Praxis Precision Medicines Q3 2024 Earnings Call Transcript

Quartr
Provided by Quartr
November 6, 2024

There are 13 speakers on the call.

Operator

Good day and thank you for standing by. Welcome to the Praxis Precision Medicine's Third Quarter 2024 Corporate Update. At this time, all participants are in a listen only mode. Please be advised that today's conference is being recorded. After the speakers' presentation, there will be a question and answer session.

Operator

I would now like to hand the conference over to your speaker today, Dan Ferry from LifeSci.

Speaker 1

Good morning, and welcome to the Praxis Precision Medicine's 3rd Quarter 2024 Financial Results and Business Update Conference Call. This call is being webcast live and can be accessed on the Investors section of the Praxis website at www.praxis medicines.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.

Speaker 1

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. 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, there will be a question and answer session. With that, it's my pleasure to turn the call over to Marcio.

Speaker 2

Thank you. Good morning, and welcome to the Praxis Q3 2024 Conference Call. This past quarter, we remain laser focused on advancing our pipeline as we gear up for next year to have 4 programs in registration totaling to a substantial multibillion dollar opportunity. The Phase 3 study in Essential Tremor, Essential 3, for our lead program, Eulix Sakaout mine, continues to progress well. We have confirmed all aspects of the interim analysis and are now updating the plans to have the results in Q1 2025.

Speaker 2

Both studies are well powered and controlled for success. Because there's a range of outcomes for each study as well as the interim analysis in the coming months, we decided that we will only share an update on timing for both Study 1 and Study 2 we have evaluated the recommendation from the interim review board for the interim analysis. In Q3, we're very excited to report the positive top line results for another asset in our pipeline, rilutrogene. In the Phase II ENBOLD trial in SCN2A and SCN8A DEEs. In the 15 patient study, rilutrogene demonstrated an impressive 46% reduction in motor seizures versus placebo, with 1 third of the patients achieving an unprecedented seizure free status.

Speaker 2

Based on those results, we initiated a second registrational cohort of the IMVOLD study, which has already started screening patients just weeks after completion of the prior cohorts. In common apraxis, bormetrogene, previously known as PRASI-six twenty eight, is starting out of the gate strong in all areas of our comprehensive energy clinical program. The innovative observational study, EMPOWUR, a first of its kind in collaboration with the epilepsy study consortium launched in the Q3. And in this short period of time, attracted the interest of over 1,000 patients we registered in the study. We expect the key learnings from EMPOWUR to impact the entire energy program.

Speaker 2

The Phase 2 REGANCE and the Phase 2, 3 POWER-one trials are on track for top line results next year. Rounding out our portfolio, as a nurse in begin dosing patients in Brazil in the Q2 for the IMBRADE study, and we continue to engage with regulatory agencies in Europe and in the U. S. To finalize the development plans in SCN2A gain upon function patients. With our strong balance sheet, we continue to be fully funded as we pursue our vision to deliver precision therapies for patients with CNS disorders.

Speaker 2

Let me now focus some more on Elexa. Our innovative ESSENTIAL-three program in ET is the biggest and most comprehensive program conducted today. We began recruiting for the 2 Phase III studies just about 1 year ago and have seen tens of thousands of patients interested in participating. This vibrant participation highlights the significant unmet needs for the millions of patients with essential tremor and their physicians and caregivers who are seeking a therapy that will allow patients to perform daily activities without impairments. The needs for treatment in essential tremor continues to be more defined as we advance this program.

Speaker 2

In a survey we conducted with over 400 patients, up to 77% of the respondents said they do not feel their ETA symptoms are managed with current treatments. In a separate survey we conducted with 153 physicians, they shared that 85% of their visits with ETA patients are focused on looking for treatments. Clearly, there is an incredible need here and we look forward to shortly completing the ESSENTIAL-three study with the goal of bringing an option to the market. As a quick refresher, the ESSENTURE III program has 2 simultaneous Phase III studies being run concurrently. Study 1 is a 12 weeks, 2 arm, placebo controlled, parallel group study and Study 2 is a 12 week randomized withdrawal study.

Speaker 2

Both studies use as primary assessments the change in the modified activity of daily living. And they are both run entirely decentralized as in the patient's home rather than at a clinical site. We shared in our last quarterly call that we decided to trigger a preplanned interim analysis when 50% to 75% of the patients have completed the 12 week Study 1. The analysis will inform us whether we should continue the study throughout completion, if the primary endpoint is matched to consider ceasing the study or to consider enrolling additional patients to ensure it's sufficiently powered for success. Based on the expectation for the sufficient number of patients to complete the study, cleaning of the data, execution of the statistical testing and analysis by independent boards and our internal operations as well as considering the operational impacts in the study completion of Study 2, we'll be finalizing the interim analysis in the Q1 of 2025.

