Q4 2020 Praxis Precision Medicines Inc Earnings Call
Ladies and gentlemen, todays conference is scheduled to begin shortly please continue the standby and thank you for your patience.
Operator: Ladies and gentlemen, today's conference is scheduled to begin shortly. Please continue to stand by, and thank you for your patience.
unknown: [inaudible] ?? Director of Photography, Frank Sinatra, K.R. D. Cooper, K.R. D. Cooper, S.J. M. M. M. M. M. M. M. M. M. M. M. M. M. M. M. M. M. M. M. M. M. M. M. M. M. [inaudible] © BF-WATCH TV 2021
Operator: Ladies and gentlemen, thank you for standing by, and welcome to Praxis Precision Medicine.
Operator: Medicine's fourth quarter and full year 2020 conference call. At this time, all participant lines are in a listening mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star zero.
Operator: I would now like to hand the conference over to your speaker today, Alex Kane, Head of Investor Relations. Thank you. Thank you, Shannon.
Alex Kane: Good morning, and thank you for joining us today to discuss Praxis' 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 Rubino. Additional members of the management team, including our Senior Vice President of Regulatory Equality, Alyssa Wyeth, and our Vice President of Finance, Lauren Mastracola, 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.
[music].
Ladies and gentlemen, thank you for standing by and welcome to the practice of precision medicines fourth quarter and full year of 2020 conference call. At this time all participant lines are in a listen only mode.
The the speaker's presentation, there will be a question and answer session. So ask the question. During the session you will need the press star one on your telephone.
Alex Kane: We will be referring to supplement slides posted in the Events and Presentations 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 harbor provisions of the Private Securities Litigation Reform Act of 1955.
Please be advised the today's conference is being recorded.
If you require any further assistance please press star zero.
I'd now like to hand, the conference over to your Speaker today, Alex Kane head of Investor Relations. Thank you. Please go ahead Sir.
Thank you Shannon good morning, and thank you for joining us today to discuss practices fourth quarter and full year of 2020 corporate update with me on today's call is our president and Chief Executive Officer of Marcio, Souza and our Chief Medical Officer, Bernard Robina additional members of the management team, including our senior Vice President of regulatory of.
Elisa wise and our Vice President Finance born Master Cola will be available for questions. Following the prepared remarks. Please.
Alex Kane: 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 are neither predictions nor guarantees of future events. However, actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with our business.
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 on the events and presentations section of our Investor Relations website throughout todays prepared remarks, so ease of access to now a few of 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.
Alex Kane: For additional detail on the risk factors associated with our business, I encourage you to consult the detailed forward-looking statements disclaimer on slide two of the supplement 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.
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 Harbor provisions of the private Securities Litigation Reform Act of $19 55.
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.
Marcio Souza: 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 home. Oftentimes, in calls like this or one-on-ones that we have, you've heard me saying that I'm living the dream when asked how I'm doing.
The 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 two of the supplement slides and our SEC filings, including our annual report on form 10-K being filed today.
Marcio Souza: Let me be clear, this is no hyperbole, and is 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. At this moment, it seems that we are starting to turn the page, following an extremely challenging global period, and we are starting to look forward to the future. It's critical that, as a company and a society, we do not avert our attention away from the escalating rates of depression, which are expected to be long-term, in the United States.
I will now turn the call over to Marcia Marcia.
Hey, Thank you, Alex and good morning to everyone joining us today.
We're thrilled to be speaking with you during our very force updated call as a public company.
Oftentimes in calls like day as our one on ones that we have you heard me, saying that I am leaving the dream, one asking the Hollywood billing.
Let me be clear this is no hyperbole.
Marcio Souza: Depression symptoms have increased by more than threefold 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 times, even with many treatment options available for people suffering from depression. A clear unmet need still remains.
Is the reflection of how fortunate I feel to be a praxis.
Leading our company and an incredible team working every day to bring novel treatments to patients.
At this moment.
Seems that we are starting to turn the page.
Following an extremely challenging global periods.
And we start to look forward to the future.
It's critical that as a company.
In our society.
We didn't have a lot of works our attention away from the escalating rates of depression.
Marcio Souza: There is a clear need for faster acting, safer options, displaying high rates of remission and durable aspects, relative to 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 213, our monotherapy phase 2-3 trial of Praxis 114 for the treatment of major depressive disorders, will start recruiting later this month. We are incredibly determined and eager to continue to advance this program.
Which are expected to be long lasting.
In the United States Depression symptoms have increased by more than three folds.
During COVID-19 and the prevalence of depression globally has increase equally.
Notably the most dramatic increase have been seen in severe depressive symptoms, which have increased by a staggering seven in the hospitals.
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 remission and durable efficacy.
Marcio Souza: We believe that 114 has the potential to be a highly differentiated option for people living with depression. I would like to now take a moment to review the upcoming trial and touch upon the registrational path for 114 in MDD. Please turn to slide three.
Relative to standard of care.
Ideally those would be complemented by simple patient centric dosing.
With that.
Were excited that earlier today, we announced that the study 203, our monotherapy phase two three trial of <unk> 114 for the treatment of major depressive disorder. We stopped recruiting later this month.
Marcio Souza: As I just mentioned, we're operationally ready and plan to restart the trial in the following week. Following positive interactions with the FDA, we have submitted a proposal to the agency that included available preclinical data. The FDA agreed with our proposal and cleared the ING for 114 late last week, which allowed us to initiate the trial. Study 213 is designed to enroll approximately 200 participants, randomize one-to-one to receive a nightly dose of either a 40 milligrams tablet of 1-on-4 or platelet.
We are incredibly determine an E.
<unk> to continue to advance this program.
We believe that one of them four has the potential to be of highly differentiated option for people living with depression.
I would like to now take of moments to review the upcoming trial and touch upon the Registrational path for 114 in MTT.
Please turn to slide three.
As I just mentioned, we're operationally ready and plant restarts of the trial with the following weeks.
Following positive interactions with the FDA, we have submitted of proposed to the agency that included available preclinical data.
Marcio Souza: Participants will receive studied drugs for 28 days in a full outpatient setting, with an additional two weeks of follow-up. The primary efficacy endpoint will be the change in the HEMD 17 at day 15, with a key secondary endpoint being the change in HEMD 17 at day 28. Historically, the placebo effect in psychiatry trials tends to be maximum near the ends of treatment.
The FDA agreed with our proposal and cleared the IND default went on for the last week.
Which allowed us to initiate the trial.
Study 213 is designed to ROE of approximately 200 participants randomized one to one to receive might bleed those of either of 40 milligrams tablets of one month four or placebo.
