Q4 2020 Altisource Portfolio Solutions SA Earnings Call
[music].
Good morning, and welcome to the bio cell therapeutics fourth quarter and full year 2020 financial results Conference call. Currently all participants are in listen only mode.
If anyone should require operator assistance during the conference. Please press star zero from your telephone keypad.
Just to remind everyone certain matters discussed in today's conference call and our answers that maybe given to questions asked are forward looking statements that are subject to risks and uncertainties relating to future events and door of the future financial performance of the company.
Actual results could differ materially from those anticipated and these forward looking statements.
The risk factors that may affect results are detailed in the company's most recent filings with the U S Securities and Exchange Commission, including its quarterly report on form 10-Q for the quarterly period ended September 30th 2020, and will be updated by its annual report on form 10-K for the year ended December 31, 2020, which can be found on its.
The website www dot bio excel therapeutics dot com or on Www Dot FCC dot Gov.
The question and answer session will follow the formal presentation.
As a reminder of this call is being recorded.
And it's now my pleasure to turn the call over to the more meta the CEO of <unk>. Please go ahead Sir.
Thank you operator, good morning, everyone and thank you for joining our conference call of the cause by some kind of.
The financial results and businesses.
For the fourth quarter and for the out of 2000 during the day.
We appreciate everyone's time and attention.
Joining me on the call today.
Turning to Steinhart, Chief Financial Officer.
Gain chief commercial officer.
Thank you Yakov Chief Scientific officer.
Vince on the Chief Medical Officer, and they knob, and Abu <unk> Chief Development Officer.
And we would like to extend a warm day would come through June.
And Javier Rodriguez through our board and management team.
Our leadership team and bringing strategic experience and support the transformation of <unk>.
This is the historic time for the buyer.
And we are preparing to transition to a commercial.
Neuroscience focused company today.
Pleased to announce that we have completed the submission of our new drug application to the EBITDA for the acute the Brian.
Of.
And the blend of of schizophrenia, and bipolar disorder related agitation.
I am proud of our team's hard work and completing this important milestone on the schedule Viva and able to accomplish the significant achievement with the impressive it's b from Washington and human.
And B is our mission and just over two years supported by our powerful AI base of discovery and development platform. This is a one plus the NDA and we believe if approved can be the first drug to have received FDA approval.
And.
And the application undergoes the Fda's review, we have taken the steps to begin the transition to airport potentially commercial stage organization and we are actively advancing our launch of Andina initiated.
In addition to establishing our commercial and medical teams with seasoned professionals, we are building, our pump and Chilean plus sector, including the design and the structure of our sales force.
Our medical Science liaison team has been hired and is completing its fair Nate the.
The team will begin and scientific exchange and infections by the end of this month.
And I'm confident that we will be relative per for.
For the potential commercialization of five or one Richie for Peru would be of unique and innovative treatment and the U S to specifically address the schizophrenia and bipolar disorder related agitation.
I'm also pleased to report the duet stacks, obviously the entity one as they need to have been accepted for presentation of this year and.
The American Psychiatric Association annual meeting in early May.
And the potential approval of <unk>, one will have paved the way for our broad neuroscience franchise expansion, establishing the kind of needed as an important new treatment across of the agitation and spectrum and multiple neuropsychiatric disorder.
Due to fiber one's unique mechanism of action. We are currently investigating the follow on indications dementia related agitation.
Relative and the lithium related agitation.
The recently highlighted in our firewall one focus gear.
All of the past 12 months, we have made tremendous progress with the Dublin.
And of the additional programs with the goal of providing and 501 if approved to the mill.
And so of neuropsychiatric patients suffering from agitation and other distress related symptoms.
We plan to submit a supplemental NDA for the follow on indications and the yields to come.
We recently announced positive data from the Tranquility study our phase one b slash two trial for the acute treatment of dementia related agitation to.
<unk> GAAP results from this trial.
<unk> was well tolerated with no severe or serious adverse events, such as syncope of fall.
Statistically significant and clinically meaningful reductions in agitation, where the team with both 30 and 60 microgram.
Cohorts at two hours post dose as measured by the SEC.
