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Praxis Precision Medicines Inc. (PRAX 2.22%)
Q4Â 2020 Earnings Call
Mar 17, 2021, 8:00 a.m. ET
Contents:
- Prepared Remarks
- Questions and Answers
- Call Participants
Prepared Remarks:
Operator
Ladies and gentlemen, thank you for standing by and welcome to the Praxis Precision Medicines fourth-quarter and full-year 2020 conference call. At this time, all participant's lines are in a listen-only mode. [Operator instructions] I would now like to hand the conference over to your speaker today, Alex Kane, head of investor relations. Thank you.
Please go ahead, sir.
Alex Kane -- Head of Investor Relations
Thank you, Shannon. Good morning and thank you for joining us today to discuss Praxis's fourth-quarter and full-year 2020 corporate update. With me on today's call is our president and chief executive officer, Marcio Souza; and our chief medical officer, Bernard Ravina. Additional members of the management team including our senior vice president of regulatory and quality, Alyssa Wyant; and our vice president of finance, Lauren Mastrocola will be available for questions following the prepared remarks.
Please note that today's prepared remarks will focus on recent business and pipeline progress. Detailed fourth-quarter and full-year 2020 financial results can be found in the press release issued this morning. We will be referring to supplement slides posted in the events and presentation section of our Investor Relations website throughout today's prepared remarks so please access them now if you have not already done so. Before we proceed, I would like to remind you that during today's call we will be making certain statements that are beliefs forward-looking and subject to various risks and uncertainties.
Any statements made during this call that are not statements of historical or current facts are intended to be forward-looking statements pursuant to the safe har -- safe harbor provisions of the Private Securities Litigation Reform Act of 1955. We want to emphasize that such forward-looking statements reflect our current expectations, assumptions, and currently available data regarding among other things, our business operations, development efforts, and regulatory strategy, and there aren't predictions nor guarantees of future events. Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with our business. For additional detail on the risk factors associated with our business, I encourage you to consult the detailed forward-looking statements disclaimer on Slide 2 of the supplemental slides and our SEC filings including our Annual Report on Form 10-K being filed today.
I will now turn the call over to Marcio. Marcio?
Marcio Souza -- President and Chief Executive Officer
Hey, thank you, Alex, and good morning to everyone joining us today. We're thrilled to be speaking with you during our very first updated call as a public company. Oftentimes in calls like this or one-on-ones that we have, you heard me saying that I'm living the dream when asked about how I'm doing. Let me be clear, this is no hyperbole, it's a reflection of how fortunate I feel to be at Praxis, leading a company and an incredible team working every day to bring novel treatments to patients.
As this -- at this moment, as it seems that we are starting to turn the page following an extremely challenging global period and we start to look forward to the future, it's critical that as a company and a society we do not abort our attention away from the escalating rates of depression, which are expected to be long lasting. In the United States, depression symptoms have increased by more than three folds during COVID, and the prevalence of depression globally has increased equally. Notably, the most dramatic increase has been seen in severe depressive symptoms, which have increased by a staggering seven and a half fold. Even with many treatment options available for people suffering from depression, a clear unmet need still remains.
There is a clear need for faster-acting, safer options displaying high rates of permission and durable efficacy relative to the standard of care. Ideally, those would be complemented by simple patient-centric dosing. With that, we're excited that earlier today we announced that study 2/3, our monotherapy phase 2/3 trial of Prax-114 treatments of major depressive disorders, we will start recruiting later this month. We are incredibly determined and eager to continue to advance this program.
We believe that 114 has the potential to be a highly differentiated option for people living with depression. I'd like to now take a moment to review the upcoming trial and touch upon the registration of the path for 114 in MDD. Please turn to Slide 3. As I just mentioned, we're operationally ready and plan to start the trial in the following weeks.
Following positive interactions with the FDA, we have submitted a proposal to the agency that included available preclinical data. The FDA agrees with our proposal and clears the IND for 114 late last week, which allowed us to initiate the trial. Study 2/3 is designed to row approximately 200 participants, randomized one-to-one to receive a nightly dose of either a 40-milligram tablet of 114 or placebo. Participants will receive a study drug for 28 days in a full outpatient setting with an additional two weeks follow-up.
