Q4 2020 Aptinyx Inc Earnings Call
[music].
Okay.
Good afternoon, and welcome to the App. The next fourth quarter and year end 2020 financial results Conference call. At this time, all participants are in a listen only mode.
On the formal remarks, we will open up the call for your questions. We used the advice that the call is being recorded at the company's request.
At this time I would like to turn the call over to Nick Smith, Vice President of corporate development and Investor Relations of Actinic. Nick. Please proceed.
Good afternoon, everyone and thank you for joining us on today's call to discuss after Nick says fourth quarter and year end 2020 of financial and operating results. Our press release, describing the financial results and business highlights is now available on our website.
Additionally for the Q&A portion of the call were joined by Andy Kidd, Our President and Chief Operating Officer, Catherine King Senior Vice President of clinical development.
Merck Vice president of medical and Pharmacovigilance I'd.
I'd like to remind everyone that statements made during this conference call will include forward looking statements within the meaning of the private Securities Litigation Reform Act of 1995, which involve risks and uncertainties that can cause actual results to differ materially any forward looking statements are made only as of today and we disclaim any obligation to update these forward looking statements.
Please see the forward looking statements disclaimer in our financial results release issued this afternoon.
And the risk factors in the company's current and subsequent filings with the SEC.
My pleasure to turn the call over to Norbert.
Thank you Nick and good afternoon, everyone.
We appreciate you taking the time to join us on today's call.
We are excited to talk with you today.
Hello rewards, what's the productive well.
It's challenging the faucet up to me.
Despite the global COVID-19 pandemic.
Our team remains focused on the responsible of decision, making and firstly to execution.
And as a result, the <unk>.
Past year has been marked by several important achievements.
In advancing our development program.
Among the key highlights of the year, what's the data from all of Phase two exploratory study of NY at 783, Inc.
Post traumatic stress disorder.
Which we reported in October.
We are truly encouraged by the early results presented by acts of an eight three.
Particularly at the time when mental health is at the forefront due to the trauma isolation and loss being experienced by so many.
Our phase <unk> studies of <unk> hundred 92, five in chronic pain.
We assumed late last year and the early metrics of execution and enrollment.
Very positive.
Our clinical development efforts within Y X four of five eight in cognitive impairment presented even greater challenges due to the pandemic.
Given the vulnerability of this patient population however.
However, we will be the commencing the study in the coming days.
And we will then again be enrolling patients in each of the phase III studies.
We had suspended last year.
We are keenly focused on executing the studies in a safe juvenile and efficient manner to complete them expeditiously.
With particular attention to the quality of the data coming out of each study.
This execution related the foundation for four phase III study Readouts.
Our novel NMDA receptor modulators, beginning in the first half of 2022.
All of this important work perseverance and attention to detail is the old.
On the possible with the dedicated and resilient team.
I am very proud of the team members, we have adapted Inc.
All of whom are very passionate about our mission to improve the lives of patients who are suffering from challenging CNS conditions.
We have a strong cash position with over $140 million at year end.
Which we expect to fund our operations through multiple phase III study readout.
And into 2023.
Let's just kind of each of our development programs, starting with <unk> hundred 92 five.
Our clinical stage development candidates under evaluation and true centralized chronic pain conditions.
Fibromyalgia and painful diabetic peripheral neuropathy or <unk>.
Following the call at the moment in both the fibromyalgia https studies.
Due to the escalation of the COVID-19 pandemic last March.
We re initiated both of them towards the end of last year.
While we havent calculated certain targeted protocol modifications to facilitate duo duo study execution and ensure the safety of patients and study personnel against the backdrop of COVID-19.
The key elements of the phase III study design have not changed.
In fibromyalgia.
The evaluating the effects of daily dosing of 50 milligrams.
And 100 milligrams of <unk> hundred 95 against placebo.
In the 12 week study.
We expect to enroll approximately 300 patients in this study.
And VPN.
We are evaluating the effect of 50 milligrams of <unk> hundred 95 against placebo.
Also all by itself week treatment period.
In this study we expect to enroll approximately 200 patients with advanced GPS.
The primary end point for both studies.
The change from baseline on the average daily pain score.
By the receivable to 10 point numeric waging scale.
So far we are pleased that enrollment in both studies has been tracking in line with our expectations.
Based on the steady execution and the enrollment progress we.
We anticipate reading out data from each of these chronic pain studies in the first half.
Of 2022.
Let's move now to <unk> 783.
Which is in development for the treatment of post traumatic stress disorder.
In October we announced positive results from our phase two exploratory study in patients with PTSD.
In the study.
And why of 780, <unk> demonstrated clinically meaningful effects on multiple efficacy endpoints.
After four weeks of treatment.
Importantly.
The sickness, we observed were very consistent with our understanding of the mechanism of NOI of 73.
The study of evaluating two doses of the NOI of seven to eight three against placebo.
153 patients over four weeks.
The effects of of Miss on the caps five.
You say holistic evaluation of the range of symptoms.
Experienced by people with PTSD.
At this point on the exploratory study and the first time in my 783, what's the value that in patients with PTSD.
We are focused primarily.
On evaluating Panorama tests, they put inform our design of future <unk>.
Well powered studies.
Including the safety and Tolerability profile.
And particularly to reach NOI of 780, <unk> exhibited efficacy of sickness across an array of endpoints.
We are encouraged by the data we obtained from the study.
And belief that NOI of 708 has the potential to become a new therapeutic option.
On an indication that has not had the new target moved in over 20 years.
As we look ahead to future clinical development we.
We will build on the following key observations from this first study.
On the caps five total score.
We saw a clinically meaningful improvement from baseline with the 50 milligram dose.
