Praxis Precision Medicines Q2 2025 & Study Result Earnings Call Transcript

Quartr
Provided by Quartr
August 4, 2025

Key Takeaways

  • Positive Sentiment: Praxis’ RADIANT study showed best-in-disease efficacy for vimatrogene in focal epilepsy, delivering a median seizure reduction of over 56%, with 60% of patients achieving ≥50% reduction and 22% becoming seizure-free in the second month.
  • Positive Sentiment: Vimatrogene demonstrated a rapid and sustained response, with 54% of patients responding by week one and response rates increasing to 67% by week eight.
  • Neutral Sentiment: The safety profile was favorable, with most adverse events being mild to moderate and resolving over time; a 23% discontinuation rate was attributed to underadjusted background ASM regimens rather than vimatrogene itself.
  • Neutral Sentiment: Based on RADIANT learnings, POWER2 will add a 40 mg dose arm and incorporate mood and depression endpoints, while POWER3 is planned as a switch-to-monotherapy study in refractory patients.
  • Positive Sentiment: Praxis reports a cash runway into 2028 and expects five clinical readouts across four late‐stage CNS assets over the next year, underscoring strong execution and pipeline breadth.
AI Generated. May Contain Errors.
Earnings Conference Call
Praxis Precision Medicines Q2 2025 & Study Result
00:00 / 00:00

Transcript Sections

Skip to Participants
Operator

Good day and welcome to the Praxis Precision Medicine's Radiant Topline Results and Second Quarter twenty twenty five Financial Results Conference Call. At this time, all participants are in a listen only mode. After the speakers' presentation, there will be a question and answer session. Instructions will be given at that time. As a reminder, this call may be recorded.

Operator

I would now like to turn the call over to Dan Ferry of LifeSci Advisors. Please go ahead.

Dan Ferry
Managing Director at LifeSci Advisors, LLC

Good morning, and welcome to the Praxis Precision Medicine's Radiant Top Line Results and Second Quarter twenty twenty five Financial Results Conference Call. This call is being webcast live and can be accessed on the Investors section of the Praxis website at www.praxismedicines.com. Please note that remarks made during this call may contain forward looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These may include statements about the company's future expectations and plans, clinical development timelines, and financial projections. While these forward looking statements represent views as of today, they should not be relied upon as representing the company views in the future.

Dan Ferry
Managing Director at LifeSci Advisors, LLC

Praxis may update these statements in the future but is not taking on an obligation to do so. Please refer to 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 Tim Kelly, Chief Financial Officer and Steve Petro, Chief Scientific Officer. After our prepared remarks, there will be a brief question and answer session. With that, it's my pleasure to turn the call over to Marcio. Marcio?

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Good morning, everyone, and welcome to the RADIANCE top line results presentation. We're incredibly excited to share this best in disease results with all of you. Before we begin, I'd like to know that today's presentations contain forward looking statements. For complete disclosures, please refer to our latest SEC filings. Praxis is in an incredible position to bring innovative drugs to patients with CNS disorders.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

We have four late stage assets, one of which we're discussing here today, and we expect five clinical readouts within the next year. That is no small feat. This progress is powered by our two robust platforms, enabling current developments and future CNS drug innovation. Our cash runway extends into 2028, supporting our ambitious clinical agenda. Today, we'll discuss the RADIANCE results for hermetragene.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

But it's worth taking a few moments to remind everyone of the rich and deep pipeline we have, with multiple results coming out in the next several quarters, which will enable Praxis to stay at the forefront of CNS drug development. Focal epilepsy is a very serious medical condition impacting about three million US patients. Contrary to common belief, most of the patients are not doing well. Over sixty percent of those patients require multiple anti seizure medications, highlighting the inadequacy of existing therapies. Patients need effective, tolerable, fast acting, and durable treatments to avoid a constant ASM cycling, and we believe VermetraGEN can deliver on that.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Starting with today's results, ormatergine is showing best in disease efficacy in the RADIANT study. That should be enough to be excited. We should not minimize the further differentiation of hermetra gene with current and in development therapies, being the only drug to combine once daily administration, fast action, no food effects, ideal tolerability, and no meaningful drug drug interactions, which importantly do not interfere with common contraceptive agents. Before I hand over the call to Steve to discuss the details of the RADIANCE study result, I want to take a step back and talk about execution. We have executed the RADIANCE study exceptionally well, initially setting an enrollment target of thirty five patients with focal epilepsy and fifteen with generalized epilepsy.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

The strong demands for focal even after we announced the closing of the enrollment for the sites demonstrate the effectiveness of our recruitment capabilities. The same engine is already at play for the POWER one and soon to be for the POWER two and POWER three studies. We have so far completed screening of ninety nine patients and those sixty one as of July 25. We expected to complete a study in the near future with approximately seventy five patients dosed. Today, we review data from thirty seven focal patients who completed the study for efficacy so far.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

We also review the safety for the overall cohort of the sixty one patients who have been dosed. We present more details from this initial cohort of patients at the upcoming International Epilepsy Conference in Lisbon later this month. The full study results are expected to be presented during the American Epilepsy Society Conference later in the year. Let me now hand over the call to Steve to discuss the results. Steve.