Yes, and modify the CMI scale.
Rapid and durable reductions in agitation, we're teamed with the 60 microgram cohort across all of efficacy endpoint with the significant reductions and agitation lasting up to $8.
So bill on the tranquility results, we have initiated of 46 patient multicenter placebo controlled tranquility expansion of study investigating of 40 microgram dose cohort of <unk> five of one with 121 randomization.
We believe the supplemental go hard will help to inform our comprehensive clinical the number and strategy targeting the free.
And the age of dementia care setting from long term care centers to add homecare.
Furthermore, our end of phase II meeting with the FDA has been scheduled for the second quarter of this year, we plan to initiate our pivotal phase III program and the second half of 2021.
Turning to the release study our phase one b plus two trial of <unk> five for one for the treatment of opioid withdrawal symptom.
And we remain on track to report top line results. Later this month to further explore <unk> potential to alleviate the debilitating side effects of withdrawal, thereby helping patients overcome their addiction.
Last month, we initiated the lastly did the trial a phase III trial of <unk>.
And then final one for the treatment of ICU patients with the lead.
And related agitation.
Expect to report top line results from this trial and B plus quarter of 2022.
Most Bolivia and patients experience agitation, which we estimate of Gardasil and approximately 4 million patients annually.
Alpha and complete gaming overall patient care and extending of hospital stays and the lithium Marcos and numerous cost per drug treatment setting, including the ICU service.
Gulf of our hospital wards and emergency departments.
Our strategy is to evaluate and 501 and believe the ambition across all of these hospitals.
Thus, making this indication highly synergistic with the medical and commercial hospital based interest sector. We are currently building and support of our cluster and yet.
Lastly, buyer of XL and its collaborators the VA, Connecticut healthcare system and the Yale University Medical school in the.
<unk> 501 for the plus time as the potential chronic treatment and then.
And at home setting for patients suffering from PPD is the related to alcohol and the substance abuse disorder under the grant from the U S Department of defense.
As you can see we are actively exploring <unk> potential across numerous neuropsychiatric and neurodegenerative disorder advancing five distinct indications with the goal of creating a highly valuable neuroscience franchise.
Our clinical trials and various disorder have shown that fiber one is well tolerated and at the mall.
Illustrated a robust treatment effect at multiple of those ranges.
The bank to support the broad market strategy for the underlying diagnosis.
We are passionate about potentially bringing this and our treatment for the millions of patients that lack of effective and tolerable options and we continue to explore additional patient populations.
The hallmark by stress related symptoms.
We believe that <unk> 501, if approved has the potential to become the standard of care for the treatment of agitation.
The significant and Dean.
Dean for the power of our AI platform.
I didn't the buying and developing potentially best in class therapy with cash.
And the new to leverage the Walgreens drug for the innovation model to identify and develop new program to expand our neuroscience pipeline and addition to 501.
Now I would like to turn the conversation to our immuno oncology clinical candidate <unk> 701.
Our oral immuno modulator designed to stimulate both being made and acquired immune system back in November we presented safety and efficacy data from the ongoing combination trials all of that one O one and Keytruda at the society of immunotherapy for cancer annual meeting.
Additionally, we provided an update on the ongoing phase <unk> trial, and the aggressive form of prostate cancer at <unk> last month.
Based on these encouraging antitumor activity seen in both core and heart tumor we believe that no one's mechanism of action when combined with a checkpoint inhibitor has the potential to enhance the NIM, a major amenity and maybe and effective targeting the figure.
To treat tumors.
We look forward to continuing to advance and one of one with plans to provide top line results from both of the phase one b.
Last two trial and aggressive forms of prostate cancer and the MD Anderson basket and advanced solid tumors and mid 2000 and currently with.
With that I would like to turn the call over to our CFO Richard Steinhart, Richard Thank you memo.
We reported a net loss of $21 1 million for the fourth quarter of 2020 compared to a net loss of $8 3 million for the same period and 2019 for.
For the full year <unk> reported a net loss of $82 2 million compared to a net loss of $33 million for the same period in 2019.
Research and development expenses totaled of 11 4 million for the fourth quarter compared to approximately $6 5 million for the same period and 2019.