Marcio Souza: 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 Manson's 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 onset and robustness of response, which is expected from this class. The key secondary endpoint of day 28 allows for assessment of durability of effect.
Participants who received study drug for 28 days in a full outpatient setting.
With an additional two weeks follow up.
The primary efficacy endpoints will be the change in the Hamdi 17 at day 15.
With a key secondary endpoints being the change in Ham D of 17 at day 28.
Historically placebo of packaging psychiatry trial stands to be maximum near the end of treatments.
As such the continuation of treatment beyond the primary endpoint is the key components of this trial design.
Marcio Souza: If approved, this would allow for a dosing paradigm that is consistent with the duration of the preface episode, typically lasting several months, and would allow for flexible treatments based on physician discretion, being easily integrated into a standard clinical practice. We have selected 40 milligrams as the target for 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.
Importantly, the design of the phase two three trial was completed with both acute.
And men since treatment of mines and was done in consultation with the FDA and the other stakeholders.
The primary endpoint at day 15 allows for assessment of the speed of phone stats in robustness of response, which is expected from this class.
The key secondary endpoint of day 28 allows for assessment of the durability of the facts.
If approved this would allow for of dosing paradigm, which is consistent with the duration of depressive episodes typically lasting several months.
Marcio Souza: But administration of the tablets generated more consistent exposure than the suspects, and we have observed accumulation of 1.3 fold. We expect that nightly dose of 40 milligram tablets will generate exposures resulting in beta power of approximately 170%, which is above the expected efficacy threshold. The 40 milligram tablet allows for more predictable therapeutic exposure, consistently at or slightly higher than previously seen with the 45 milligram suspension. Based on the quantitative, e.g.
And was the allow for flexible treatments based on physician discretion.
Easily integrated into the standard clinical practice.
We have selected the 40 milligram the target dose 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 administration of the tablets generated more consistent exposure than the suspension.
Marcio Souza: The preliminary efficacy from Part A, the PK Bridging Study, and accumulated safety data. We believe that this dose offers an optimal benefit-risk profile to move the program forward, as an exosynaptic GABA-E receptor preferring positive allosteric modulators. One on four has unique properties compared to other molecules in development in this class.
And we have absorbed accumulation of 1.3 folds.
We expect the nicely those with 40 milligram tablets will generate exposure, resulting in data power of approximately 170%.
Which is above the expected efficacy threshold.
The 40 milligram tablets allows far more predictable therapeutic exposures.
Marcio Souza: We believe that these properties support 114's profile today, including the wide therapeutic window for achieving high levels of GABAergic activation with an advantageous tolerability profile, or Nurture Day. We shared additional results from Part C of the 114 Phase IIa trial. This trial is important in that it was the first time a GABA-8M has been studied for the treatment of MDD with daily dosing for 28 days.
She simply assets.
All of the slightly higher debt previously seen with the 45 milligram suspension.
Based on the current stated EG.
The preliminary efficacy from parts a day.
PK bridging study and the accumulated safety data.
We believe that this dose offers on the optimal benefit risk to move the product forward.
As an extra synaptic Gaba a receptor prefer a positive allosteric modulator.
One four has unique properties compared to other molecules in development in this class.
Marcio Souza: And this data, along with other study learnings, were informative for designing our upcoming Phase 2-3 trial. As a reminder, our Phase IIa study included 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 explore durability of effects from day 15 to 28. In Part C, 13 patients with moderate to severe MDD were enrolled.
We believe that these properties supports one of our profile to date.
Including the wide therapeutic window.
And achieving high levels of <unk> activation with advantages Tolerability profile.
Earlier today.
We share the additional results from part C of the one one for our phase Iia trial.
This drive of importance in that he was the first time of Gaba Pam has been studied for the treatment of MTG with daily dosing for 28 day.
And these data along with other study learnings were informative for designing our upcoming phase III trial.
Marcio Souza: 114 was generally well tolerated, and no change in face profile was observed when compared to previous clinical experience. While the sample size itself is too small to draw an efficacy conclusion, we see the same trends produced previously with 114, leading to a rapid and marked improvement in HAM-D scores that remained stable through the ends of the active treatment period. For reference, Part C was conducted in Australia from mid to late last year, and this timing corresponds with a highly restrictive public health lockdown due to the COVID-19 pandemic.
As a reminder, our phase Iia study into the three parts.
<unk> eight which has been completed.
D, which is currently enrolling patients with experimental Paul's depression, and part C, which was intended to evaluate the safety of four week outpatient dosing and explored there are billions of effects from the 15 to 28.
In part C 13 patients with moderate to severe and did the awarding volts.
114 was generally well tolerated and no change in sales profile was observed when compare to previous clinical experience.
Marcio Souza: As a result, we are required to make changes to the trial column. Those changes included the use of telehealth for study visits, male self-report assessment, and delivery of study drugs to participants via courier. The changes and that I've been fortunate since they served as learning experiences and have now been integrated into the design and operational plans for the upcoming Phase II-III clinical study. Let me quickly touch upon the Registrational Path 4114.
While the sample size of itself is too small to draw in the efficacy of conclusion we.
We see the same trends produce previously with Walmart for the.
Moving to a rapid and marked improvements in Ham D scores debt remains stable through the end of the active treatment periods.
For reference <unk> T was conducted in Australia from needs to late last year.
Marcio Souza: The upcoming Sainsbury's study is paused, and is intended to serve as one of the two monotherapy MTD registrational trials required by the FDA to support clinical efforts. We expect to report top-line data from this trial in the first half of next year. We also expect to initiate a second...
The styling correspond with a highly restrictive public health locked down due to the COVID-19 pandemic.
As a result, we are required to make changes to the trial conduct.
Those changes include the use of telehealth for the study visits.
Marcio Souza: Phase 2 Dose Range Finding Trial for 114 in Adjunctive Treatment Settings, in the third quarter of this year. This trial will provide information about lower doses and supporting data in an adjunctive setting for MDGs. Together with a long-term safety follow-up study, those trials would represent the expected registration of 4114 as both monotherapy and adjunctive, as both acute and menstruation. 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 trial. Please turn to slide four.
<unk> self report the assessment in the liver of study throughout the two participants via Korea.
The change and there are been fortunate since they served as learnings and have now been integrated into the design and operational plans for the upcoming phase two three clinical study.
Let me quickly touch upon the Registrational path for 114.
The upcoming phase II III study if positive.
Intended to serve as one of the two monotherapy mgd of 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.
Marcio Souza: 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 helped mitigate variability and placebo effects. Those can be broken down into three distinct areas.