Steven Petrou
Steven Petrou
Co-Founder & Chief Scientific Officer at Praxis Precision Medicines

Thanks, Marcio. Let me walk you through the design of the RADIAN study. We began with a twenty eight day observation period during which patients stayed on their existing anti seizure medications while we monitored seizure activity. Following that, participants received thirty milligrams of vermatrigine once daily for eight weeks. An optional two week safety follow-up was also available at the end of the treatment phase.

Steven Petrou
Steven Petrou
Co-Founder & Chief Scientific Officer at Praxis Precision Medicines

We're proud to have enrolled a representative sample of the refractory epilepsy population here in The US, predominantly female with a high baseline seizure burden. The median monthly seizure count was 12, and most participants were on multiple anti seizure medications. Looking ahead, we expect the population in our upcoming POWER-one study to closely reflect what we've seen here in RADIANT. That alignment gives us a strong foundation and confidence in how we're approaching the next phase of development. Now let's turn to the part that we're most excited about, the results.

Steven Petrou
Steven Petrou
Co-Founder & Chief Scientific Officer at Praxis Precision Medicines

Vlmitrijene delivered a truly remarkable performance in the RADIAN study. We observed a median seizure reduction of over fifty six percent, And importantly, that effect came on quickly and was sustained throughout the treatment period. Even more compelling, sixty percent of patients achieved at least a fifty percent reduction in seizures. That's one of the highest responder rates we've seen in recent epilepsy trials, and it speaks to the potential impact for matrigine could have for this community. What's especially striking is how quickly these responses emerged and how they continued to improve over time.

Steven Petrou
Steven Petrou
Co-Founder & Chief Scientific Officer at Praxis Precision Medicines

By just week one, fifty four percent of patients had already responded. That number climbed to sixty seven percent by week eight, showing a clear and encouraging trend of improvement. Even more notable, over twenty two percent of patients, more than one in five, were completely seizure free during the second month of treatment. That kind of outcome not only underscores vimatrogene's potential, but also sets the stage for what we hope to see in the longer twelve week POWER one and POWER two studies. Looking more closely at the data, formatrogene's efficacy held strong across all patient subgroups, regardless of baseline seizure burden.

Steven Petrou
Steven Petrou
Co-Founder & Chief Scientific Officer at Praxis Precision Medicines

We specifically analyzed outcomes by splitting patients at the median baseline seizure frequency to explore whether those with a higher or lower seizure loads responded differently. As you can see in the figure, the drug performed consistently well across both groups. That kind of robust and uniform response is a strong signal of reliability in a heterogeneous epilepsy population. Taking a step back, it's important to remember what treatments these patients were already receiving when they entered the study. The bar in was especially high.

Steven Petrou
Steven Petrou
Co-Founder & Chief Scientific Officer at Praxis Precision Medicines

This was the first epilepsy study launched and reported in The US following widespread adoption of synovomat. In fact, thirty percent of RADIANT participants were already on synovomate, meaning vimatrigine had to demonstrate efficacy on top of an already aggressive background regimen. That context makes the results even more compelling. When we looked at response rates based on the most commonly used background ASMs, the results remained consistently strong. Patients showed excellent responses, whether they were on one or more sodium channel blockers, SV2A modulators, or even synovomate.

Steven Petrou
Steven Petrou
Co-Founder & Chief Scientific Officer at Praxis Precision Medicines

This level of consistency in both efficacy and tolerability across different treatment backgrounds speaks to vormatrogene's versatility. It reinforces the idea that this is a therapy with broad applicability, not limited by the complexity of background regimens. Turning now to safety and tolerability. Bormatrigine demonstrated a favorable overall profile. Most adverse events were mild to moderate and tended to resolve over time.

Steven Petrou
Steven Petrou
Co-Founder & Chief Scientific Officer at Praxis Precision Medicines

We did observe a twenty three percent discontinuation rate, which in many cases was linked to a lack of background ASM dose adjustment, despite protocol guidance. Importantly, in six instances where investigators proactively reduced background ASMs, both adverse events and discontinuations were avoided entirely. We see this not as a safety signal related to vermatrogene itself, but rather a manageable interaction dynamic that can be addressed with appropriate background therapy management. I'll close by saying how proud we are to share these results today. RADIANT was a high bar study in a complex and underserved patient population.

Steven Petrou
Steven Petrou
Co-Founder & Chief Scientific Officer at Praxis Precision Medicines

We believe the data clearly support vimatrogene's potential to make a real difference for people living with refractory epilepsy. With that, I'll now hand the call back to Marcio.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

I'm sure you are as excited as I am about the strength of the RADIANT data Steve just reviewed. As we move forward, we must remember that one of the key motivations to conduct RADIANT was to better inform the final design of POWER two. In that regard, one of the key aspects Steve did not discuss was the preliminary modeling for dosing and efficacy. We have concluded that it would be beneficial to add a dose arm of forty milligrams to the POWER two study, bringing to life the potential of even greater efficacy. We also intend to be more deliberate in our instruction CPI on how to dose reduce the background ASM for even better management of patients.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Another incredibly interesting piece of information we learned in the RADIANT study is the reported positive impact in moods observed in patients. With that in mind, we decided to include a depression and moods endpoints to the POWER two design. We're ready to start rolling out POWER two, and it goes without saying that the full force of the practice recruitment engine would be at it. The final design of power two enroll approximately four hundred refractory epilepsy patients testing vormetrin dose of twenty, thirty, or forty milligrams against placebo over 12. The enrollment is expected to complete in 2026.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

