Q1 2021 Minerva Neurosciences Inc Earnings Call
Good day, and thank you for standing by and welcome to the Minerva Neurosciences first quarter 2021 conference call.
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And now with the hand the conference over to your host today, Mr. William Boni, Vice President of Investor Relations. Please go ahead.
Good morning, everyone.
Yes release with the company's first quarter 2021 financial results and business highlights became available at 730, a M. Eastern time today and can be found on the investors section of our website.
Our quarterly report on form 10-Q was also filed electronically with the SEC. This morning and can be found on the SEC's website at Www Dot FCC Dot Gov.
Joining me on the call today from Minerva are Dr. Remy metering are executive Chairman and Chief Executive Officer, and Mr. Geoff race, Executive Vice President and Chief Financial Officer, and Chief Business Officer.
Following our prepared remarks, we will open the call for Q&A.
Before we begin I would like to remind you that today's discussion will include statements about the company's future expectations plans and prospects that constitute forward looking statements for purposes of the safe Harbor provisions under the private Securities Litigation Reform Act of 1995.
We caution that these forward looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated.
These forward looking statements are based on our current expectations and may differ materially from actual results due to a variety of factors that are more fully detailed under the caption risk factors and our filings with the SEC, including our quarterly report on form 10-Q for the quarter ended March 31st.
Two 2021 filed with the SEC earlier today.
Any forward looking statements made on this call speak only as of today's date Wednesday May 12, 2021, and the company disclaims any obligation to update any of these forward looking statements to reflect events or circumstances that occur after today's call except as required by law.
I would now like to turn the call over to Remy Lutheran yarn.
Thank you bill Thank you so much.
Hello, everybody.
Great and really very proud and very excited to focus through this.
We shouldn't forget that it's about the open label extension of our Phase III studies and I think these data are.
And important additional piece of information concerning royalty pare it down and then treat my boss negative sheep, Thompson and schizophrenia and before before jumping into the data and <unk>.
We would like to thank once more on older patients or their families. All the cash gave us that Michelle and shows a kidney compliance here and to U S and in Europe, who have.
Our anticipated towards the Central Bank.
And I knew difficulty piece to be and are trying formosa and won't be areas.
So let me jump into that and just a day tenants and.
And what we can see on on slide four is but one of the objectives on seats.
Open label extension.
So first on point and with these transitions and policy is to look at the long term safety and this is to take the Bulks about one year on administration of the drug and but I think it is also very very important in order to give us a better understanding of the long term safety and tolerability of from the paradigm.
And Oh.
As you will see.
And this is a very important and extremely and <unk>.
Raging and good for you on the paradigm, but obviously because of <unk>.
And as you know negative symptoms he's a Z.
On a core symptoms of disease and schizophrenia, but it is also the zone the symptoms, which are really long lasting houses and those.
And they get the symptoms are present, even before a patient the first and that gives us the positive symptoms and and it is what it is a chronic possible from holds a disease.
So clearly it is very important to continue to follow for longer periods of time and what is going on in terms of negative symptoms. So what day.
And we'll walk you through zone.
And as a primary endpoint, which is a margin negative symptom score.
Which is a worthy and validated tools to measure negative symptoms and.
Basketball, but obviously, it's important to put this into context on the overall psychopathology on as a disease and that.
And we'll give you also some key information about what is going on and we've got one drug overly.
Extension of nine months and on the overall one year treatment period.
Terms of CGI S and terms of is it pans total score and although a bunch of items.
What is also important as you know because keep in mind with them and as they study has been carried out with the mono several peaceful and as these patients why only treated.
Obviously these other drugs vs royalty paradox during the double blind faith, and imagine and was placebo, but afterwards Luis the open label extension and everybody was in monotherapy.
Monotherapy and for all the paradigm for nine months. So so this is obviously important to look to relapse rates.
And this is a little ways on something which is.
Portland, which is Oh worrisome and east.
And there's a relapse rates on under control I think dishes and very very importantly positive attribute who's a drunk.
Clearly I mean this is also something I would show you and.
All these false negative symptoms improvement overall psychopathology improvement to ease.
Oh really important Ethan and you can demonstrate that that maintenance. This is translating into a functional improvement and.
I will answer both slowly.
S P, which is a personal and social and social performance and tokens.
Sure.
As you know on each of our key secondary endpoint and just studying and drive.
Not least because no we have generated a lot of efficacy and safety data with a drug test.
He is a phase <unk> study is a phase III study I would try to summarize on recent to integrate on recent too and said we gave you the next steps afterwards.
And we're going to hit next slide which is slide five and just.
Our small and helps US a reminder, about the study design and so as you can see.
After the screening purion won't cause of patients.
We're entering into the double blind phase for 12 weeks or three months.
And Oh, we had three treatment arms 62 limited Grandma troubled rock 64 meeting run and the placebo and afterwards and engage the patients and the clinical sides.
We're thinking that this makes sense and means of patients where proposals are to enter into an extension phase.
And what is really important to understand here is that.
Uh huh.
These patients.
And our before entering the study treated most of assemblies anti psychotics and they need to be stable over a period of six months in terms of positive symptoms. So in other words I should not the trade too much in terms of positive symptoms and obviously they need to have a certain level.
On the negative symptoms.
Order to and as a standard.
What is also important to understand and I'm well aware of that I mean, and as you open label extension use more loans are placebo controlled but what do we have to be aware and I think this keeps even more value and more weighted to this open label extension data is that.
And the clinical sites on the P I.
And are not aware about that.
Those are the patients are receiving and the open label extension majors of patients on work about the dose and receiving.
And the same is true as well for and.
As a patients aware and on placebo and switched to Arctic dropped all the patients will stay on active drug and this is completely.