The increase was generally due to growth and clinical trial expenses for our <unk> 501 trials and related compensation costs.
Research and development expenses were $58 million for the full year 2020, as compared to $25 8 million for the same period and 2019.
The increase in R&D cost for the full year 2020 was generally related to rise and clinical trial activity and the attendant personnel and professional research costs necessary to perform the trials.
General and administrative expenses and the fourth quarter of 2020 were approximately $9 7 million compared to about $1 9 million for the fourth quarter of 2019.
The increase was primarily due to higher compensation related costs and increase and professional fees for legal and patent services, along with higher insurance premiums and market research fees.
General and administrative expenses were $24 3 million for the full year 2020, as compared to $7 8 million for the same period and 2019.
The higher general and administrative expenses.
Consisted of increased compensation costs related to the companys growth and preparation of the potential launch of <unk> five of one.
There were also increases and professional fees for legal and Investor relations expenses and insurance costs.
We had cash and cash equivalents of $213 $1 million as of December 31, 2020.
That concludes our fourth quarter and full year 2020 financial review.
Now I'd like to turn the call back to demo for any further comments demo.
Thanks Richard.
And now like to open the call for questions operator.
Thank you well now be conducting the question and answer session.
And to ask the question. Please press star one from your telephone keypad and of <unk>.
Information total indicate your line is and the question queue.
The interest start to feel like to move for your question from the queue.
And sort of using speaker equipment and may be necessary to pick up your handset before pressing the star keys, one moment. Please fill the poll for questions.
Thank you.
Our first question comes from the line of Geoff Meacham with Bank of America. Please proceed with your question.
Hey, guys. Thanks for the question and congrats on the NDA and and all the progress.
Two quick ones and mostly on 501.
When could you have data from the 40 microgram cohort of Gist and shrink quilty.
I'm just curious of how that would impact your pivotal development plans would you delay starting.
Pivotal do include debt and then the second question is obviously you guys have a very broad clinical plan for 501.
Are there any other indications where agitation plays the role that you guys could explore.
Down the road it seems to me like the a pretty broad.
Indication base beyond what you guys have talked about across the the neuroscience field. Thank you.
Jeff. Thanks for your question. This is the model.
To answer the question about the 40 microgram dose cohort.
We will expect the data that you don't sometime this week this year.
Don't expect any delay and initiation of our phase III trial.
Because we already have due to the 30 microgram and 60 microgram both of the statistically significant and.
And and we had good response rates as you have seen with the both the ability.
So we plan to initiate our phase II trial after meeting with the FDA getting the agreement with them on the doors on the trial design as well as on the endpoint one of our phase II meeting, we will initiate our phase III trial, and we expect the trial to begin in second half.
For this year.
Coming back to your other question, yes, we do have a very broad clinical development plan and strategy. We continue to explore working with our experts in addition to using our AI platform to expand the potential of 501, the upcoming five indications.
We are committed and we have ongoing trials in all of them and we already have proof of concept.
And in three indications schizophrenia, and bipolar disorder, and dementia and opioid withdrawal of data is expected sometime this month.
Our next indication that we're looking and where we have some.
Im good evidence is depression related agitation.
Some of the patients and our bipolar.
The patient population, where the pressure the preservation and we saw a robust responses. So we're exploring that.
Looking at <unk> and some of the other areas where the <unk>.
Mechanism of fiber one.
Israel, even and this is the ongoing exercise and we believe and seeding that our IP position is up to 2039 with our plus Barton we have a lot of IP life to be able to bring these new.
And the NDA is through the marketplace.
Okay. Thank you Bill.
Okay.
Yes.
The next question is from the line of Greg <unk> with Goldman Sachs. Please proceed with your question.
Hey, good morning, Thanks for taking my question and congrats on the progress of the filing.
Just a couple of questions one.
As you and filed the NDA and I'm just trying to think.
About your continued pre commercialization activities and primarily around how you can build awareness.
And for.
The product with with physicians and so my question is.
What is your sense of the current awareness of your product.
And how much education do you think youre going to do.
Yes.