I want to now focus the next few minutes into a very important and often neglected part of drug development in epilepsy. As you can see here, we're presenting some data from a very large US claims analysis in patients with epilepsy conducted by practice, which covers almost half a million patients' worth of data. The message is very clear. The majority of the patients are not doing okay, and virtually two thirds of them fail their first line treatments. And after that, a very improvised layering of multiple agents begin.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

This is not good for patients or the health care system. Clearly, there's a critical need for simpler, more effective treatments like formattergine, ones that combine the fast acting mechanism with minimum restrictions With that in mind, we'll be launching POWER3, which aims to establish for metrogen as standalone therapy, in when refractory epilepsy patients transitioning off currently ASM. This study leveraged historical understanding benchmarks and safety measures to protect the integrity of the patients and the results of it. And we plan to initiate POWER three in early twenty twenty six. To wrap up the call about lormatrigine, it's incredibly exciting to be in the point where we can confidently say it has emerged as best in disease ASM, distinguished by rapid seizure reduction, favorable safety, ease of use and sustained effectiveness across diverse patient group.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

The RADIANCE results significant bolster our confidence in the ongoing and upcoming studies for vimetra gene. Before we move to Q and A, and reminding that today's results is about celebrating formatterjene, I want to emphasize that practice remains deeply committed to revolutionize epilepsy treatments from common focal epilepsy to rare DE conditions. I'm sure you have seen the fantastic news of raletirgene being granted breakthrough designation here in The US, which will allow us to move even faster towards registration in patients with SCN2A and SCN8A. Lastly, we extend our sincere thanks to our investigators, patients, site staff, and practice team for their contributions to the success of the epilepsy program in overall. We now open the call to q and a. Operator?

Operator

Thank you. Our first question comes from Yasmeen Rahimi with Piper Sandler. Your line is open.

Yasmeen Rahimi
Yasmeen Rahimi
Senior Research Analyst at Piper Sandler Companies

Team, congrats really to the outstanding data both in treatment response as well as seizure free, especially as the majority of the patients are on background therapy. I guess the first question is, if you looked in terms of the background therapies, were you able to look at if there was a difference in response rate, if they were on different products? That's sort of question number one. And then question number two is just given the incredible execution into Radian and you provided color around Power II reading out in Power II finishing in the back half of twenty twenty six, Could you maybe help us understand sort of, I think we get that question a lot. What were sort of the nuggets that leads you to execute really strongly through the study?

Yasmeen Rahimi
Yasmeen Rahimi
Senior Research Analyst at Piper Sandler Companies

And then the timing of Power I, I think a lot of, it sounded like you're on track to finish POWER one at year end, but if you could just reconfirm guidance around timing of POWER one, that could be very helpful.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

That was great. Thanks, Yas. Incredibly enthusiastic, right? As we come out here, when you look into focal epilepsy background in general, I think your question is exactly on the specifics. The first question is on the specifics for the background.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

If you look across Keppra or any of the SPHUAs, and it's on our slide 13, we saw incredibly robust effects on certain general blockers in general. Some patients were on one, some patients were on two. You wouldn't expect much of an effect there.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

I think there was some of the skepticism before, and we've seen incredibly robust effect as well with over fifty seven percent of patients having a response. But maybe the most striking result on that same slide is patients on this study, over thirty percent of them were on three hundred milligrams or even more, sometimes four hundred, four fifty of cenrolamates. This was not your mildly treated run of the mill patient then and on those patients have seen over fifty five percent response. So if there's any doubts on the placements in terms of refractory, I think that should be no more. We did talk as well on what we believe to be the proper way for this drug to be used.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

It's really moving towards first therapy and first line. And that's why we're starting the POWER-three study. But I'm sure we can discuss that soon. So going back to your question, right, we set up to recruit a smaller group of patients, and we end up recruiting. That should be a big checkmark on our ability to recruit this population that as you've seen on the demographics slide, it's your classical refractory, seizing a lot, multi treated, patient population in The United States and in Europe.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

So I'm pretty happy with that. Not happy for the patients on being treated with those drugs, but happy on the fact that we can recruit them well. That is already happening on Power One, the acceleration, We did in our corporate release and our Form 10 Q, which should be filed right now. And you can refer to, like, reinforce the guidance that we previously gave on finalizing POWER one this year. POWER two is not off the ground yet.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

So one should always be careful on making predictions of studies that have not started. But based on our engine, particularly here in The US, what are really able to get high quality sites and to help the sites with their own recruitment efforts, with our own recruitment efforts to get more patients. We believe more patients in our site is a good thing, because then they have more experience, the quality is higher, the overall operations run smoother. So that is going incredibly well. So we're going to transfer that enthusiasm towards POWER two and pretty soon in the future POWER three as well.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

So it's on and off, it's not only a phenomenal result as we see for patients today, but in general, it brings us a step closer or an inch closer to completing POWER one and to getting POWER three and getting that registrational. It's particularly sad as others struggle here to recruit on the same population, and one must ask why. But on our case, we are incredibly happy of our execution and our team's focus on getting these patients on these studies.