Speaker 2

Given the range of outcomes, we will not speculate on scenarios or timing for results of Study 1 and Study 2 until we hear from the interim review boards at which time we'll be better informed to provide an update. Regardless, preparations continue to file the NDA as expected in 2025. Now moving on to our highly differentiated epilepsy portfolio. Bermotrigine, previously known as PRAS-six twenty eight, is a next generation functionally selective small molecule being developed as a once daily oral treatment for adults with epilepsy. We know that treatment options for common epilepsies are lacking in both efficacy and tolerability, and we believe the profile emerging with Bromatrogene will provide a highly differentiated paradigm shifting way to treat this disease.

Speaker 2

Last quarter, we introduced our broad energy clinical program for grommetro gene in focal angiomyzed epilepsies. And I'm glad to share that the ambitious multi study goal we aim to achieve are advancing well. Energies comprised of 4 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 METROGENE. Three trials of Energi are to evaluate the efficacy and safety. The first of this is RADIANCE, an open label study that enroll patients with either focal or generalized epilepsy who will receive our metrogene for 8 weeks with a safe follow-up of 2 weeks.

Speaker 2

We are on track to deliver on top line results in the first half of twenty twenty five, which should help us better understand the effectiveness levels of our metrogene and its pharmacology in the patient population. The POWER-one and POWER-two studies are 12 week Phase twothree studies in patients with focal onset seizures. POWER-one is underway and we anticipate top line results towards the end of 2025. We will slightly stagger the initiation of POWER-two to begin recruiting in the first half of twenty twenty five. The combined studies are expected to enroll approximately 500 patients globally.

Speaker 2

As we consider other areas where brometrogene can play an important role, it's clear that its activity in nab1.7 and nab1.8 coupled with fast acting pharmacology and safety profile could play an important role in pain management. We are concluding our assessments about the potential role of omermatrogine in pain and we'll be sharing more in the near future. Now turning to our rilezrogen, a functioning state modulator that is formulated for pediatric use in these, a group of severe epilepsies characterized by developmental delays with early onset, with SCN2A and SN8A being one of the most severe and refractory forms of these. And where currently there is no approved treatment. As a reminder, relitrogen has orphan and rare pediatric designation for these two indications.

Speaker 2

We're thrilled and humbled to share the unparalleled results we observed in Phase II in BALD trial cohort 1 in SCN2A and VIIIA last quarter, where riliterogene demonstrated a number of impressive and unprecedented data points. This 2 arm study was run over 16 weeks with 4 4 week periods. Patients in the placebo arm were administered placebo for 1 period and rilevergene for the other three periods. And neither the patients or investigators were aware which period was on placebo. 15 patients completed a study and patients had the option to continue to an open label extension after the 16 weeks.

Speaker 2

Our robust 46% placebo adjusted reduction in motor seizures over the period was observed, with 33% or 5 out of 15 patients achieving seizure free status that notably was never seen before in this severe patient population. In addition, we saw disease modifying impact noticed in the study by both caregivers and clinicians with pralazergine leading to meaningful improvements in overall well-being of patients in areas of seizure severity and intensity, alertness and other important measures. It's also very impressive and encouraging finding given not only the severity of the disease, but also the lack of improvements in these areas with currently available treatments. Lastly, riliterogene was generally well tolerated with no drug related series of birth events or dose reductions required during the study. These results further set up riliterogene as the potential first and best in class treatment.

Speaker 2

And following the successful proof of concept, we initiated screening for Cohort 2 of the study, which aims to enroll 80 patients and has been receiving interest from physicians and caregivers, moving us closer to our goal of bringing a potential precision therapy for those severe patients. In addition, across all DAEs, which affected nearly 200,000 people in the U. S, 70% to 80% of the patients are currently on a sodium channel block. When we see the data from LetroGen, which use a more target approach on the sodium channel mechanism of action, We believe there is a broader potential for relistrogen across all GEs. With that in mind, we're already diligently working with the regulatory agencies to finalize the AMROAD study protocol for all GEs.

Speaker 2

We expect to finalize by the end of this quarter and initiate in 2025. We're very excited by both the potential and the progress of our sodium channel modulators, vermetrogene and rilatrogene, and there's a lot more to come in 2025. Running out our clinical epilepsy program is our first ASO, elzinecen, designed to selectively decrease expression of the SCN2A gene and directly target the underlying cause in early onset seizures in SCN2A DE. Last quarter, we continued Part A of the INBRADE protocol in Brazil. This part of the study will provide important control data, examine the safety and effectiveness of healthy nursing in a very severe disease population.