The primary efficacy endpoints will be changing the HAM-D17 on day 15. With key secondary endpoints being the change in HAM-D17 on day 28. Historically, the placebo effect in psychiatry trials tends to be maximal, near the end of treatments. As such, the continuation of treatment beyond the primary endpoints is a key component of this trial design.
Importantly, the design of the phase 2/3 trial was completed with both acute and maintenance treatment in mind and was done in consultation with the FDA and other stakeholders. The primary endpoints at day 15 allow for assessment of the speed of all steps and robustness of response, which is expected from this class. The key secondary endpoint on day 28, allows for assessment of the durability of effects. If approved, this would allow for a dosing paradigm which is consistent with the duration of depressive episodes, typically lasting several months, and would allow for flexible treatments based on physician discretion being easily integrated into standard clinical practice.
We have selected the 40 milligrams a target those for the registrational studies and potential commercial use. This was based on data from our PK bridging study where the overall PK profile of the tablets was found to be comparable to that of the suspension. But the administration of the tablets generated more consistent exposure than the suspension, and we have observed an accumulation of 1.3 faults. We expect that a nightly dose with 40-milligram tablets will generate exposure resulting in beta power of approximately 170%, which is above the expected efficacy thresholds.
The 40 milligram tablets allows for more predictable therapeutic exposures consistently at or slightly higher than previously seen with the 45-milligram suspension. Based on the qEEG, the preliminary efficacy from part a, the PK bridging study, and accumulated safety data, we believe that this dose offers an optimal benefits risk to move the program forward. As an extrasynaptic GABAA receptor preferring positive allosteric modulator, 114 has unique properties compared to other molecules in development in this class. We believe that these properties support 114 profile to date, including the wide therapeutic window in achieving high levels of GABAA activation with an advantages tolerability profile.
Earlier today, we shared additional results of part c of the 114 phase 2a trial. This trial is important in that it was the first time a GABAA PAM has been studied for the treatment of MDD with daily doses for 28 days. And these data, along with other study learnings, were informative for designing our upcoming phase 2/3 trial. As a reminder, our phase 2a study includes the three parts: part a, which has been completed; part b which is currently enrolling patients with perimenopause depression; and part c, which was intended to evaluate the safety of four-week outpatient dosing and explored the arbiters of effects from day 15 to 28.
In part c, 13 patients with moderate to severe MDD were enrolled. 114 was generally well tolerated and no change in safe profile was observed when compared to previous clinical experience. While the sample size itself is too small to draw in the efficacy conclusion, we see the same trends produced previously with 114, leading to rapid and marked improvements in HAM-D scores that remain stable through the end of the active treatment period. For reference, part c was conducted in Australia from mid to late last year.
This timing corresponds with a highly restrictive public health lockdown due to the COVID-19 pandemic. As a result, we are required to make changes to the trial combat, those changes included the use of telehealth for the study visits, Mayo self-report assessment, in-deliver of study drugs to participants via courier. These changes and that I've been fortunate since they served as learnings and have now been integrated into the design and operational plans for the upcoming phase 2/3 clinical study. Let me quickly touch upon the registrational pack 114.
The upcoming phase 2/3 study, if positive, is intended to serve as one of the two monotherapy MDD registrational trials required by the FDA to support clinical efficacy. We expect to report top-line data from this trial in the first half of next year. We also expect to initiate a second phase 2 dose range-finding trial for 114 in adjunctive treatment setting in the third quarter of this year. This trial would provide information about lower dose and supporting data in adjunctive setting for MDD.
Together with a long-term safety follow-up study, those trials would represent the expected registrational for 114 as both monotherapy and adjunctive as both acute and maintenance treatments. I now would like to highlight some key operational controls that we have put in place to further attempts to minimize variability in the upcoming trials. Please turn to Slide 4. Rigor and discipline in clinical conduct are essential across each of our programs.