Completely blinded and cause a clinical site and does a patient. So so again this is important to keep in mind that because it gives us in my opinion and many of them more value and more weighted to this extension data.
So on.
The bottom of the slide you have the different power meters and you're already one suite. So the needs are to stay longer on <unk>.
And so on slide six.
Use of disposition.
And as you can open label extension.
Do you see that I mean, we started this.
The double blind phase of these 500 search and patients who could and of the one of part of the safety population.
ITT population is the same number of patients and what you can see.
When youre going to cause a force rule youll see that Minerva.
On a lot of patients from the different items went into the extension, which is obviously a very very good and the 333 patients wanted to the extension.
And.
And as you can see it's quite homogeneous distributed among the different treatment arms when youre looking to two.
Different reasons, why some of the patients dropped out of them and bundles and main reason. These are informed consent withdrawal, which is not a surprise because those issues are very low savvy and.
The rest are we do go into the details a bit later on.
I think a very balanced.
And very interestingly enough I mean, a lot of patience and.
And investigators who have decided that it is worthwhile to enter into an extension.
So if I'm going to next slide and this is a.
And there are primary endpoint, which is a modest negative score. So once you can see here and it needs a little bit of explanation, obviously about the about the slides on slide you presented so once you can see.
On the left side on the slide I show you Youll.
And you'll observe data was a three treatment arms of the double blind phase and blue.
And so you'll have the placebo and green you have 32 milligram and in Red and you have the 64 milligram.
And what you can see it is obviously is that when you are ending just double blind phase you can go into the extension and afterwards and what I'm showing you here on this slide.
Are all the patients who are receiving 64 and read all the patients who are receiving 32 in green.
Can see at week <unk>.
And 52 of them and the treatment was stopped them afterwards, it means that patients who are <unk>. So you have and addition of measurement point after the treatment has been stopped.
After 52 weeks of treatment and the button.
But more details, but I mean, I have a summary slide off towards.
And all these results. So so from the moment it is not necessarily to focus on and obviously as you can see was agreed and adderall I mean and improvement from negative symptoms is.
And he's a he's a curve going down.
And so what you can see I mean is it.
Clearly.
When you continue to treat patients and patients will stay in the study.
For one year on nine months extension.
Negative symptoms. According because a modest negative score continuously improve and we are reaching levels of improvement which are.
Quite high and we are at around seven points of improvement in terms of the month and they get to school.
So does this translate into functional improvement that this is on on the next slide.
Here, we have the PSP.
Core again, the only difference here is obviously easier and improvement in terms of function and in terms of everyday life.
Sanctioning of these patients which is assessed by the PSP and <unk>.
The decrease of the curve yesterday or.
And so currently and G I.
And because of Green and I always line up so higher is better.
So what we can see again here when youre looking to the double blind phase of this is something we were ready.
And it's clearly described.
And when we released the Z double blind part of these phase III and <unk> all chose a chase.
Our phase two B 64 meeting run seems to do a little bit better job in terms of PSP in terms of functional improvement.
As compared to 232 milligram.
But again when you are looking to the open label extension of about nine months to see what that means is improvement continues and becomes more and more important which which is obviously.
Great News and shows that I mean the.
What I mean and royalty paradigm is doing in terms of improving negative symptoms is translating at the end of the day into a functional improvements, which is what you need to see yes, because our agenda. Today. What is important is all of these patients are functioning better.
Keep in mind. This is a key secondary endpoint to be heading under study.
If I'm moving to the next slide which is slide nine on.
Just wanted to give you some additional color on all day session on how.
And with royalty paradigm is and ease.
Is is knowing during the nine months extension some zone on the top left you have CGI S and you can see that indeed.
And your opinion on <unk>.
And so there's a doctor or at least knowingly observation clearly I mean, he sees is the improvement which is really good news when youre, bringing down left so these are positive symptoms and and.
And clothing Tomorrow and this is really important information so.
If you remember we took these patients once they were stable in terms on positive symptoms on the level of positive symptoms like around the 14th 15 points.
Which is obviously a quite low level on positive symptoms, but keep in mind that that means that we're on managing psychotics, we switched them to mono therapy or from the Paragon and that's what you can see here interestingly enough you still have left some room for improvement, but I think without emphasizing the improvement that I think it is fair to state.
And then the positive symptoms and minimum stayed extremely stable.
But what is interesting if you're going to the upper part of the slide on the right side. So this is upon slippage quote and I saw so this is a complete the or improvement you can see on the scale and you'll see that.
Again on a total pumps core is improving from the two doses and.
It is improving to two and very nice level around the 16 points. So what this means is that I mean, if you you should punster was the improvement we have seen on negative symptoms and the improvement on positive symptoms and this improvement on the potent pumps.
And is obviously related to these two improvements but that means a general psychopathology is also improving.
And if you treat these patients long enough in monotherapy with a weighted paradigm and lastly on the case that the bottom right I mean I gave you.
And the top score of a modest negative score, which is emotional expression and the Aussie low.
Yeah.
From the studies, which have been done this pop on this subpart of the margin negative score as Aesop Papa negative symptoms at the end of the day is highly.
Explaining the functional improvement always correlated and was a function of improvement.
So I think what I tried to bring over here on this slide is that.
All these are all department as you constantly are improving and in addition, the improvements you'll see are technically signaling very nicely at the name on a functional level and was a patients are improving.
If we go in and out because that summary table, which is on on slide 10, and so this gives us a complete inc.
Formation about the power meters and have shown you. Some C zone on the right side. The two the two columns on the right side resolves and results have shown here on the slides and.
And afterwards and he sees that you have the details and some meetings middle columns and <unk>.
And all the patients who received <unk> 32, or 64 and me to Guam was a complete duration of the trial, so one year and on.
On the left side the two columns on the left side since it's also a patients.
