Q1 2022 Praxis Precision Medicines Inc Earnings Call
Good afternoon, ladies and gentlemen. This is your operator your conference will begin momentarily. Please continue to standby.
Once again this is your offer here your conference will begin momentarily. Please continue to standby.
[music].
Good day, and thank you for standing by and welcome to the practices precision medicines first quarter 2022, corporate update question and answer conference call.
Operator: and this is your op. Good day and thank you for standing, Welcome to the Praxis Precision Medicine's First Quarter 2022 Corp. At this time, all participants are in a listen only mode. After a short remark, there will be a question and answer session. Star Wars, If you require any further, Star Zero.
At this time all participants are in a listen only mode. After a short remark there will be a question and answer session and to ask a question during that session. You will need to press star one on your telephone if you require any further assistance. Please press star zero and now it is my pleasure to hand, the conference over to your speaker today Alex scheme.
Alex Kane: And now, it is my pleasure to hand it on. Today, Alex Kane, Vice, Thank you, Paul. Good afternoon, everyone. And thank you for joining us today for our first quarter 2022 Corporate Update Q&A call. With me on the call is our President and Chief Executive Officer, Marcio Souza, our Chief Medical Officer, Bernardo Vina, and our CFO, Tim Kelly. Following the press releases and video update issued this afternoon, we will focus today's call on your question.
<unk>, Vice President Investor Relations and corporate communications at <unk>.
Thank you. Please go ahead.
Alex Kane: We ask that you keep to one question initially, and then please feel free to rejoin the queue for follow-up questions as needed. Before we proceed, I would like to remind you that during today's call, we may make certain statements that are beliefs forward looking and subject to various risks and uncertain, For additional detail on forward-looking statements and the risks associated with our business, I encourage you to consult our SEC file. With that, I will now pass the call over to the operator to open up the line for Q&A. Operator?
Thank you Paul Good afternoon, everyone and thank you for joining us today for our first quarter 2022, corporate update Q&A call with me on the call is our president and Chief Executive Officer, Marcio Souza, our Chief Medical Officer, and Bernard Arena, and our CFO Jim Kelly.
Following the press releases and video update issued this afternoon, we will focus today's call on your questions. We ask that you keep to one question. Initially and then please feel free to rejoin the queue for follow up questions as needed.
Before we proceed I would like to remind you that during today's call. We may make certain statements that are beliefs forward looking and subject to various risks and uncertainties for additional detail on forward looking statements and the risks associated with our business I encourage you to consult our SEC filings.
With that I will now pass the call over to the operator to open up the line for Q&A operator.
Thank you Sir we will now begin the question and answer session. If you would like to ask a question. Please press star one now again.
Operator: We will now begin the question and answer session. If you would like to ask a question, please press star 1. Again, it's star one on your telephone. Wollicabrali, Your first... Hey guys, thanks so much. This is Lauren on Priyaz.
Our one telephone keypad, please standby, while we compile the Q&A roster.
Your first question is from the Aspen Rahimi with Piper Sandler. Please go ahead.
Marcio Souza: I have a couple questions. So the first one, what are some of the key lessons you guys learned from PROC 944 data that could impact your views into the essential phase 2b study? And then speaking a little bit to the enrollment, how that's going into that study, and do you think that the essential population will capture a similar demographic? Thank you. Thanks so much for the question. I would say, maybe I'll start through the end there, like the enrollment population for Essential One is slightly different than 944-221 that we're just very proud and very excited to have released today.
Hey, guys. Thanks, so much this is lauren on for yet.
I have a couple of questions. So the first one what are the key lessons you guys learned from <unk> 94 data that could impact your views into the essential phase <unk> study.
And then speaking a little bit the enrollment how thats going into that study and do you think that the essential population will capture stimulate demographic. Thank you.
Thanks, so much for the question.
Maybe I'll start with the <unk>, they're like the enrollments a population for essential one is slightly different than stem mindful March one bedroom and Joseph.
Very proud and very excited to have the big is today.
Marcio Souza: The key components there that is different is that we did not allow for patients with Tetra's upper limb score less than 10 on Essential One, which is also kind of related to your first question. That's what we learned conducting these studies and looking to other data in this space as well. There has to be, in order to be like a little bit more homogeneous, a certain level of framework at baseline.
The key components. There is difference that we did not allow our patience with that trust upper limb score less than an essential one which is also kind of related to your first question is why do we large conducting two studies and look into all their data in this space as well.
It has to be.
In order to be like a little bit more in Virginia.
A certain level of Sam Moore.
At baseline so we went through a fairly broad <expletive>.
Marcio Souza: So we went through a fairly broad, as 944-221 was, to a little bit more restrictive, so only higher than 10. And that would allow us, we expect, to show even more clear results, not that we think we need it, based on today's data, on the essential one coming up. And the enrollment on the trial is going pretty well. We reinforced today, and we continue to reinforce the results by the end of. Day here, but I'll hand over to Bernard for any other comments here about the lessons.
94% to one was to a little bit more restrictive.
The higher dividend and that would allow us we expect to show even more clear results not that way.
If we need it based on today's data on the essential one coming up as the enrollment on the trial is going pretty well.
We are we will reinforce today and will continue to reinforce the results by the end of the day.
But I'll hand over to Bernard.
All the comments here about the lapses.
Bernardo Vina: Yeah, that point about the population is a key one, and then I think, yeah, a couple of the other key lessons, one is we learned that we could get most people up to the high end of the dose rate. And we've previously shown we've got a very well-substantiated dose range based on that mechanistic biomarker of quantitative EEG. So it really confirms we've got a 20x dose range that we can work in where the drug appears to be active and has potential to improve tremor.