Importantly, looking at responder rates.
Significantly greater proportion of patients receiving 50 milligrams at.
We achieved a clinically meaningful improvement on the <unk> total score.
Two of the placebo group.
These observed effects on the cash totaled <unk> five total score.
We're driven by consistent and robust improvements from baseline.
Of course, three of its force symptom clusters of course.
<unk> 73 exhibited a very favorable safety profile.
With no talks related serious adverse events.
And as the overall adverse event profile.
This was in line with placebo.
We also learned about certain patient characteristics the day.
Ph to influence the overall was pumps to NY exterminate the please.
Which we will incorporate into the design of the next study.
These promising signals.
Which we have seen with four weeks of treatment of.
<unk> us with confidence to move forward in this indication.
We are pleased that these data have been accepted for presentation at the upcoming society of biological Psychiatry annual meeting.
Cash flow to take place virtually.
April of 2009.
Well may 1st.
In addition, we have been granted the type C meeting with the FDA on April 29.
To discuss the design of the next study.
The path to an NDA in PTSD.
While the specific study design details have not been finalized.
We expect the next study to be of Phase <unk> study.
There's legislation support of design.
Focused on the caps five total score.
Consistent with other pivotal studies in PTSD.
We plan to commence the study in the second half of this year Andrew.
And we will provide more details at the appropriate time.
I am pleased with our progress with NY of seven to eight three and maybe most importantly.
The data from this phase II study now provides a third clinical validation.
Of the activity of the novel NMDA receptor modulators on our platform.
Of course, two chronic pain studies and this PTSD study.
We have seen the conference from of our platform show improvements on validated clinical endpoints.
Giving us the solid foundation to confirm the sickness in the larger.
More conclusive clinical study.
Let's now discuss relevant updates on.
On the NYSE four of five eight which is in development for the treatment of cognitive impairment.
Moving to the suspension of our Phase Iia study last March.
I am pleased to report the peer now just days away from the link commencing patient screening in this study.
We have incorporated several of the targeted protocol changes designed.
Designed to simplify study execution.
And to optimize our chances for detecting signals of efficacy.
While of course, ensuring the safety of patients and study personnel.
This phase II study is a randomized.
Total blind placebo controlled study.
To evaluate the safety and potential cognitive benefits of antibody X four of five eight and approximately 100 patients.
Because when we initially started the study we were enrolling patients with mild cognitive impairment in Parkinson's disease.
We are now expanding this patient population.
You also include mild dementia, and Parkinson's disease, and dementia with Lewy bodies.
It is recognized that these diagnosis.
Represented continue with the same health plus nuclear unrelated pathophysiology.
Which we believe <unk> four of 5% to eight is well suited to address.
In particular.
Nuclear and buildup has been implicated as a causal factor for cognitive impairment and.
Further it has been demonstrated the increases in alpha side nuclear in the levels resulted in decreased NMDA receptor expression and activity.
We therefore believe the enhancement of NMDA receptor activity within <unk> four of five eight.
Has the potential to address this cognitive impairment.
The study will involve two treatment arms.
Daily dosing of either 30 milligrams of <unk> four of five eight of placebo.
And we'll evaluate the safety.
Tolerability and cognitive effects on patients over a 12 week period.
This is our first study of a new mechanism in patients with cognitive impairment.
And it is critical for us to explore multiple cognitive endpoints.
Characterize the activity of antibiotics for price mix.
Accordingly.
We will leverage multiple computer of ice neurocognitive assessments to evaluate the effects of course, the key cognitive domains.
<unk> in this patient population.
Following significant progress over the last few months.
We are pleased to be hosting a virtual investigator meeting March 26th.
And we'll then begin screening and enrolling patients.
We have received good initial feedback from clinical study sites.
On the changes we are incorporating and anticipate the.
<unk> data from the study in the second half of 2022.
To summarize I'm immensely Paul.
Of the way our team has navigated the challenges of the past year.
The data we read out in 2020.
Combined with the tremendous work to get our preclinical studies pick up and running.
Have enabled us to advance our development efforts across each of our programs.
With that I would.
I'll now hand, the call over to Ashish to discuss of our full year 2020, and fourth quarter financial results.
Thank you Norbert.
Beginning with the balance sheet, we ended the fourth quarter, where the $141 million in cash on cash equivalents compared to $98 $8 million at the end of 2009.
To reiterate Norbert earlier remarks.
We expect our current cash to fund our operations into 2023 and support achieving multiple important clinical milestones.
With respect to our income statement, our revenues have historically been related to our research collaboration with Allergan now of subsidiary of Abbvie.
The jointly funded activities under this research collaboration came to their contractual conclusion in August of 2020.
So as expected.
We had zero revenues in the fourth quarter of 2020 as compared to $1 million from the fourth quarter of 2019.
Importantly, we are not reliant on these revenues to fund our operations.
The majority of our spend remains heavily concentrated in research and development on.
R&D expenses totaled $6 $8 million and $32 $8 million from the fourth quarter and full year 2020, respectively.
As compared to $10 6 million and $44 $3 million from the same periods in 2019.
The decrease in R&D expenses in 2020.
Was primarily the result of the temporary pauses to patient enrollment across three of our four of phase II studies.
As well as the conclusion of the phase II study on PTSD.
We expect R&D spend to increase throughout the year with all three studies back up and running.
We reported G&A expenses of $4 8 million and $19 5 million for the fourth quarter and full year of 2020, respectively.
As compared to $4 $5 million and $19 million from the same periods in 2019.
Finally, we reported a net loss of $11 $5 million and $50 1 million for the fourth quarter and full year of 2020, respectively as compared to a net loss of $13 8 million.