Speaker 2

This continues to be an exciting time for Praxis, and 2024 has been a transformative year. Looking ahead to 2025, we have a number of inflection points and we remain the rigorous focus on execution. We look forward to our potential first of many NDA submissions in 2025. With that in mind, let me now turn the call over to our Chief Financial Officer, Tim Kelly. Tim?

Speaker 3

Thanks, Marcio, and good morning, everybody, and thank you for joining today's call. I'll provide a quick summary on our Q3 financials. In Q3, our operating expenses were $57,100,000 with $41,900,000 of that for R and D and the remaining $15,300,000 for G and A and reflects an increased amount of clinical activity in our movement disorder and epilepsy programs. During the Q3, Praxis spent $27,700,000 in operating cash similar to the Q2 of 2024 and it reflects our focus on working capital. We ended Q3 with $411,200,000 in cash, cash equivalents and marketable securities, which compares to $81,300,000 of cash at December 31, 2023, with the increase primarily due to the net proceeds from Praxis follow on public offerings earlier this year.

Speaker 3

Our cash supports the 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.

Speaker 4

Thank you, Tim. I'm now going to open the call for Q and A. Operator?

Operator

Thank you. Our first question comes from Ritu Baral with TD Cowen. You may proceed.

Speaker 5

Good morning, guys. Thanks for taking the question. A couple of questions on ROLUTRAGEEN, 562 for TEE. Specifically, as you think about the AD patients in the expanded cohort for 80 patient expanded cohort sufficient for registration. Will the enrollment criteria for that 80 patients be any different than the original 15 patients?

Speaker 5

And if so, do you expect it to result in any or prospectively expect it to result in any changes to efficacy or safety? And then the second part of that question is, you mentioned that you are seeking alignment with regulators in the first half. 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 on Emerald? Thanks.

Speaker 4

Sounds good. Thanks, Ritu,

Speaker 2

for the question. So on the

Speaker 4

first one for the 80 additional patients that are enrolling on the second cohort on the study right now. So number 1, like there are active patients. So we've been eye screening those patients in and getting them into the study, which is very good news in our view. The major difference outcome on this study is actually the start dose for the patients randomized to drug. So starting on the previous study was at 0.5 milligram per kilogram per day and this one is 1 milligram per kilogram per day.

Speaker 4

So it's straight up into the one we believe to be the most efficacious. So we believe the impact is going to be on that. It's just a fast or faster, may I say, effect in terms of like separation and a deeper effect possibly maintaining or even expanding the number of seizure free days and number of patients there. No real major like change on the inclusion criteria. So from a patient population perspective, we're not expecting to see a different one here.

Speaker 4

And then on the timing for EnROL, 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, 1 to 1, 12 weeks. What we are aligning is really the inclusion of those patients.

Speaker 4

So our view and our position right now is that we can phenotypically define patients with D independently of their genotypical like ideology. And for as long as they have no sensitivity to the mechanism, number 1 and 2, seizure burden that are consistent with what we believe we can play a high impact that should be sufficient. So just double checking that like a number of like small details in terms of how to randomize and size and things like that, which should be done 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 5

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

Speaker 4

for it. That is right.

Speaker 5

Okay, got it. Thank you.

Speaker 4

Thank you.

Operator

Thank you. Our next question comes from Yasmeen Rahimi with Piper Sandler. You may proceed.

Speaker 6

Good morning, team. Thank you so much for all the thoughtful comments. Few questions on the interim analysis. I think investors were just wondering, I think the interim was expected to happen end of year, maybe just some color around why it got a little bit moved into 1Q 2025? And then it appears based on the remarks you've made that we are Study 2 will not read out before the interim or at the interim we'll get an insight about 1 and 2.

Speaker 6

I just want to make sure just to get in, if you could just walk us through sort of the disclosures around both of the studies that could be helpful. And then last question is, I think you guys noted that upon the outcome of the data in AT, you would reinitiate a Parkinson's disease program in 2025. Could you maybe comment on like the success in AT would move you into Parkinson's or would that be a Phase 2 study, Phase 3 study? Any color around that would be and I'll jump back into the queue.

Speaker 4

Sounds good, Thad. Thanks, Yas. So starting on the interim, right? So I'll start by saying we're very confident on the execution for the interim I like every aspect that our monitoring and every discussion just increase our confidence on a successful like execution. Of course, it is biased towards our success to begin with and making sure we wrap up the program like concomitantly to slash shortly thereafter to the end trend.

Speaker 4

And that was the, I would say, the main driver here, right? So what we are trying to do to take a step back is to deliver a successful program that we can file an NDA and can be incredibly clear the efficacy, the safety of elixa calvamide hydrochlorate for these patients. When you look into that, there was a number of things that were either bumping up in terms of availability of iGMC members, their ability to conduct the analysis, cleaning of the data. And I'll argue the most important factor here is the influence on Study 2. That is the second part of your question, right?