Point about the population is a key one and then I think.
A couple of the other key.
Key lessons one as we learned that we can get the most people up to the high end of the dose range.
And we've previously shall we got very well substantiated dose range based on that.
Mechanistic biomarker of quantitative EEG, so really confirms who've got it got it.
<unk> dose range that we can work and where the drug appears to be active and has potential to improve tremor and then I think we've learned a lot about the endpoints too.
Bernardo Vina: And then I think we've learned a lot about the endpoints, too, and we agree with the agency's suggestions about ADLs and particularly modified ADLs, and we've seen what a responsive measure that is. I think it really helps us focus in on function and understand that that is a reliable measure that integrates a lot of tremor in activities that patients come across every day. Thank you so much for that information.
We agree with the agencies suggestions about adl's and particularly modified Adl's, we've seen what a response a measure that is.
Including in the randomized withdrawal.
At that blinded period, and so I think.
It really helps us focus on function and understand is that is a reliable measure that integrates.
A lot of tremor in activities that patients come across every day.
Marcio Souza: Sorry, just one more question. What were the reasons for the three discontinuations in the Praxis 144 study? Yeah, so there were, there was one person who had a discontinuation totally unrelated to Practice 944. So they needed a procedure for something that they, you know, had a medical condition they had going in.
Thank you so much for that information sorry, just one more question what were the reasons for the <unk> discontinuation in the <unk> four study.
Yes. So there were there was one person.
Who had discontinuation totally unrelated.
Next time port for so they needed a procedure for something that they.
Marcio Souza: So it's totally unrelated. And then the other discontinuations, one was dizziness and the other was primarily fatigue. So all the AEs there were mild to moderate. There was only one severe AE, which was worsening of tremor when drug was withdrawn. So overall, really well tolerated.
Medical condition that had going in so it's totally unrelated.
And then the other.
Discontinuation is one was dizziness.
Other was primarily fatigue.
So.
All the Aes there were mild or moderate there was only one severe AE, which was worsening.
Tremor when drug was withdrawn so overall really well tolerated.
Great. Thank you so much guys.
Thank you.
Your next question is from Laura Chico with Wedbush. Please go ahead.
Operator: Great, thank you so much. Thank you. Good afternoon.
Good afternoon, thanks, very much for taking the question I'll take this one here I guess I just wanted to verify or clarify some of the comments you had in the video with respect to essential one so.
Marcio Souza: Thanks very much for taking the question, and I'll stick with one here. I guess I just wanted to verify or clarify some of the comments you had in the video with respect to Essential 1. So, you're updating the primary endpoint to this modified ADL, and it sounds like you have agency support here. I'm just trying to understand, could Essential 1 serve as a registrational study? I believe enrollment is around 115, 120 subjects.
Updating the primary endpoint to this modified ADL and it sounds like you have agency support here I'm, just trying to understand could essential one serve as a registrational study I believe enrolment is around 115 to 120 subjects just trying to understand a does this become a registrational study and also.
Marcio Souza: Just trying to understand, A, does this become a registrational study? And also, B, are there any mechanics behind changing the endpoints and how that might affect enrollment? Thank you. Yes, Laura.
Are there any mechanics behind changing the endpoints and how that might affect enrollment. Thank you.
Yes, Laura.
Marcio Souza: There are a lot of mechanics behind it, and that's one of the reasons why we mentioned in the video, we're working through it, so we're going to be informing all of you about those mechanics. Also, specifically, there are so many alternatives right now, as you can imagine, with such a robust rebound after we remove the drug, it gives us a lot more confidence on some of the aspects that were unclear, like which those should be targeting and things like that, so we're working on all of that.
There are a lot of mechanics behind us and Thats one of the reasons why we mentioned in the video we're working through ads will it be informing all a few amounts that those mechanics.
Specifically, what's theres. So many alternatives right now as you can imagine with such a robust rebound after removing the drug.
It gives us more confidence on some of the aspects that were unclear like.
Which dose would be targeting and things like that so we're working all of that.
Marcio Souza: In terms of the endpoints, this was incredibly clear with us and with others as well in the space on measures that very clearly affect function for those patients. So, when you look into the ADL, originally, as designed, it was already a pretty good assessment of function, but lost the ability to detect more of the floor. That's one of the reasons why the agency suggested, very strongly, may I say, that we modify the way the floor was assessed.
In terms of the endpoints.
Just was incredibly clear with us and with others is wildly space.
Measures that would clearly affect function for those patients.
So when you're looking to the AGL originally.
As defined was already.
Pretty good assessment of function the loss.
Village that thats more of the smaller.
That's one of the reasons why the agency has suggested there is stronger than EMEA I would say that we modified the way the floor was SaaS.
Marcio Souza: And I make a point that by doing that, we reduce the score by about 30%. If you were to have used that, the results today would be even more positive, not that they needed to be. But it's a lot more trustworthy, I would say, the way that it's being done right now. So we're very convinced by the feedback today that the end point is very clear. Now whether or not the new design will be registrational, that's a matter of discussions with the FDA after we found that design.
Let me make a point that by doing that we reduce they score by about 30% if.
If you were to have to use that the results are they will be even more positive about that they needed to be.
But it's a lot more plus royalty I'll say the wage on that is being done right. Now. So we're very convinced by the feedback to date, that's the endpoint, it's very clear now whether or not the new design will be registrational.
Discussions with the FDA after we buy.
