Praxis Precision Medicines, Inc. Q3 FY2024 Earnings Call

Good day and thank you for standing by. Welcome to the Praxis Precision Medicines 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. Please refer to the Operator Instructions. I would now like to hand the conference over to your speaker today, Dan Ferry from LifeSci.

Good morning, and welcome to Praxis Precision Medicines third quarter 2024 financial results and business update conference call. This call is being webcast live and can be accessed on the Investors section of Praxis' website at www.praxismedicines.com. Please note that remarks made during this call may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These may include statements about the company's future expectations and plans, clinical development timelines, and financial projections. While these forward-looking statements represent Praxis views as of today, they should not be relied upon as representing the company's views in the future. Praxis may update these statements in the future, but is not taking on an obligation to do so. Please refer to Praxis' most recent filings with the Securities and Exchange Commission for a discussion of certain risks and uncertainties associated with the company's business. 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 brief question-and-answer session. With that, it's my pleasure to turn the call over to Marcio.

Thank you. Good morning, and welcome to the Praxis third quarter 2024 conference call. This past quarter, we have remained laser-focused on advancing our pipeline as we gear up for next year to have four programs in registration totaling a substantial multibillion dollar opportunity. The Phase 3 study in Essential Tremor Essential3 for our lead program ulixacaltamide 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. Both studies are well-powered and controlled for success because there are 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 once we have evaluated the recommendation from the interim review board for the interim analysis. In Q3, we are very excited to report the positive top-line results for another asset in our pipeline, relutrigine, in the Phase 2 EMBOLD trial in SCN2A and SCN8A-DEEs. In the 15 patient study, relutrigine demonstrated an impressive 46% reduction in motor seizures versus placebo, with one-third of the patients achieving an unprecedented seizure-free status. Based on those results, we initiated a second registrational cohort of the EMBOLD study, which has already started screening patients just weeks after completion of the prior cohorts. In common epilepsies, vormatrigine, previously known as PRAX-628, is starting out of the gate strong in all areas of our comprehensive ENERGY clinical program. The innovative observational study EMPOWER, a first of its kind in collaboration with the Epilepsy Study Consortium, launched in the third quarter and in this short period of time attracted the interest of over 1,000 patients who registered in the study. We expect the key learnings from EMPOWER to impact the entire Energy program. The Phase 2 RADIANT and the Phase 2/3 POWER1 trials are on track for top-line results next year. Rounding out our portfolio, Elsunersen began dosing patients in Brazil in the second quarter for the EMBRAVE study, and we continue to engage with regulatory agencies in Europe and in the U.S. to finalize the development plans in SCN2A gain of 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. Let me now focus some more on ulixacaltamide. Our innovative Essential3 program in ET is the biggest and most comprehensive program conducted to date. We began recruiting for the two Phase 3 studies just about one year ago and have seen tens of thousands of patients interested in participating. This vibrant participation highlights the significant unmet need 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 need for treatments in Essential Tremor continues to be more defined as we advance this program. In a survey we conducted with over 400 patients, up to 77% of the respondents said they do not feel their ET symptoms are managed with current treatments. In a separate survey, we conducted with 150 treating physicians, they shared that 85% of their visits with ET patients are focused on looking for treatments. Clearly, there is an incredible need here and we look forward to shortly completing the Essential3 study with the goal of bringing an option to the market. As a quick refresher, the Essential3 program has two simultaneous Phase 3 studies being run concurrently. Study 1 is a 12-week two-arm placebo-controlled Parallel Group Study and Study 2 is a 12-week Randomized Withdrawal Study. 