Speaker 4

In the eventuality, which is quite a possibility that the interim analysis work exactly as we expect, so very positive. We wanted to make sure the result of Study 2 is about the same time to shortly thereafter, number 1. But 2, that there is no influence and by influence, I mean negative influence on Study 2 readouts. So when you're looking into as a program, it made sense for us to make this, which in our view small and slight chain that is safeguarding the overall like positive results in our view of the combined studies, right, Study 1, Study 2, its combination and the package for the NDA. So that is the main rationale on our end.

Speaker 4

Everything is progressing brilliantly so far. Then on the Parkinson's disease study, I think that as our confidence grows into the outcome on Essential Tremor, we need to really be ready to the expansion, right, like time is an incredibly important asset on this business. We want to make sure that the an indication of value for ourselves, for potential strategic and so on and so forth gets off the grounds. We had I've got some feedback from the FDA last time in terms of what they would like to see on a PD study. So we have a very good idea to design a Phase IIIII study in Parkinson's that would significantly advance this program as well.

Speaker 4

So we're just restarting that in terms of the planning. So we are ready at that time to kick off and restart. So we have a portfolio of indications in polyolexor instead of just one.

Speaker 6

Great. Thank you. And I'll jump back in the queue.

Speaker 4

Sounds good.

Operator

Thank you. Our next question comes from Joon Lee with Truist Securities. You may proceed.

Speaker 7

Thanks for the updates guys. Just a quick clarification. Will you be including Lenogasto in the broader DEE study because there's genetic basis for Lenoxetal and you seem to want to stick to aesthetic epilepsy based on your response to Ritu's question? And I have a follow-up.

Speaker 4

Sounds good. John, we will include LGS. Patients on this who attempt to the answer again to read to before. We are providing and attempting to collect as much genotype information. Sometimes, as you know, they're going to be phenotypically defined, clinically defined and not have like a final diagnose there.

Speaker 4

But we believe that as these patients are right now and you're looking to actually data on the literature, on claims data for LGS, it's one of the highest use of the active subgen channel mechanism 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 that. At the same time, that is part of like this entire discussion about inclusion criteria and measuring is the discussion we're having right now.

Speaker 7

Great. So it's a true VE study, great. For the interim analysis for essential program, just wanted to clarify that your when you sit and refer to interim analysis, you're referring to the Study 1 interim. So your randomized withdrawal trial top line will depend on the interim from the parallel comparator trial. Is that correct?

Speaker 7

Yes. Yes. Yes. Yes. Yes.

Speaker 7

No, go ahead, Jim. Sorry. Yes. And then number part 2 is that is there or is there no inferiority analysis baked into that interim analysis?

Speaker 2

Yes. So the interim analysis

Speaker 4

is on Study 1 only, as you mentioned, right? We don't believe that would be necessary or appropriate for an interim study 2. Basically, there's an alignment in terms of like database, log planning between the multiple events that we're talking here. So that is could be somewhat of an influence because those studies are recruited concomitantly, right, as you know, from the same pool of patients and they are randomized to these studies. So that's why there could be some influence or depending on the outcome of the internal as well.

Speaker 4

We will be reading out Study 2, of course, shortly thereafter. On the end trend, That is easier, one could argue, study to monitor base on like event rates and things like that. So quite bullish about that to begin with. What was the second part of your question? About the inferiority or sorry.

Speaker 4

So there is a futility margin on the lower end of the conditional power as it's the standards, right, on instruments like that. So fairly standard in terms of the bottom there, a fairly wise, I would say, sample size of the estimation zone because that's why the reason why they study or the Internet was designed to begin with. And on the other hand as well, which should be considered that is a stop for overwhelming efficacy as well. New order wanted to balance all of that, of course, from an information fraction perspective and from our spending perspective and the overall execution to drive toward the success for outcome.

Speaker 7

Great. And then last question. As we look to the very likely approval of Sogetrijum from Avertis 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 peripheral nervous system. So it's actually interesting that you're advanced looking at your formal teaching in pain as well, which targets 2 out of the 3 pain receptors or not receptors, but voltage gated channels. Any anecdotal evidence of pain reduction from your Phase 1 or any other studies?

Speaker 7

Thank you.

Speaker 4

Yes. So the like we're super excited about this as well. We've been looking to 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. We do have a very strong preclinical evidence in pain models and in general like very potent inhibitor of 17 and 18.

Speaker 4

As you know, that mechanism and the duality of the mechanism is quite important in pain generally, acute and sub chronic and chronic pain, we thought that, yes, we are we're excited with what you're seeing. And we think that what's most appropriate for us is just to finalize everything, look into from a competitive standpoint as well, make sure that we'd be competitive and then talk about plan early in the year with all of you.