Yasmeen Rahimi
Yasmeen Rahimi
Senior Research Analyst at Piper Sandler Companies

Thank you so much. Congrats again.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Of course.

Operator

Thank you. Our next question comes from Ritu Baral with TD Cowen. Your line is open.

Ritu Baral
MD & Senior Biotechnology Analyst at TD Cowen

Hey, guys. Good morning and congratulations on this really, really good data. I've gotten a bunch of questions this morning just being driven by this twenty two percent seizure free rate and this sort of large percentage of patients that responded very rapidly. Marcia and Steve, what do you think is driving this increase in efficacy on all these measures? Excuse me, even after steady state plasma is achieved in patients and do you have any exposure response analysis done which is contributing to the twenty milligram dose that you now plan on including in POWER two?

Ritu Baral
MD & Senior Biotechnology Analyst at TD Cowen

And then I've got just a quick housekeeping follow-up. Thanks.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Yeah. Thank you so much, Ritu. So we do have the exposures and I would say that the raw exposures are already quite well processed and the preliminary exposure response well underway as well. So I'll make a couple of comments about that. And then I'll hand over to Steve to talk about why we were expecting and we're seeing this phenomenal results.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

So we do see steady state being reached quite quickly here between the first and the second week of treatments. As you've seen on these slides, off the gate to get very good results. It deepens quite considerably. We thought the most scientifically relevant way to present was actually feeding the LoS to the charts, because we know epilepsy is not a weekly process, right? Like the patients don't see otherwise, we'll observe them for a week, and then just treat for a week or two afterwards.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

And it's the overall month, I think the metric here. But we do see less, I think the overall concept is that less seizures leads to less seizures. So we see this deepening over time, which bodes incredibly well for power one, which is twelve weeks long. And POWER two is going to be twelve weeks long as well on that regard. The twenty milligram dose that we are using for the first six weeks of POWER one is rising to the range where you are seeing this incredible efficacy, clearly the 30 as well.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

But what you've seen is a potential for a fairly significantly higher when you go to the much higher sides of the exposure of these patients to get an even bigger results here. Not that we need it, not like this is the highest seizure reduction ever seen on an epilepsy study. Not that we need anymore, but I think these patients do deserve more and they're going to drive that. And that's why we added the forty milligrams. So in a sense, it's good to be stepping into power two, expecting all three dose to be quite effective and giving this flexibility for the patients.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

But maybe Steve can talk about why we think the deepening is granted.

Steven Petrou
Steven Petrou
Co-Founder & Chief Scientific Officer at Praxis Precision Medicines

Yeah, just to speak to the issue you raised, Marcio, about fuel seizures causing fuel seizures. And the same thing, the old saying in epilepsy is seizures beget seizures, and that's a process of really resetting the activity level of a neuron. That's a molecular process that takes time to occur. Conversely, when you give an agent like vimatrogene, you immediately decrease activity, and that's actually starting to reset the level of neuronal activity. That process takes time to unwind as it took time to wind up.

Steven Petrou
Steven Petrou
Co-Founder & Chief Scientific Officer at Praxis Precision Medicines

So we just think it's really the opposite corollary of increasing seizures as a patient first presents. And there's well known physiological mechanisms, homeostatic plasticity, etcetera, that are known to underlie this phenomenon.

Ritu Baral
MD & Senior Biotechnology Analyst at TD Cowen

Super helpful. And then Marcia, you knew this was coming. The upcoming POWER one data, you mentioned you would finish enrollment and have data by end of year. Is there any more granularity that you can give us around where enrollment currently stands, And will you announce completion of enrollment for that study?

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Yeah, we probably will announce the completion. And I would say at this point today is the day to celebrate Radiant. But yes, I could see this coming. I appreciate you professing with that. Enrollment is incredibly strong.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

I just had a call this morning with most investigators and the enthusiasm of everyone that is on POWER one is really great to see. I know it wasn't a slide and I reinforce it, but one of the things of Radiance that we were not expecting was really this overwhelming feedback from patients and investigators on their improvements in moods, on their ability to cope better with their day. And I think investigators like that a lot as well. That is certainly helping with even more patients being funneled towards this study versus other things going on out there.

Ritu Baral
MD & Senior Biotechnology Analyst at TD Cowen

Great. I'll hop back in the queue. Thanks.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Thanks.

Operator

Thank you. Our next question comes from June Lee with Truist Securities. Your line is open.