Who switched from placebo and the double blind phase two two active treatment and the engine into the open label extension So again.
Going into the details, but I mean, you you have and those numbers will be presented before but.
And again, you'll see that the negative clause PSP functioning totally pumps core.
All of this our meters and all evolving into the right direction here.
No coming too so it's a very important point that I highlighted at the beginning.
Which is on the next slide.
About relapses.
So really I mean, as you know is a definition of relapses.
We can find different different seasonal difference.
Definitions of off time of relapse Facebook I mean, what we took as ours on the.
A definition is really on.
And you can see at the bottom ease and patients.
Patients who are.
Dropped out from the study due to.
Schizophrenia symptoms and so and so this is a destination we have used.
And what you can see on this slide and maintenance on the pop up the slide and then you have the.
So we lapse rate all the number of patients dropping out for schizophrenia are things that they are blind packs and.
And but at the bottom you have the numbers of patients who dropped out doing Z open label extension.
So when youre looking to the overall.
And we lapse rate, which is a.
Even though it's a bottom I mean the yards around the 11, 7% on 12 persons.
Which obviously is extremely low and I am sure somebody will get we will get a lot of.
Criticism about this and how long these as possible and Guam and we'll give you at the end of my explanation of why is this is possible, but I mean, what is very clear.
Is it in May and and you should treat long enough patients means on the drug.
And in mono therapy.
Right, he's extremely and control and.
And the things he sees a take home message of center of the slide.
No.
On the next slide I mean, this is a safety aspect that we have observed so and we go through the different points and make it make some comments because I've seen they are extremely important to give you a little bit more color on fish, but.
As you can see I mean volume paired with them head to two doses both doses.
The extremely safe and.
Well tolerated.
And when Youre looking to the treatment emergent adverse events.
And generally mild to moderate yes in terms of severity.
And you know looking at to see you know frequency frequently reported free.
And the emergent adverse events.
And this is 32.
And so 333 patients.
And as my you in doing the open label phase, you'll see that they're made and that Oh you have a.
26 patients on reporting headaches.
And obviously schizophrenia and worsening 18 patients so $5 four persons and you have insomnia in there and 15 patients.
Let me just make a small comment about about insomnia.
What we have to keep and might even if we are here and Volvo.
And one of them and most of our.
Mostly reported.
Events keep in mind that I mean, it is very well described and the Zip.
And literature about does the incidence of insomnia and schizophrenia patients suffering from schizophrenia, and incidentally is more than 50%.
And the patients suffering from schizophrenia. So again, even if I mean, we have some cases have been some yes, if the conditions. The overall context on the disease, Wyoming and some day as radio maybe unimportant.
And parameter.
On a symptom.
When youre looking now to Tuesday Tuesday.
And so to say or number of patients who had a serious adverse event. We have 26 patients who have had a serious adverse event and five which is really I mean, a very low number.
Compared to the number of patients that are exposed to the drop and the duration of treatment. We have five wireman Z as it has.
As a consequence of that I mean.
It is adverse event was related to the drug.
It is worthwhile to mention that on one patient.
Died after he has been discontinued from the treatment and those are obviously not related to two volume Paragon, but I mean are related to respiratory failure, but the gains is patient already was no longer treated with Robert Baird.
So when you're looking to sort of the there's a number of upfront of of patients.
Treatment emergent adverse events and entities are around 11% 11%.
And we use a 25 patients who had relapsed systems. This is referring to the slides presented.
Before and.
And and the recipes are there's a variety of events which are on.
Superior or equal to 1% of the patients so <unk> and even the events, which are just occurring and in one or two patients.
And they're placed in terms of Q T C.
And you see that them and we.
We had really a very limited number of <unk> increases so one one patient.
<unk> reached the stopping criteria and just 60 60 milligram dose.
Just to be clear I mean, these patients in terms of absolute value did not go above 500 milliseconds or it was below 500 milliseconds that I mean, why he has been stopped at the one on the stopping criteria ease.
The Delta increase is more than 60 milliseconds.
At the two measurement points separated by search and minutes and then you you'll have to stop these patients. So this is why.
Why are these patients has been stopped in terms of and <unk>.
And so.
If I'm going to the next slide how can be summarized all day since I mean.
Clearly I think and what does the open label extension.
Confirming or giving us the inflammation and the gain I think that this is really very important information is that.
We have a continuous and really sustained improvement of negative symptoms.
And going to complete duration of the study and doing the open label extension.
We have also as I already mentioned, the continuous improvement of daily functioning or on it.
And there was a patient already better and they're functioning better.
On a tier.
Information coming out from the PSP.
This happens in a context part means psychotic slush and positive symptoms are.
On a stable and why we have the.
Really few relapses over one year and.
And as this happens and it.
We said the rock, which is a safe and well tolerated that I didn't mentioned, obviously and the N. Gen Z on safety part of them and we did not see any weight gain we did not see any EPS. We did not see any product increase and we did not see any sedation I think we had two patients and Russia patient was.
And so just to give you.
Flavor almost all for houses it looks like.
Well, how can we interpret this data and I think.
There are two interpretations here, which are possible and which are the most.
Closing, but one oh and I think that.
Interpretations on not exclusive ex out probably and working together, but I mean, the first explanation is about.
And as the pharmacology of volume paradigm.
And so remember.
Early paradigm is not directly blocking dopaminergic pathways and particularly from a blocking a.
<unk> positive uptick a receptor. So clearly we have no direct open and urgent care.
Blocking effect and Thats, what we have here is a molecule, which has and antagonistic activity on Z and.
So we're putting <unk> five percentage each way.
Receptor, we have the molecule heading out and well and the effect on the Sigma tool with.
Sector also and I think when you stick effect.
And we have worked a lot to have even more insight.