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 clinical sites. We shared on our last quarterly call that we decided to trigger a pre-planned 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 met, to consider ceasing the study, or to consider enrolling additional patients to ensure it's sufficiently powered for success. Given the expectation for a sufficient number of patients to complete 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 impact in the study completion of Study 2, we will be finalizing the interim analysis in the first quarter of 2025. Regardless, preparations continue to file the NDA as expected in 2025. Now, moving on to our highly differentiated epilepsy portfolio. Vormatrigine, previously known as PRAX-628, 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 vormatrigine will provide a highly differentiated, paradigm-shifting way to treat this disease. Last quarter, we introduced our broad ENERGY clinical program for vormatrigine in focal and generalized epilepsy and I'm glad to share that the ambitious multi-study goals we aim to achieve are advancing well. ENERGY is comprised of four studies aiming to build a strong base of patients for our trial while generating multiple data points over the next 18 months to support the differentiated profile of vormatrigine. Three trials of ENERGY are to evaluate efficacy and safety. The first of this is RADIANT, an open-label study that will enroll patients with either focal or generalized epilepsy who will receive vormatrigine for eight weeks with update follow-up of two weeks. We are on track to deliver on top-line results in the first half of 2025, which should help us better understand the effectiveness levels of vormatrigine and its pharmacology in the patient population. The POWER1 and POWER2 studies are 12-week Phase 2/3 studies in patients with focal onset seizures. POWER1 is underway and we anticipate top-line results towards the end of 2025. We will slightly stagger the initiation of POWER2 to begin recruiting in the first half of 2025. The combined studies are expected to enroll approximately 500 patients globally. As we consider other areas where vormatrigine can play an important role, it's clear that its activities in Nav 1.7 and Nav 1.8, 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 vormatrigine in pain and will be sharing more in the near future. Now turning to our relutrigine, a functioning state modulator that is formulated for pediatric use in DEEs, a group of severe epilepsies characterized by developmental delays with early onset. With SCN2A and SCN8A being two of the most severe and refractory forms of these and where currently there is no approved treatment. As a reminder, relutrigine has orphan and rare pediatric designation for these two indications. We are thrilled and humbled to share the unparalleled results we observed in the Phase 2 EMBOLD trial Cohort 1 in SCN2A and 8A last quarter where relutrigine demonstrated a number of impressive and unprecedented data points. This two-arm study was run over 16 weeks with four, four-week periods. Patients in the placebo arm were administered placebo for one period and relutrigine for the other three periods and neither the patient nor investigators were aware, which period was on placebo. 15 patients completed the study and patients had the option to continue to an open-label extension after the 16 weeks. A 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, which notably was never seen before in the severe patient population. In addition, we saw a disease-modifying impact noted in the study by both caregivers and clinicians, with relutrigine leading to meaningful improvements in overall wellbeing of patients in areas of seizure severity, intensity, alertness, and other important measures. This is also very impressive and an encouraging finding given not only the severity of the disease but also the lack of improvements in these areas with currently available treatments. Lastly, relutrigine was generally well tolerated with no drug-related serious adverse events or dose reductions required during the study. These results further set up relutrigine as the potential first and best-in-class treatment and following the successful proof of concept, we initiated screening for Cohort 2 update 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 these, 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 relutrigine, which uses a more targeted approach on the sodium channel mechanism of action, we believe there is broader potential for relutrigine across all DEEs. With that in mind, we are already diligently working with the regulatory agencies to finalize the EMERALD study protocol for all DEEs. We expect to finalize by the end of this quarter and initiate in 2025. We are very excited about both the potential and the progress of our sodium channel modulators, vormatrigine and relutrigine, and there's a lot more to come in 2025. Rounding out our clinical epilepsy program is our first ASO Elsunersen, designed to selectively decrease expression of the SCN2A gene and directly target the underlying cause in early onset seizures in SCN2A-DEE. Last quarter, we continued Part A of the EMBRAVE protocol in Brazil. This part of the study will provide important control data to examine the safety and effectiveness of Elsunersen in a very severe disease population. 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 rigorously focused 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?