$57 $4 million from the same periods in 2019.
I will now turn the call back over to Norbert.
Thank you Ashish.
Yes, we advanced our development candidates of course chronic pain PTA.
PTSD and cognitive impairment.
Look forward to multiple potentially catalytic milestones beginning of the first half of next year.
Turning to page to 2021.
We are pleased to be well positioned both financially.
And of course, our clinical operations to continue moving on our pipeline of novel.
<unk> NMDA receptor modulators of forwards.
We will be happy to begin taking your questions now.
Yes.
At this time I would like to remind everyone in order to ask the question Press Star then the number one on your telephone keypad again that historic then the number one on your telephone keypad, we'll pause for just a moment to compile the Q&A roster.
We have our first question coming from the line of Ritu <unk> with Cowen Your line is open.
Okay.
Good afternoon, guys. Thanks for taking the question.
I guess my focus here is on the April 2009.
For the three.
Sweet.
You mentioned that obviously the primary endpoint is TBD, but could you talk about what other questions you'll likely be ASCII FBA at that meeting what are the other main topics of discussion around that trial design with the thank you.
The secondary endpoints.
Severity on inclusion criteria of patients.
On the safety database that you would need before.
That would contribute to the pivotal.
Yes.
Yes, so the two eyes.
The dolphins and he can maybe chime in here.
So of course low debt, we have completed the PTSD study of it has already given us relatively good guidance.
Two of the patient population the heck out whats the nature of the patient population.
Well, it's a signal finding each pillar of choice study, but it informs the next study and the key questions exited the key points I should say.
Really our thinking about just the design of debt next study and the development path as I mentioned true with an NDA filing.
Includes for example questions related to duration of therapy.
Integration of daily treatment I should say.
And questions of that nature of that really has to do with the goal of SB eight studies that can serve in a registration supportive manner.
And that's what the discussions with FDA, the mainly percentile of all.
Yes.
Yes, I think the only thing I'd add is really although the output of the discussion will inform the next study.
Norbert alluded to our key goal on the meeting is to try to have a better understanding of what the requirements are to reach an NDA in PTSD. There isn't the published guidance on on that and so therefore, we wanted to have the discussion at the stage so on.
The next study can be.
Basically is.
As close as possible and serve as registration supportive and lay the foundation for the rest of the development program.
I understand everything that's needed. So as you would expect most of the major study design elements.
We would need to understand some of them are <unk>.
More open question on others. Some of them are more of just looking for a kind of a confirmation.
But that's really the goal is to set the next step up in the context of what it takes to achieve an MBA.
Got it and just a quick follow up on on 29 25 of.
Your.
Enrollment has been proceeding has the geographical distribution of enrollment varied from your.
Initial expectations just given the.
The COVID-19 shutdowns in reopening in waves of cross.
The cross sell.
The world right now.
Great I'm going to have cash flow.
The question for you.
Yeah. Thanks, our sites are in the U S.
So we're seeing pretty much according to plan enrollment across our U S centers I think we see from time to time and impact of Covid on the center.
But in general with a couple of weeks of.
<unk>, perhaps some substitute staff.
The <unk> function pretty well at this time, so we're working according to plan across all of our centers here on the U S.
Yeah.
Great. Thanks for taking the questions.
Thank you.
We have our next question coming from the line of Marc Goodman.
BB real low.
Your line is open.
Hi, Thanks for taking my question. So this is Rudy on the line for Mark.
Two questions first is regarding the phase Iia study of <unk>.
The 458, so given that you're enrolling roughly of 100 patients in total of just wondering how many of them will be <unk> patients and the study work you plan to the brown label to treat cognitive impairments across neuro degenerative disorders in future studies.
And secondly can you provide more color on the R&D expenses in 2021.
You have four phase II study up running by year end.
Give us a sense about the cash burn.
Great great questions. So let's tackle the first one regarding the <unk>.
Inclusion of Lewy body of disease as you pointed out and I can confirm the goal here is to save the cost is a very common underlying pathophysiology, which.
A key focus on alpha of nuclear and how is that in past NMDA receptor activity on Nick's question.
We think it makes sense to expand to basically be more inclusive of patients that have debt hallmark of alpha nucleon abnormalities.
At this point.
I think yes.
Pointed out we are looking at 100 and how the patients I think it is not exactly clear to answer today.
The executives at distribution the will actually fall between Hawkins in Lewy body dementia, but.
I would assume we would look for a relatively even distribution between the two.
Yes, I think it's Andy here I think according to the numbers of patients that are out there.
There will be a good spread I think across the three there are slightly fewer patients in the dementia with lewy bodies category as compared with the.
The Parkinson's disease population.
But I think there's certainly enough in all three groups that we would expect to get a good a good distribution and with respect to your question on broad label. I think this is an exploratory study. So it's a little premature to talk about label, but I do think thats indicates as Norbert mentioned in the main remarks, we believe that our merch.
Kind of it can work across the entire continuum.
And we felt that it was the right decision to include all of the potential patients.
The sort of of Lewy body of Parkinson's grouping at the stage.
Let's pause there and see if the answer to your question before I ask Ashish to address the the R&D budget that you would have the as the second Chris.
Okay.
So as I mentioned earlier on the call.
R&D expenses in the last quarter of 2020, we're just shy of $7 million we would.
Expect.
We expect that to the increase in.
In the coming year in 2021, as we are Recommencing have recommenced. The two pain studies will be recommencing. The study in patients with cognitive impairment.
See it increase further later this year as we startup and initiate screening and enrollment.
And the way that we anticipate the due with the next study in PTSD.