A pharmacology when was the last year or so and it is also clear that in addition to these two targets. The molecule has also now to one.
Antagonistic activity. So those interest rate is a pharmacological profile and we really would like to emphasize it I mean, indeed I mean.
And this molecule has it farfetch and toy activity, which is important but and maybe it is much more <unk>.
We have the sigma to activity and just for one night.
And it is very well described and a more and more because SYGMA too is becoming an extremely hot topic in terms of research and the terms of huh.
Trying to come up with innovative treatments. It is very wide and the ones that are Sigma tool is probably having an impact on the glutamate and particularly on <unk> and MBA pathways and just to give you.
Hard to say so one.
One one of the of the activities you can see when you are working with the specific Sigma two molecules.
No.
I think <unk> I mean, the beauty here is that I mean, we have a molecule, which is safe and due to the pharmacological profile, but which is also targeting specifically negative symptoms that has.
And overall effect on the overall psychopathology.
We will in the future report more on pharmacology, because I think it is important that I think it is fair to say that probably is a pharmacology here he's a quite adaptive pharmacology to achieve what we have achieved.
What are your paradigm and so far and.
And the other explanation, which can explain these data is that fair.
You know when youre improving negative symptoms and this is extremely well described and a recent sherwin go one day improving negative symptoms. You know patients are starting to function better patients are more adaptive to you know what is going on the wrong zone in terms of family life and terms if they have a job.
So basically they are much more able to cope with everyday life and at the end of the day. They are all showing improvements in general broke psychopathology and.
And this is maybe another extraordinary so I'd, probably say two things are.
<unk> seen those synergistic in terms of what we see with our molecule. So that was the last explanation, but I will not on precise it because they have only.
Preclinical.
The trove of data that I mean, this is something we continue to to two to test or to work on remember that that maybe we weren't able to show them and Oh.
When we did the rugged parent dun.
You can see a very nice increase and bdnf, GDNF and and so and so you can you can also raise the hyper cases that may be we are really helping these patients by doing something in terms of that.
Neuroplasticity and overland.
So really I think this is the best explanation and see which is obviously very exciting and when you integrate this into the east.
Magic words totality of evidence I think oh.
This data and I just presented to you over the last 15 minutes on just giving an additional level of evidence that I mean, the loyalty paradigm is a drug which.
And these are probably helping agenda of the day patients to improve in terms of negative symptoms and.
And and that will grow functioning.
And last but not least before I give over to Geoff suppose a financial update.
What is next so what is next.
We have just recently started the.
Z bio equivalent study.
These private held back by the equivalent study in healthy subjects and.
As you and those issues are one of the activities we ex the carryout.
In order to check the boxes on a different comments.
In March we received from the EBITDA and our type.
Type C meeting from last November and so is this is ongoing and and obviously one of the one who has a day thing and we will report on this data.
We continue all of the other activities, which are needed to be integrated and our.
NDA preparation and.
We are also.
And putting together all the data analyzing the data and the right way.
To go for a pre NDA meeting as soon as all the different points and referencing here are completed.
So I think I'll stop here and I give over to Geoff on the financial update and and obviously I'm looking forward to.
Hopefully all your questions and interest and questions. After Jeff has done is update Jeff. Please.
Thank you Remy.
Earlier. This morning, we issued a press release summarizing our operating results for the first quarter ended March 31st 2021.
A more detailed discussion of our results may be found in our quarterly report on form 10-Q filed with the SEC earlier today.
Cash cash equivalents and restricted cash at March 31st 2021 were approximately $82 million compared to $25 $5 million as of December 31st 2020.
And January 'twenty, 'twenty, one and the company received a $60 million of cash upfront payment from royalty pharma and connection with royalty pharma is acquisition of the company's royalty interest and sell direct.
We also have the potential to receive up to a further and $95 million and additional payments contingent on the achievement of certain clinical regulatory and commercialization milestones.
The significant non dilutive funding provided by our agreement with royalty pharma, both immediate and potentially over the longer term will support our top priority. The continued development of roller paradigm and our lead asset <unk>.
Recall that south direction. That's currently in phase III clinical development by Janssen Pharmaceuticals, a subsidiary of Johnson and Johnson for the adjunctive treatment of major depressive disorder with insomnia symptoms and.
We presently expect that the company's existing cash and cash equivalents will be sufficient to meet its anticipated capital requirements for at least the next 12 months from today based on our current operating plan.
Assumptions upon which this estimate.
Just on routinely evaluated and may be subject to change.
Research and development expenses were $3 3 million and $8 1 million for the three months ended March 31st 2021, and 2020, respectively, a decrease of approximately $4 $8 million.
The decrease in R&D expenses was primarily due to lower costs for the phase III clinical trial of ROE and the paradigm as a result of the completion in May 2020 of the three month course study portion of this trial.
Noncash stock compensation expense included in R&D expenses was <unk> dollars $6 million and seven.
$7 million for the three months ended March 31, 2021, and 2020, respectively.
G&A expenses were $4 $2 million for both the three months ended March 31, 2021 and 2020.
G&A expenses included compensation costs consulting expenses and insurance premiums noncash.
Noncash stock compensation expense included in G&A expenses was <unk> $9 million and $1 $5 million for the three months ended March 31, 2021, and 2020, respectively.
Net loss was $8 $8 million for the first quarter of 2021 or a loss per share of 21 cents basic and diluted compared to a net loss of $12 $2 million for the first quarter of 2020 or a loss per share of 31 basic and diluted.
Now I'd like to turn the call over to the operator for any questions operator.
And as a reminder, if you'd like to ask a question at this time things and press the star and the number one key on your Touchtone telephone.
To withdraw your question press the pound key.
Our first question comes from Jason Butler with JMP Securities.
Hi, Thanks for taking the questions and remember we really appreciate you going through all the details there.