Joon Lee
Joon Lee
MD & Senior Biotech Analyst at Truist Securities

Hey, guys, congrats on the beta and thanks for taking our question. Can you elaborate a little bit more on the discontinuation rates in the radian and how that was imputed into the seizure reduction data, if at all? And also for the forthcoming power one, would it be fair to assume the placebo rates will be lower than those reported for synovial maiden, know, a drug given the more refractory populations in power one? Thank you.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Yeah, no, thanks. Thanks, John. So why we if we could do better on the discontinuation, right? Like if you're looking to competitively our other studies, it's fairly similar, as I'm sure you've already done the comparison in overall. So not quite completely satisfied there yet, because we've seen what happens when investigators actually follow the billets they had on the protocol.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Doesn't happen, right, or happens at a very low rate. And I think that's what we're going to see moving forward. Having talked with some of them already over the weekend and so on, I think some regrets they would then have removed some of the drug. So not as much on the impact, to your question, on the ability to reduce seizures. But just that is a lot on top of these patients.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

And I think that that's what is leading primarily here for patients not wanting to stay. That's what needs this study to come out as well. When you are in the open label setting, it's certainly more reports of side effects in general and easier to discontinue. So I'm not completely surprised, a little bit higher than we expected, but it's still lower than Sunnova made, compared to drugs in the market with lower efficacy. Oh, and you mentioned what we should be expecting for POWER-one.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

I agree. In general, what you're seeing this patient population are two things. So one is the background, as you mentioned, very difficult, very refractory in general. And then the second is really the quality of the sites, the quality of the patients that are coming in, the stability of these patients on their seizures beforehand. So I think when you get like higher number of patients per site, higher quality of assessment, good level of stability in terms of the seizures beforehand, that all contributes lower potential placebo rates.

Joon Lee
Joon Lee
MD & Senior Biotech Analyst at Truist Securities

Thanks, guys.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Of course.

Operator

Thank you. Our next question comes from Douglas Tsao with H. C. Wainwright. Your line is open.

Doug Tsao
MD & Senior Healthcare Analyst at H.C. Wainwright & Co.

Hi, good morning and congrats on the data. I guess as a starting point, in terms of the added effect of increasing efficacy that we see over time, that was something that we saw with the LUTRA gene as well. And I'm just curious, the two molecules are similar in many respects. Do you think that that is a function of how they interact with the sodium channel uniquely, that you sort of get this dekindling effect, which sort of I think Steve sort of talked to, I think, in response to Richie's question? And then I have a follow-up.

Steven Petrou
Steven Petrou
Co-Founder & Chief Scientific Officer at Praxis Precision Medicines

Yeah, maybe just to further what I said before, Doug, that's very specific and different to how any other molecule interacts with the sodium channel, their biophysical profile. And we think that's got a lot to do with this effect because they target the activity more than they target normal function. They target the epileptic activity. But think that profile leads to this rapid and then this growing because we're having such good acute efficacy, That encourages this longer term efficacy to grow over time. So very much associated with that biophysical character.

Doug Tsao
MD & Senior Healthcare Analyst at H.C. Wainwright & Co.

Okay, great. And I guess on the side effect profile, I'm just curious, Marcio or Steve, the extent that you've been able to sort of detangle the effect that some of these side effects were, or AEs were related to formatter gene versus the background therapy. And as you look to the the POWER studies, thinking about enabling some reduction in dosing in background ASMs, which obviously probably contribute to many of the side effects experienced by patients.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Yeah, so absolutely right. But maybe before they are all ground us on the table on our slides 23. The bormatrigine treatment emerging AEs is over 20% lower than any other drug out there, 20% less patients. But if you're talking about any other therapeutic area, this is like 100 miles from anything else. On CNS related, it's about twenty percent as well.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

So we're already not other like universe when it comes to these other drugs that are unfortunately in the background, right? So we can't disentangle what these other things are doing. But what we know, because we ran the experiment is it gets reduced or removed when the background drugs are reduced, which ultimately is what these patients do and what the physicians do. So we see that as incredibly positive, not only for patients continuing RADIAN since we have a significant more now and for open label extension as well, but for the POWER one and POWER two and potentially POWER three studies as well. So yes, I think the trajectory, while we should ground on the numbers and be happy about being best in class and here in best in disease, that is a space to get better. That's why we're moving forward.

Doug Tsao
MD & Senior Healthcare Analyst at H.C. Wainwright & Co.

Okay, and if I can, one follow-up. I'm just curious on the mood benefits that you saw. I'm just curious, was that based on sort of anecdotal feedback, or was there any kind of inventory on emotional state taken?

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Yeah, so you will start systematically reported by sites. But unfortunately, we have not designed an instrument to collect that from the very beginning. And that's where we are incorporating the power to design. It's not completely unexpected, right? I think there's other drugs in this class that have approval for bipolar, for example, like lamotrigine, but they just can't be used broadly because of the other issues, including like the allergic reactions to the drug.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

So not again, not completely unexpected, but you all have very welcome comments that we got across the board from investigators.

Doug Tsao
MD & Senior Healthcare Analyst at H.C. Wainwright & Co.

Okay, great. I'll hop out of the queue. Thank you.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Thanks.

Operator

Thank you. Our next question comes from Yatin Suneja with Guggenheim. Your line is open.

Yatin Suneja
Biotechnology Research Analyst at Guggenheim Partners

Hey guys, thank you for taking my question and let me add my congratulations. Very nice results. Again, congratulations to the team. So a couple for me. So the first one is, could you talk about the kinetics of responses in the sense that are you seeing improvement in efficacy over time for most patient and then when you do a twelve week study you probably get more benefit?