Typically give quarter by quarter guidance. It is lumpy as well half of these are these initiations, but surely we'll see.
And overall cash burn and R&D expenses.
In general of the guidance we gave.
Remains that the.
Our cash burn expectations in.
And our current balance sheet.
And cash runway that extends into 2023.
Got it.
That's very helpful.
Thank you.
We have our next question coming from the line of Chris Raymond with Piper Sandler Your line is open.
Thanks, Hey, Norbert I was kind of intrigued by your prepared comments.
73.
And may be seeing.
A prospective characteristic of patients that could respond better.
PTSD I Wonder I'm, assuming maybe this is something that I want to save for when the full data presented at <unk>, but.
Can you give us some of them.
The more color on what you're talking about there and is there.
On opportunity for sort of.
The prospective identification of those patients.
So.
Thanks for the question I will have to activity.
Have you wait on can we have had our presentation and disclosure. After the addition of information at the society of biological Psychiatry meeting.
Despite the of criteria in bi alloy stick before the top 123 and information that comes out of meeting. So maybe if you have another discussion after that and follow up with you.
Got it okay.
Just just to highlight what we're talking about I think it is things that can be implemented on the clinical development stage.
To have the right population on the clinical trial I don't think we're talking about anything that would be one of label implications would reduce the size of the eligible patient population are kind of require any kind of.
Prior testing its more just ways to refine the clinical developments of criteria.
Got it okay, Okay, and then just.
Maybe a follow up on 458 so.
Just wonder if you could give a little bit more detail I know you focused on the 30 milligram dose but.
And for simplification.
Was there something that you saw.
So on the 10 on the 100 that led to this decision or is this just.
Again, just the.
The decision that was made otherwise.
Yeah, Great question. So the reason that we actually upped it for the one dose is.
We have now actually done heavily clinical studies as you know in fibromyalgia and VPN in PTSD.
And because we do a very very small characterization of the pharmacokinetics and pharmacodynamics of our compounds.
Both at the preclinical level of behavior of the module ASP.
Well as in phase one in healthy volunteers, maybe mezz.
Yes.
Level itself compound as a surrogate for brain exposure and then the actual data from the patient studies.
We have a very good understanding I believe asked too rich.
Is the does that sort of gradually pick up the signal.
Instead of making this early exploratory study fundamentally a dose ranging study, which is not intended to be tended to be of signal finding study.
It's just more efficient to actually do it in debt sequence, we pick the dose that we predict and I think can reliably predict to be efficacious.
To define the dose it's all of it.
Do you find these days.
And make sure the compound is behaving the way we wanted to and then we look for dose ranging in subsequent studies day. After I think the is serving us well.
That is actually now that is actually why we are making the modification in the way out to go from.
Key active arms.
It also.
The benefits tip of.
Can the two studies have a low.
It'll be less revenue than on the ability and more.
More of I think accuracy and the data overall, so it comes through sort of added benefit but the fundamentals I should know this will be out on the claim for you it's not dose ranging of superfund.
Great.
Thank you.
Yep.
We have our next question coming from the line of Joon Lee with true Security. Your line is open.
Hi, Thanks for taking our questions. Thanks for the update.
So it appears that you'll be pursuing caps five total score azure endpoint of the upcoming phase two b trial.
I was on the impression that the more the.
The hope that the potential for sub score.
Or.
The responder analysis, where you had a much stronger effect with the sort of in play as well. So is that totally out of the question is that something that you will.
That's my first question on the second question is what about 548 makes it better suited for cognizant of impairment due to Parkinson's Lewy body.
As opposed to the Alzheimer's because based on some of the data coming out of your competitors.
And the only seems to have a very strong signal in the Alabama, especially agitation. So I was just curious about your strategy for Parkinson's and move the needle.
In the case, thank you Yep Yep, great. Thank you.
So look on the PTSD study SB keep pointing out kept five total is comprised of four sub scores.
And when the reported the data in October we paid particular attention to the fact that the rate activity in the core.
<unk> achieved statistical significance. Despite the fact that it was a small.
Four week study only.
But it's very clear from the study is also of that kept the highest total cash.
Give us a very clear separation between active and placebo.
<unk> trended exactly where it needs to trade for it to be.
Really suitable.
I did not mean to imply then that we would rely on those alternatives to feel that we were confident in conducting the next study.
So because of the guideline to day sets PTSD studies showed you was kept five of the total score and because of <unk>. Five is comprised of four sub scores three of which gave us a very clear strong result in the study.
Perfectly comfortable using kept fibers of the timeline.
On your second question why not 45 day.
Disease.
This type of Covid.
Have been re basically created app to Nick.
By selling no extra al again in 2015.
We did not we obtained the rights to Alzheimers disease as an indication.
Ms disease some of those.
The latest dementia is not accessible to us however, all other forms of cognitive impairment and dementia.
And we feel the Parkinson's disease is therefore, a very logical.
And of course, we have the biologic linked at the pointed out, namely that the particular correlation between the alpha side nuclear in the NMDA receptor activity.
A very appealing mechanism to us because of <unk> five basis everything clean.
Positive allosteric modulator of NMDA receptor with no off target binding.
Causing synaptic plasticity.
Enhancing cognition learning and memory in all of our models and so it just makes perfect sense of what's to say thats photography of true.
Got it one quick follow up if I could so regarding the first question on the cap side. So the.
And the data presentation at the rupee the.
The fair to assume that it will be related to the new data will be.
Could be low.
Related to how you would enrich for the responders in Europe.
Correct.
Maybe we can look forward to it.
Yes, possibly.
In the script and the hit from the remarks.
Mark we have not yet nail to go on.