Thanks, Marcio, and good morning, everybody, and thank you for joining today's call. I'll provide a quick summary on our third quarter financials. In Q3, our operating expenses were $57.1 million, with $41.9 million of that for R&D, and the remaining $15.3 million for G&A and reflects an increased amount of clinical activity in our movement disorder and epilepsy programs. During the third quarter, Praxis spent $27.7 million in operating cash, similar to the second quarter of 2024, and it reflects our focus on working capital. We ended Q3 with $411.2 million in cash, cash equivalents, and marketable securities, which compares to $81.3 million of cash at December 31, 2023, with the increase primarily due to the net proceeds from Praxis follow-on public offerings earlier this year. 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.

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

Thank you. Please refer to the Operator Instructions. Our first question comes from Ritu Baral with TD Cowen. You may proceed.

Good morning, guys. Thanks for taking the question. A couple of questions on relutrigine for DEE. Specifically, as you think about the 80 patients in the expanded cohort, will the enrollment criteria for that 80 patients be any different than the original 15 patients? And if so, do you 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 2 to change based on feedback? And any specifics on what you're asking on EMERALD? Thanks.

Sounds good. Thanks, Ritu, for the question. So on the first one for the 80 additional patients that are enrolling in the second cohort of the study right now, number one, we have actively been screening those patients and getting them into the study, which is very good news in our view. The major difference I would call on this study is actually the start dose for the patients randomized to drug. Starting in the previous study was at 0.5 mg/kg per day and this one is 1 mg/kg per day. So we believe this will be the most efficacious. So we expect the impact will be a faster effect in terms of separation and possibly maintaining or even expanding the number of seizure-free days and the number of patients there. No real major changes on the inclusion criteria. So from a patient population perspective, we're not expecting to see a different one here. And then on the timing for EMERALD, we do have a protocol. We are aligning on specifics there. I would say it's a little bit more traditional as I would call it; we're expecting to run like a Parallel Group 1 to 1 for 12 weeks. We are aligning on the inclusion of those patients. Our view and our position right now is that we can phenotypically define patients with DEE independently of their genotypical etiology. As long as they have a non-sensitive mechanism number one and two, seizure burden consistent with high impact expectations, that should be sufficient. We just need to double-check a number of small details in terms of how to randomize and size, and things like that, which we expect to be done by the very end of the year and then we will be able to operationalize by the very beginning of next year.

I want to clarify that you will be genotyping these patients, but all they need is a genetic mechanism that is rational for the study.

That is right.

Okay. Got it. Thank you.

You're welcome. Thank you.

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

Good morning, team. Thank you so much for all the thoughtful comments. A few questions on the interim analysis. I think investors are 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 Study 2 will not readout before the interim or at the interim. Could you just walk us through sort of the disclosures around both of the studies that could be helpful? And lastly, I think you guys noted that upon the outcome of the data in ET, you would reinitiate a Parkinson's disease program in 2025. Could you maybe comment on like the success an ET would move you into Parkinson's or would that be a Phase 2 study, Phase 3 study? Any color around that would be helpful and I'll jump back into the queue.

Sounds good, Yas, and thanks, Yas. So starting on the interim, I'll start by saying we're very confident on the execution for the interim. Every aspect that our monitoring and every discussion just increases our confidence in a successful execution. Of course, it is biased towards our success to begin with and making sure we wrap up the program shortly thereafter. That was the main driver here. So what we're trying to do is to deliver a successful program that we can file an NDA for, ensuring we are clear on the efficacy, the safety of ulixacaltamide hydrochloride for these patients. As there are a number of factors that were influencing things—availability of top identity members, their ability to conduct the analysis, cleaning up the data—arguably the most important factor here is the influence on Study 2 which you mentioned as a part of your question. In the eventuality, which is quite a possibility that the interim analysis works exactly as we expect, very positively, we wanted to make sure that the results of Study 2 come about the same time to shortly thereafter, number one. But two, we wanted to ensure there is no negative influence on Study 2 readouts. So when looking at this as a program, it made sense for us to make this, which in our view is a small change; we're safeguarding the overall positive results of both of these studies. Everything is progressing brilliantly so far. As for Parkinson's disease study, I think that as our confidence grows in the outcome of Essential Tremor, we need to be ready for expansion—time is an incredibly important asset in this business. We want to ensure that an indication of value for ourselves and for potential strategics gets off the ground. We received some feedback from the FDA last time in terms of what they would like to see on a PD study, so we have a good idea to design a Phase 2/3 study in Parkinson's that would significantly advance this program as well. We are restarting that in terms of the planning, so we are ready to kick off when we have the outcome on Essential3.

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

Sounds good.

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

Hey, thanks for the updates, guys. Just a quick clarification. Will you be including Lennox-Gastaut in the broader DEE study? Because there's no genetic basis for Lennox-Gastaut, and you seem to want to stick to genetic epilepsy based on your response to Ritu's question. And I have a follow-up.

Sounds good. Joon, we will include Lennox-Gastaut patients in this. As I attempted to answer before, we are providing an attempt to collect as much genotype information, sometimes as you know they're going to be defined phenotypically, clinically defined, and not have a final diagnosis. However, we believe that as they are, and given the data on the literature on claims data for LGS, it's one of the highest uses of the actual sodium 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. But at the same time, that is part of this entire discussion about inclusion criteria and measurement, which is the discussion we're having right now.

Great. So it's a two DEE study. Great. For the interim analysis for Essential programs, just wanted to clarify that when you 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?

Yes.

Yes. So is there or is there no inferiority analysis baked into that interim analysis?