Just thinking about I guess about the magnitude and progression of improvement.
Are there historical data and.
For patients with negative symptoms, but that kind of speaks to what you know how likely they would be to.
To recover and that manner without treatment intervention.
Both again, but the magnitude and the progression of improvement over the full one year.
Hi, John Judge on that.
So great question on another stable and expecting this kind of question.
First I think it's it's important dimensions with them and and May be the study design and the abuse is not absolutely the same.
And so what you can findings and the literature, but nevertheless, I mean, you can find the <unk>.
Situations, while you have a similar study design and and I'm glad you could get some on.
Some more color on this momentum by comparing holiday to two existing data. So I think what we're.
What is very clear is that.
And most of the cases I have seen in them and.
Uh huh.
And the literature is that.
Usually are made and you'll have a and improvement which is occurring quite charleston, and off to a distinction and I'll really flattening.
When you are going on there are set.
It'll weeks and and obviously several months and flow. So things are flattening and very quickly, yes, I mean in terms of improvement and I'm speaking here about the negative symptoms if you'd go with patients with head and neck shoot relapse of positive symptoms as you know when you bring them down.
And so.
And I'll have to say, having a small improvement on negative symptoms, which is observed day effect that I mean, afterwards and seeing some flattening so basically what it means and I.
Is that I mean, you have no real specific improvement from negative symptoms lousy and Alba case I think it's.
And all the precautions.
The study design that you hope and day.
And extension.
I think it is fair to say that this continuous improvement over time is something which and my best of my knowledge to us.
And the term is.
Is unique in terms of.
The level of decrease.
Again I think.
And we have to positions of context.
On the patient population and Claude.
And despite the remember that the.
And we wanted to have the patients who have a minimum score of 20 points in turn.
And so for negative symptoms and they needed to be stable.
Before entering our study and and basically we ended up with patients who.
We will have a habit.
Score at baseline of around 2025, 26 points in terms of negative symptoms. So keep in mind that the minimum.
And seven points and that's because of maybe one day or using the patents and there is no zero one is absence of force.
Of symptoms on each item, but when you're all well.
And as a consensus is that I mean, if you bring back to someone.
Two.
220 points and below.
And all these patients are probably starting to function again of functioning better which by the way is demonstrated with our PSP data. So I think we are really at the level one and indeed, you know based on on what is somehow consensus in terms of why does it need to be.
In terms of negative symptoms to be able to function.
So this is I think what can be the answer to your question to compare this to anti psychotics on whatever I think it's not it's not really a <unk>.
And do it because we are not ready.
They didn't use the same pharmacology and the bleeding and exactly the same.
Drug yes here so so.
And this is what I can answer to your question.
That's helpful. Thanks, and then just just regarding next steps with the FDA what would be the trigger for the next FDA interaction is at completion of the Bioequivalence study obviously, we'd expect you to submit a package that also includes the.
New OLED data, but.
And any sense of why I like I said, what the trigger would be for the next meeting on when the next interaction with FDA formal interaction with FDA could could happen.
Yeah.
Formerly traction is the right term because I mean, we are interacting with the FDA, because we interrupted with USDA.
When we when we before we started over of a bioequivalence study, because we see and Shenzhen and Coca Cola, We also have already.
And so some of the questions, which came out from a type C meeting, but it is a single extremely clear that one important.
0.2 box to check is about.
The bioequivalence between is a formulation, which has been used and face to be and phase III and.
And when we establish completed and indeed, we will really start to finalize all what we need in terms of whole bird.
Taking both documentation in order to go back to the.
And <unk> to discuss our net.
And next step on and yes, but the but yeah. So this is a timing on it.
And so sequence of events, which will happen before we go on the game.
And FDA.
Okay, great. Thank you and thanks for taking my questions.
Thank you Jason.
Our next question comes from Tom Shrader with BTG.
Hi, good morning, congratulations on the data and also on the perseverance and it's really remarkable over especially on the face of a second pretty good drug and so.
My question has to do with your final points you hit on that are.
I think quite interesting this idea that the drug gets patients towards good enough state in terms of negative symptoms that then they were able to form routines and sort of get going on life again, and so you have this long term effect.
Do you need to.
Sort out the role of the clinical trial environment and that do you think you need to do a year of placebo controlled now and it's that hard.
And then the follow up is do you think the Inc.
And the continued improvement and positive symptoms argues that it is a pharmacologic effect. So I'd just like to hear your thoughts on that on that idea.
Yeah. So.
And I I on the PMA.
Your opinion and SMA.
I think what youre going.
According to our guidance and 2019 each day.
And English and then Mike.
Medical leave that on the.
And if you have radio and as a package. We have today I think we have enough data to go to see.
The agency again, that's on the.
And obviously, we are really listening to all the different comp.
Commenced we are receiving.
Uh huh.
Do we need to study, what we are doing and Oh.
And your placebo controlled and is it possible.
I think it is possible to run a study like this I think on the CS that it will give additional color.
How meaningful all just easily have here, but nevertheless, keep in mind that.
And there is some blinding and this data nevertheless, and he's starting to comp and reason are really speaking of trailer.
Data, but if we have to do such kind of study and I think it is an important study I I think that I mean, because we all hear facing such an unmet medical need.
This would be a study which has to be done and place corner and.
So I'm much more other studies, which could be done and play sports just shows the full potential.
Of the drug yes, I mean.
Now concerning the pharmacology point you are raising.
Obviously, you know to be very honest when ice topic and this is no long time will go to work on on this molecule.
And I was convinced that means a pharmacology and the right pharmacology too.
And to keep a positive net income stable ought to improve that and that's Uh huh.
Long time ago, when I was very young I mean, I wasn't first one working on Mcl 109 month, shuttled, which is which is a pure price that your toy antagonist and he knows that he started it was a story of this molecule.