All of the details of that study, but of course, whatever whatever you think is biologically relevant and helpful.
Looking at this patient population.
We should be considering to use to throw the stratified primarily for the purpose of making sure that the therapies is targeted as current as it can be.
Clearly with all of it with all of its one thing to call. It out in the past will be basically end up in some niche indications.
The.
With all of the category of PTSD is our target category.
Okay.
Thank you.
We have our next question coming from the line of Gary Nachman with BMO capital markets. Your line is open.
Sure.
Hi, guys.
Stay tuned on two sides Youre looking at the same primary from both fiber and EPS on the change in NRI. So how important will the secondary endpoints be to better inform you on efficacy in the different patient populations. What are the key secondary endpoints, just remind us that and also remind us why the 100 milligram dosing phibro, but not in <unk>.
P M.
The first we have five questions that you ask Gary on.
The answer.
Anyway.
So look I'll start with the last one yw studying 50, and 100 and fiber mileage and the only 50 and TPN debt.
Has to do with having studied 10 50 and 200 in our first 300 patients EPS study.
And from that study will be concluded that the 50 milligram dose was by far the right dose.
Debt again goes back to having being able to predict debt from our preclinical work on from the phase one data in which we also did.
Engagement studies in phase one.
So that's the reason why we actually wanted to expand in pebble mouse it because of the <unk> study.
That gave us Fabulous confirmatory biomarker and patient reported results for end buy X 295 by its very nature of being a <unk> study in spectroscopy study it has to be small at only was about 23 patients.
We wanted to make sure that in this next study we range it a bit harder with the 50 of the 100 milligram dose net build.
By the way also if necessary the further inform the TPN study.
Total debt to the reasons why we opted to do a 50 and $101 50 on the other.
No I can't remember what else you asked early on.
So on the.
Secondary endpoints given that the primary is the same in both and I guess, let me just jump in the bigger question. If ultimately you look at having just a broad chronic pain indication.
You have these two different studies in different patient populations, just wanted to get comfortable how youre going to be able to merge that potentially into a broader chronic pain indication.
Yeah. So.
And this is kind of the answer that for you, but just quickly the primary endpoint as you just mentioned sort.
Of course daily pain as it is reported by patients.
And then the secondary endpoints in particular couple of marriage I have to do with what is the hallmark of fibromyalgia captured in the problem as a questionnaire in the.
<unk> scores very much aligned with our earlier studies and I'm glad you asked the question because it gives me the opportunity to reiterate that we don't rely in either of the fibromyalgia on the VPN study on.
On just one end point keeping up the positive squeeze on every measure we have taken in these patient populations.
Has to do with the symptomatology and pain issues that patients have have given us very clear positive results in both of these studies and of course debt is a really good starting point and these confirmatory studies.
And now I'm going to ask Andrew to address the broader question of indication in label, absolutely moving to call the pain.
Yes, Thanks, Gary.
There was the prior guidance that FDA had.
Draft guidance for the FDA published on them and then they withdrew it.
And in that guidance there was.
<unk> laid out for Hyatt to achieve different label language and chronic pain.
And the central or peripheral neuropathic pain, musculoskeletal pain, and so on and there was sort of of Formula you can follow up for how many studies that have any indications to get what the breadth of label.
We don't.
No exactly what the requirements would be right now because we know that one of the purposes of reconsidering the guidance.
Was to try to.
We think make it more straightforward to bring.
The safe well tolerated non opioid pain.
Pain therapies to patients and so I think that's something we'd be very keen to discuss with the agency at the end of phase II meeting obviously.
Obviously like you said, we have these two indications VPN, obviously in Europe Pathic pain fibromyalgia has been classified by FDA not as neuropathic pain is a lots of different pain condition.
And so and as you know we're interested in all kinds of other pain conditions neuropathic pain on musculoskeletal and other so we'd be very interested to see how that would work.
It's interesting I think the deep VPN probably.
Of course, it's part of diabetes, but the VPN.
Condition is more clearly characterized by pain and so we have other endpoints as Norbert mentioned to look at worst pain pain on walking as well as the primary endpoint of average daily pain, but fibromyalgia any of the broader condition and I do think that's an interesting question over how important some of those other endpoints as Norbert mentioned the <unk> the revised <unk>.
Our instrument.
And some of the promise of scale in areas like fatigue, and so forth. So we do look at fiber of little bit maybe more broadly from the perspective of the secondary endpoints and kind of interested to see how those could be positioned from a regulatory point of view and then what's the space on the broader label that's something we're very.
Key into.
<unk> at the end of phase two.
Okay, Great and then just one on 783 I know you don't want to preempt the FDA meeting but.
Do you think that Youll just need one pivotal study or you would likely need of second pivotal study in any scenario I just wanted to see is it possible that maybe you could have this one next study and that would be sufficient to file if you think thats a possibility.
Kevin I think that's actually really spec speculation at this point right because so much of any discussion of along those lines one of the hidden.
The guidance part of the results of the study.
And so I.
Think of them much more comfortable saying that's two of the study.
See what the results show and then perhaps engage with the agency at the time and understand to what extent that is sufficient or insufficient on the past two of the NDA I think it's just too soon at this point.
Okay.
Not ruling it out I mean, it is possible I guess also given the PTSD maybe its more at the forefront.
You said earlier.
Yes, I wouldn't I wouldn't rule anything out of at this point, but I think it clearly since we are aiming for.
All of the chronic administration here this is the.
Unlike some other psychiatric conditions that are more episodic PTSD is pretty much a consistent chronic.
Disorder.
And as such they are likely to be requirements for a numbers of exposures needed for certain durations of time from a safety point of view to get through on NDA, but.