For our upcoming phase 2/3 trial, we have implemented several measures that have historically held mitigate variability and placebo facts. Those can be broken down into three distinct areas: one, rigorous patient selection; two, using only high-quality sites; and three, ensuring optimal trial design and execution. Let me take a minute to further define these measures. In relation to inclusion criteria, the 114 clinical program requires that patients have had at least one prior episode of MDD.
This is important in the current environment, where acute stressors may cause mood and anxiety symptoms which could mimic MDD as a diagnosis. Also, we have implemented the safer screening process, which provides for the second level of independent clinical interviews to conform patient's inclusion and diagnosis. In addition, we are working closely with sites that have proven track records of generating high-quality data. We have also integrated the placebo control reminder script for patients at every visit.
Finally, we are using AiCure as a smartphone-based compliance monitoring system to ensure adherence. Combine, we believe that this degree of rigor in clinical conduct will result in the maintenance of data integrity and minimization of placebo effects. I'll now turn the call over to Bernard to discuss recent progress with our second clinical program, 944, a T-type calcium channel inhibitor which is in development for essential tremor. Bernard?
Bernard Ravina -- Chief Medical Officer
Thanks, Marcio. I'd like to echo Marcio's comments about how excited we are to start the Prax-114 phase 2/3 trial in the coming days. We're equally enthusiastic about the progress we have made in our Prax-944 program for essential tremors in the work yet to come. To set the stage, we're currently conducting a two-cohort phase 2a open-label of PRAX-944 in patients with ET.
We expect top-line open-label [Audio gap] safety, tolerability, and efficacy data -- data for the high-dose cohort in the middle of this year. We also anticipate initiating a phase 2b dose-ranging randomized placebo-controlled trial of PRAX-944 in ET later this year. On Slide 5, you'll see data from six participants in the low-dose cohort of our phase 2a trial. This cohort included daily morning dosing of PRAX-944 at 20 milligrams during the first week, followed by 40 milligrams in the second week, and then wash up.
The chart on the left shows change from baseline in the TETRAS score, both in the total performance scale and the upper-limb's subscore. For the primary efficacy outcome, we're using change from baseline in the upper-limb items of the TETRAS because all patients suffer from upper-limb tremor and these items are rated reliably. The chart on the right displays these data as a percent change in tremor amplitude. A reduction of greater than 40% in upper-limb tremor amplitude compares favorably to pharmacological standard of care such as propranolol.
Similar patterns of improvement were observed in accelerometers' scores. There is also a strong correlation between the TETRAS site investigator ratings and central ratings. This concordance among various approaches to rating tremor gives us confidence in the reliability of the observed effect. Importantly, five of the six participants remained on propranolol during this study.
This suggests that PRAX-944 can be efficacious as both an adjunctive treatment and as monotherapy. Based on the observed safety profile in the preliminary efficacy shown in the low-dose cohort, we believe that PRAX-944 is a titratable drug with a wide therapeutic range. As such, we added a second cohort in which up to 12 ET patients will be titrated up to 120 milligrams per day. On the following slide, Slide 6, we've provided a schematic of the trial design for part b.
Part b will include an open-label titration period over 28 days, followed by two weeks on a stable high dose, after which there'll be a two-week randomized withdrawal. The randomized withdrawal stage is intended to assess the durability of effect for this key mechanism of action and -- and will provide blinded ratings to confirm the effect from the open-label portion. ET affects up to 7 million people in the U.S. alone and a new pharmacological option for these patients hasn't been approved for more than 50 years.
What often gets missed with understanding the burden of ET is that tremor limits function and impair social interactions throughout the entire waking day. ET manifests in upper-limb-action tremor that impacts everyday activities such as writing and typing, eating and drinking, and getting dressed. Patients are looking for a treatment option that reduces tremor, improves their function, and has a tolerability profile that won't interfere with their daily activities. Current pharmacological standard of care has limitations in both efficacy and tolerability leading to an estimated 80% discontinuation rate.
With this in mind, the initial efficacy data and observed safety data for 944 give us confidence as we move forward. We're optimistic that PRAX-944 allows for convenient, once-daily dosing with the potential to control tremors throughout the day without clinically significant sedation. We haven't observed any SAEs or severe AEs and the majority of observed AEs have been mild, transient, and resolved without any intervention. We believe that the tolerability and prolonged exposure of the MR formulation currently being used in our phase 2a study are well suited to the treatment of ET.