It's probably coming everything is virtual so I'm just trying to get a sense of how you intend to build up your.
And perhaps mind share with physicians.
And of my first question of sorts and then secondly.
And just give us a sense of where you are on manufacturing CMC as we tried to think about the.
And the filing and making sure all of the boxes are checked.
And given an update there and then lastly, just any comments and how we should think about.
The model and 2021, especially given the ramp up.
And I assume and and commercialization activities ahead of the launch of how we should be thinking about.
On a quarter by quarter basis, or maybe just directionally.
The operating expenses, particularly the SG&A.
Thanks, Greg. This is the model I will take the CMC question, and then I will invite my colleagues.
Well and the need to answer.
Sure.
And we had and escalation as the part of our pre commercialization strategy.
<unk> like <unk>.
Limited process, we use that to build batches for our phase III trial.
The scaled up <unk>.
And more of our forecast and projection is for up to next several years like 2025 or beyond we have the capacity and the same scalable process by increasing the shift you can increase the throughput you can add and I know that automated process and.
And you can and key the throughput so we believe from the CMC perspective and the capacity.
<unk>, we are in good shape to scale up for the commercialization perspective with that I will pass it on to will and they.
Now to address your question.
Sure. Thanks, everyone. Good morning, Greg This is will.
So relative to raising awareness, obviously, we see this as a great opportunity on two fronts one.
Introducing bio and cell therapeutics to the marketplace and establishing.
A reputation there as an innovator and neuro psychiatric drug development and also raising the bar. If you will on the the treatment of patients who experience agitation associated with their their mental health conditions, and our market research and theirs.
High level of awareness about agitation, obviously and the impact it can have on on patients and also on the clinicians who treat them.
There's also a high awareness of current therapy and some of the potential limitations of that therapy. So the profile that has emerged on five of one.
As well received so our plan is two fold over the next several weeks actually starting this month when we deploy the.
The medical science liaison team.
Both from a clinical perspective and of payer perspective, and so they obviously will begin scientific medical to medical exchange to begin to educate.
And to be able to respond to questions regarding the program et cetera.
And then secondly, we are advancing development of and educational campaign, which we are planning to launch in May which is mental health awareness month.
And also the month of the API meeting to raise awareness about agitation and its impact on patients and also clinicians as a way to begin the process too.
And to lay the foundation for why a launch of a potential launch of five of one could be could be helpful and the treatment of those patients. So we have.
We have solid plans and they are starting to rollout.
Thank you will so and.
And the momentum we've got two posters accepted at 88 and <unk>.
And we're working very closely with this medical association to sales scientific exchange virtual venues with our MSL and medical information team.
The poster presentations actually Dave would be virtual and virtual poster Hall from May stars. The June 1st and we still don't have all the details, but we're going to have approximately 12 sessions of those clusters.
Greg.
The expense Yeah, and then just maybe on the on the on the model on the modeling questions on how to think about SG&A throughout the year.
So.
In terms of.
And specific guidance, we haven't provided that specific guidance, yet because our pre commercialization and commercialization plans.
The evolving and getting warmed up.
Our cash position as the <unk>, two and and $13 million as of December 31.
This cash position is good to execute on key milestones that we have laid out today, and 2000 and Tony one and well into 2022, so as we move along we'll provide more guidance as our plans for months.
Okay. Thank you for taking my questions.
The next question is from the line of Chris Howerton with Jefferies. Please proceed with your questions.
Great. Thanks, so much for taking the questions.
I guess, just two quick ones for me first.
With respect to the NDA submission.
And what if any kind of communications can we expect.
Throughout kind of the coming months in terms of the interactions with the FDA and.
And the acceptance and just kind of what might be of expectations. There and then question two is.
With respect to the 701 data and the middle of this year I guess.
Just help us maybe understand.
For frame the expectations that we should have for what the quote unquote top line results should be in the middle of the year relative to what we already know.
Thanks, so much.
Thanks, Chris This is the model in terms of our communication and we just submitted the NDA will go through the process, which is like and now <unk>.
The 60 day review process, which will.