Marcio Souza: I think what we're going to be very clearly driving to is for clinically and statistically significant change, and then have a discussion with the agency once the results are in, whether or not that could serve as one of two trials, or if we have to run two more trials, which would be incredibly pleased to do it as well with a drug that is so active. Thanks very much.
So I think we're going to be driving chinas clinically and statistically significant change and then have a discussion with the agency once the results are and whether or not that could serve as one of two trials audits. We have to run the <unk> drives which will be used to do it as well with our drug <unk>.
Select.
Thanks very much congratulations.
Thank you.
Ritu Baral: Congratulations. Thank you. Your next question is from Ritu Baral. Good afternoon, guys.
Your next question is from Red to borrow with Cowen. Please go ahead.
Marcio Souza: Thanks for taking the question. I want now that you've gotten last patient last visit in ARIA, I just wanted to check in on, you know, final, final conduct, data, data retention, etc. And can you tell us when last patient last visit is? And then further, given gabapam precedent showing deltas of two points in in sort of larger, Phase 2, Phase 3 trials. You've mentioned that you've powered this for a three-point difference.
Good afternoon, guys. Thanks for taking my question.
Now that.
You've gotten last patient last visit.
I just wanted to check in on.
Final.
Conduct.
Data data retention et cetera, and can you tell us when the last patient last visit is.
And then further just given.
Gaba Pam precedent showing delta of two points in <unk>.
Larger.
Phase II phase III trials.
Mentioned that you powered at.
At three point difference.
Marcio Souza: Is this mainly because you think that you've got better placebo contact, or do you think that this could be driven by just sheer differential efficacy? Thanks. Yeah, of course, I appreciate the question. So a couple of things here. One, we're.
Is this mainly because you think that you've got better placebo contract or do you think that this could.
Driven by just sheer differential efficacy.
Yes of course.
I appreciate the question so a couple of things here one.
Sure.
Marcio Souza: Wishful that the clinicaltrials.gov post will be up as we speak with you. You're going to see that hopefully in the next few hours or by tomorrow. But the last patient last visit was on May 5th, so last week. That is the safety visits, obviously those was before that, a few weeks before that. So that's really the last piece of data we needed to be completed. The patient showed up at the day it was supposed to and so we were able to complete the study by itself.
<unk>, that's the clinical trials about golf balls would be up as we speak with you if youre going to see that hopefully in the next few hours or by tomorrow, but the last patient last visit was on May 5th I saw last week.
That is the safety visits obviously those was before that a few weeks before that.
So thats really the last piece of data that we needed to be completed the patient showed up at the day was supposed to so we were able to complete the.
The study by itself now the next phase years, obviously cleaning up the data, making sure that we can lock the database in due time and then reports from our underlying assumptions perspective, as we mentioned in the video we're pretty happy with.
Marcio Souza: Now, the next phase here is obviously clean up all the data, making sure that we can lock the database in due time and then report. From an underlying assumptions perspective, as we mentioned in the video, we're pretty happy with all the assumptions that went in. Now, this is blinded.
All the assumptions that went 10 now this is blinded. So we haven't seen the unblinded data, yes of course, the database is not a lot.
Marcio Souza: We haven't seen the unblinded data yet. Of course, the database is not locked, but it gives us great confidence that from a conduct perspective, we are in conflict. Two aspects here.
Gives us great confidence that from a comp perspective.
We are in Great Britain.
Two aspects here.
Marcio Souza: Every time we run a controlled trial, both the drug and placebo have to behave as one expects. I think we're more confident than ever that placebo's gift behaves the way we expect it by everything we know, but that alone wouldn't give us the separation and the overall profile that we expect. Why are we so confident that drugs behave the same way?
Every time, we run.
Joel trial.
Both the drug and placebo.
He has one expect.
I think with more confidence than ever that placebos.
The way, we factored by by everything we know.
So that alone wouldn't give us the separation and the overall profile that we expect.
Why are we so often drug behave the same way.
Marcio Souza: To our knowledge, this is the only drug in development that has predictable exposure, which we give to the patient. We feel without food, we feel without a chips burger before bedtime, that they're gonna get the exposures that are necessary. That is fundamental right?
To our knowledge. This is the only drug in development that has predictable exposure once we give to the patient with or without food.
Without a cheeseburger before bed time.
To get exposures that are necessary.
That is fundamental.
Marcio Souza: There's no drug in the brain, no effects, and no carry over to the next stage. So the ability to dose the drug, what we've seen from a side effect profile and the conduct itself, being obsessed with conduct from day one, not changing the end point. We're sticking to the conduct, we're sticking with a few sites, being really adamant and a little bit OCD about how to conduct, gets us to this point that now we are just cleaning the data and we're going to have the results to discuss in due time. We'll have to talk about why you hate midnight cheeseburgers.
The brain or effects and no carryover to the next phase so the ability to dose the drug what we've seen from a side effect profile and the conduct itself.
SaaS with contracts from day, one not.
Not changing the endpoints.
Sticking to the conduct to sticking with.
Fuel side.
Being really either maintain a little bit about how to conduct yes.
So to this point now we are just cleaning the data and we're going to have the results to discuss in due time.
Marcio Souza: But thanks. Thanks for taking the question. I don't hate them.
We'll have to talk about why you hate midnight cheeseburgers, but thanks, thanks for taking the questions.
Douglas Tsao: But I'm also not depressed. Not every night. Your next question is from Douglas Tsao. Wayne Wright, please go ahead.
I don't hate them.
But I'm also not depressed.
But not every night.
Yes.
Yes.
Your next question is from Douglas Chao is.
H C. Wainwright. Please go ahead.