Before we wrap up the prepared remarks and open the call to questions, I wanted to pass the call back to Marcio to briefly touch on the new collaboration we announced this morning with the Florey Institute. Marcio?
Marcio Souza -- President and Chief Executive Officer
Hey, thanks, Bernard. As a CNS-focused company deeply rooted in genetic epilepsies, it's very important for us that we continue to lead in this area. The research collaboration announced earlier today with the Florey allow us to do just that. With the addition of three novel ASO targets to our pipeline.
Under the collaboration, research will be conducted by the world-class team at the Florey Institutes, an Australian-based medical research entity that specialize in neuroscience. Each of the three programs focus on where it lapses with very high unmet needs in limited or no research and development ongoing. Quite importantly, efforts on all these programs had been under way. The lead program from this partnership is an ASO for the treatment of SCN2A loss of function, which is the leading cause of genetically associated autism.
Together with PRAX-222, our ASO program for the treatment of SCN2A gain-of-function mutations. We have demonstrated our commitment to the SCN2A community and continue to build a leadership position in sodium channel research. As a company, we now have six distinct epilepsy programs including four ASOs. In the past several months, we have seen promising advancements in our two lead rare disease programs.
Earlier this year, the FDA granted both rare pediatric and orphan drug designation for PRAX-222 for the treatment of SCN2A-DEE. We have ongoing IND-enabling toxicology studies for 222 and expect them to be completed by the end of the year with an IND to follow in early 2022. The FDA also granted rare pediatric designation for PRAX-562 for the treatment of SCN2A and SCN8A GEUs. For 562, our most advanced small-molecule rare disease program, we've completed the single-ascending-doses stage of the phase 1 study and have advanced to the multiple-ascending dose.
This said stage was completed up to the maximum plan dose with no dose-limiting toxicities. We are currently at the highest pre-plan dose in the MAD phase which are reaching exposures that exceeds the predicted therapeutic concentrations in animal models of seizure in epilepsy. We intend to escalate those further if the drug continues to be generally well-tolerated. We expect to initiate the first proof-of-concept trial for 562 in the second half of this year which will be in rare adult cephalgias.
We recently expanded a scope of this upcoming trial to include trigeminal neuralgia, in addition to SUNCT and SUNA patients. We believe that 562 has broad potential in rare disease and we choose to follow a deliberate approach to clinical developments. We intend to expand next into a range of rare pediatric epilepsies. As you can see on Slide 7, Praxis has built a novel, diversified pipeline with multiple potential value-creating milestones in the next 12-plus months.
We look forward to continuing to report our progress and to interact with all of you throughout the year. With that, we're now going to open the call for questions. Operator?
Questions & Answers:
Operator
[Operator instructions] Our first question comes from Ritu Baral with Cowen. Your line is open.
Ritu Baral -- Cowen & Company -- Analyst
Good morning. Thanks for taking the question. Marcio, I want to make sure I understand correctly. Did Day 28 secondary endpoint that key secondary endpoint if -- if the trials don't reach statistical significance at Day 28, will you be moving forward or will FDA require you to move forward with the sort of episodic Day 14 indications similar to stages? Or even if you have trends, can you be talking about a chronic label? And then I've got a couple of follow-ups.
Marcio Souza -- President and Chief Executive Officer
Good. Hey, Ritu, good morning. I hope all is good. The -- the conversations with the FDA in relation to 28-day, it's really as we mentioned as a key secondary endpoint, right? So, that would be by definition an additional claim.
We see as the huge opportunity to actually have the 15 as we mentioned on the prepared remarks as the primary since that would be what would declare -- excuse me, the trial of -- if -- if positive or not. Now, it's all dependent as always of the FDA reviewing the result. And so long, we fully expect that that's going to be maintenance of effect at Day 28 and then we'd have both claims. As a reminder as well, as we discussed previously, the FDA did insisted that we follow these patients for more than 15 days on drug in order to qualify for a monotherapy label in MGG.
