? And was there a slowdown in the enrollment rate that caused the shift in the timeline?
Kennen MacKay: Maybe I'll ask my next question after you answer this one.
Speaker Change: Sure. So, I mean, we're not going to talk about that right now, as you mentioned, right, on the prepared remarks and in the press release, but what I can tell you that is no...
Speaker Change: is slowed down on what we expected from randomization or from patients on screening.
Kennen MacKay: I think we continue and we saw historically we expected to continue to see if we decide to increase the size of the study in Q1, a fairly robust number of patients coming through. I think we intentionally.
Kennen MacKay: being managing that. So, so we can get like the best possible outcome for for the studies that are to positive studies, like right after the insurance. So, it's been a lot on us. And of course, it's gathering our patients and things like that, which influence, but I'm not a meaningful
Speaker Change: Okay, and then on vomotrigine in the radium study.
Speaker Change: Can you talk about how many patients you're targeting or sort of the mix of patients?
Kennen MacKay: between focal and generalized and and how that might inform your plans to develop it further in generalized epilepsy.
Speaker Change: Yeah, so the goal is to have 50 patients on Radiant.
Kennen MacKay: what we are seeing again on
Speaker Change: Unknown Speaker 30 days, but what we're seeing is about like the expected 30% generalized 70% focal interest.
Kennen MacKay: for like in general, particularly like on the sides with target that here we were
Kennen MacKay: I'll say relatively selective in terms of the number of sites because that is, again, a huge interest and we didn't want to completely, I'm going to say, lose control of the number of patients and get significantly more than we expect here.
Kennen MacKay: So we kept that a little bit tight in terms of the 50 or so patients that we expect.
Kennen MacKay: out in the world.
Kennen MacKay: that should be sufficient as we go like across, and it's an open language study, right? So I'm going to continuously seeing and adapt as needed in terms of maybe reducing or increasing the total number of patients based on the overall interest. But...
Kennen MacKay: 30 out of 70 from generalized and focal is what we're going to expect to see at the end.
Speaker Change: Understood. Maybe just a last question from me. As you design the MLDE study, what assumptions would you be making with regards to regulatory performance in the patient population relative to the data that you saw?
Kennen MacKay: you know, an SDN to re-enable.
Kennen MacKay: Yeah.
Kennen MacKay: So arguably, SN2A and 8A were the hardest.
Kennen MacKay: of those conditions to treat. When you when you look across the board, yeah, there are a few other GEs that are incredibly difficult to treat, but those were definitely incredibly hard to see reduction, to see severe freedom.
Kennen MacKay: mortality in two way for example is like six times higher than for this, right? So in infancy so, this is significant complete, like, higher bar. So we expect Fs are above the the efficacy levels that we were seeing, of course, not powering the study.
Kennen MacKay: For that, we're being a little bit more conservative, but I don't think it's unreasonable to assume that this would be best-in-class for this patient.
Speaker Change: Thank you. Thank you.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Joel Beattie with Baird. You may proceed.
Joel Beattie: Okay, thanks for the updates. The first one is on ElexaCultivide. If the interim is successful, could we get final results at that same time that we learned the interim was successful, or will there inherently be some amount of time between those two events?
Speaker Change: Yeah, no, Joel, thanks for that. In the Internet, it's successful, so it's divided for an equivocal efficacy, it's crossed. We will have results at the same time.
Kennen MacKay: Thanks. And then in DEEs, should we think about ralutragine as kind of just working in patients who are already responsive to calcium channel blockers or could you talk about the potential to work beyond DEE patients who are responsive to those agents?
Kennen MacKay: Yeah, so it's quite interesting. I think that is like when you're looking to recruit clinically and all the work we did.
Kennen MacKay: It does not look like it could or should be restrictive to patients who had prior
Kennen MacKay: response or data that are expected to.
Kennen MacKay: If you look into all the work we did with the two compounds published a little back.
Speaker Change: Unknown Speaker The results on the dynamics of the neurons among the animal models, for example, in Dravet syndrome, are quite similar.
Kennen MacKay: as the authors put, unexpected, meaning are significantly better than you would expect on that, which is, there is a bias towards maybe some first generation, southern channel blockers wouldn't work on that population, right? So clearly not the case here.
Kennen MacKay: And then there's a few other ideas that we would a priori expect to have efficacy, that we've seen efficacy on preclinical models.