Operator: Hi, good afternoon. Thanks for taking the questions and congrats on the data. Maybe it'd be helpful to just walk through, the sort of implications, if you will, of changing the primary endpoint to efficacy. And also, if you could just remind us what some of the differences between Essential One and the 2A study are. Perfect, Doug.
Hi, good afternoon, Thanks for taking my questions and congrats on the data.
Maybe it'd be helpful to just walk through.
So the implications if you will of changing the primary endpoint to efficacy.
And also if you could just remind us what some of the differences between.
Our central one and two way steady are.
Bernardo Vina: I'm going to hand this over straight to Bernard so he can walk you through that. Yeah, so I think one of the previous questions, what do we learn? I think we, the reason we're, Changing it to an efficacy study is because we've learned what we need to know to conduct an efficacy study. And so those big questions are who's the right population and who can you measure a response when we talk about people with adequate baseline severity, do we understand the dose range? We do and we understand that we can titrate people up with good tolerability.
Perfect, Doug I'm going to hand over straight to Bernard So you kind of walk us through that.
Yes, so I think one of the previous questions what do we learn anything.
The reason were.
Changing it to a central onto an efficacy study because we've learned what we need to know to conduct an efficacy study.
And so those.
The big questions are who's the right population and who can you measure response, when we talk about people with adequate baseline severity do we understand the dose range.
We do and we understand that we can tell we can.
Titrate people up with good Tolerability, we have a clear efficacy signal.
Bernardo Vina: We have a clear efficacy signal, which I think is remarkably clear from both the open label and the randomized withdrawal, and we understand the endpoint. And so the implications are, you know, we understand how to put together an efficacy study now. And then I think it's a matter of discussion with the agency, like Marcio said, will this be served as one of the pivotal studies. But it has all the key ingredients and we'll come back with more specifics about what that amendment and redesign will look like, you know, within the footprint of what we already have going in the Essential 1 study.
I think it's remarkably clear from both the open label and the randomized withdrawal.
And we understand the endpoint and so the implications are.
<unk>.
Understand.
Put together an efficacy study now.
And then I think it's a matter of discussion with the agency like Marcio settle this served as one of the pivot.
Pivotal studies, but it has all the key ingredients and we will come back with more specifics about what that amendment and redesign will look like.
Within the footprint of what we already have going in the essential one study.
Okay.
Bernardo Vina: And just as a follow up, have you or do you plan to engage with the agency in terms of this switch, just to ensure that there are elements that you might need to make change to make sure that this sort of stat plan in particular is done appropriately so that it could function as a registrational study? Yes, Doug, the interesting thing is when we submitted the original proposal for the program rifle as a CDP to the agency, They specifically noticed what we would have to do in order to make Essential 1 registrational.
And just as a follow up.
Do you or do you plan to engage with the agency in terms of this switch just to ensure that there are elements that you might need to make to make sure that the sort of that plan. In particular is done appropriately so that it could function as a registrational study.
Yes, Doug.
Interesting thing is when we submitted the original proposal four for the program right at the CGP to the agency.
Specifically noted one would have to do.
In order to make essential one registrational.
Marcio Souza: We chose at that point in time not to, but we have a very good idea of what the criteria is, and we would be adhering to it 100%, as we always do, and then have a discussion with them. Now, if we deem necessary, The changes are more than simply like in terms of the size or the actual order of the endpoints. We obviously would reach out, make sure we have their buy-in before the SAP is finalized.
That's why I'm not sure.
But we have a very good idea of what's the criteria.
And we would be adhering to it 100% as we always do.
Then have a discussion right now it <unk> necessary.
The changes are more than simply like.
In terms of the size of <unk> larger off the endpoints.
Lastly, I'll reach out make sure we have there.
Before.
<unk> is finalized.
Operator: Okay, great. I'll hop back in the queue. Your next question is from Myles Minter with William. Yeah, you're going to hate me but back on essential one and the potential trial modifications here, are you looking at increasing the patient enrollment number and also on the STATS plan considering it's now going to be an efficacy trial, how are you going to adjust for multiplicity between the doses there? I only make mention of that because there's been some recent FDA interactions in the schizophrenia space where if not all doses are positive and it's not aligned with the STATS plan, it technically is not a positive trial.
Okay, Great I'll hop back in the queue.
Sure.
Your next question is from Myles Minter with William Blair. Please go ahead.
Yeah, you're going to hate me.
Back on essential one and the potential trial modifications here youre looking at increasing the patient enrollment number and also on the stats plan consider it's now going to pay an efficacy trial. How are you going to adjust the multiplicity between the doses that Mike mentioned that because there's been some.
FDA interactions in the schizophrenia space.
But if not all the doses are positive, but it's not a lot of as you start to plan that technically is not a positive trials what are your thoughts around that thank you.
Operator: So what are your thoughts all around that? Thank you. Miles, there are a number of ways to do it, as you well know, and this is still pretty much in flux right now. We do believe we have a very good understanding of which of those should be the most used, and we're going to hold that a little bit close to the vest right now. You're going to hear that soon.
Yes.
There are number of ways to do it right.
Well now.
So pretty much in flux right now we do believe we have a very good understanding of which those should be the both of us.
And we're going to hold that a little bit closer to the best right now.
I hear that soon.
Marcio Souza: So there are ways to prioritize one of those, if we choose to do that, and make the other ones a secondary, or even to combine exposures at a given dose, at a given time point. So we're exploring different ways. I completely agree, I think we all here completely agree with your statements.
So there are ways to prioritize those if we choose to do that.
The other ones are secondary.
<unk> already been through combined exposures at a given those at a given time points. So we're exploring different ways.