So, it -- it caps a number of topics, right? So, one is serving as a secondary endpoint which was obviously quite important, but also serving as a determination of like the safety of looking to these patients for more than 15 days and securing with the trial being positive or the second trial being positive to support the label. So, a -- a number of things. But maybe going more simplistically, I believe that if there was a small change there on Day 28 and for some reason, something happened that would still be a path forward with the claim of Day 15 very clearly.
Ritu Baral -- Cowen & Company -- Analyst
Got it. OK. And then the 40 milligram, is that -- based on your beta power studies, is that the top of the dose-response curve? I may have forgotten to write it down in my notes, but the phase 2 dose-ranging that you're doing later this year, are you planning on going up or down with doses there?
Marcio Souza -- President and Chief Executive Officer
Yeah. So -- so, the -- the beta power that we are seeing with the 40 milligrams with the tablet formulation is around 1.7. So, 100%, right, with baselines normalized to 1. That is far more than what we would expect for the effect here.
Now, for -- for the DRF trial, I'm going to hand over to Bernhard to explain how we are thinking about that, why we are doing that, and the dose range that we would be exploring. Bernard?
Bernard Ravina -- Chief Medical Officer
Yeah, Ritu. So, right, the 40-milligram doses to -- of beta power of -- on average, 1.7. And we have said. based on the accumulated data, in our pre-clinical data that we wanted to be around 1.5, 1.6, or above.
So, we think this is getting a full pharmacological effect that -- at those exposures. The -- for that dose-range-finding trial, we are planning on going to lower doses, as far down as 10 and 20. And we believe we'll still maintain pretty significant beta power in that dose range. That's the main part of the curve we want to explore because as you saw with the open-label data and part a, it looks like we're at the plateau of the dose response.
We -- we do expect however to include a higher dose as well, and that offsets any risks in terms of diminishing efficacy in the lower part of the dose range.
Ritu Baral -- Cowen & Company -- Analyst
Got it. And then just the fact that that trial is adjunctive, are you going to be investigating any, I guess, any cohorts that look at adjunctive versus non-adjunctive to sort of piece apart any potential effect? And -- and are you going to be investigating, like one of your competitors, sort of simultaneous combination, initiation of treatment?
Bernard Ravina -- Chief Medical Officer
So, that trial which we call as Study 214 is solely in adjunctive setting. And the -- and the benefits here is one, get a clean set. The second is really operation and enrollment, right? We're going to be doing this trial virtually in parallel with Study 213 that is the phase 2/3 in monotherapy. And it gives an alternative for the sites to screen patients for both trials really and to like select them to the trial that makes the most sense.
Bringing both in one trial, it's normally more of a confounder effect than the knots. And -- and we wanted to make sure whatever results we got on the other end is interpretable and we can clearly express that.
Ritu Baral -- Cowen & Company -- Analyst
Totally understand. I have a bunch more questions, but I'll hop back in the queue. Thanks, guys.
Bernard Ravina -- Chief Medical Officer
Thank you so much, Ritu.
Operator
Thank you. Our next question comes from Laura Chico with Wedbush Securities. Your line is open.
Laura Chico -- Wedbush Securities -- Analyst
Hey, good morning, guys. Thanks for taking my questions and congrats on the progress. I -- I guess I just wanted to circle back one more time on the -- on the dose selection for 114 and just switching against to kind of all the data putting it together, the beta power, the accumulation. Just to clarify, will the 40-milligram dose be analogous to one of those suspension doses that you already covered in the part a study? I guess I'm trying to just contextualize what the -- the 40-milligram tablet is equivalent to.
Marcio Souza -- President and Chief Executive Officer
Yeah and absolutely. And hey, Laura, good to hear from you. The -- the suspension those, right, that we tested before, just to recall, they did not show any differentiation in terms of the -- the effect we're seeing. But there was, as we escalated the dose, more prevalence of AE's monotherapy severity on that.
And what we are looking at is to stay above that 1.4, 1.5 in the beta power in general as we are guiding dose, right, since we're using quantitative Ag. The tablets' profile, what we see was a number of things, right? So, the general profile were very similar which was good. We learned a little bit more about the time-of-day dosing as Bernard mentioned. But one thing that was quite important is the variability is reduced.