Speaker 7

Thanks for all your answers.

Speaker 4

Of course. Thank you.

Operator

Thank you. Our next question comes from Francois Brisebois with Oppenheimer. You may proceed.

Speaker 8

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 impact of Study 1 on Study 2. So but in terms of what to share on the interim, is it 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 can we be assured that the actual top line of Study 1 will be after Study 2 that might come short after the interim look? Just any help there understanding the timeline of the top line versus the interim for Study 1?

Speaker 4

Yes. Sounds good. Thank you. So the like I think the scenario is like if I think about both hands here. So one, as you mentioned, like the potential to stop like for overall efficacy, obviously, it's not the base case.

Speaker 4

Let's just play that out. And then both studies would be having the results at the same time, right? Like Study 1 and Study 2 at that point in time, which obviously would be quite positive, complete package and so on. I think that is now an opportunity as well to increase the size of Study 1. And on that case, the conversation we'll be having is we're moving Study 1 forward, we're increasing the size.

Speaker 4

And for the study 2, we should have the results like very quickly as well. So that's when it dissociates the 2. That is the highest priority probability that will happen is on that just because the range of the conditional power is the largest or the widest on that zone. So I think that's the 2, I would say, we should plan the most around with the first one having the highest impact, right, in terms of like operationally making sure we're ready to like wrap it up the other two studies and so on. So that's what we one of the considerations and how we look into being ready for the interim.

Speaker 8

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 U. S, ex U.

Speaker 8

S, how you think about the commercial potential here?

Speaker 4

Yes. The vast majority of the business and I would say from a dollar value perspective is in the United States. Our modeling shows around 70% in the U. S. And then the about 30% outside of the U.

Speaker 4

S. For our PIK. We're talking about a multibillion dollar PIC here in GEEs, right? We just completed yet like another refinement of the epidemiology in the U. S.

Speaker 4

And looking into the utilization of the mechanism limitations and so on. And it's a little bit shy of 200,000 patients in the U. S. When you consider that even relatively small market share gets to quite important figures in terms of like the potential big revenue. And then the outside of the U.

Speaker 4

S. Becomes a little bit more, I'm going to call, opportunistic from a business perspective. Obviously, it's important to have access to patients as well, but not as important to get the drug off the ground and get quite meaningful revenue. So about 2 thirds in the U. S, 1 third outside of the U.

Speaker 4

S, that's how we've been modeling.

Speaker 8

Thank you.

Speaker 4

Thank you.

Operator

Thank you. Our next question comes from Yatin Sunej with Guggenheim. You may proceed.

Speaker 9

Hey guys, thank you for taking my question. Just a couple for me as well, mostly on the Ity side. Could you provide us where you are at least on the enrollment front? Like how many patients have been enrolled in Study 12, if you could? And then we understand this in time, could you also talk about and maybe put some numbers around the possible sample size adjustment ranges based on the pre specified plan?

Speaker 9

Like how long would that take at the maximum if we decide to increase the size and let's say you go with the maximum number of patients that are allowed, how long will that take? Thank you. Yes.

Speaker 4

Absolutely. So I'll give as much as we feel that we could give right now in order like to preserve all the optionality for us. So the current steady 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. So when you look into what we can maintain confidently, it's anywhere between 20 30 patients per week randomized new patients. So if you fast forward to potential scenario here, so I'm going to use like 2 scenarios where I can increase of 100 and an increase of 200 patients.

Speaker 4

You can see that that could be achieved in like anywhere between like 3 to 6 weeks of randomization. Of course, you need 12 weeks after that to completion of the study, but it is very fast in terms of accruing new patients to the study if needed.

Speaker 9

Thank you. Of course.

Operator

Thank you. Our next question comes from Douglas Tsao with H. C. Wainwright. You may proceed.

Speaker 10

Hi, good morning. Thanks for taking the questions. Just to confirm, Marcio, what you just said. So I think you indicated 30 patients. Is that enrolled and randomized?

Speaker 10

Or is that simply enrolled into the study in the scenario that you expand the patient population for ESSENTIAL-three?

Speaker 4

Yes. So that is the what we very, very comfortable from our like base of our randomization that we can achieve very, I would say, relatively easily. I'm not going to say easily because there's a lot that goes on on their randomized patients in a given week. Okay.

Speaker 10

Okay, great. That's helpful. And then just if you could provide a little more color in terms of moving vormortigene into these pain indications? And what type of work you're going to be doing or need to do before coming out with a more sort of expansion or sort of coming forward with the full development plan?