Completely agree I think we all hear competes regulatory statements whatever we do has to be.
Marcio Souza: Whatever you do has to be very clearly justified and spelled out in the new protocol, because we're going to have to submit an amendment, and subsequently on the Statistical Analysis Plan, and that's sent to the agency, wait for comments, and so on. We're in a very fortuitous period, because we're in May, we know all of this right now, we have plenty of time to consult with the agents while we continue to enroll and make the adjustments to essential one.
There is clearly justified and spelled out in the new protocol, because what I have just submit an amendment and subsequently on the statistical analysis plan and that's sent to the agency wait for comments and so on we're not very close to its peers.
Cause when made.
We know all of this right now.
Have plenty of time to consult with the agents why would continue if you will and make the adjustments to essential one but very very good points.
Marcio Souza: But very, very good point, as we are learning more about the time dependence of the effect, which kind of dose that would saturate the effect, I think this is going to be fairly straightforward, but we're not going to cross, we're not going to cut any corners, we're going to cross every T and dot every I towards the end of this study. Great. I'll hop back in the queue.
As we are learning more about the time dependence of the effects, which kind of goes that would saturate. The effect I think theres going to be pretty straight forward, but we're going to not going across we're not going to cut any corners, we're going to cross that Ritchie and thought that.
Towards the end of this debt.
Great I'll hop back in the queue. Thanks.
Sure.
Operator: Thanks. Once again, ladies and gentlemen, if you have a question, you may press star 1. Star 1, from Laura.
Once again, ladies and gentlemen, if you have a question you May press Star One now again star one on your telephone keypad.
Question is from Laura Chico with Wedbush. Please go ahead.
Laura Chico: Hey guys, sorry, just one quick follow up. I think Cache Runway actually changed from 2Q23 into 3Q23. I guess I just wanted to maybe take a step back. With a number of these studies still set to start in the second half of the year, I'm just trying to understand kind of what flexibility you might have in terms of prioritization of efforts, but also further extension of cash runway. Thanks very much. Sure, thanks, Laura, very much for the question. And overall, we're very conservative when we look at our cash runway.
Hey, guys, sorry, just one quick follow up I think cash runway actually changed from <unk> to 'twenty three into <unk> 'twenty three.
I guess I just wanted to maybe take a step back.
With a number of these studies still set to start in the second half of the year I'm just trying to understand kind of what flexibility you might have in terms of prioritization of efforts, but also no further extension cash runway thanks very much.
Sure. Thanks, Laura very much for the question overall, we're very conservative when we look at our cash runway.
Marcio Souza: And by that, we mean we plan for success with our studies. And so when we looked at things like, you know, our portfolio prioritization with the 562 Saksuna indication falling out with a little bit of a delay in our PD study with the way we're looking at 222 now, it created just a bit more space in our runway. So we moved now into Q3 of 23. Your next question is from Miles.
And by that we mean, we plan for success with our studies and so when we went to things like our portfolio prioritization with.
If I had <unk> indication following out.
With a little bit of a delay in our PD study with the way we're looking at Q2 to now it created just a bit more space in our runway so do we.
We move now into Q3 of 'twenty three.
Your next question is from Myles Minter with William Blair. Please go ahead Sir.
Myles Minter: Yeah, just on slide eight of the data released this afternoon, it does look as if when those patients come off drug that they pretty much cannot draw in a circle, but they kind of could at baseline. So I'm wondering what your theory is there, is there a dependency that's developing on 944? Or like, why would a patient that's come off drugs? not be able to draw that circle if they could at baseline.
Yes, just on Florida.
The data released this afternoon adult smokers quite nice patients come off jobs.
It's pretty much kind of drawing a circle.
On the pipeline side I'm wondering what your theory is that fair.
Dependency.
Our non Paul Farr will like why would a patient that's come off job.
Not being able to draw that couldnt stay cornered by fund and all that.
Bernardo Vina: And I know that that's just one patient. Did that happen for everyone who had a response to 944 on the trial? Thank.
Just one patient did not happen for everyone, who had a response to not fulfill on that Charles.
Operator: Thanks for the question, Miles. There's definitely, when you remove a drug in people with tremor, a drug that's working, there can be grief, you know, transient, kind of overshoot, worsening, really not a physiologic dependence. There's nothing like that.
Thanks for the question Mike.
Currently.
When you remove a drug in people with tremor drug that's working there can be brief trades in kind of overshoot worsening.
Not a physiologic dependence is nothing like that.
There are no signs of withdraw its just kind of the tremor rebounds.
Bernardo Vina: There are no signs of withdrawal. It's just kind of the tremor rebound. And so they see, like, that's a, you know, day 56, at day 70, they kind of go back to their baseline. So, no, it does not happen in everybody. It is not unique to this class, because you see it with other medications, including clinically, and it's transient. Thanks. Your next question is from Ritu Baral with. Hi, guys.
And so then you would see like Thats a date.
A 56%.
<unk> 70.
They kind of go back to their baseline so no it does not happen and everybody.
It is not unique to this class because you see it with other medications, including clinically.
And it's transient.
Thanks.
Beth.
Your next question is from Ritu <unk> with Cowen. Please go ahead.
Marcio Souza: So I think you mentioned that eight of the 11 patients, I believe, if I was reading this, reading my notes correctly, eight of 11 patients were able to complete the open label at full dose. Can you talk about why the I believe the three had to dose reduce? What were the symptoms that drove it and what dose they had to dose reduce to? Yeah, and maybe just a reminder here, right, Ritu, and I'll hand over to Leonardo on this. We allowed for those chains until day 36 on day 30, and after that, they had to be stable to enter into the randomizers throughout day 42.