So we drive exposures that are at or higher than the 45 on the previous suspension trial or the -- and that's where the overlap for your question is. But because the variability is smaller on the exposure, we end up getting more patient. Our prediction is that we're going to get basically all patients to -- to the beta power we are expecting and, therefore, on the efficacious range there. So you could looking to between the two lower dose that we did part of phase 2a.
So bet -- between 45 and 60. I would say the surrogates in terms of the exposure there, but we are cons -- consistently seeing on the 40 in the tablets at -- at or higher than 45 for the previous one.
Laura Chico -- Wedbush Securities -- Analyst
OK, that's helpful, Marcio.
Marcio Souza -- President and Chief Executive Officer
Of course.
Laura Chico -- Wedbush Securities -- Analyst
OK. And then maybe a follow-up question here. Just -- well, maybe two -- two follow-ups, I'm sorry. On 114 for the registrational path, I just wanted to clarify.
Will the initial plan then to be pursuing both monotherapy and adjunctive labels at the same time for the initial filing? And then on 944, also kind of clarifying there. I guess you're looking to do the separate titration study with the phase 1 work. Would that be a gating factor to starting that phase 2b study as well with 944? And any thoughts on whether or on how you would channel patients already on propranolol? Thanks, guys.
Marcio Souza -- President and Chief Executive Officer
Absolutely. So maybe -- maybe I'll get the -- the first question on the 944 question to Bernard's, and then we can go back and talk a little bit about the registrational path for -- for both of them. Ber -- Bernard, why don't you talk a little bit about that.
Bernard Ravina -- Chief Medical Officer
Yeah. For -- so for 944, right, we've -- we now understand that we can get up to 120 milligrams in healthy volunteers. We're going to explore that now in the part b study in ET patients. And really, the goal there is to make sure that in the generally older population of ET patients who are taking a bunch of concomitant medications that they can tolerate that as well.
So we'll -- we'll be having those data around midyear and we'll get a sense in that pool of subjects up to about 12, you know, what kinds of treatment effects we're seeing in ET. In parallel with that, we're going to explore some different titration schemes, and we'll be looking to see if we can titrate up a little bit faster and what kind of increments we can go in. And then putting those two pieces of information together, I think we'll be very well positioned to [Audio gap] to arranging RCT toward the end of the year. But both of those pieces of information are going to be informative for a well-designed RCT.
Marcio Souza -- President and Chief Executive Officer
And -- and going back to -- to your 114 question. So the -- the base plan here is to get to a monotherapy label with the phase 2/3 that we are starting in the next couple of weeks and a second phase 3 after that. We are starting phase 2 for 114 as we mentioned for adjunctive as well. Based on the results of that study, we'd have a conversation with the FDA on whether or not an additional study for adjunctive would be necessary.
I think it's largely on their hands in terms of that. They -- they might require another one. I feel pretty good based on precedents that the adjunctive with two positive trials in mono might be possible to be, but it's very hard to guide right now to or exactly where the label would be. But the -- the base cases, monotherapy with shortly thereafter all in parallel had an adjunctive in the label.
Laura Chico -- Wedbush Securities -- Analyst
All right. Thanks, guys.
Marcio Souza -- President and Chief Executive Officer
Of course.
Operator
Thank you. Our next question comes from Tyler Van Buren with Piper Sandler. Your line is open.
Tyler Van Buren -- Piper Sandler -- Analyst
Hey, guys. Good morning. Congrats on the progress. Definitely an unusual amount of clinical activity for a recent IPO.
I -- I have three for you. Forgive me for asking another beta power question, but when you talk about the consistent exposure, if I look at the prior beta-powered qEEG data, that spike that occurs appears to last for about one to two hours if I'm not mistaken. So is that increase in beta power over a longer period of time, and is it possible to quantify that for us at the 40-milligram tablet dose? And then the second question is just you mentioned kind of maxing out on efficacy but also having the ability to improve tolerability. Can you just confirm that you've never seen any sedation, kind of these levels at -- at these doses relative to I guess the equivalent of the suspension dose or that it's been very low, and then also what the kind of rate of somnolence has been? Because, clearly, those two things are quite different as I understand.