Yes. So the interim analysis is on Study 1 only as you mentioned, right? We don't believe that would be necessary or appropriate for an interim on Study 2. There is alignment in database log claiming between the multiple events that we're talking here. It could be somewhat of an influence because those studies are recruited concomitantly from the same pool of patients, and they are randomized to their studies. So that's why there could be some influence depending on the outcome of the interim analysis as well. We will be reading out Study 2 of course shortly thereafter; it's easier one could argue study to monitor based on 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? Sorry. So that is a fertility margin on the lower end of the conditional power as it standards, right, on interims like that. So fairly standard in terms of the bottom there, a fairly wide I would say sample size re-estimation zone because that's why the reason why the study or the interim analysis was designed to begin with, and on the other end as well—we should consider that there is a stop for overwhelming efficacy as well. You want to balance all of that from an information fraction perspective and spending perspective as well, and the overall execution to drive toward a successful outcome.

Great. And then last question, as we look to the very likely approval of Relutrigine in January, it's impressive that it even works at all because it only targets one of the three voltage-gated sodium channels in the peripheral nervous system. So it's interesting that you're advancing and looking at formulating in pain as well, which targets two out of the three pain receptors or voltage-gated channels. Any anecdotal evidence of pain reduction from your Phase 1 or any other studies? Thank you.

Yes. We're super excited about this as well. We've been looking into this for a while. It's not something that made sense from a priority execution, capital allocation in the past for us, but now we believe it does. We have very strong preclinical evidence in pain models showing it to be a very potent inhibitor of 1.7 and 1.8. 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 are excited with what we're seeing and we think that what's most appropriate for us is just to finalize everything, look into from a competitive standpoint, make sure that we are competitive and then talk about our plan early in the year with all of you. Yes. So to answer your question, we're working on collecting data on pain and expect to share insights early next year.

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

Yes. So the way we've been looking into Elsunersen is about twofold. One, we consider it important to explore particularly the safety at different exposure levels. That's a lot of what's being done in Brazil right now. On the second cohort, we are running a randomized study with patients receiving drug or placebo or drug alone. We're exploring a range of doses sequentially increasing the dose on those patients. We are doing all the other assessments as well, as you can imagine, so it was important for us to keep that separated from what we believe to be a very good long-term efficacious exposure dose, which is the 1 milligram per month for the global study. We have very good alignments already in general on what is needed there, but we do have still a meeting pending this year with the FDA on finalizing our expectations from when the meeting will occur. So nothing problematic there, but scheduling has driven the fact that we need just a little bit more time to ensure we have confidence in the final protocol so we can initiate it. So that is the bottom line for that one.

Okay. And so with the patients being studied in Brazil now, are you looking at some additional doses? If the results warrant, is there a chance that you'd explore higher doses in the U.S. and European registrational studies?

Yes. We must follow the science. What we've seen so far in the patients in the U.S. and the patients in Europe and Australia is that there's not a meaningful difference in terms of overall control gains on development milestones and things like that. Now, we have to remain open to the possibility that it could be meaningfully different and faster; 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. We will be driven by the results that we see here. The timelines for the original patients to be dosed are perfectly aligned with the enrollment timeline for the global study, so it shouldn't be complex in terms of how to get the best possible results for those patients.

Good morning, team. A couple of questions for me. The placebo response was pretty well controlled in Essential1. Essential3 has a more innovative decentralized design. What steps have you taken to control placebo response in Study 1 in Essential3? And then, as a second kind of set of questions, maybe on vormatrigine. What have sodium channel blockers demonstrated historically in PGTC seizures? And what would a registrational program consist of in generalized epilepsy? Thank you.

Sure. Thanks, Kambiz. So the placebo was already pretty well controlled in Essential1. When you look into Essential3, there was one aspect that we wanted to add to further control that. What we've seen is there is a slight but important change on patients that are less stable at baseline. There were pre-screening assessments or pre-randomization assessments on study on Essential1 in a baseline assessment. Patients that vary more in between those tended to be a little bit higher on placebo. Now, that study was at the end of the day about 4 times smaller than Essential3. So we wanted to ask the question whether or not the influence is going to be similar. So we chose to add maximum variability parameters between those visits and formally have visits pre-randomization. We believe that we can monitor patients throughout the study and know how long it takes for the drug to start working. We're confident on controlling that, and making sure that the patients are similar to what we want from E1. We don't want to depart from the cohorts too much. We want to ensure we tighten variability that is not due to drug effect, but rather to placebo effect. So we are very confident on the measures that we have put in place to control placebo there. And then, on your second question, on generalized epilepsy, historically sodium channel blockers have shown mixed results. There has been notable interest in the generalized epilepsy space, as the premature generalized tonic-clonic seizures can be particularly difficult to control. What’s interesting is how we view vormatrigine as a differentiated approach that could ideally target aspects of these seizures, making our registrational program unique.