Hi, guys.
You mentioned that.
Eight of the 11 patients I believe.
Thank you my notes correctly eight of 11 patients were able to.
Complete the open label.
Full dose can you talk about why.
I believe three have to dose reduce.
What are the symptoms that drove it.
They had to dose reduce too.
Yes, and maybe just a reminder, horizon, two and I'll hand over to Bernard as we allowed for those chains and through day 36.
They study and after that they had to be stable to enter into the randomized withdrawal of <unk> 42.
Marcio Souza: So that's one important phenomenon here. The second is, when you look into our PG curves versus concentration, which is the sigma bands, we tap out around 80 milligrams, between 80 and 100. We wanted to push to 120 to make sure you are safe and if other patients needed to go there. Now, we knew all along that some of them would, and some of them would not, so we're actually very pleased with the proportion of patients that were there. But I'll get Bernard to talk a little bit about the optionality here and what we've seen. Yeah. Yeah. So as you pointed out, Ritu, thanks for the question. It's really well-tolerated.
So that's one important panel in the next year. The second is when you're looking at your BD.
Carbs versus concentration, which is that Sigma bench, we step out of around 80 milligrams between 80 and one hundreds we wanted to push to 120 to make sure you all safe and other patients needed to go there now we knew all along that some of that was somewhat.
That would not actually very pleased with the.
The proportion of patients that were there but.
Bernard you talked a little bit about the optionality here and what you've seen.
So thanks.
Thanks for the question overall really well tolerated most of the people were able to get up to the highest dose there.
Bernardo Vina: Most of the people were able to get up to the highest dose there. The people who down titrated or just didn't titrate up, it was a range of kind of common AEs that you see with CNS drugs, dizziness, there was difficulty paying attention, focusing. For the most part, those AEs occur early.
The people who.
Down titrated or just didn't titrated up it was at a range of kind of.
Common aes that you see with CNS drugs.
Dizziness, there was difficulty paying attention and focusing.
But for the most part those aes occur early so people are going to have them.
Bernardo Vina: So if people are going to have them, they tend to have them early. And so once they're titrating up, they generally do fine. And so what we've done in Essential One, and we plan to continue this, is we've lowered the starting dose so that people can get just a bit of a smoother ramp, and we believe that that's going to happen. Got it. Thanks. Once again, if you have a question... Star One Now, do have follow-up. Star One Now.
They tend to have an early and so.
And once they are tight trading out.
Generally do fine and so what we've done in essential one and we plan to continue this as we've lowered the starting dose of their people and get just a bit of a smoother ramp.
And we believe that.
That's going to help.
Got it thanks.
Okay.
Once again, if you have a question. Please press star one now or if you had do have follow ups. Please press star one now.
Operator: Your next question is from Douglas Tsao. Hi, thanks for taking up the follow-ups. Just quickly, I mean, obviously, it's a small number of patients and the ADELE score improvements are really impressive. I'm just curious.
Your next question is from Douglas Tsao with H H.
H C. Wainwright. Please go ahead.
Hi, Thanks for taking up.
Just quickly.
I mean, obviously, it's a small number of patients and the ADL score improvements are are really impressive I'm just curious.
Douglas Tsao: If you have a sense of what proportion of the patients responded with sort of clinically meaningful responses and how much variability across the patient population was there in terms of improvements. Yeah, Doug, that is an incredibly important question and one that was one of the first things that we looked into this data when we got like the last few days. All right.
If you have a sense of what proportion of the patients responded.
What sort of clinically meaningful responses.
And how much variability across the patient population was there in terms of improvement. Thank you.
Yes.
That is an incredibly important question and one that was one of the first things that we looked into this data wouldn't go up like the last few days so.
Marcio Souza: So the vast majority of the patients responded on the AGL. And all the patients, once you remove the drug, loss of response. I think that's quite important because obviously they didn't know if they were on drug, right? So they... And this is a seven-day look back on their lives, on the things that they were able to do or not do.
The vast majority of the patients respond that's on the AGL.
And all the patients once you remove the drug loss response.
And I think that's quite important because obviously they didn't know they were on drug right. So.
And this is a seven day look back on their lives on the things that the way what you do or not do.
Marcio Souza: One of the interesting things about the future, when the FDA asked us to rescore the ADL, is that by removing the zero, right, in each one of those items, You make every other item clinically meaningful because now every change is from not being able to do something to being able to do something, or unfortunately, in some cases, after they removed the drug, they lost that ability. So what we're seeing is a very clear gaining functions back on their lives. And then when you remove the drug, progressively losing those funds.
One of these risks.
Think about the future when the FDA asked us to risk or the AGL.
By removing the zero right.
Each one of those items.
Every other item clinically meaningful.
Because now every change is from not being able to do something to be able to do something.
Unfortunately in some case here.
We want the drug to be lost that ability.
So what we're seeing is a very clear gain new functions back on their lives.
And then when you remove the drug progressively losing both functions.
Marcio Souza: The half-life of 944 is fairly, I would say, short, was by design that way, so we can get coverage during the day, but it's very clear it's necessary to continue dosing, otherwise it gets like a worse hit. So it's unequivocal in our view that any change on the ADL would be important, and that the vast majority of the patients got those changes. The ones that did not respond at all, which were a few, of the patients in this study, they really didn't respond throughout, which gives us confidence, one, if it was only open label, that there are responders and non-responders, but now we have the benefit of randomizing these patients, right? They wouldn't know, once more, if they end up on drug or placebo. There is no functional unbinding here, as Bernard just mentioned, that DAEs happen at the beginning of the treatments.