Yatin Suneja
Biotechnology Research Analyst at Guggenheim Partners

And the reason I ask is because I couldn't really figure out from the chart that you have, are you seeing sort of deepening of this efficacy throughout the period? So that's first. Second one is, you know, what should be the read through to generalized data that you will have for the same asset? What should be the expectation there? And then finally, on the safety, which I'll ask, I mean you should be very comfortable with the safety, especially the tolerability, if you are going with the forty milligram in the future study. So yeah, those are the three questions. Thank you.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Yeah. So thanks, Yad. On the kinetics of the response, it is very clear. We thought it would be disingenuous to just get a straight line there to fit like a linear. But if that was the case, and you can do it yourself, since the data, would see it's a very significant deepening between the first month and the second month, which we expect to continue as we treat this patient further.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

So for POWER-one, the translation should be even deeper response there. Of course, we're going have to wait for that study to read out, but that is the expectation based on the data we have. And that is kind of the read through that was the second part of your question. When you look into safety, yes, we're very comfortable going to forty milligrams. We really see this association being a lot more related to the time and type of managements by the investigators than the drug itself.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

And we do see, as I mentioned, one of the previous questions, on the higher end of the exposure response, we see even further efficacy response or deepening. So when you combine that with another month of treatments, we should expect significantly better results here. Again, not that it's needed, right? This is already the best results in an epilepsy study.

Operator

Thank you. Our next question comes from Ami Fadia. I'm sorry, Amy left the queue. One moment, please. Our next question comes from David Hung with Deutsche Bank. Your line is open.

David Hoang
David Hoang
Director & Senior Analyst - Biotechnology at Deutsche Bank

Hi there. Congrats on the data and thanks for taking my questions. So I just wanted to ask about some of these other work that you mentioned you're doing with the program here in terms of, I guess, mood endpoint and Empower three looking at a role for monotherapy. How do you envision some of these other endpoints and additional studies here? Could are you looking at, I guess, to enhance the label or get some label differentiation versus what's currently available and what else is in the pipeline? Thanks.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Thanks, Dave. So on the moods benefits, right? As I mentioned a couple of minutes back, that is an expectation that a drug that reduces the seizures make these patients feel like more relieved from that hyperacidability overactivity, and with this mechanism that is known for, in a specific way to improve mood in general to be a positive. So we are looking for adding that as an endpoint, potentially a label claim, of course, based on the results there. On the POWER three switch to monotherapy study, I think that is a game changer.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

We haven't really had a drug for many, many years that is able to move to those one hundred percent of the patients there at the beginning versus the thirty percent on the bottom. So when you're talking about the refractory, hyper refractory patients like four or fifth line, as we show on the charts on the slide, we're talking about a $2,000,000,000 to $3,000,000,000 market opportunity there. When you move up to the first line, second line, we're talking about several folds that's potential. So from a market opportunity perspective, it makes a lot of sense, number one. But from a drug profile, it's the only drug that makes sense.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Let me remind everyone that Keppra, which is now the drug that people use off the gates, showed an efficacy of like thirty percent, basically no seizure freedom, and with very similar pharmacological properties and overall toxicological properties of formattergine. So we're not talking about a high bar to replace there. We're just talking about the fact that no other drug were able to. So that is expected to get off the ground pretty soon and if completed before the NDA submission, beyond the potential NDA, if not, to be a quick add on to the label there.

Operator

Thank you. Our next question comes from Ami Fadia with Needham and Company. Your line is open.

Ami Fadia
Senior Analyst at Needham & Company

Hi, good morning. Thanks for taking my question and congratulations on this really strong and impressive data. I wanted to sort of better understand the discontinuation rates. If the physicians were allowed to discontinue any background therapies, why did they not do that? And for the six or so patients where they were discontinued, was there any change or can you kind of talk about the change in the efficacy as well as the safety adverse events that were noted after the background therapies were removed.

Ami Fadia
Senior Analyst at Needham & Company

And then maybe a related question on power three. What additional data do you think you need to generate perhaps in an open label portion to convince physicians to switch out patients from their existing background therapies and then move patients to omitrogen? Thank you.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Yeah, absolutely. So, Amy, on why people haven't done something is going to be kind of a speculation on a bit on my end, right? But it's informed speculation since we had that conversation. And I'll refer to one conversation, for example, I had with an investigator in the last few days who was a little bit slow to start reducing. And I think his point to us was, and to me particularly, we're so used about keep adding and just doing nothing and then cycling these patients on that the reaction time for some of them this is a big European leader, someone who's very important for the space of the number of patients on the trial.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

And then when he realized it was the first few patients that was not the case. And then for the following ones, he was able to and worked really well. So I think it's a timing thing and really people learning a little bit the drug at the end of the day. That's why we did a study as well. On the ones that did remove, I think we mentioned that on the slide as well.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

It's not only resolved the AEs, right? Was efficacy is not impacted, like at all. Well, in the long run, efficacy is actually better on those patients. But we should always be careful to talk about individual patient results on things like this. So that's why it would give us it is not that reducing the background made the patients worse, which is the general concern, right, one would have in linking to your question about POWER three.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

I think that would be concerning if that was the case, but it's not the case at all. In a sense, I think what we established is that the background therapy is not doing anything but causing side effects, and bromatrogene is getting these patients better. So a monotherapy study, a switch to monotherapy, makes a lot of sense. We pulled a number of physicians over the last few days as they are under CTA with us. And I think that is an incredible enthusiasm for POWER3, because they really believe on lipomaetrazine, but they didn't have an opportunity to do something like that before with any other drug.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

So not hearing a lot of concerns. Of course, there are ways to do it. There are dynamics on the study, but not really an overwhelming concern about it.