Kennen MacKay: and therefore we should expect to have as well. When a seizure is happening, right, if we could observe, like, the neuron, sodium channels are going crazy.
Kennen MacKay: So stopping that activity is very, very important for seizure control independently of the etiology of the seizure or a general even.
Kennen MacKay: or origin in the brain anatomically. So we expect quite wide range here of efficacy. I think what we have to ask the question as well is how consistent is the seizure.
Kennen MacKay: because we want to count them similarly, right? We're going to do one study. It can't be, for example, some patients have clusters, others don't have clusters, so we shouldn't put them together. So that's more of a restriction than anything else.
Speaker Change: Thank you.
Speaker Change: Thank you.
Kennen MacKay: Our next question comes from Laura Chico with Wedbush Securities. You may proceed.
Laura Chico: Good morning, very much. Thanks for taking the question. Two clarification questions for me. First on the interim for elixir caldamide.
Laura Chico: I understand that the timing for the interim has extended to the first quarter 25. What I'm trying to clarify, though, is
Laura Chico: Does it does the actual
Kennen MacKay: at which the interim is executed. Is that also changing? And I guess maybe asking it differently is
Kennen MacKay: If this was expected to be conducted at 50%, for example, does this now shift to 60%? Hopefully that makes sense. Then I have a follow up.
Speaker Change: Now it makes a lot of sense. Thanks for the question, Laura. So the range that we gave for the information fraction, right, if I understand correctly, that's your question, was between 50% and 75%.
Kennen MacKay: So the range for for the information does not change. Of course it is a range because like depends on the exact day of the data transfer and the calculations by the IDMC but we did not change that.
Speaker Change: Okay, that's helpful. And then I guess.
Kennen MacKay: I understand your comments also about with respect to study conduct and integrity and the ramifications to study to my understanding was that these are conducted under the same protocol.
Speaker Change: I'm trying to understand the separation of the release of results. And have you had any feedback from FDA on how they would like to see results communication? Thanks.
Speaker Change: Yeah, so the last part is easy. So we did not, and I don't think they often opine on how results should be communicated. They did, though, reveal the integrated statistical analysis plan, which analyzed these studies separately.
Kennen MacKay: and and then there's a another yet another analysis plan just for the internal analysis so that that was
Kennen MacKay: is more of the influence of.
Kennen MacKay: potential impression of failure by patients who are on study two as they finalize a study.
Kennen MacKay: by a potential news, since they wouldn't know they're on study two, or study one. So we didn't do unduly influence or create quasi placebo effect by potentially
Kennen MacKay: In the positive case, to be perfectly honest, here, creating a potential impact on what we expect to be a quite successful study, that is study two. So maybe overly cautious on our end, but again, trying to safeguard the integrity of the entire program.
Speaker Change: Okay, that's helpful, Marcio. Maybe last question for me. I think I missed this. And I know you commented on earlier, but
Kennen MacKay: Could you expand a little bit more on the rationale to restart in the Parkinson's indication? I guess I'm trying to better understand what would be the mechanistic read-through from the ET studies to Parkinson's.
Kennen MacKay: Thanks very much.
Speaker Change: We want to be ready at the time of the essential three results to re-initiate Parkinson's.
Speaker Change: so maybe that's more of the message there than to have a delay and not necessarily use the mechanism. I think there's a far that is both
Kennen MacKay: I go to market strategy here where while movement disorder specialists only have about five to ten percent of the patients.
Kennen MacKay: those 5% to 10% of the patients coexist a lot more with Parkinson's patients. So that is a kind of a penetration of the market strategy that is important. And the other is just engagement in general, of course it goes without saying that we think we can have a meaningful impact.
Kennen MacKay: on Parkinson's patients as well.
Speaker Change: Thanks very much. Of course.
Speaker Change: Thank you. I would now like to turn the call back over to Marcio Sousa for any closing remarks.
Marcio Sousa: Thank you so much. I really appreciate everyone joining the call and staying with us.
Kennen MacKay: as the company continued to evolve quite positively, was a lot went on, on the last 10 months.
Speaker Change: Unknown Speaker 9 months in terms of the transformation of the company for what is going to be our next year for registration of programs and potentially one NDA submitted mid-year or so for Elixir-Calcimide. As we continue to progress...
Speaker Change: Thank you. This concludes the conference. Thank you for your participation. You may now disconnect.
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