They have life of mine portfolio, it's fairly outpace shorts was by design that way. So we can get coverage during the day, but it's very clear it's necessary to continue dosing otherwise it gets like awards yet so.
Unequivocal in our view that's the any change on the AGL would be Barton and the vast majority of the patients got those change.
The ones that did not respond at all with where our field.
Of the patients in this study.
Really different response through outlets, which gives us confidence one.
Zandi open label that there are responders and non responders, but now we have the benefit of randomized into space right.
No once more if they end up on drug or placebo. There is no functional binding here is not just mentioned that.
This happened at the beginning of the treatments. So at the time. They go out to day 42, that's really not a lot going on in terms of adverse events. So they really do that now and then when you remove the drugs such as dramatic.
Marcio Souza: So at the time they got to day 42, there's really not a lot going on in terms of adverse events, so they really didn't know, and then when you remove the drug, such a dramatic change on the ADLs and not happening the same on the ones that keep on the drug, that just gives us confidence that now we just run to the next tier of the race to make sure we can get this drug to patients in the market. The next thing I'd like to add is about ADLs.
Change on the <unk>.
Not happening the same on the ones that keep on the drug that just gives us confidence that now we just runs to the to the natsios the race to make sure we can get patients in the markets.
Senator.
Adl's is alright.
Marcio Souza: Right, it's the adverse events, predominantly CNS, but the ADLs really integrate, any side effects you might have, along with the benefit on tremor, because how they're functioning with that. So to see that really marked upside improvement in function tells you a lot about the benefits. Thank you so much. Once again, if you have a question, please press star 1, from Myles. William Blair, [inaudible] Yeah, thanks.
Alright.
Adverse events predominantly CNS, but the ABL is really integrates any side effects you might have along with the benefit on tremor because of how they're functioning with that so.
See that really mark.
Upside improvement.
Function tells you a lot about the benefit risk.
Great. Thank you so much.
Once again, if you have a question. Please press star one now the next question is from Myles Minter with William Blair. Please go ahead.
Myles Minter: Last one from me. On slide six, are you disclosing, I guess, how many patients actually had a response to 944 and then got randomised to placebo or, for that matter, didn't respond and got randomised to placebo because theoretically, you know, those patients should be flat over the 56-day period with their tremor, right? So I'm just wondering how much they actually contributed to the data that we're seeing here. Thanks. Yes, so, Miles, the patients, there's no objective measure of response, right? But I'll give you a little bit of an idea of what happened here.
Yes, Thanks last one from me.
On slide six.
This quarter, you're seeing I guess, how many patients actually had a response to non pull forward and then got randomized to placebo or for that matter data respond.
Randomized to placebo because theoretically those patients should be flat over the 56 day period with <unk>. So I'm just wondering how much that actually contributed to the data that we're seeing here. Thanks.
Yes, so myles the patients Theres no Jack.
Measure of response, right, but I'll give you a little bit of an idea.
Marcio Souza: We had one more patient randomized, as you know, to one group than the others, since it was an odd number. The patients that were randomized to placebo had a numerically bigger response before. It should be obvious by the numbers.
What happened we had one more patients.
Ill randomize as you've now to one group that the others since a while but the patients that were randomized to placebo had numerically bigger response before is should it be office by the numbers, but just reinforcing that.
Marcio Souza: We're just reinforcing that. But the one interesting thing is every one of them returned to our baseline. So there was no super responder or loss of responder and others that stayed flat. While the ones that stayed on 9-4-4, they manifested more like the typical group that stayed on drugs, which made this incredibly clear that the drug wasn't still active, we're just seeing small variabilities here and there on the one with 9-4-4, but very large chains, virtually all of them moving back to baseline, or even overshooting a little bit, which is not uncommon with CMS active drugs, as you all know. Cool. Thanks for the collar and all of the questions. Appreciate it.
But the one interesting thing is.
Every one of them return towards baseline. So there was no super responder or loss of responder and others that stayed flat.
The one that is stable online in port <unk>.
Many facets more like the typical group that has failed drug which make this incredibly clear that that was the drop was two active we're just seeing small Barnett bill, let's say is here and there although one was $90 four but very large chains.
Virtually all of them moving back to baseline or even over shooting a little bit which is not uncommon with CNS active drugs as you all know.
Cool thanks for the color on all the questions appreciate it.
Operator: Once again, if you have a question... Star One, [inaudible] Star 1, Do you have a follow-up or additional question from... Hi guys, thanks again. So one last question, how is, or I guess any comments on screen failure rates or the screening protocol going into the Essential One study to help to understand to capture a homogenous population? So any color on that would be helpful.
Once again, if you have a question. Please press star one now.
Ken.
Star one on your telephone keypad.
You have a follow up or additional questions from me as well.
Do you mean with Piper Sandler. Please go ahead.
Hi, guys. Thanks again, so one last question Howard.
Or I guess any comments on screen failure rates or the screening protocol going into the essential one study.
To help to understand the capture of homogenous populations. So any color on that would be helpful. Thank you.
Operator: Thank you. Thanks for the question. Again, we haven't discussed that before, but it might be a good point to discuss how we do it. Just like ARIA, and you all heard myself, Bernard, Tim, the entire team here at Praxis reinforcing how strict our screening criteria is for MTG. It's not any different for Essential 1.
Thanks for the question again, we haven't discussed that before but it might be a good points to discuss how we do it right.
Just like ARIA and you also are myself Bernard Tam.
Our team here at Drax is reinforcing how restricts our screening criteria is for MTG, it's not any difference for a central one.