Speaker 4

Yes. So we're working and I'll say thanks for others working on this space, right? There's a lot that's been done on the last few years here as well. When you look into what it's important for us, a couple of things, right? So one is the pharmacology itself, right?

Speaker 4

Like can we have the relief of like can you get to CEMEX and to relationships with CEMEX like quickly enough for certain types of pain, what is the ideal types of pain? What is our confidence in terms of preclinically and potentially early clinical data, biomarker data, etcetera, that could get us to a point that we're incredibly confident as we were in epilepsy for when we like moving into focal to have a similar package, I would say. And then like really understanding the impact, what we're talking about here and I think differently from other things being developed, both central and peripheral aspects of the disease. So how much more can we expect from this mechanism? What is, again, ideal indication, ideal study to show that and cost in that study and things like that?

Speaker 4

So that's the work's being done literally as we speak. 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 10

Okay, great. And then just one more on elcinercin. I think with last quarter, you indicated that the first patient was being enrolled in sort of the global registration study. But I think today, you indicated that they're sort of being added to IMbrave. And I just want to understand if there's been any change, as you think forward about the global registration program for that drug?

Speaker 4

Yes. So that's a very important aspect as well. So the way we've been looking into ELZURTHER since that twofold here. So one, we consider to be important to explore particularly the safety at different exposure levels and that a lot of what's being done in Brazil. Right now, on the second cohort is 1 to 3 randomized like patient cohort to drug or placebo or to drug or sham.

Speaker 4

On that case, we're exploring a range of dose sequentially 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 and cautious exposure dose as the 1 milligram per month for the global study. We have very good alignment already in general what is needed there. But we do have still a meeting pending this year with the FDA on finalizing, which was likely a change on their end on the our expectations from when the meeting will occur.

Speaker 4

So nothing problematic there, but scheduling kind of drove the fact that we need just a little bit more time to make sure we have confidence on the final protocol so we can initiate it. So that is the that's the bottom line for that one.

Speaker 10

Okay. And so with the patients being 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 1 milligram per kg dose. I mean, is there a chance that if results warrant that you would potentially look at higher doses in the U. S.

Speaker 10

And European registrational studies?

Speaker 4

Yes. We must follow the science, right, Doug. 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 than in the U. S.

Speaker 4

It's not meaningfully different in terms of failure control gains on like development milestones and things like that. Now we've got to remain open to the possibility that, yes, it's going to be meaningfully different and meaningfully faster, whatever. And if that's the case, 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 it will be driven by the results that we see here. But the timelines in terms of like the original four patients that they're going to be those there are perfectly aligned with the enrollment timelines we have for the GLOBAL study.

Speaker 4

So it shouldn't be a conflict in terms of how to get to the best possible results for those patients.

Speaker 10

Okay, great. Thank you very much.

Operator

Thank you. Our next question comes from Kempe Jazvi with Jefferies. You may proceed.

Speaker 7

Morning team. A couple of questions from me. The placebo response was pretty well controlled in Essential 1. Essential 3 has a more innovative decentralized design. What steps have you taken to control placebo response in Study 1 in ESSENTIAL III?

Speaker 7

And then as a second kind of set of questions, maybe on vermatrogene, what has sodium channel blockers demonstrated historically in PGTC seizures? And what would a registrational program consist of in generalized epilepsy? Thank you.

Speaker 4

Sure. Thanks, Camet. So placebo was already pretty well controlled, as you said, on Essential 1. When you're looking to Essential 3, there was one aspect that we wanted to add to further control that. So what we're seeing is that is, I would say, a slight but important change on patients that are less stable at baseline.

Speaker 4

And what I mean by that is there were pre screening assessments or sorry, pre randomization assessments on study on ESSENTIAL-one and a baseline assessment. So when you look into those patients that vary more in between those, they tended to be a little bit higher on placebo. Now that study was, again, at the end of the day, it's going to be like 4 times smaller than 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 end visits, the preorganization ones.

Speaker 4

We believe because you can monitor patients throughout the study and we know how long it takes for the drug to start working that we're very successful on controlling that, on making sure that the patients that are similar to what we want from E1, right, we don't want to depart from the cohorts on E1, but we want to make sure we tighten potentially variability that is not due to drug effects, but rather to placebo effect. So we're very, very confident on the measures that we put in place to control placebo there. And then on your second question on generalized either primary or not, it's mixed the results historically. And I think partially because that isn't really being a surgeon channel blocker that is very selective and that really works on as these neurons are like firing a lot and expanding a lot in terms of like the loss of control, I'm going to call, on the action potentials that can really block the pathological events, but not the physiological for these patients. That is a very good evidence with more selective or partially more selective drugs.