Great. Thank you.

Hi, good morning. Thanks for all the updates. A couple of quick questions for me. Firstly on ulixacaltamide, can you comment on the enrollment and how what percent of patients have completed randomization relative to the target enrollment for the two studies? And was there a slowdown in the enrollment rate that caused the shift in the timeline? Maybe I'll ask my next question after you answer this one.

Sure. Ami, we're not going to talk about that right now, as we mentioned on the prepared remarks and in the press release. But what I can tell you is that there is no slowdown on what we expected from randomization or from patients on screening. We continue to see, if we decide to increase the size of the study in Q1, a fairly robust number of patients coming through. We have been intentionally managing that so we can achieve the best possible outcome for the studies. These are two positive studies, like right after the entrance, and we have seen a lot of scheduling of patients, which influences, but not meaningfully.

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

Yes. The goal is to have 50 patients in RADIANT. What we are seeing, again, in early days, is about the expected 30% generalized, 70% focal interest for, in general, particularly in the sites we targeted. We were relatively selective in terms of the number of sites because that is again a huge interest but we didn't want to lose control of the number of patients and get significantly more than we expect. 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 across, and it’s an open-label study, so we can continuously see and adapt as needed, perhaps reducing or increasing the total number of patients based on overall interest, but we expect about 30% from generalized and 70% from focal in the end.

Understood. Maybe just a last question from me. As you design the DEE study, what assumptions would you be making with respect to regulatory performance in this patient population relative to the data that you saw in SCN2A and 8A?

Yes. Arguably SCN2A and SCN8A were the hardest of those conditions to treat. There are few other DEEs that are incredibly difficult to treat, but those were indeed incredibly hard to see a reduction, and seizure freedom mortality in SCN2A, for example, is 6 times higher than elsewhere. We expect X or above the efficacy levels that we've seen from SCN2A, of course, powering this study 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.

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

Yes. No, Joe, if the interim is successful, we will have results at the same time.

Thanks. And then in DEEs, should we think about relutrigine as kind of just working in patients who are already responsive to calcium channel blockers? Or could you talk about the potential to work beyond DEE patients who are responsive to those agents?

Yes. So it's quite interesting. It does not look like it could or should be restrictive to patients who had prior responses, or those who are expected to. If you look into all the work we did with the two compounds published a little while back, the results on the dynamics of the neurons among the animal models are quite unexpected, with significantly better outcomes than anticipated in patients with classic epilepsy. So clearly, that has been proven not to be the case here. We expect a wide range of efficacy without restricting based on treatment history.

Hey, good morning, very much. Thanks for taking the question. Two clarification questions for me. First, on the interim for ulixacaltamide. I understand that the timing for the interim has extended to the first quarter of 2025. What I'm trying to clarify, though, is does the actual timing at which the interim is executed change? And if this was expected to be conducted at 50%, for example, does this now shift to 60%? Hopefully, that makes sense. I have a follow-up.

Yes. It makes a lot of sense. Thanks for the question, Laura. So the range that we gave for the information fraction, if I understand correctly, that's your question, was between 50% and 75%. So the range for the information does not change. Of course, it is a range based on the exact day of the data transfer and the calculations by the IDMC. But we did not change that.

Okay. That's helpful. And then, I guess, I understand your comments also about study conduct and integrity and the ramifications for 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. Have you had any feedback from the FDA on how they would like to see results communicated? Thanks.

Yes. So the last part is easy. The FDA did not provide feedback on how results should be communicated. They did review the integrated statistical analysis plan, which analyzed these studies separately. So that was reviewed, and we received feedback many months ago from the FDA on that. So the influence is less operational—the studies are randomized. Patients are randomized to one study or 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 a potential news, since they wouldn't know the outcome between Study 2 or Study 1. So we wanted to safeguard the integrity of the overall program. Thank you so much. I really appreciate everyone joining the call and staying with us, as the company continues to evolve quite positively; a lot went on over the last several months in terms of the transformation of the company, with what's going to come next year. We look forward to providing updates in the near future and I'm sure you're going to be in touch. Thank you.

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