I'll stop because it goes on that turns on.
And then Oh.
And haloperidol and in terms of controlling positive symptoms, but it is completely clear is that the five.
And five sites each way.
And if that was able to do something on positive symptoms and I'd say that the mean of 560, <unk> antagonist, and youre able to control and acute episodes on positive symptoms.
We have much and good drug structure that results with Jersey antipsychotic system and that was a mutual blocking molecules <unk> zone something.
Something going on there is also interestingly enough.
Good literature out there showing that them and.
For younger patients was a disease is really not.
Already chronic.
Treatment was a high budget Hawaii.
On a molecule.
Probably.
Butler zone.
Going to change out and was a diesel blocking molecule so on.
And so quite convincing literature out there. So again I mean this is an additional layer heading out growth I mean.
While improving negative symptoms on a positive symptoms excuse me and last but not least the east you're going back to the history of power.
Sigma.
And that means on well to Sigma license and development, a long time ago and buy those invoked and one which was a sigma Sigma molecules from Sanofi and test It and my Research Institute when I was running by Research Institute and.
Antihypertensive, Saar and settlement and Sigma is module eighteens and the dopaminergic tolling yeah and.
As you know schizophrenia is not about only hyper demand dopaminergic activity. It's also about hypo scope.
We know what peak activity in the prefrontal hobby as of the brain, which might also be linked to negative symptoms. So yeah I agree with you I think the pharmacology is definitely contribute again.
And if I can just ask a quick follow up what's the removal of drugs for positive symptoms for the entire OLED was that a complexity where these patients that were essentially so sure those drugs working for them, but it was not an issue with treaters.
I think I think it was no longer and issue because we.
We had a.
These are data from the phase two b keep in mind that interface to be if we had the.
A six months extension.
And there's a 12 week double blind zone, So I think.
Yeah.
Going to the actually get compensated and so on at the beginning of May and I'm speaking at the beginning of the project I mean, it's speaking here about the phase Iia, Yes, I mean, it was obviously a challenge because that's a everybody believes and believed a modestly seems that our data are no.
Three two and a lot of research about.
And what you should do to really help these patients and to keeps on obviously are stable and types of positive symptoms and avoiding relapses and central a lot is going on but so I think we already had a good data indicating that.
The risk is not really important keep also in mind.
Do you ever have the work and integrity facilities.
You know a patient becomes not.
I'll, just say activity terms on positive symptoms it has not and not shoot relapse, even if we call this acute and.
In one hour and yes, I mean, this is a process which is going on.
And for several days or several weeks before it means a relapse.
Coors Aussie necessitate necessity on post utilization zone.
And I'd be broken and this is the reason why I mentioned also.
From day part because I mean, often some of the symptoms. All for example, obviously more agitation and little bit more on with CVT, but also benefit.
And in some young and so so so again.
I think our scale the investigators on <unk>.
And we're about this and and Jay Z hedged and tools in order to pick up someone who might reduction.
And basically if you end up with it.
Great. Thank you very much for all the details and congratulations again.
So thank you so much.
Our next question comes from Jay Olson with Oppenheimer.
Oh, great. Congrats on this new data and thanks for taking the questions.
Can you just talk about the performance of the patients and the open label extension, who switched from placebo to active and how those patients compared to the patients who are on active all along and what you might have learned from that comparison.
Wow. This is a this is really a great question and.
I'm, sorry on slide 10, and yes, I mean on the summary table here.
So basically I think.
And the best interpretation IC from this data sheets and patients who completed the double.
Light phase.
Sydney and placebo.
Let me close and placebo responder and so I mean.
But what you can see when you are looking to comparing.
He knows a different Oh, you know on.
On groups here and <unk>.
Very tactically.
The patients who have been treated for the complete duration of the study with active drug versus is the one who.
Who switched to active drug after the double blind phase I think what.
What what is added to these patients in terms of improvement is the.
And the improvement in terms of Uh huh.
It was a specific aspect of negative symptoms, which is related to functioning AR, which is emotional experience.
And you'll see that that means a PSP is really picking up so basically I think what we are doing here.
Putting that.
And I'll have drug on board and to patients who have the.
And response to placebo and does that mean, you are really improving them specifically in terms of negative symptoms and in terms of function. So this needs more and more detailed analysis, but I mean this is what is pumping up when you're really trying to integrate the data.
And so that's clear.
Clearly I mean are there Israel improving and.
The.
Best of luck I can see from the data as of today is that that means you're just having the additional boost here in terms of specific effected zone in terms of negative symptoms and function.
Okay, great. Thank you for that.
And then maybe if you could talk about from a big picture perspective, why has it been so difficult to develop drugs to treat the negative symptoms of schizophrenia, and then from a competitive perspective, maybe if you could compare.
Roller pare it down to <unk> adventure and in terms of the mechanism and the data that you have.
Or any other drugs and development for negative symptoms and thank you.
Yeah.
It's a great question and I should not be too long and speaking about here I could go on forever, but the.
But.
And you have to you have to recognize that schizophrenia is basically about negative symptoms.
And this is.
And so most enduring.
Symptom onset of symptoms to have us in.
And the <unk>.
She is present and a $1 sounds before it was a handful of food loans disease and.
And extremely chronic on the title.
And so really two targets and this aspect and needs to have a drag quite I mean, you did that.
And the key on public.
Targeting the right past plays well into brain and I think.
It's clear from them in and this is my dreams and post approval. We will do some studies what are you going to lead to adolescent patients at risk to force IPF patients because that means Allison zone.
So the likelihood to help these patients and he is.
And you go.
So and so what I also think as that.
You know.
And dumped on don't take me wrong antipsychotic so on.
In other words dopamine blocking molecules are important molecules, but.