We also expect to initiate a second phase two dose range finding trial for 114 in the gym tip treatment setting.
In the third quarter of states here.
This trial will provide information about lower dose and supporting data and adjunctive setting for the MTGE.
Marcio Souza: One, rigorous patient selection, using only high-quality files, and three, ensuring optimal trial design and execution. Let me take a minute to further define these. In relation to inclusion criteria, the one-on-four clinical program requires that patients have had at least one prior episode of MDT. This is important in the current environment, where acute stress may cause mood and anxiety symptoms that could mimic MDZ as a diagnosis. Also, we have implemented the Safer Screening process, which provides for a second level of independent clinical interview to conform to patient inclusion and diagnosis.
Together with the long term safety follow up study dose trials would represents the expected registration of <unk> 114, as both monotherapy and adjunctive as both acute and medicines 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 four.
Rigor and discipline in clinical conduct is the essential across each of our programs.
For our upcoming phase III trial, we have implemented several measures.
Have storage really helps mitigate of our pellets and placebo effects.
Those can be broken down into three distinct areas.
<unk> rigorous.
Rigorous patient selection.
Marcio Souza: In addition, we are working closely with sites that have proven track records of generating high-quality data. We have also integrated placebo control reminders for patients at every visit. Finally, we're using AI-Cure, a smartphone-based compliance monitoring system, to ensure adherence. Combined, we believe that this degree of rigor in clinical conduct will result in the maintenance of data integrity and the 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 in development for essential tremor.
Using only high quality sites.
And three ensuring optimal trial design and execution.
Let me think of minutes to Florida.
I find this measures.
In relation to inclusion criteria the woman for clinical problem requires that patients have had at least one prior episodes of MTGE.
This is the importance in the current environments, where acute stressors may cause mood and anxiety symptoms, we could mimic.
MTG as of diagnosis.
Also we have implemented the safer screening process.
Bernard Rubino: I'd like to echo Marcio's comments about how excited we are to start the PRAX114 Phase 2-3 trial in the coming days. We're equally enthusiastic about the progress we have made in our Praxis 944 program for essential tremor and the work yet to come.
Which provides for a second level of independence clinical of interviews to conform patient inclusion and diagnosis.
In addition, we are working closely with sites. They have a proven track records of generating high quality data.
We have also integrated the placebo control reminders of scripts for patients at every debt.
Bernard Rubino: To set the stage, we're currently conducting a two-cohort H2A open-label trial of Prax944 in patients with ET. We expect top-line open-label safety, tolerability, and efficacy 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 Prax944 in ET later this year. On slide five, you'll see data from six participants in the low-dose cohort of our Phase 2a trial. This cohort included daily morning doses of Prax944 at 20mg during the first week, followed by 40mg in the second week, and then washout.
Finally, we are using AI cure, a smartphone based compliance monitoring system to ensure adherence.
Combined we believe that this degree of rigor income clinical contacts will result in 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 progress 944 of.
T type calcium channel inhibitor, which are in development for essential tremor Bernard.
Thanks Marcia.
I'd like to Echo Marshalls comments about how excited we are the start the perhaps one for phase two three trial in the coming days.
We're equally enthusiastic about the progress we have made in our practice of 94 four program for essential tremor and the work yet to come.
Bernard Rubino: The chart on the left shows change from baseline in the TETRA score, both in the total performance scale and the upper limb subscale. For the primary efficacy outcome, we're using change from baseline in the upper limb items of the Tetris because all patients suffer from upper limb tremor and these items are rated reliably. The chart on the right displays these data as percent change in tremor amplitude; a reduction of greater than 40% in upper limb tremor amplitude compares favorably to pharmacologic standards of care such as propranolol. Similar patterns of improvement were observed in accelerometry scores. There's also a strong correlation between the Tetris site investigator ratings and central.
To set the stage. We're currently conducting of two cohort phase Iia open label trial of <unk> in patients with <unk>.
We expect top line open label safety, Tolerability and efficacy data for the high dose cohort in the middle of this year.
We also anticipate initiating a phase <unk> dose ranging randomized placebo controlled trial of <unk>.
<unk> 94 for any team later this year.
On slide five you'll see data from six participants in the low dose cohort of our phase Iia trial.
This cohort include of daily morning, dosing of <unk> 94 at 20 milligrams. During the first week, followed by 40 milligrams from the second week and then washout.
Bernard Rubino: 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 Prax944 could be efficacious as both an adjunctive treatment and as monotherapy. Based on its observed safety profile and the preliminary efficacy shown in the low-dose cohort, we believe that Prax944 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 mg per day on the following slide, slide six.
The chart on the left shows change from baseline in the Tetra score.
And the total performance scale and the upper limb sub score.
For the primary efficacy outcome, we're using change from baseline in the upper limb items of the Tetris, because all patients suffer from upper limb tremor and these items are reported reliably.
The chart on the right displays these data as a percent change in tremor amplitude.
The reduction of greater than the 40% and upper limb tremor amplitude.
Compares favorably to pharmacologic standard of care such as per per annum of law.
Bernard Rubino: We've provided a schematic of the trial design for Part B. RP will include an open-label titration period over 28 days, followed by two weeks on a stable high dose. After that, there will be a two-week randomized withdrawal.
Similar patterns of the improvement were observed in the accelerometer scores.
There's also a strong correlation between the Tetris site investigator ratings and central ratings.
Bernard Rubino: The randomized withdrawal stage is intended to assess the durability of effect for this key mechanism of action and will provide blinded ratings to confirm the effects from the open label. ET affects up to 7 million people in the U.S. alone, and a new pharmacologic 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 impairs social interactions throughout the entire waking day. manifests an upper limb action tremor that impacts everyday activities such as writing and typing, eating and drinking, and getting dressed.
This concordance among the various approaches to rating tremor gives us confidence in the reliability of the observed effect.
Importantly, <unk>.
Five of the six participants remained on propranolol during the study.
This suggests that practice 94, four kind of be efficacious.
<unk> is both an adjunctive treatment.
And as monotherapy.
Based on the observed safety profile and the preliminary efficacy shown in the low dose cohort. We believe that <unk> 944 is the titratable drug with a wide therapeutic range.
As such we added the second cohort.
Which up to 12 patients will be titrated up to 120 milligrams per day.
Bernard Rubino: 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 activity. The current pharmacologic standard of care has limitations in both efficacy and tolerability, leading to an estimated 80% discontinuation. 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 tremor 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.
On the following slide slide six we've provided the schematic of the trial design for part B.
<unk> will include an open label titration period over 28 days.
Followed by two weeks on the stable high dose <unk>.
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 we will provide blinded ratings to confirm the effects from the open label portion.