Speaker 4

So we are interesting enough, I would say anecdotally, the conversations that we've been having like a lot of the conversations that as we said, we get off the ground and sites get excited, a lot of people are equally or more excited actually about the generalized what was a little bit surprising to me that there is so much excitement on generalized with bromatriptyline. And I believe it's because there is a huge amount there. And obviously, those seizures are incredibly important as well. They happen from a severity and potential impact and in terms of fatality as well for this patient. So we're going to see soon enough, I would say, from Radianz what kind of impact we can have there.

Speaker 4

And Radianz is going to serve as a kind of springboard for us and to design what we would expect should be a registrational phase study for Generalize as well.

Speaker 7

Great. Thank you. Of course.

Operator

Thank you. Our next question comes from Ami Fadia with Needham. You may proceed.

Speaker 11

Hi, good morning. Thanks for all the updates. A couple of quick questions from me. Firstly, on Alexa, can you comment on the enrollment and how what percent of patients have completed randomization relative to the target enrollment for the 2 studies? And was there a slowdown in the enrollment rate that caused the shift in the time line?

Speaker 11

Maybe I'll ask my next question after you on

Speaker 9

this one.

Speaker 4

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, there is no slowdown on what we expected from organization or from patients on screening. 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 been managing that so we can get like the best possible outcome for the study.

Speaker 4

There are 2 positive studies like right after the interim. So, it's been a lot on us and of course, the scheduling of patients and things like that, which influence, but are nothing meaningful.

Speaker 10

Got it.

Speaker 11

Okay. And then on vomeritogene in the radiance study, can you talk about how many patients you're targeting or sort of the mix of patients between focal and generalized and how that might inform your plans to develop it further in generalized epilepsy?

Speaker 4

Yes. So the goal is to have 50 patients on reagents. What we are seeing, again, on early days, but what we are seeing is about like the expected 30% generalized, 70% focal interest for like in general, particularly like on the sites we targeted here, we were, 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. So we kept that a little bit tight in terms of the 50 or so patients that we expect to enroll. That should be sufficient as we go like across and it's an open label study, right?

Speaker 4

So we're 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 30, 70 from generalized and focal is what we're going to expect to see at the

Speaker 11

end. Understood. Maybe just a last question from me. As you design the EMBLVE study, what assumptions would you be making with regards to regulatory performance in this patient population relative to the data that you saw in SCN2A and AA?

Speaker 4

Yes. So arguably SCN2A and AA were the hardest of those conditions to treat. When you look across the board, yes, there are few allergies that are incredibly difficult to treat, but those were definitely incredibly hard to see reduction, to see severe freeze and mortality in 2A, for example, is like 6 times higher than Rovir, right, so in infancy. So this is significantly like higher bar. So we expect at or above the efficacy levels that we're seeing, of course, not powering the study.

Speaker 4

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 these patients.

Speaker 8

Thank you. Thank you.

Operator

Thank you. Our next question comes from Joel Beatty with Baird. You may proceed.

Speaker 3

Thanks for the updates. The first one is on ulexiculteride. If the interim is successful, could we get final results at the same time that we learned the interim was successful? Or will there inherently be some amount of time between those two events?

Speaker 4

Yes. Joe, like thanks for that. If interim is successful, so it's the boundary for an equivocal efficacy is crossed. We will have results at the same time.

Speaker 3

Thanks. And then in DEEs, should we think about Rilutrogene 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 the patients who are responsive to those agents?

Speaker 4

Yes. So it's quite interesting. I think that is like when you're looking to preclinically and all the work we did, it does not look like it could or should be restrictive to patients who had prior response or that are expected to. If you look into all the work we did with 2 compounds published a little back, The results on actual the dynamics of the neurons among the animal models, for example, in Dravet syndrome are quite, as the authors put, unexpected, meaning are significantly better than you would expect on that, which is there is a bias towards maybe some 1st generation of certain channel blockers wouldn't work on that population, right? So clearly not the case here.

Speaker 4

The and then there's a few other IDs that we wouldn't a priority expect to have efficacy that we're seeing efficacy on preclinical models 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. That's in a very late term way to describe it. So stopping that activity is very, very important for seizure control independently of the etiology of the seizure or in general even or origin in the brain anatomically. So we expect quite wide range here of efficacy.

Speaker 4

I think what we have to ask the question as well is how consistent is the seizure 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 putting them together. So that's more of a restriction than anything else.

Speaker 9

Thank you.

Speaker 2

Thank you.

Operator

Our next question comes from Laura Chico with Wedbush Securities. You may proceed.

Speaker 12

Hey, good morning very much. Thanks for taking the question. Two clarification questions for me. First on the interim for leucocaltamide. I understand that the timing for the interim has extended to the Q1 of 'twenty five.