And then NDA will get accepted then it's fine and then it will go through the rest of the process from until the approval. So thats. What we expect we are preparing internally for the commercial launch on the standard review process, which is the 10 month and in case, we get priority review.
And then we will be really two loans the product in Q4 of this year, so our commercial teams and medical.
The R&D medical affairs team that preparing for both scenarios our base case scenario is.
The standard.
And coming back to your question related to the 701, what do we expect.
Both trials.
The aggressive form of the prostate cancer with the CNBC and <unk> and then we have <unk>.
<unk>, which is with MD Anderson.
We expect the boarder what initial signs of activity we have seen.
That data will mature and motivation and data will come that will build our for the.
Country than what activities, we are seeing in the corner tumors and.
And in the hard tumors, which is the basket trial, which is primarily the keytruda refractory ore to the naive patients. So it will be the more mature data, which provides the clarity which direction. We want to move the program and the next step in terms of a brewery the pads are in terms of of late stage.
So those are the decisions we liked the reach once the data from these two trials have been completed.
Okay, that's great thanks very much.
Okay.
Our next question is coming from the line of sort of month Kulkarni with Canaccord. Please proceed with your question.
Brian and thanks for taking my questions I have a couple of recent key opinion leader event. It seemed like there was a consistent theme that the real opportunity for 501 seems to be and and at home use setting at least initially of product will be used in the <unk> setting.
Specifically, what steps do you need to take the been the product home from a regulatory perspective, how soon after approval and the first indications might you be able to achieve that goal and would that meaningfully change of commercial infrastructure needs and that's the first.
The question and the second one is given the recent developments and the dementia related psychosis space do you have any specific plans with respect to the potential use of fiber one of the VIP setting either side of our subtonic basis.
And two great questions. So let me take the first question and I will invite will do and more.
In terms of our plan.
Initially we are building our commercial interest for the institution setting and.
And we will know once we get our label from our first NDA with the label.
And we get with the FDA once we know the labor.
And if it has become the trial was conducted and the institution of there being that institution and restriction and then we will work with the EBITDA that what do we need to do to take it into the home care setting and that would and wall and this is not based on our conversations based on our experts and internal things.
King.
And will require.
Providing additional evidence to EBITDA that in a home setting there is the safety and Tolerability for debt I just wanted to remind everyone that in our phase one two trial of escape. The Affinia, we saw that even lower doses than one during the 80 microgram, even the <unk>.
<unk> was numerically separating so we have a very good dose response and this gives us lot of flexibility, how we design our strategy to take this drug and the home setting.
Partly in dementia, we initiated the 40 microgram dose cohort because we are thinking now long term will and his team has done quite a bit of assessment of the dementia market.
And it's very clear the market is almost divided into 50 50, and the long term care centers as well as at the home care Center.
The.
Sales, we started seeing statistical significance with lower doses with 501 and there is a very good reason why VLT because the exposure levels of much higher.
And the dementia patient, which we have observed in our PK PD modeling it gives us a lot of flexibility in terms of the dosing that how do we think and built optionality for the long term care setting our phase III trial, where we have to clear and doses 30, and 60 to initiate the phase III trial and 40 gives us.
Additional optionality to be able to exploit when we do.
Homecare setting and when we have conversations with the FDA, So thats kind of our.
Overall, the thinking around how we take it into the home care and really do you want to add a little bit about the marketing side.
Sure good morning, some and.
So let me characterize it this way there is lots of opportunity and.
<unk> multiple of treatment settings with the 501.
And I don't want to minimize the importance of the institutional setting because many many patients channel through that whether they have schizophrenia bipolar disorder and dementia delirium etcetera.
In order to get help and treatment for the agitation symptoms that they are experiencing so as one of all pointed out as we look across at least the initial three schizophrenia bipolar and dementia, the institutional setting as a place of high frequency of agitation episodes and and treatment. So that's why we believe.
Out of the gate with the label that enables us to to start there we'll be able to to.
To achieve.
A good rate of adoption.
Longer term, though obviously, we can take the product.
And in the community setting based on how the <unk> outlined our plan to get there. The community setting is an important one for a couple of reasons and not the least of which is theres, obviously and high volume of patients.