E T effects up to 7 million people in the U S alone and the new pharmacologic option for these patients hasnt been approved from more than 50 years.
What often gets missed with understanding the burden of the T is that tremor limit function and the pairs social interactions throughout the entire waking day.
Bernard Rubino: 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 Flory Institute.
E T manifest in the upper limb action tremor that impacts every day activities, such as writing and typing.
Adding in drinking and getting dressed.
Patients are looking for a treatment option that reduces tremor and.
The improved their function.
And has the tolerability profile of that wont interfere with their daily active.
Current pharmacologic standard of care has limitations on both efficacy and tolerability, leading to an estimated 80% discontinuation rate.
Marcio Souza: Hey, thanks, Bernard. As a CNS focused company deeply rooted in genetics, profit labs. It's very important for us that we continue to lead in this area, and the research collaboration announced earlier today with FLORI will 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 Florence Institute, an Australian-based medical research entity that specializes in neuroscience. Each of the three programs focus on rare epilepsies with very high unmet needs and limited or no research and development. Quite importantly, efforts on all these problems have been underway.
With this in mind, the initial efficacy data and observed safety data for 94, four gives us confidence as we move from our work.
We are optimistic the practice nine port four allows for convenient once daily dosing with the potential to control of tremor throughout the day without clinically significant sedation.
We haven't observed any assay ease or severe aes and the majority of observed <unk> had the.
Mild transient and resolved without any intervention.
We believe that the tolerability of prolonged exposure of the MLR formulation currently being used in our phase Iia study are well suited to the treatment of V. P.
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 flooring Institute.
Marcio Souza: The lead problem from this partnership is an ASO for the treatment of SCN2A loss of function, which is the leading cause of genetically associated autism. Together, we'll practice future change. Our ASO Program for the Treatment of SCN2A Gain-of-Function Deficit. 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 for ASO. In the past several months, we have seen promising advances in our two-lead rare disease program.
Yeah.
Hey, Thanks Bernard.
As the CNS focused company deeply rooted in generics of Suffolk lap seat.
It's very important for us that we continue to lead in the area.
The research collaboration announced earlier today with the flurry allow us to do just that.
With the addition of three novel Aes Sul targets to all of our pipeline.
Under the collaboration research will be conducted by the World class team at the floor Institutes and Australian based medical research entity that has specialized in neuroscience.
Marcio Souza: Earlier this year, the FDA granted both rare pediatric and orphan drug designations for Prax222 for the treatment of STM2AZ. We have ongoing ING-enabling toxic studies for Q2-2 and expect them to be completed by the end of the year, with an IMG to follow in early 2022.
Each of the three broadens focus on rare epilepsies with very high unmet needs and limited or no research and developments ongoing.
Quite importantly efforts on all of these problems have been underway.
The leapfrogging from this partnership is an ASR for the treatments of SCN <unk> loss of function.
Which is the leading cause of genetically associated autism.
Marcio Souza: The FDA also granted Rare Pediatric Designation for Praxis 560, for the treatment of SCN2A-N8A-GE. For 5-6-2, our most advanced small-molecule rare disease program. We completed the single ascending dose stage of the phase one study and have advanced to the multiple ascending dose stage. The third stage was completed up to the maximum planned dose with no dose-limiting toxicity, and we are currently at the highest pre-planned dose in the med phase, which is reaching exposures that exceed the predicted therapeutic concentrations in animal models of seizure and epilepsy.
Together with practice due to true.
ASO program for the treatment of SDN to a gain of function mutations.
We have demonstrated our commitment to the <unk> to a community.
<unk> continued to build our leadership position in sojourn channel research.
As a company, we now have six distinct epilepsy programs, including for <unk>.
In the past several months, we have seen promising advancements in our two lead rare disease programs.
Earlier this year, the FDA granted both rapid yesterday and the orphan drug designation for <unk> for the treatment of <unk>.
Marcio Souza: 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 5.62 in the second half of this year, which will be in rare adult cephalogy. We recently expanded the scope of this upcoming trial to include trigeminal neuralgia in addition to SUNS and SUNA patients. We believe that 5-6-2 has broad potential in rare diseases, and we choose to follow a deliberate approach to clinical development.
We have ongoing I N G, enabling talk the studies for tier two tier and expect them to be completed by the end of the year.
Within the IMG to follow in early 2020 true.
The FDA also granted rare pediatric designation of <unk>.
The treatment of SDN, <unk> and eight eight day.
456, <unk>, our most advanced the small molecule rare disease program, we completed the single ascending dose the stage of the phase one study and have advanced to the multiple ascending dose.
Marcio Souza: We intend to expand next into a range of rare pediatric epilepsy, as you can see on slide seven. Praxis has built a novel, diversified pipeline with multiple potential value-creating milestones over 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 to questions.
The third stage was completed up to the maximum planned dose with no dose limiting toxicities.
We're currently at the highest three plan does in the Mad phase.
Which are reaching exposures that exceeds the predicted therapeutic concentrations in the animal models of seizure and epilepsy.
We intend to escalate those further.
Operator: Thank you. As a reminder, to ask a question, you will need...
Drug continues to be generally well tolerated.
We expect to initiate the first proof of concept trial for <unk> in the second half of this year.
Operator: If you find or cast a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key.
Which will be in rare adults apologists.
We recently expanded the scope of this upcoming trial to include stride Jimmy on neurologists.
Operator: Please stand by while we compile the Q&A roster. Our first question comes from Ritu Baral on Cowen. Your line is open. Good morning. Thanks for taking the time to answer the question. Marcio, I want to make sure I understand correctly. The day 28 secondary endpoint, that key secondary endpoint, 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 indication similar to stages? Or even if you have trends, can you be talking about a chronic label?
In addition to Sun and soon of patients.
We believe that <unk> has broad potential.
In rare disease, and we choose to follow a deliberate approach to clinical development.
We intend to expand next into a range of rare pediatric epilepsy.
As you can see on slide seven Pratt.
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 true all day here.
With that's when all of the now open the call for questions operator.
Thank you as a reminder to ask the question you will need the press star one of your telephone to withdraw your question press the pound key.
Ritu Subhalaksmi Baral: And then I've got a couple of follow-ups. Good morning. I hope all is well. The conversation with the FCA in relation to the 28th day.
The standby, what we can pop Q&A roster.
Our first question comes from Ritu <unk> with Cowen Your line is open.
Good morning, Thanks for taking the question.
Marcio Souza: It's really, as we mentioned, a key secondary answer.