Ami Fadia
Senior Analyst at Needham & Company

That's helpful. Thank you.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Thank you.

Operator

Thank you. Our next question comes from Jay Olson with Oppenheimer. Your line is open.

Jay Olson
MD & Senior Analyst - Biotechnology at Oppenheimer & Co. Inc.

Oh hey, congrats on these impressive results and thanks for providing the update. Since you mentioned the observation that seizures begets seizures, is there a way to show that formatrogene could potentially have a disease modifying benefit?

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Yeah. Thanks, Jay. I would, again, argue, I'll ask Steve to comment here as well. That's what we already seen when we have the direct benefit of seizure control, and then the indirect benefit of patients just feeling generally better, better moods, better relationship with the site and with their own families, and so on. And ultimately, I think what we are looking for here is to change epilepsy as we know it.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Take a look at our slides when we're looking to people keep saying thirty percent of patients are refractory. That's one of the biggest BS that anyone can say in epilepsy. It's like over sixty percent of those patients are on several therapies. And that is just not acceptable. Those things are not benign, as we know.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

So they affect the well-being of patients as well. When you remove that, get an effective drug that not only reduce the seizures, but improve their overall well-being and particularly moods, as we discussed, I think we have an opportunity to really change everything here. But maybe Sifa can talk about it.

Steven Petrou
Steven Petrou
Co-Founder & Chief Scientific Officer at Praxis Precision Medicines

And I think it's back to that earlier point about seizures, beginning seizures, is the disease that it's a new set point for the brain where a higher level of activity, a higher threshold for triggering seizures, it becomes the new normal. And this reduction over time in seizures that we saw and that we talked about earlier is a sign that we're reversing that process. And that can be exactly what you're talking about, disease modification. And then all the attendant things that happen. If you've got a brain that's hyperexcitable, mood disturbances and other things emerge, and the fact that we saw changes in other domains, I think it's very encouraging that we are really tackling some fundamental issues of what epilepsy is.

Steven Petrou
Steven Petrou
Co-Founder & Chief Scientific Officer at Praxis Precision Medicines

We see this across rare, severe epilepsies, common epilepsies like focal as well, that it is a disorder of seizures and excitability, and resetting that set point is key to disease modification and improvement across multiple areas.

Jay Olson
MD & Senior Analyst - Biotechnology at Oppenheimer & Co. Inc.

Thank you for that. And maybe if I could just ask one follow on. Do these impressive RADIANT results give you any hint that vormatrogene potentially could have benefit in DEE?

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

In theory, yes. I think we can. The good news is the Relitrigine is quite strongly set for DEs and Emerald is off the ground that you might have seen on our corporate release a couple of minutes ago, enrolling patients. We do expect to have very strong enrollment and results there as well on the GE side. There are things, features that are important for the patients that you might not be able to fulfill with a solid form that is bermatrogene.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

But in theory, these drugs are dampening hyperexcitability on a hyperexcitable neuron that is seizing a lot. So yes, there is no reason to believe not, but we're really looking straight on and quite focused for rilutrogen for these and for bromatrogen for adults epilepsy.

Jay Olson
MD & Senior Analyst - Biotechnology at Oppenheimer & Co. Inc.

Great, thanks for taking the questions.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Of course, thank you.

Operator

Thank you. Our next question comes from Brian Skorney with Baird. Your line is open.

Brian Skorney
Senior Research Analyst at Baird

Hey, good morning, everyone. Thank you for taking the question. Let me extend my congratulations as well on nice data. I like the chart on Slide 13 you have breaking out the efficacy by background med. So I'm just wondering in that vein, if on kind of pushing on some of the color on the safety profile, do you have a similar slide deck to kind of look at how safety breaks down by background? ASMs, obviously, some of these are pretty potent sedatives.

Brian Skorney
Senior Research Analyst at Baird

So I wonder if there's just a driving force behind some of the dizziness and somnolence that can be discombobulated from drug? And just to confirm, are these all focal onset patients in this data set? Or are there any grand mal patients here? Thanks.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Yeah. So Brian, this is all focal onset seizures. We're going to have the primary generalized later in the year at AES here. So maybe get that out of the way. As you can see on both the demographics table and on that slide, this number sums to much more than one hundred percent in terms of the overall.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

So patients were in a multitude of anti seizure medications, which makes that analysis of what is actually the culprit a little harder. But I think what I can say is we look into not only the ASM they're in, but the actual ASM levels in their bloods. And when you look into that, it is very clear that a significant proportion of those patients are on toxic concentrations, meaning higher than the maximum allowed concentration in The United States. And you do see somewhat of an association on those cases. So people are now monitoring from therapeutic drug monitoring perspective to frequently and heavily these patients, I would argue they should.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

And obviously, are a lot more prone to have side effects. One of the reasons why we're being a lot more proactive on the reduction of the dose of the background.