And then the third one is on the central tremor. I believe you said six -- that data is from six patients in the slide. I think we have five recently. So could you just comment on that sixth patient and also, you know, your confidence in clinical trials moving forward with respect to people who respond or don't respond and -- and any sort of placebo response?
Marcio Souza -- President and Chief Executive Officer
Yeah. So I'll try to unpack. Hey, Tyler, good to hear from you as well. The -- to unpack like the 100 questions you've got there.
But appreciate the nice attempt to unpack a bunch of them. So -- so, beta power -- so maybe to clarify that, right? So the -- the way we're looking into beta power and -- and I, actually, would -- would guide you guys toward our Form 10-K that was just posted at the SEC website because we're talking about the first time about the -- the alpha bands as well in the quantitative EEG in relation to 114. So something that might be interesting for some of the follow-up calls. We were looking through that is whether or not we're being able to expose patients to therapeutic dose.
So it's a surrogate to -- to whether or not we crossed that threshold, right? So we -- we believe that is incredibly important that we have to do that. We doubt the drawbacks that you talked about. So just to be exquisitely clear, we've never seen next-day somnolence, sedation, or worse yet, tremor. So we haven't seen those things that might have been seen with the class or expected with the class on next day.
So for us, it's incredibly important that because next-day somnolence, for example, or sedation might be seen as depression by these patients. So we wanted to separate that. Now, a hypnotic effect is expected and desirable from this. So we want them, patients, to feel at ease, quote-unquote, and hypnotic before going into beds without any requirements that they are in any given state of feeding our minds before going to bed, just taking the drug and really being able to sleep and feel better about their depression.
So the 40 milligrams with the tablet gives us the best possible to this day as we just mentioned of unexplored lower dose profile that wraps the expected efficacy, which we'll hopefully going to be seeing at the end of study 2 and 3 with our safest profile to date in terms of the rates of somnolence. And we haven't seen trying sedation as we mentioned before, just going to reinforce that even at much higher dose than 40, but definitely not at 40. That had answered the -- the 114 part of the question?
Tyler Van Buren -- Piper Sandler -- Analyst
Yup, thank you.
Marcio Souza -- President and Chief Executive Officer
Sounds good. So on the -- on the ET part for 944, right? So you -- you might recall at the time we filed just one late last year, we had five preliminary patients. That data was like coming off the PRAX. We needed to basically do a number of things like coming that up to the extend that was required, run the assessments for concordance with the other endpoints, and then add in the other patients.
So we had seven patients on the safety database. One of those patients did not complete any of the efficacy measures. So we are showing data for six patients on the -- on the efficacy measures. And the -- the good news here is, one, it's a very robust average reduction in the tremor as measured on this trial.
But the second thing is that by the first time and why we believe that our difficulty is on measuring tremors using the clearance standards, a trial was able to show concordance between blinded central readings and the sight reading. That sight readings, the standard of care is one most goes through it. There's a lot of validity to there, but it was important for us since this is open-label to gaps that continuation. So we feel really good about the results we're having right now and that's what led us to move and accelerated further to the previous question from Laura in terms of getting the next two trials running and starting the phase 2b by the end of the year.
So it was eventful, as you said, between the IPO and now. It's definitely even more eventful for the next six months. So we're really looking forward to it.
Tyler Van Buren -- Piper Sandler -- Analyst
Great. Thanks for taking the questions.
Marcio Souza -- President and Chief Executive Officer
Of course.
Operator
Thank you. Our next question comes from Ritu Baral with Cowen. Your line is open.
Ritu Baral -- Cowen & Company -- Analyst
Hey, guys, sorry, I was -- I was muted on this. One critical question, what is placebo-controlled reminder script that you described as part of the depression study? I -- I don't recall ever encountering that before. And then can you quickly -- and again, sorry if I missed this, but you -- can you go over what you've seen to date on the side effects tolerability of 944 at the 40-milligram dose? And -- and given the mechanism of 944, what do you think is the side effect to watch when it comes to tolerability and compliance in like a real-world setting for the drug?