Everything is always at the it depends on the perspective of the urgency of the unmet need as well of course.
We have our next question coming from the line of Charleston, with Cantor Fitzgerald. Your line is open.
Okay. Thank you for taking my question Norbert and team.
Great questions asked already all trying to pull the few others out.
Quickly on 783, I'm not sure if I caught what the duration of treatment for this next study could be and the and I know that you haven't yet met with the agency, but can you give us some range on those two considerations in terms of the time.
Non lines for 783 study.
Yes.
Yes Charles.
We're currently considering a range of eight to 12 weeks right now.
And we.
We will see where that we'll see where that comes out.
And the sample size.
Approximately what yes, I think sample size to give you a rough guidance I think it will be at least in line with our chronic pain studies, if not slightly larger I think.
We certainly want to make sure that it's well powered.
Charles I was still there.
I think we lost a chunk of it.
Charles.
Okay, great you're still debt.
Yes. This one is still open.
Okay.
Thank you.
So are you.
So I am asking.
The other question from you before we proceed.
Okay.
Yeah.
Again, if you wanted to ask the question Press Star one on your telephone.
Our next question coming from the line of Laura Chico with Wedbush Securities. Your line is open.
Hey, Thanks, guys for squeezing me on I appreciate it I just have a couple of on 783. So obviously you have the FDA meeting coming up the <unk> I'm wondering if you could just take a step back perhaps.
I wanted to kind of revisit response rates in the context of perhaps zoloft impactful.
Both studies.
<unk> response rates between the four and 12 in the.
I'm trying to understand how that might impact your thinking on the phase two b design related to that.
How are you also thinking about adding in the second to that study.
The kind of policy, we should be thinking about that there and then I have one follow up question for you.
So, yes, Laura I think.
Definitely its our assumption that response rate and magnitude of effect will increase over time.
Probably not indefinitely, but we definitely think it will increase over time and so that's part of our thinking and the answer to the previous question on the eight to 12 week range that we're considering on the.
There's obviously some other factors.
<unk> trade off against that in particular with the PTSD, whereas as you know from the last study and we this has been seen across the PTSD studies, it's at the higher end of the spectrum for a patient discontinuation rates.
Compared to some other indications and so the.
That's a little bit of something you just have the tradeoff as you look at even longer durations. So.
So we think that in that eight to 12 week range is probably the sweet spot.
Yes, well, we'll will obviously come to a decision on that.
With respect to a second dose.
I think Thats also something that we're still kind of thinking through we would be.
Already comfortable I think moving ahead with just the 50 milligram dose.
And we'll again be updating later on as to whether we stick with just the 50 milligram dose or have a second dose as well I think likely if we did of a second dose it would be higher than 50 milligrams.
Well.
Obviously be working through that.
Okay. That's helpful. Thank Andy and then I guess I wanted to circle back on one question more of from a strategic perspective, I think Norbert you mentioned some of the indications.
Related to.
I guess, some indications may not be accessible in terms of development.
On currently but I was.
During just the fundamentally would you also consider branching more towards.
I guess neuropsychiatric condition with four of five day kind of beyond the Parkinson's disease cognitive impairment setting and just how we should be thinking about that more philosophically Inc.
Yes Hello.
The question when we look at our public policy.
A very extensive profiling.
Of these components of it caused numerous behavioral models of disease.
We do test the meeting.
The models of pain psychiatry the.
Cognition.
Thats, how we empirically based on the data we get assigned the two there is indeed saw into various indications I should say so two 9% to five despite part of the best compounds in our pain models seven nights, a cleaning of the psychiatric models in full price, making cultivation impairment.
And so I think along those lines, we would expand.
Those compounds, but we've seen those categories of either.
Nick Hiatt sleep or pain or cognition slash memo.
And so on.
That's more along the lines of how we actually shape indication expansion and choose which compound from the strategic point of view is best suited COVID-19 set of indications.
Thanks, guys I appreciate it.
We have our next question coming from the line of Myles Minter with William Blair. Your line is open.
Hi, guys. Thanks for taking the questions just curious on the potential higher dose for seven of 93.
Great.
Youre really good of characterizing the all of those molecules in preclinical models Theres, obviously, a U shaped dose response curve here how high of about 50, Megs could you theoretically and still expect efficacy and.
And how would you balance bringing that into the trial I guess with the risk of being pricing plus the bar.
The expectations from from the bots of just bringing in another actually dive into two of the trial.
How to answer that because it would require that we extrapolate directly from preclinical to human sort of like conditions.
Let's say if I take you back to the two 9% to five study in TPN debt, we take the he chose the range of.
Of 10 to 200 milligrams of daily dosing.
The 200 milligram dose was efficacious.
I think begin to plateau.
For a longer period of daily administration, the west the 50 milligram dose.
<unk> to show a very linear improvement from week, one to week to week to week four.
And so I think we can go higher but it would clearly be of studies that would have to tell us when we would begin to see a plateauing of effect.
Let me make this is my opportunity to share with you and the team on the phone here that we have this other unique I would say opportunity to push the dose high because of the so kind of safety and tolerability profile of our component of site.
Don't have the issue that many other compounds have debt basically are limited by a very narrow therapeutic window of index as it relates to where you were sort of like to get the best dose before you begin to see safety until the liability concerns and so from that point of view we.
In our phase one study has gone through like the Gram quantities and single administration and not seen any adverse effects, but thats actually form a point of view of what's the relative until our purity goes much much less important and so I go back to my earlier comment and say I think we have learned of our preclinical models.
Three of the sweet spot the assessment going to clinical studies with patients and.