Brian Skorney
Senior Research Analyst at Baird

Great, thank you.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Of course.

Operator

Thank you. Our next question comes from Rudy Lee with Chardan. Your line is open.

Rudy Li
Senior Research Analyst at Chardan Capital Markets

Hi, thanks for taking my question. Congrats again on the strong results. Just a quick follow-up to the question regarding the background therapies. So can you provide additional color on the potential impact testing of current background therapies. I'm just curious how that change your enrollment criteria, selecting the right patient for the pivotal trials, and what kind of additional data you think would be necessary to support its use in combination with other sodium channel blockers in practice? Thanks.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Rudy, I think what you're seeing here is the only real sample of how patients are treated currently. Unfortunately, I'll say adjunctive therapy on this layering of ASMs is just a common practice. There is no reason to be worried or concerned about the combination. If anything, again, I urge everyone to look into slide 23. This is the lowest rate of side effects on the therapy developments or develops for focal onset seizures.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Despite the fact that the combination was probably the most aggressive at baseline. So no concern whatsoever. We need to deal with the market as the market stands. And that's what we are doing here. I particularly with over like thirty percent of patients on cinnovate, and I would say that's what the market is.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

We're very confident that both the phase and the efficacy are incredibly strong there. So no real expected change other than the instructions, as we mentioned before, for physicians to be more cautious about the reduction on the background ASM.

Rudy Li
Senior Research Analyst at Chardan Capital Markets

Got it. Very helpful. Thanks.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Thank you.

Operator

Thank you. Our next question comes from Ritu Baral with TD Cowen. Your line is open.

Ritu Baral
MD & Senior Biotechnology Analyst at TD Cowen

Hi, guys. Thanks for taking the follow-up. I just wanted to ask a little more detail on the side effect profile and specifically the comment on the severe patients and this comment about recovered and resolved. Can you give us a little more detail on the moderate to severe and serious side effects and that recovered and resolved comment? And then I've got a follow-up.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Yeah, yeah. So on the severe specifically, Ritu, one of the patients had a dizziness. So I would say that was clearly on targets, and on targets not only for therapy, but for the combinations that they were in. The other ones were background illness, like particularly an infection that leads to aspiration pneumonia. So not too concerned about that.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

The fact that they all resolved, I think that's the most important and resolved very quickly is the most important part here. So not too concerned, I think we wanted to be very transparent and show the rates there and show the results, but not anything we're very concerned about.

Ritu Baral
MD & Senior Biotechnology Analyst at TD Cowen

And was it resolved with removal of drug or adjustment of background meds?

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Oh, very good question. Sorry for misunderstanding before. No, it was actually just resolved, like with with congenital dosing.

Ritu Baral
MD & Senior Biotechnology Analyst at TD Cowen

Okay. Okay. That was the follow-up question. Thank you.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Thank you.

Operator

Thank you. I'm showing no further questions at this time. I'd like to turn the call back over to Marcio for closing remarks.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

Thanks everyone for joining. We are thrilled on these results. I think it's important for all of us, but it's particularly important for patients living with focal onset seizures and with epilepsy in general. It's not every day that we get a field that's been going on for like one hundred years since the a little bit over one hundred years since the first treatment. And you can deliver after more than 25 drugs in the market, over fifty percent reduction, sixty percent overall response rate of patients.

Marcio Souza
Marcio Souza
President & CEO at Praxis Precision Medicines, Inc.

It's quite remarkable to put in context. I wanted to take a second to show my appreciation for all the patients participating on this study and all the other studies and for everyone at Praxis and our investigators and site staff. Thank you so much. Exciting days ahead of us. Appreciate the support and looking forward to interacting with all of you.

Operator

Thank you for your participation. You may now disconnect. Everyone, have a great day.

Executives
    • Marcio Souza
      Marcio Souza
      President & CEO
    • Steven Petrou
      Steven Petrou
      Co-Founder & Chief Scientific Officer
Analysts
    • Dan Ferry
      Managing Director at LifeSci Advisors, LLC
    • Yasmeen Rahimi
      Senior Research Analyst at Piper Sandler Companies
    • Ritu Baral
      MD & Senior Biotechnology Analyst at TD Cowen
    • Joon Lee
      MD & Senior Biotech Analyst at Truist Securities
    • Doug Tsao
      MD & Senior Healthcare Analyst at H.C. Wainwright & Co.
    • Yatin Suneja
      Biotechnology Research Analyst at Guggenheim Partners
    • David Hoang
      Director & Senior Analyst - Biotechnology at Deutsche Bank
    • Ami Fadia
      Senior Analyst at Needham & Company
    • Jay Olson
      MD & Senior Analyst - Biotechnology at Oppenheimer & Co. Inc.
    • Brian Skorney
      Senior Research Analyst at Baird
    • Rudy Li
      Senior Research Analyst at Chardan Capital Markets
Powered by Quartr