These are major tranquilizers, such a well developed as major trunk line just to treat weighted the acute parcels of diseases and I think it's good to see that they've been low we have some treatments, even blocking dopamine who are lesser banking less and pairing and also less and thats impairing in terms of negative symptoms.
The bank assurance that on your lowering.
And deep Psychotics exporter, you see on sort of a patient's functional and winter.
And would you be medicine, and so so I think this is the most difficult parts of to treat keep let's say and minds up on the negative symptoms is a.
And as a construct for us because we have Oh and you have a militia you have on the day one yes.
And but we'll just kind of all your personal and things that are.
And you need to look at and effects on abolition.
Why because.
And when you think about these patients that were really good but it's cooled and we're interested in a lot of things that suddenly.
Moving this capacity to be to be Inc.
Adjusted and something and this is the beginning of all the symptoms to you might see afterwards.
<unk>.
I really think that that made what our data is showing us that doesn't mean that we are improving abolition on baas towards you know you have this positive low spotting and so so again.
Long story short on.
Thank you need to have a drug which is not and power and you need to have a drug that she is doing the right jump in terms on targeting the right pathway and the.
Brain, which are in the low to negative symptoms and.
And afterwards on things a patient as his insights with you heartburn.
Hi.
And I gave her on the and.
Uh huh.
And the people across the hospitals a psychologist on Wednesday.
Slowly, but surely are coming back from that.
Able to cope with your everyday life.
So this is a is a reason why we know no.
Comparing to two <unk>.
Competition on what that was a term.
Yes.
Hi.
And as you're taking the dose a central mainland, but and you heard me already things that like <unk> and supply takes you 12 activities and important activity.
Wanted to really treat the overall psychopathology and particularly <unk>.
Positive symptoms and keep in mind also that.
Five inch its way molecule.
And so.
Having any effect on sleep, which can be related to memory consolidation and cognition, but honestly I think it is not completely enough in order to have really a complete recovery and patient who has a functioning at the end of the dania. So so again.
And.
This is the reason why I guess and.
I think I should stop here compared with a reason to come to competition.
And because it would not be start to my colleagues, who are trying to come up with this awesome and innovative treatments.
Great. Thank you very much that's super helpful. I appreciate you taking the questions.
Thank you.
Our next question comes from Douglas Tsao with H C Wainwright.
Hi, good afternoon.
Good morning, Thanks for taking my questions.
You know I think after we saw the data from the placebo controlled portion of the study and you sort of indicated that you're really working to sort of focus in on 64 milligram dose.
Given what we saw.
And from the open label extension and just sort of really the robustness of what we saw with 32 milligram and and I know it was sort of it seems very manageable. We did see some TG prolongation does that sort of.
Make you think or sort of increase to the.
The reason for pushing and development with a 32 milligram as well just to have that and that's the therapeutic option.
Uh huh.
You know we discuss this on.
And I'm reading favor always.
Always a having a.
Different different.
And but what is it.
And as an option for treating their condition and something.
And it extends chose the Domingos this is very helpful.
They save them and when you're looking to the data.
I think yes, I mean, it's a fair statement to say that the two dose is showing a.
Very very very similar research, but what it is also I think it is also fair to say is that 64 ships to do a better job in terms of a functional improvement.
It's quite clear that I mean.
In terms of PSP or 64 is getting it back to jump on let's say 32 is not doing anything.
Oh, yes, definitely probing patients, but 64 seems to be better and.
And did not experience a sedation and we have no EPS nothing like day, SASSA, So probably and maybe 64 is probably on.
And with better on dental doors and in order to really help patients with medium on the beginning of treatments. So so long story short I think if we could convince a Z <unk> and if it means that two of those is helpful.
Helpful, Maybe search it to us and maintenance those on 64 hours on those.
You can help patient initiation of treatment or even though.
And when needed and joins a course of treatment I think this would be great news keep also on minds up on uncertainty tool is.
Those we will continue to work on because Oh.
On post approval, we will have to do E Z.
And your uptick studies on the pediatric studies searches toward meeting rumba is one of those we are comfortable with you. So so we'd be lucky and relate date also research and so really Graham.
But I agree with you and <unk>, even so I think 64 is a little bit more.
Effective in terms of hot and cold.
And functional.
And and Remi, just as a follow up on the Joe's, saying and talking to clinicians and clearly I think you've demonstrated that this drug can have significant utility as monotherapy.
And just talking to some clinicians and any sort of talk about this as being used on with.
Income combination with another anti psychotic and do you think and Matt context, perhaps the 32 milligram might be the way to go or do you think even there you would you would you would prefer to 64 and I had one other quick follow up after that after that.
Yeah, and I'd say it's.
It's a great question.
Uh huh.
I think I think we'll just data will generate us a lot of discussion about the building.
Do we need and in older patients.
Sonic trades on are funded and psychotic says this is a radio.
Broader question on going largely beyond the Minerva.
But I think right is it that maybe we could think about.
Our strategy to treat patients, Wyoming, and a 72 milligram would be the maintenance dose and you had the ASR 64 milligram or an antipsychotic to help going on there's a handful from acute episodes of agitation.
Some and some and some are more predominant.
Positive symptoms and on demand.
This might be the way to move and move to move forward on this.
So this is how I see it yes, so probably I mean this opens on the space of a lot of different strategies.
For a large a larger number of patients suffering from schizophrenia.
Okay, and then just I know.
You know, we're certainly and the strength of the data certainly would suggest you have a have an approvable drug just didn't and.
If the agency work and sort of still requesting an additional phase III just given what we saw from the open label sort of maybe building on sort of what Tom's question about how you seem to have you know.
As time goes on and the benefits seem to accrue I mean would there be.