Marcio I want to make sure I understand.
unknown: [inaudible] Now, it's all dependent, as always, on the FDA reviewing the results and so on. We fully expect that that's going to be maintenance of effects at day 28, and then we'll have both claims. As a reminder, as well, as we discussed previously, the FDA did insist that we follow these patients for more than 15 days on the drug in order to qualify for a monotherapy label in MGD. So it covers a number of topics, right?
Secondly, the day 28 secondary endpoint that key secondary endpoint.
Yes.
If the trials go weak signal.
Again at day 28.
Will you be moving forward or will FDA require you to move forward with the sort of episodic day 14 indication similar two stages or even if you have trends can you be talking about of chronic label and then I've got a couple of follow ups.
unknown: So one is serving as a secondary endpoint, which is obviously quite important, but also serving as a determination of, like, the safety of looking at these patients for more than 15 days and securing with the trial being positive, and a second trial being positive, to support the label. So 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, there would still be a path forward with the claim of day 15, very clearly. Okay.
Homegoods, Hey, Rick Good morning, I hope all of those goods.
The the conversation with the FCA in relation to <unk> 28 day, it's really as we mentioned as a key secondary end points right. So that would be by definition of additional claim we see the huge opportunity to activate you'll have the <unk> as you mentioned on the prepared remarks as the primary thing.
That would be what would the Claire excuse me the trial of its spot of positive or not.
Now, it's all dependent as always of the FDA reviewing the results and so long we fully expect that that's going to be maintenance of the facts at day 28, and then it would have both claims.
As a reminder, as wall as we discussed previously the FDA did insisted that we followed the space on the while more than 15 days one drug in more of their to qualify for a monotherapy label and MTG. So it kept a number of topics right. So one is serving.
Marcio Souza: 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 two dose ranging that you're doing later this year, are you planning on going up or down in doses there? Yeah, so the data power that we are seeing with the 40 milligrams of the tablet formulation is around 1.7, so 170%, right, since baseline is normalized to one.
As a secondary endpoint with obviously the quieting Barton.
But also serving as the determination of like the safety of looking to this patients for more than 15 days.
And securing what the driving positive with effect from trial being positive to support the label. So a number of things, but maybe going more simplistically.
Marcio Souza: That is far more than what we would expect for the effects here. Now, for the GRF trial, I'm gonna hand over to Bernard to explain how we are thinking about that, why we are doing that, and the dose range that we'll be exploring.
I believe that the wall is mall chains, there on day 28 and for some reason something happened that would still be a path forward with the kind of the getting very cleared.
Got it Okay and then.
The 40 milligram is that.
Based on your beta power.
Bernard Rubino: Yeah, Ritu, so, right, the 40 milligrams gets us to a beta power of, on average, about 1.7. And we had said, based on the accumulated data and our preclinical data, that we want it to be around 1.5, 1.6, or above. So we think this is getting a full pharmacologic effect at those exposures. Then, 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 a pretty significant beta power in that dose range, and that's the main part of the curve we want to explore, because as you saw with the open-label data in Part A, it looks like we're We do expect, however, to include a higher dose as well, and that offsets any risk in terms of diminishing efficacy in the lower part of the dose.
Studies, if off the top of the dose response curve.
They have forgotten to write down in my notes that the phase II dose ranging that youre doing later this year are you planning on going up or down dip Joseph per yeah. So so the the beta powered debt we are seeing with the 40 milligram with the tablet.
Tablet formulation is around one seven.
So the 170 percents right since the baseline is normalized to one.
That is far more than what do we have the expect for the effect here now for the <unk> trial I'm going to handle a bunch of Bernard to explain how we are thinking about that's why we are doing that and the dose range that would be exploring.
We're not.
Yeah.
Right, the 40 milligram doses to update of power.
On average about 1.7 weighted sort of based on the.
The accumulated data in our preclinical data that we wanted to be around 1516 or Bob. So we think this is getting the full pharmacologic effect of those.
The exposures the.
The for that dose range finding trial, we are planning on going to lower doses.
Marcio Souza: 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 tease apart any potential effects? And are you going to be investigating, like one of your competitors, sort of simultaneous combination initiation of treatment? So, that trial, which we call Study 214, is solely in a junket setting, and the benefits here are, one, to get a clean set.
As far down the 10.
And 20, and we believe we will still maintain.
Pretty significant data power and the dose range net.
The main part of the curve, we want to explore because as you saw with the open label data in part a of 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 risk in terms of diminishing efficacy in the lower part of the dose range.
Got it and then just the fact that that trial is adjunct tests are you going to be investigating any.
Marcio Souza: The second is really operational enrollment, right? So, we're going to be doing this trial virtually in parallel with Study 213, that is the Phase 2-3 monotherapy, and it gives an alternative for the sites to screen patients for both trials and to, like, select them for the trial that makes the most sense. Bringing both in one trial normally has more of a confounder effect than not.
I guess any cohorts that look at dunkin' versus non adjunctive to sort of tease apart.
So the effect on <unk>.
Are you going to the investigator like one of your competitor sort of.
Simultaneous combination initiation of treatment.
So that trial, which we call. The study 214 is solely in the junk of setting.
And the and the benefits here, it's one get of clean.
That's the second is really operation on the enrollments right, we're going to be doing this trial virtually in parallel with two studies 213 that is the phase III three monotherapy and.
Marcio Souza: And we wanted to make sure whatever results we get on the other end are interpretable, and we can clearly express. Totally understand. I have a bunch more questions, but I'll hop back in the queue. Thanks guys. Cool. Thank you so much for the, Thank you. Our next question comes from Laura Chico with Redwoods Securities. Your line is open.
And it gives them an alternative for the sites to screen patients for both trials are really into like select down to the thrive that makes the most sense.
Bringing both in one trial, it's normally more of a Fox cofounder of facts, then the Knox and wanted to make sure whatever result of get all of the other hand is in capital and we can clear the expressway.
Totally understand I have a bunch more questions, but I'll hop back in the queue. Thanks guys.
Thank you so much of it.
Thank you. Our next question comes from the Laura Chico with Wedbush Securities. Your line is open.
Laura Kathryn Chico: Hey, good morning, guys. Thanks for taking the questions and congrats on the progress. I guess we just wanted to circle back one more time on the dose selection for 114. And just with regard to kind of all the data, putting it together, the beta power, the accumulation.
Hey, good morning, guys. Thanks for taking my question and congrats on the progress I guess I just wanted to circle back where much of them on the on the dose selection for 114, and just with regards to kind of all of the data putting it together the beta part of the accumulation.
Just to clarify would the 40 milligram dose the analogous to one of the suspension doses that you already covered.