Marcio Souza: We have a central reviewer of severity. It has to be general concordance. Otherwise, the patients are excluded. We are seeing a number of patients getting excluded because they are not stable or they're not severe enough. I think we just saw here how important it is that we stay true to that measure. It's ramping up. I would say that it's not necessarily critical mass that I would start talking about exactly what the ratio is.
We have a central reviewer of severity.
Should be general concordance, otherwise the patients are excluded we are seeing a number of patients getting excluded because they are not stable or theyre not sit here now.
Just saw year, how important it is that we stay true to that measure.
It's ramping up I would say that is not necessarily critical mass.
With that I would start talking about exactly what the ratio is I think once we started talking about for outerwear. For example, we are like three quarters of the enrollments and gives us better confidence on the numbers, but it's not as small we are excluding a significant number of patients coming.
Marcio Souza: I think once we started talking about, for ARIA, for example, we are like three quarters of the enrollments and gives us better confidence on the numbers, but it's not small. We are excluding a significant number of patients from coming to trial because they cannot show that they are severe enough to participate, which gives us, great comforts actually that that's the right thing to do. We might now be able to provide other alternatives to this patient through like different mechanisms, but to be able to show this drug is efficacious, meets the regulatory statutory definition and get the drug approved, I think we have to stay the course. Enrollment though was going pretty well before.
The trial because they cannot show that there are severe enough to participate which gives us great comfort.
That is that's the right thing to do we might now be able to provide other alternatives to this patients through different mechanisms.
To be able to show this drug is efficacious.
The regulatory statutory.
Definitions and got the drug approved that you could have to stay the course enrollments, though while going through well before insurance is going to continue to grow even better now that we have the majority of the sites in the U S. Open recruiting patients screening that actively every week.
Marcio Souza: I'm sure it's going to continue to go even better now that we have the majority of the sites in the U.S. open, recruiting patients, screening them actively every week. Yes, I'd add that the way we do the reviews here, we do video, so it is paired with the history of their tremor. So it helps us confirm the diagnosis, which I think is very important because you can get, you wanna screen out the mimics, just like we've talked about in ARIA.
Yes, I would add the way we do that.
The reviews here than we do video.
It is paired with the history of their tremor. So it helps us to confirm the diagnosis.
I think is very important because you can get you want to screen out the mimics just like we've talked about and ARIA.
Marcio Souza: So you wanna get the correct diagnosis and we confirm severity. We've said that central review, you lose a little granularity in the amplitude, but you could still confirm that it, at or above 10 points upper limit.
Want to get the correct diagnosis and we confirm severity.
And we said that Central review you lose a little granularity in the amplitude, but you can still confirm that it's.
Above at or above 10 points upper limb.
Bernardo Vina: Great, thanks. Once again, if you have a question or a follow-up, please press star 1. Thar One, [inaudible] There are no, Follow-Ups. I'll now... Conference, back to Marcio. Video for a...
Great. Thank you.
Once again, if you have a question or a follow up please press star one now again star one on your telephone keypad.
Yeah.
Yes.
Okay.
No additional questions or follow ups.
I'll now hand, the conference back to Marcio Souza CEO for any final comments.
Marcio Souza: So, thank you so much and thanks for everyone for joining, for supporting us and all those patients throughout the journey here. A couple of points I wanted to make just to close. We promised to deliver those results in May. Here we are. We delivered, we promised to deliver the results for ARA in June, and that we're going to be delivering those results and then four more results after that. All of this taking very good care for the shareholders, all the other stakeholders, and for the cash we have in hands.
So thank you so much and thanks for everyone for joining for supporting Us and all of those patients up for all the journey here.
Couple of points, we wanted to make just to close.
We promise to deliver those results in May.
So we are.
We deliver we promise to deliver the results for our in June and that we're going to be delivering those results and then four more rebalanced after that.
All of this taking very good care for the shareholders.
All the other stakeholders and for the cash we have in hand, so can deliver those drugs to more and more patients. So we haven't changed anything in terms of just how disciplined we are on the use of capital use of resource being serious and clear with the science.
Marcio Souza: So, we can deliver those drugs to more and more patients. So we haven't changed anything in terms of just how disciplined we are on the use of capital, use of resource, being serious and clear with the science. The science today is speaking volumes for us to continue 944, and we will, but if it was not the case, we would be serious as well about not continuing, and we believe strongly here at Praxis to stay to our pillars. Every Drug Screened for Genetics.
Science today speaking volumes for us to continue $90 floor and we will.
But if it was not the case, we will be series as well about not contiguous and we believe strongly here at practices III stage while dealers.
Every drug screen for genetics.
Operator: Very good translational data, and I want to remind everyone, we have beautiful translational data for 944 that was presented at AM last month. Here we are, translational data, giving clinical data to these patients. We have beautiful translational data for 114, and we're all excited to be sharing that soon as well, and many more drugs to come in the future. So thank again for all the patients that participated in the trial, for our investigators, and for all the practitioners that worked day and night to get to this moment, and talk to you all soon. Koshini Naru, [inaudible] Kambiz Pashneh. Thanks for watching
The translational data I want to remind everyone. We have beautiful translational data for $9 four that was presented at AAN last month.
Our translational data, giving clinical data onto these patients have beautiful translational data for one of our four.
And we're all excited to be sharing that soon as well and many more drugs to come in the future. So thank you again for all the patients that participate in the trial for our investigators.
For all the Frac since they're worth DNI to get to this moment.
Talk to you all soon.
This concludes today's question and answer session.
Thank you for participating you may now disconnect have a great day.
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