And that has now actually it turned out to be pretty predictable in cases, where we have some of it and so.
That's probably a better way of looking at the <unk>.
I can't give you the next day and because the base now so that's like 100% culinary shouldn't be the preclinical that number of models in humans of patient population.
Yes fair.
Fair enough and then on full of five eight.
On the Parkinson's disease population specifically.
What the exclusion criteria for the most of this.
On churn in those patients I'm curious because you are subjecting them to key cheetah rise cognitive tasks.
ISG now has to pass and be able to do these tasks at baseline to be involved in the trial, but just wondering whether you can say on any complications on the motor function thought of gist patients being able to complete based cognitive tasks that you're trying to assess.
No absolutely miles so we definitely have.
The series of inclusion exclusion criteria for these patients.
On a few different things.
Motor symptoms on the overall progression of the broader pockets of sometimes is definitely part of the inclusion exclusion criteria for that exact reason to make sure that we have patients who as most of our symptoms arent so severe that day.
The mask the ability to accurately measure cognitive.
Our staff of some cognitive impairment and Theres, nothing theres, others, as well and I think maybe this is a good time to also say as we broaden the diagnostic groups that are allowed to be included within the office of nuclear and kind of family.
We are applying all of the same inclusion and exclusion criteria to all of those patients. So there's a lot of the potential things that you could be worried about.
Confounding are making.
Introducing heterogeneity, we had already kind of considered on already decided you know what does the patient population we want to look at on be applying those same criteria to all of the patients snag within that alpha nucleon continuum of diagnosis.
Hey, guys. So just to clarify the the Montreal cognitive assessment scores requalify those questions would still rather than the 17 points, regardless of whether they have to pay day, although we bought the dementia coming of the trial.
Exactly.
Really good example, so so as we go from the Mci to mild dementia, we haven't changed the floor. If you like the the lower by the end of the of the Moca score range that you have to have.
And we believe the that lower band is still going to pick up quite a few patients that are in that mild dementia dementia with lewy body of grouping, which is the fact that as part of our rationale for being very comfortable and broadening of that.
Thanks appreciate the clarity.
Thank you Mike.
Yes.
We have our next question coming from the line of Ram Silverado with H C. Wainwright. Your line is open.
Hello, everyone. This is months speaking on behalf of from Great questions. Great discussion. We also appreciate the detailed press release three.
Three of four from me if I if I may.
The question applies to the phase to be ongoing.
95.
The.
Full of five to eight as well.
Has the recent acceleration in the Sars cov, two vaccination assets affected the timing of these readouts tool.
Especially in times of 45 day.
Vince.
Particularly given the age group in the trial would have been the first.
Among.
Those to the electrical who vaccination.
I'm going to have Kathryn the tests the question for you.
But I think generally speaking we have money towards the environment enough to know debt clinical study sites and patients.
Again safe in conducting these studies, which is of course, what we've got.
Hoping and waiting for it.
Instead of it turns out to be confirmed by looking at the enrollment rate.
Good day.
I don't think that is fundamentally different for the upcoming four of five day study in Parkinson's, but let me have the Kessler of maybe additional color to the comments I just made.
Yeah, I think that's right Norbert and I think we're on track with enrollment, perhaps the vaccination acceleration has help to remove an obstacle to enrolment for some patients but.
But in general we're progressing very much according to plan.
Okay perfect.
On Lula.
We're looking forward to be the sort of BP meeting.
April.
Yes.
Can you give us the flavor of what kind of data analysis will be presenting.
The anything new here.
Okay.
How about maybe you addressed the.
Chris.
It was a little difficult to hear did you understand the question highlight because okay. Yes.
I think I got this so basically you did quite an extensive data analysis will be based on the understanding of the disorder as the board we looked into things, which have been described in the literature of predicting the.
Outcome, we looked into the pack on the date.
Eight of them say.
In Italy.
Prevent things, which apply all of the business is not.
Of the fishing expedition, which we did but something we just guided by signs I think we would have been described in literature, and we consolidate our data assets.
Confidence on what you're describing is this gives us confidence that with those determinations, we will improve the signal for the upcoming trial.
Okay.
Thanks.
So regarding your recent of a few inc.
I mentioned in the drug discovery.
If you will of pocketing any day.
In addition to.
Otherwise.
Maybe.
Package of data for.
Dietary PTSD with you already.
Each of the impairment.
Great.
I apologize I don't I don't think the your question clearly the line was not clear that you were speaking on.
We are asking the holding.
The class when you were asking about other review articles that we might anticipate.
Yes on the review articles in the tissue.
So maybe.
Neuropsychiatry angle on the ticket.
Aiman.
Yes, I think absolutely so.
We do have some some things teed up in terms of additional preclinical data that we can.
It's in the queue for publication on the other preclinical.
The remains ongoing even in our clinical indications because we always wanted to understand the mechanism of action better and I think the paper that we published on the.
Do you pay for the kind of pulling a lot of that together and chronic pain.
That was of great opportunity to kind of tie a lot of that published data together in one place and we certainly would like to do that in the future in other areas.
I'm not sure.
We don't have anything sort of imminently in the works, but I think that as we accumulate data, we'll certainly look to repeat that kind of publication.
I think maybe to add onto that.
The keep pointing out we have the opportunities that what we're doing the training of the case based on very extensive preclinical work we conduct.
And so in particular, the 292 five paper as the mechanistic paper showing act.
The activity in numerous models of chronic pain.
What was meant to substantiate the.
The enormous amount of work, we do before we actually elevated components to become out of India ready and go into human studies.
And so we have similarly comprehensive data takes of quality on preclinical data on 708 total.
On 708, three and psychiatric module as well as four of five eight.