Marcio Souza: Just to clarify, would 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 40 mg tablet is equivalent to. Yeah, no, absolutely. And hey, Laura, good to hear from you.
And the part a study I guess I'm trying to just contextualize, what the 40 Meg tablet is equivalent to.
Yeah, no absolutely and the Halo of I'll go to hear from you. The this suspension does rights that we pass it before just to recall they did not show any differentiation in terms of.
Marcio Souza: The suspension dose, right, that we tested before, just to recall, they did not show any differentiation in terms of the effect we're seeing. But there was, as we escalated the dose, more prevalence of AEs, not necessarily severity on that. The tablet profile, what we see was a number of things, right? So the general profile was very similar, which was good. We learned a little bit more about time of day dosing, as Bernard mentioned.
Of the fact, we are seeing but the wall as west collated the adults.
More prevalence of.
Not necessarily severity.
On that and what Youre looking as true stay above the 1415 in the beta power in general as we're guiding dose right to ensure the reason quite state of the EG.
The tablets profile, while the receivables of number of things right. So the general profile of very similar which was goods, we learned a little bit of more about the time of day dosing as Bernard mentioned.
Marcio Souza: But one thing that was quite important is that variability is reduced. So, we drive exposures that are at or higher than the 45 on the previous suspension trial, and that's where the overlap for your question is. But because the variability is smaller on the exposure, we end up getting more patients. Our prediction is that we're going to get basically all patients to the beta power we were expecting, and therefore to the efficacious range there.
But one thing that was quite important is the variability is reduced.
So we drive exposures that are assets are higher than the 45% on the previous suspension trial or the.
And that's where the overlap part of your question is.
But because of our ability the smaller on the exposure we end up getting more patients. Our prediction is that we're going to get basically all patients true to the beta Paula we are expecting.
And therefore the efficacious.
Marcio Souza: So, you could look into between the two lower doses that we did for phase 2a, so between 45 and 60, I would say as a surrogate in terms of the exposure there, but we are consistently seeing 40 in the tablets at or higher than 45 for the previous one.
Range there so you could.
Looking to between the two lower dose that we did part of the phase Iia. So the between 45 and six day I would say of a surrogate in terms of the exposure there, but we are kind of consistent.
Consistently seeing of the 40 in the tablets at or higher than 45 for the previous one.
Marcio Souza: Okay, that's helpful, Marcio. Of course. Okay. And then maybe a follow-up question here. Just, well, maybe two, two follow-ups. Sorry.
Okay. That's helpful of Marcia.
Of course, Okay, and then maybe a follow up question here.
Just maybe two follow ups.
Laura Kathryn Chico: On 114 for the registrational path, I just wanted to clarify, would the initial plan then be to pursue both monotherapy and injunctive 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 one work. Would that be a gating factor to starting that phase two B study as well with 944? And any thoughts on whether or how you would channel patients already on propranolol?
One fourth of the Registrational path.
Wanted to clarify what the initial plan them to be pursuing both monotherapy and adjunctive labels at the same time for the initial filing and then of 94 four.
Also as kind of clarifying there.
I guess youre.
You are looking to do the separate titration study with the phase one work.
Would that be a gating factor to starting the phase <unk> study as well with 94, four and any thoughts on whether on how you would channel patients already on the per panel. Thanks guys.
Laura Kathryn Chico: Thanks, guys. Absolutely. Maybe, maybe I'll get the first question on the 944 question to Bernard, and then we can go back and talk a little bit about the registration path for both of them. Bernard, why don't you talk a little bit about it?
Absolutely.
So.
Maybe I'll get the the first question of the 94 for a question to Bernards and then it kind of go back and talk a little bit about the registration path for both of them.
But not of why don't you talk a little bit of buyback.
Yeah for so from 944 waves.
Bernard Rubino: Yeah, so for 944, right, 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 that generally older population of ET patients who are taking a bunch of concomitant medications, that they can tolerate that as well.
We now understand that we can get up to 120 milligrams in healthy volunteers.
We're going to explore of that now in the part B study in E T patients and really the goal there is to make sure that in the.
The generally older population of <unk> patients are taken a bunch of cash.
Covenant medications that they can tolerate that as well.
We'll be having those data around mid year, we will get a sense.
Bernard Rubino: So we'll be having those data around mid-year. 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 start. ranging RCT towards the end of the year. But both of those pieces of information are going to be helpful for a well-designed RCT.
In the pool of subjects up to about 12, what kinds of treatment effects, we're seeing in E T.
Parallel with that we're going to explore some different titration schemes.
And we will 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 will be very well positioned.
Strange Yang RCT towards the end of the year, but both of those pieces of information I'm gonna be informative for well design RCT.
Marcio Souza: And going back to your 1.1.4 question, so 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 Study 2.1.4, as we mentioned, for adjunctive purposes as well. Based on the results of that study, we'll have a conversation with the FDA on whether or not an additional study for adjunctive therapy would be necessary.
And going back to <unk> for questions. So the base plan here is to get to a monotherapy label with the phase three that we are starting in the next couple of weeks.
Second phase three after that.
We are starting the study to one four as we mentioned four of Gen <unk> as well.
Based on the results of that study would 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 match required and the other one.
Marcio Souza: I think it's largely on their hands in terms of that. They might require another one. I feel pretty good based on precedent that the adjunctive with two positive trials in mono might be possible to be, but it's very hard to guide right now to exactly what the label would be. The base case is monotherapy, with shorter than after or in parallel having an adjunctive in the label.
I feel pretty good based on precedent and staffed the adjunctive with two positive trials in mono might be possible to be but it's very hard to guide right now.
To exactly what the label would be but the the base cases.
Monotherapy with sharp in debt after auditing part of allow hadn't adjunctive in the label.
Operator: Thank you. Our next question comes from Kyla Van Buren with Piper City.
Alright, thanks, guys.
Of course.
Thank you. Our next question comes from Tyler Van Buren with Piper Sandler Your line is open.
Operator: Van Buren with Piper Sandler, your line is open. Hey, guys. Good morning. Congrats on the progress. Definitely an unusual amount of clinical activity for a recent IPO. I have three for you. Forgive me for asking another beta power question.
Hey, guys. Good morning, Congrats on the progress definitely an unusual amount of clinical activity for recent IPO 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.
unknown: But when you talk about 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 an 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.
Data powered Q E. G data that spike that occurs appears to last for about one to two hours of 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 of the 40 milligram tablet dose and then the second question is just.
You mentioned kind of maxing out on the efficacy, but also having the ability to improve tolerability can you just confirm.
unknown: Can you just confirm that you've never seen any sedation at kind of these levels, 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 rate of somnolence has been, because clearly those two things are quite different, as I understand it.