Marcio Souza -- President and Chief Executive Officer
Yeah, no, absolutely. The -- the reminder scripts, Ritu, it -- it's actually something that sounds very simple on the surface, but it's incredibly powerful. We have added the reference for that in a -- in a recent paper to our slides and -- and the -- in our SEC filings. So I -- I recommend like take a look at that afterwards.
But basically, they're structured way to remind the patients or in a very simplistic manner that they are in an experimental drug that is blinded and, therefore, there should be no expectation of effects since there is a 50% chance they are not on drug. By doing that systematically using a script in every visit, it has been show to further significantly separates the -- the pla -- placebo patients from -- from not so control further placebo effects. A lot of what we are doing is to make sure the trial's operation, the sounds is not only that we show a separation from 114 at the end, but then that we can control the placebo effects to historical rates in our controlled trials. So I'll punch this one to Bernard as well to talk a little bit more in terms of what's his idea and his team idea to implement this so thoughtfully and did he study.
Bernard.
Bernard Ravina -- Chief Medical Officer
Yeah, like Marcio said, there's -- there are really nice data to support that. So basically, our placebo effect is driven by expectations. And what the placebo reminder script is really meant to do is kind of refocused people on expectations, remind them that they're in a clinical trial, that it's an experimental agent. It's not known to work yet.
And so it just, you know, kind of sets expectations, remind them that they're not in a treatment setting. So it's -- this kind of approach is actually shown pretty robust effects in terms of, you know, maintaining a less of a placebo effect. So it's been used in a number of -- this kind of approach has been used in a number of different kinds of psychiatric trials, pain studies, and other places where placebo effects and expectation the highest can -- can really cause trouble for trials. So -- and our -- our psychs are experienced with using it.
And the way it's implemented, Ritu, is that it's simply not read but presented to the patient, kind of discussed prior to conducting the main assessment, the primary key secondary assessment.
Ritu Baral -- Cowen & Company -- Analyst
And the 944 tolerability? Thanks.
Bernard Ravina -- Chief Medical Officer
Yes, and -- and on the 944 tolerability, so that -- that's been very, very good and -- right? So -- so going into this, we knew what kind of AEs to look for. So the -- the main AEs are around nausea, dizziness, light-headed. And what we -- what we see is that, yes, people may have those, but they tend to occur at the beginning of titration and then they seem to tolerize. We know the EEG effects don't tolerize, but those AEs tend to.
And so they seem up front, they're mild, they're transient, and really don't need to do anything in terms of any intervention. The main thing to do is just let people know that they will subside and just have the right expectations around that. And, you know, I think that -- that's just part of the mechanism and getting started. But the key is they go away.
They do not increase with titration.
Ritu Baral -- Cowen & Company -- Analyst
Got it. Thanks.
Operator
Thank you. [Operator instructions] And I'm currently showing no further questions at this time. I like to turn the call back over Marcio Souza for closing remarks.
Marcio Souza -- President and Chief Executive Officer
Thank you very much, Operator, and thank you, everyone, for joining today. We're incredibly thrilled to be on this first public call with all of you. And most importantly, advancing all these therapies to patients. This is very close to our hearts here at Praxis and -- and what keeps us up at night sometimes and definitely very early in the morning, making sure we can advance.
I believe you all would agree with me that in the last five months since we became public, there is a tremendous amount of progress in operational promise from the company moving each one of our programs and more toward the clinic or at the clinic to help those patients. So very proud of the team of people that are behind Bernard and I and others in this call, really helping us move this to -- to patients. So thank you very much for supporting Praxis and everything we do and looking forward to all of you.
Operator
[Operator signoff]
Duration: 54 minutes
Call participants:
Alex Kane -- Head of Investor Relations
Marcio Souza -- President and Chief Executive Officer
Bernard Ravina -- Chief Medical Officer
Ritu Baral -- Cowen & Company -- Analyst
Laura Chico -- Wedbush Securities -- Analyst
Tyler Van Buren -- Piper Sandler -- Analyst