As Andy said I think over time, we will actually.
Makes sense more of sort of like visibility in how we actually put it in the bulk of it.
Application performance.
Okay.
We have our next question coming from the line of Jessica Fye with JP Morgan Your line is open.
Hey, guys. Good evening, Thanks for taking my question.
Quick one on following up on the VPN question.
So the <unk> study for 2925.
What do you want to see in that study to feel confident the youll have.
A clinically meaningful signal in phase III, So I guess well look.
What would represent a clinically meaningful separation from placebo on a phase III and how much buffer do you want to have the around that in <unk>.
Yeah. Thanks, Jeff that's a good question I mean as you recall that the study is essentially of prospective validation of what we found in the in the prior.
DPM study and.
I think the.
The clinical meaningfulness.
Something that has to be kind of calibrated against the safety and Tolerability profile.
Drugs out there if you ask the clinician typically I think about a 0.5 difference from placebo on the and RF scale sort of gets you in the conversation, but it does depend a little bit on the safety and Tolerability profile, obviously, we feel our safety and tolerate the tolerability profile is very strong. So I think thats sort of where we would be we would be comfortable with average.
In and around that.
Obviously saw a difference in the longer disease duration population of Dpm's was much larger than that.
In the first study.
And so.
So I think that that's sort of the range.
Of that we're looking in.
We are I think powered to detect signs of the the lower end of the clinically meaningful range, but hopeful based on the prior study that we would be about that.
Great. Thank you.
We have our last question coming from the line of Charleston from when Cantor Fitzgerald. Your line is open.
Yes. Thank you for taking our follow up and apologize to everyone on the call for our issues.
One quick follow up on four of five eight and then and then a broader question.
Regarding biz Dev on <unk>.
<unk> five day with regard to the conduct of the cognitive impairment study I guess I'm wondering you mentioned that this is signal seeking study.
Clearly, perhaps looking at earlier stage patients are these patients going to be on background.
Therapy.
And if not.
Is that call it components in terms of the conduct of this study.
Great. Thanks, Chuck how low can you take the question. Please.
Yes.
So most.
Motor dysfunction, particularly when the Parkinson's.
Parkinson's disease dementia, so they're allowed to be on medication, particularly treating those motor dysfunction, but they have to be on stable on medication.
Actually broadened the Newton.
The.
Medications, which patients can be on to get into the just try but I think the important is that those medications has to be stable. We do not expect to see any major end of few in Dubai, which of compounds have no effect on the motivation of.
Necessarily on gross quantitative aspects, which we are focusing on so that's definitely something which has.
Level of independence, we don't expect any industry and so thank you Bob.
Okay very good that's helpful and then with regard to the concept of NMDA Hypofunction.
You did of mechanism.
<unk>.
Of these indications I guess I'm wondering could you could you see this program being expanded with four of five day to say other highly prevalent disorders, such as cognitive dysfunction associated with schizophrenia.
Or could you, perhaps more likely see it moving to the orphan space, where you see your development until disease that involves.
MDA Hypofunction.
Net of impairment.
I would answer it by saying both.
Charles.
Because as you pointed out is the unknown.
Lying dislike relation is that hypofunction off and then be able to check the activity.
I think there would be a scientific rationale to consider indications.
Most of the categories that you just touched on.
Okay last question regarding corporate collaboration activity I guess I'm wondering as you look about kras here Brian.
Broadening pipeline I'm wondering if there is a point.
At which you might consider.
Corporate collaboration activity for some of the higher more highly prevalent.
Clearly indications of Youre looking at perhaps with 292 five in.
When do you think it would make sense, perhaps post data in phase III and would it be more ex U S type thing on.
Type of collaboration activity or Pan the Pan and global.
Yes, Thanks, Charles this is ashish.
We are well funded and well equipped.
And the very much focused in underway in getting the next data in.
All of our indications either with the studies that are ongoing or soon to be recommencing per wouldn't be initiated later this year, we think that those studies across the pipeline offer meaningful input.
And data that.
What meaningfully in the form.
And enhance the value of any collaborative discussions.
And so we're focused on getting those and have the support of investors on our balance sheet to do that.
I think we've talked about in the past that as we think about our pipeline.
The area of chronic pain.
If we're able to see a replication of the effects that we saw on our first phase II studies.
Hi.
The therapeutic opportunities.
Very broad and addresses a number of physician call points that probably has the most credibly addressed with a partnership when it comes to commercialization and so that's something certainly that we would.
We'd be interested in exploring.
At the time when it can be.
Bye bye meaningful data and.
Add value to the program.
Rapid and efficient and responsible advancement.
On the shareholder value, we think of the next juncture.
The next studies offer an opportunity for that.
But we were well equipped to take this as far as we need to ensure that we are that we can add that value.
Sure.
About <unk>.
Different types of collaborations and structures on.
On scopes of partnership is another good one.
There are certain areas, where we are not actively advancing our programs.
Again, we'd be open to.
Any discussion.
Can meaningfully enhance the progress we're making.
Toward advancing these programs toward toward regulatory endpoints.
But we're not reliant on those and.
And we are very much focused on getting the data that are coming next which we think again with meaningfully in the form any such discussions.
That's helpful on Ashish Norbert Thanks for taking my follow up.
Thank you Charles.
There are no further questions at this time I will now turn the call back over to Norbert for closing remarks.
Thank you operator, and thank you all for your thoughtful questions.
Being on the call.
We appreciate your time and your attention.
Please stay safe be well and enjoy the rest of your day the rest of your weekend.
The upcoming spring time talk to you soon thank you bye bye.
This concludes today's conference call you may now disconnect.
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