Firm that you've never seen in the sedation.
All of these levels at these doses relative to I guess, the equivalent of the suspension of 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.
unknown: And then the third one is on the central tremor. I believe you said six, that data's from six patients on this slide. I think we had 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 any sort of placebo response.
I believe you said six Davis from six patients in the slide I think we are thought of recently so could you just comment on that six patient and also.
Your confidence in clinical trials moving forward with respect to people, who respond or don't respond in any sort of the placebo response.
Yes, so I'll try to unpack Hey, Tyler good to hear from you is while the true impact like the 100 questions you got there, but I appreciate the nice attempt to earn back of a bunch of them. So so a beta of power. So maybe to clarify that's right. So the way we're looking into.
unknown: Yeah, so I'll try to unpack. Hey, Tyler, good to hear from you as well.
Marcio Souza: To unpack like the 100 questions you got there, but I appreciate the nice attempt to unpack a bunch of them. So, beta power, so maybe to clarify that, right, the way we're looking into beta power, and I actually would guide you guys towards our forum 10k that was just posted on the FCC website, because we're talking for the first time about 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.
Beta power in and of actually Woods.
With guide you guys towards our form 10-K that was just posted at the FCC of website, because we're talking about the first time about the alpha bands.
While in the current state of EG in relation to one four so something that might be interesting for some of the follow up calls.
Marcio Souza: What we're looking at is whether or not we're being able to expose patients to therapeutic doses. So it's a surrogate for whether or not we cross the thresholds, right? So we believe that it's incredibly important that you have to do that without the drawbacks that you talked about. So just to be. Quizzically Clear.
Looking to that is whether or not we are.
Being able to expose patients to therapeutic dose. So it is a surrogate to whether or not we cross the thresholds right. So believe that is incredibly important debt you have to do that.
Doubts the drawbacks that he's talked about so just to be.
Quizzically clear.
Marcio Souza: We've never seen, next day, somnolence, sedation, or worse yet, Trevor. 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 this patient. So we wanted to separate that.
We'd never seen them next day.
The lengths sedation.
Or worse, yes travel so.
So we haven't seen those things that might have been seeing.
With the class of our expected out of the class on next day, so for US it's incredibly important stats because net.
Next day terminal ends for example, or sedation might be seen as depression by disc patients. So wanted to just cap rate. That's now I have not equifax is expected and desirable from debt. So we want them patients took deal at ease kind of on coal and if not ex before going.
Marcio Souza: Now, a hypnotic effect is expected and desirable from this. So we want patients to feel at ease, quote unquote, and hypnotic before going to bed without any requirements that they are in any given state of feeding their 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, the best possible to this day. As we just mentioned, we're gonna explore lower-dose profiles that wrap the expected efficacy, which we're hopefully gonna be seeing at the end of Study 213, with our safest profile to date in terms of the rates of somnolence.
Too bad with Delta and the requirements that they are in any given the state of feeding our mines.
I'm going to add just taking the drug and really being able to sleep and feel better about their depression.
So the 40 milligrams with the tablet gives up.
The best possible to this day as we just mentioned of unexplored lower dose.
The profile of that wraps the expected efficacy.
Hopefully going to be seeing at the end of study two and three with our safest profile of two dates in terms of the rates of somnolence and we havent seen Frank sedation as we mentioned before just wanted to reinforce that even at the much higher doses of <unk> 40, but back on some of the non of flooring.
Marcio Souza: And we haven't seen frank sedation, as we mentioned before, just going to reinforce that, even at much higher doses than 40, but definitely not at 40, that had answered the one-on-four part of the question. Yep, thank you, sounds good.
That answered the the one on for a part of the question.
Yep. Thank you.
Sounds good.
Marcio Souza: So on the T part for 944, right, so you might recall at the time we filed the S-1 late last year, we had five preliminary patients. The data was like coming off the press. We needed to basically do a number of things, like clean it up to the extent that was required, run the assessments for concordance with the other endpoints, and then add any other patients. So we had seven patients in the safety database. One of those patients did not complete any of the efficacy measures.
So on the on the C. R. Bard for 944 right. So.
Recall at the time, we filed the S. One.
Late last year, we had five preliminary patients that.
That data walks like coming off the crowds, we needed to basically do a number of things like cutting debt up to the extent that was required.
The run the assessments for concordance with the other endpoints and then add any other patients. So we had seven patients on the safety database one of those patients did not complete any of the efficacy.
Marcio Souza: So we're showing data for six patients on the efficacy measures. And the good news here is that one, it's a very robust average reduction in tremor as measured in this trial. But the second thing is that for the first time, and while we believe that our difficulty is measuring tremors using the current standards, a trial was able to show concordance between blinded central readings and the sight readings. The sight readings, the standard of care is what most goes to, there's a lot of validity there, but it was important for us since this is open label to get that confirmation.
So we're showing data for six patients on the on the efficacy of managers and the good news here is one of very robust average a reduction in the tumor as measured on this trial, but the.
The second thing is that by the first time and while we believe that our difficulty is on measuring tremors using the clearance.
Sanders.
So I was able to show compartments between blinded central readings and the sites are waiting the psych ratings they standard of care.
The one most go through it there's a lot of I need you to there, but it was important for us because it's open label two gaps that confirmation. So we feel really good about the results. We're having right now and that's what led us to move an accelerated Florida to the previous question from Laura in terms of getting the next two of <unk>.
Marcio Souza: So we feel really good about the results we're having right now, and that's what led us to move and accelerate it further to the previous question from Laura in terms of getting the next two trials running and starting the phase to be 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.
<unk> are running any starting the phase should be by the end of the year. So it was eventful as you said between the IPO now it's definitely the more eventful for the next six months. So we are really looking forward to it.
Great. Thanks for taking the questions.
unknown: Great, thanks for taking the question. Of course.
Of course.
Thank you. Our next question comes from Richard the wrong with Cowen Your line is open.
Ritu Subhalaksmi Baral: Thank you. Our next question comes from Ritu Baral on Cowen. Your line is open. Hey, guys, sorry, I was muted on this. One protocol question. What is this placebo-controlled reminder script that you described as part of the depression study? I don't recall ever encountering that before. And then, can you briefly, and again, sorry if I missed this, but can you go over what you've seen to date on the side effect tolerability of 944 at the 40 milligram dose? And given the mechanism of 944, what do you think is the side effect to watch when it comes to tolerability and
Hey, guys, sorry, I was the either.
On the.
The one.
The protocol question what.
Placebo controlled reminder, scripts that you described as part of the.
Depression study I don't recall ever.