Worthwhile reconsidering and sort of having a longer double blind placebo controlled section I mean, I know, it's sort of a it reduces some of the comparability, but just clearly it sounds like it looks like the deep ex continued to build over time and presumably that would a longer study, we would sort of mitigate some of the waxing and waning of proposals on the placebo arm as well.
Thank you.
Yes.
Great question Doug.
And I just I mean, you can look into the data.
But remember I mean, we had we had the P value.
And at four weeks and eight weeks and that they are.
Placebo compared to 64 interest in this trial is a double blind phase and we had obviously.
On a significant differentiator as a phase <unk> study.
Refresh peoples and mindset.
The modified ITT population, we have and nominal P value on every six months to form and so I think really we have really suffered about the faster than many other and extremely positive phase <unk> study and and.
And because of our growth is not cannot pick up tend not be picked up excuse me.
Due to side effects and we.
And we suffered a little bit from a profit.
Bill.
Inflation has I mean, although is a double blind and things.
All these state I mean, Doug and I agree with you.
I think longer.
Is that sort of in order to get the placebo effect under control and so I'm not saying that we should do a longer study and just saying that this assumption to consider east I mean, and we think about the next trials with other type of trials, which is one of them.
Okay, great. Thank you so much and congrats on the open label data.
Thank you Doug.
Our next question comes from Myles Minter with William Blair.
Hi, everyone and congrats on the data and thanks for taking the questions that 11, 7% very lots right seems pretty impressive.
And definitely above the expectations are.
Clinicians that I've spoke to on on roller paradigm monotherapy here, yes.
A brief look at literature would suggest that at least and acute side prices patients is as high as like 40% to 80% relapse over 12 months when you withdraw therapy on.
This is a completely different patient populations. So I like how do we think about that 11, 7% relative to what we would expect and the real world with this particular patient population and the phase III.
Yes, great question.
So.
Obviously I mean.
On the clinical trial and that means there is always.
Something which is absolutely the same auditing and real world and blood.
And your clinical practice.
I mean, we tried ready to go.
According to clinical practice and 7000 words, we switched quite quickly from Salon to chug Cortez and two hour clock and monotherapy and all this is very similar to what youre doing and in.
And clinical practices.
I think it can be comparable to what will happen and.
And really like.
The question about the vs passive.
Vic and study population.
And not with you here in terms of specialty.
Study population I mean, I think we just took the patients at a different level.
And then on what Youre doing usually and acutely and relapsed patients so basically.
And remember what Youre looking to our inclusion exclusion criterias are very similar to what you have now.
As of trials, yes, Indeed, I mean, we don't types of criteria and was a cookie pumps.
We have the criteria of checking and other means these patients have a.
A certain level of for negative symptoms and indeed, we are switching them from ontic psychotic two hour treatment Wednesday are stable in terms of positive symptoms and except to say that as a positive symptoms 14, 16 points is quite low and that's all.
On the completed reviews and I mean, this is a different patient population.
And do you know when youre going according to the literature based on our eligibility criteria and and this represents around 60% to 65% of the of.
Of the patients and visited agnostic of schizophrenia and saw so again I mean, it needs to be fine tuned the I'm, not claiming and gains.
Our drug to debate and we have current dependence and rock which helps.
Acute episodes on positive symptoms and I thought the whole I'm not saying this but.
And the completed we use and this is a completely different populations on.
Population and we are currently seeing in clinical trials on population you have to treat and our clinical practice and so this is my answer to your question.
Yep, that's not completely understood.
Alright lots right, regardless it is definitely in pressure from 91 on the bioequivalence study as well.
And that there was a mentioned and the press release this morning that you'd be testing and additional commercial and scalable formulation or at least one of them is.
Is that I'm and this Charles fielded.
Chairman and non inferiority between the phase two bay, the phase three and commercial formulations and sensitive area under the cap expires Oh are we going to be looking at that day of fate <unk> hundred 20, metabolite again that on and I was the sort of concern with the Q&A statewide prolongation and set the face to any and.
Thoughts there would be helpful.
Not all of them.
Completely described it correctly.
And the treaty.
Remember, we know that that means you actually cash is driven by exposure.
And because we did a lot of PK PD modeling and obviously, we will do these series of data.
Including the extension data.
So this is a primary objective for sure and we didn't.
On the contrary to control those on multiple items DNP fashion on tea and Pascua Lama.
And we completed described what is your objective and system.
Okay and the final one is just for Jeff.
And $95 million and potential milestones from the sell through rates and royalties out a royalty pharma.
Some of those linked to clinical milestones, there's a lot of phase III trial, its counting on at Janssen for that product.
And your comment were there any of those milestones are weighted to like the right out of one of those trials and the whole program has to be completed before you would potentially reshape and milestone there.
And any anything you can disclose that'd be great.
Yeah, so there's a mixture of of triggers.
Triggers.
Part of it is due to clinic.
Clinical progress.
And part of it is due to regulatory approval and different geographies and there's some sales bonuses there as well.
Okay cool thanks for the questions and congrats on the data looks right.
Thank you thanks miles.
That concludes today's question and answer session I'd like to turn the call back and running for closing remark.
Yeah. Thank you.
So thank you all and that's and.
And I hope you enjoyed it.
I think.
And we continue to work hard.
To put together the best package here.
That's Inc.
Extremely months or anything that day to be assumed today and.
And I think it is also extremely important.
And as we said Rockies moving.
Towards our patients need on club.
And you'll treatments on negative symptoms because keep in mind with average new no.
No treatment.
Approved as of today and less for negative symptoms. So I'm really looking forward to update you very soon.
About Oh.
And the Bioequivalence study about the pharmacology about the old news coming on coming up.
Central game on and stuff.
And hope to speak with you about my.
I think a nice day.
This concludes today's conference call. Thank you for participating you may now disconnect.
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