Speaker 12

What I'm trying to clarify though is, does the actual at which the interim is executed, is that also changing? And I guess maybe asking it differently is if this was expected to be conducted at 50%, for example, does this now shift to 60%? Hopefully that makes sense. And then

Speaker 6

I have a follow-up.

Speaker 7

No, it makes a lot

Speaker 4

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% 75%. So the range 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 ADMC, but we did not change that.

Speaker 12

Okay. That's helpful. And then I guess, I understand your comments also about with respect to study conduct and integrity and the ramifications to Study 2. My understanding was that these are conducted under the same protocol. So I'm trying to understand the separation of the release of results.

Speaker 12

And have you had any feedback from FDA on how they would like to see results communication? Thanks.

Speaker 4

Yes. So the last part is CNC. So we did not. And I don't think they often opine on how results should be communicated. They did though reveal the integrated iSATISCOM has plan, which analyzed these studies separately.

Speaker 4

And then there's another yet another analysis plan just for the interim analysis. So that was revealed, and we received it back many months ago from the FDA on that. So we're covering that. So the influence is less operational on the I Street Census like definition of operation, meaning you're absolutely correct. These studies are randomized.

Speaker 4

Patients are randomized to one study or to the other. It's more on the influence of potential impression of failure by patients who are on Study 2 as they finalize a study by potential NEOs since they wouldn't know they're on Study 2 or Study 1. So we didn't to unduly influence or create quasi placebo effects by potentially in the positive case, to be perfectly honest, here creating a potential impact on what we expect to be applied successfully studied as a study too. So maybe overly cautious on our end, but again, trying to safeguard the entire program.

Speaker 12

Okay. That's helpful, Marcio. And maybe last question for me. I think I missed this, and I know you commented that on it earlier. But could you expand a little bit more on the rationale and the restart in the Parkinson's indication?

Speaker 12

I guess I'm trying to better understand what would be the mechanistic read through from the ET studies to Parkinson's? Thanks very much.

Speaker 4

Yes. No, no, absolutely. So I think the from a scientific rationale is very strong to begin with in Parkinson's, right? Where the last time when we actually stopped the Parkinson's study had very little to do with our expectation in terms of results for that study and a lot to do with availability of capital. I think as we fast forward that we have significantly more safety data.

Speaker 4

Of course, we are excited and we expect the Study 1 and Study 2 to be positive for essential timelure. The data from a scientific standpoint did not get weaker. They got stronger from a Parkinson's rationale. So why are not going to be like using like significant amount of capital to actually reinitiate before the results? We want to be ready at the time of the Essential 3 results to reinitiate Parkinson's.

Speaker 4

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 a go to market strategy here where while movement disorder, especially it's only have about 5% to 10% of the patients. Those 5% to 10% of the patients coexist a lot more with Parkinson's patients. So that is kind of a penetration of the market strategy that is important. And the other is just engagement in general of key opinion leaders.

Speaker 4

Of course, it goes without saying that we think we can have a meaningful impact on Parkinson's patients as

Speaker 12

well. Thanks very much.

Speaker 9

Of course.

Operator

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

Speaker 4

Thank you so much. I really appreciate everyone joining the call and staying with us as the company continued to evolve quite positively. Once a lot went on over the last 10 months 9 months if you count the quarter in terms of the transformation of the company for what is going to be next year for registration of programs and potentially one NDA submitted mid year or so for eulixa cosmodium. As we continue to progress, millions of patients will be positively impacted by those drugs and 1,000,000,000 of dollars in value will be created to all of us shareholders. So we appreciate it.

Speaker 4

Looking forward to providing more updates in the near future, and I'm sure we're going to be in touch. Thank you so much.

Operator

Thank you. This concludes the conference. Thank you for your participation. You may now disconnect.

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Key Takeaways

  • Praxis is aiming to have four programs in registration by next year, targeting a substantial multibillion-dollar opportunity in central nervous system disorders.
  • The Phase 3 ESSENTIAL-3 trials for the lead essential tremor candidate are progressing well with a 50–75% interim analysis slated for Q1 2025 and an NDA submission planned for 2025.
  • In the Phase 2 ENBOLD trial, rilutrogene achieved a 46% reduction in motor seizures versus placebo and 33% of patients became seizure-free, prompting initiation of an 80-patient registrational cohort.
  • Brometrogene’s ENERGY program launched the EMPOWUR observational study, enrolling over 1,000 patients, while Phase 2 REGANCE and Phase 2/3 POWER-one studies remain on track for top-line results in 1H 2025 and late 2025, respectively.
  • Praxis closed Q3 with $411.2 million in cash, cash equivalents and marketable securities, funding operations through 2027.
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Earnings Conference Call
Praxis Precision Medicines Q3 2024
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