And countering that first of all.
And then can you quickly.
Again, I'm sorry, the Thunder, but you can go from what you've seen to date on the side effects tolerability of $90 four per 40 milligram dose.
And given the mechanism of $90 four what do you think of the side effect to watch when it comes to Tolerability and compliance.
unknown: and Compliance in is like a real-world setting for the drug.
Sales were all credit before the truck.
Bernard Rubino: Yeah, no, absolutely. The reminder scripts, Ritu, is actually something that sounds very simple on the surface, but it's incredibly powerful. We have added the reference to that in a recent paper to our slides and our SEC filings. So I recommend you, like, take a look at that afterwards.
Yes, absolutely at the.
The the reminder of scripts.
It's actually something that sounds very simple on the surface.
But it is incredibly powerful.
We have added the reference for that and the recent paper to our slides.
In the in our SEC filings, so I recommend like take a look back off the awards, but it basically is a structured way to Ah reminds of the patients are in the very simplistic manner that they are in an experimental drug that is blinded.
Marcio Souza: But it basically is a structured way to remind the patient, or in a very simplistic manner, that they are on 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 the drug. By doing that systematically using a script at every visit, it has been shown to fairly significantly separate the placebo patients from us, so controlling for the placebo effects.
And therefore, there should be no expectation of the facts since that is of 50% chance they are not on drug.
By doing that systematically using a script in average visits it has been shown to fairly significantly separates the placebo patients from thrown out so control for the placebo attack a.
Marcio Souza: A lot of what we are doing is to make sure the trial's operation, the sound, is not only that we show a separation from 114 at the end, but then we can control the placebo effects to historical rates in our controlled trials. So punch this one in to Bernard as well to talk a little bit more since it was his idea and his team's idea to implement this so thoughtfully in this study. Bernard?
A lot of what we are doing is to make sure that drives operation of the sounds he is not only that of a show of separation from 114 at the end, but then that we can control of the placebo effect to historical rates in our controlled trials.
All of a bunch of us want to Bernard is relative talk a little bit more time swaps his idea and his team idea to implement the sole thoughtfully ended the study or not.
Bernard Rubino: Yeah, like Marcio said, there's, there are really nice data to support this. So basically, right, the placebo effect is driven by expectations, and what the placebo reminder script is really meant to do is kind of refocus 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, reminds them that they're not in a treatment setting.
Yes.
Moshe.
They're really nice day of the support the so basically the right placebo effect is driven by expectations and what the placebo reminder, script is really meant to do is kind of a re focus people on expectations remind them that they are in a clinical trial.
And experimental agent it is not known to work yet.
And so it just kind of set expectations.
Reminds them that are not in the treatment setting.
Bernard Rubino: So this kind of approach has actually shown pretty robust effects in terms of, you know, maintaining less of a placebo effect. So it's been used in a number of different kinds of psychiatric trials, pain studies, and other places where placebo effects and expectation bias can really cause trouble for trials. So, and our sites are experienced with using it. And the way it's implemented, Ritu, is that it's simply not read but presented to the patient, and kind of discussed prior to conducting the main assessments, the primary and key secondary.
Those kind of approaches actually shown pretty robust effects in terms of.
Yeah.
Maintaining.
The <unk>.
Less of a placebo effect so.
It's been used in the number of the.
This kind of approach been using the number of different kinds of psychiatric trials pain studies, and other places where placebo effects and expectation bias can it can really cause trouble free trials.
And our sites are experienced with the isn't it.
It is the way it's implemented Ritu is that simply.
It's not red, but presented to the patient kind of discussed.
Prior to conducting the main assessments of the primary and key secondary assessments.
unknown: and then 944 Tolerability. Yes, and on the 944
And the non core point comparability.
Bernard Rubino: Yes, and on the 944 tolerability, so that's been very, very good, right? So going into this, we knew what kind of AEs to look for. So the main AEs are around nausea, dizziness, lightheadedness, and 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 tolerate them. We know the EEG effects don't tolerate them, but those AEs tend to, and so you see them up front.
Yes.
On the ninth force for Tolerability.
So that's been very very good right. So so.
Going into this.
We knew what kind of aes to look for.
So the main aes or.
No.
In the 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 tolerate <unk>, we know the EEG effects don't tolerate but.
Those are the east tend to and so.
Bernard Rubino: They're mild, and they're transient. You really don't need to do anything in terms of any interventions. The main thing to do is just let people know that they will subside and just have the right to. And, you know, I think that's just part of the mechanism in getting started. But the key is that they go away, and they do not increase with titration.
You see them upfront, they're mild they're transient really don't need to do anything in terms of the.
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 I think that's just part of the mechanism and getting started but the key is that go away. The date do not increase with titration.
unknown: Got it. Thanks. Thank you. Once again, ladies and gentlemen, if you wish to ask a question at this time, please press star, then one, or you touch some telephone.
Got it thanks.
Thank you once again, ladies and gentlemen, if you wish to ask the question at this time. Please press Star then one of you touched on the telephone.
Operator: And I'm currently showing no further questions at this time. I'll turn the call back over to Marcio Souza for closing remarks. Thank you very much, operators, and thank you, everyone, for joining us today. We're incredibly thrilled to be on this first public call with all of you, and, most importantly, to advance all these therapies to patients. This is very close to our hearts here at Praxis and what keeps us up at night sometimes and definitely very early in the morning, making sure we can advance.
And I'm currently showing no further questions at this time I'd like to turn the call back over to Marcio Souza for closing remarks.
Thank you very much operator, and thanks to everyone for joining each day.
The materials should be on the as far as public call with fall of few and most importantly.
Then seeing all of these therapies to patients. This is very close to all of our hearts here the practices and what keeps us up.
At the night, sometimes I'm 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 debt is a tremendous amount of progress.
Operator: I believe you all would agree with me that in the last five months, since we became public, there has been a tremendous amount of progress and operational progress from the company on moving each one of our programs and more towards the clinic or at the clinic to help those patients. So, I'm very proud of the team of people that are behind Bernard and me and others on this call, really helping us move this to patients. Thank you very much for supporting Praxis and everything we do. I'm looking forward to talking to all of you. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.
The problem is off from the company are moving each one of our problems and more towards.
Towards 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 will be helping us move bits to the patient. So thank you very much of our supporting our praxis and everything we do and looking forward to talk to all of you.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.
Yes.
Yes.
Yeah.
[music].
Yes.
Okay.
Yeah.
Great.
[music].
Okay.
[music].
Yeah.
[music].
Yes.
Marcio Souza: BF-WATCH TV 2021
Yeah.
Yes.