And our living either in.
Nursing homes et cetera.
And one context or literally at home and the dimension of population and that number is going to grow as the Alzheimer's patient increases rapidly over the next 20 years and.
So in terms of of how we think about the commercial kind of infrastructure. If you will we have our land and expand approach, where we'll land obviously based on our initial label and the hospital and as the label allows for expansion. We can build sequentially from from the hospital setting to them to the assisted living nursing home setting and then eventually at home and when we get to that point, we can decide how best.
To do that commercially in terms of whether we go it alone or we bring on additional co promotion helped.
To answer your second question about the cycle.
No agitation and psychosis and dementia patients and a part of it the spectrum.
And that's very clear and our 501 works and the agitation and Thats, where we have proven the efficacy of <unk> hundred one and back which is the <unk>.
And when we use for agitation is the subset of the band which measures psychosis. So as we continue to evolve our program. We will continue to assess and see what the impact 501 can have outside agitation and psychosis and then we will be and <unk>.
<unk> to discuss like what possibilities are there for 501 I would say the agitation currently we are laser focused on the agitation.
And I on the expansion into other indications.
Got it thanks.
Our next.
And is from the line of Robin Carnahan with <unk>. Please proceed with your question Hi.
Hi, guys. Thanks for my question and congratulations and the progress I have three I'll try to read them slowly so why non clubs Sydney, one and release and one on your filing.
I guess, the first and the filing I know the and tranquility you did not the age related increase side effects from exposure and I'm, just curious if proactively you'll be including that the bench of data in your filing.
Just trying to get a sense of if theres. The chance if you have to you might say hey.
You may want it the data in patients over 65.
The the label and debt.
That's the question there of how youre going to advantage of that because the FDA has been asking are behaving and ways I think that the wall Street might day is a little different.
Second question is on relief.
And the upcoming trial could you set the bar for what is good data on the account and the South point.
And can you affirm that we'll be getting all five debt.
And the more classic lay vs dementia, we only got a few doses.
And then for <unk>.
Obviously, you're looking again at different doses and also the older patients.
And while Youre, saying, Dave is coming first quarter of 2022, I guess the question of.
And sort of what happened and the debenture trial are you planning and just waiting till you get all of that data from all of the different doses or do you expect you might be might be able to stop the trial at some point early and.
And if youre seeing a dose that is a little bit more.
And.
And if youre seeing a group of patients that are more sensitive like the over 65 population of America, the getting half of the dose.
And so I'm happy to rephrase does that doesn't make for your question.
And thank you Robyn and I have jotted them down so I will try to address one by one and.
And also invite and my colleagues. So your first question related to the NDA.
And providing any additional data we just submitted the NDA and we have of Endo phase II meeting coming up at the EBITDA for the dementia.
We don't have any inclination of any conversation that any additional data is needed and once we had a pre NDA meeting with the FDA whatever was needed and whatever was the agreed.
And provided that as the part of our NDA submission.
Youre right, there and patients with schizophrenia, and bipolar patients 65, and older and they were and our trial and it's very interesting that whenever we have done any analysis of subset analyses, we haven't seen much difference in those patients versus the younger schizophrenia and bipolar patients.
For dementia patients what we are seeing may be very specific and these patients as well as and these elderly patients.
Coming back to your question about the bond for the release trial.
The most important questions that we will be or we are trying to address and our trial is what is the safety and tolerability and that's the first.
Because for the first time this drug is being dosed two times of day for seven to 10 day 12 hour of part so it's almost of sub chronic dosing. So we wanted to understand that and as you said we are testing five dose cohort and you will get the data from all of those cohorts.
And second and.
In terms of.
And the tension leg and know how long these patients will get retained on the drug is of very very important efficacy benchmark because keeping them within the program has embarked on and sort of retention and <unk>.
And then some of the non opioid bids that have been approved and there is only one with the similar mechanism.
So the retention is important and second and the third piece will be what the.
And calls the reduction is and at what doses, we start seeing efficacy. So that's those are the kind of things I would say.
We are trying to achieve so that we can take this data to the FDA and have a conversation with them about the next steps and what the next trial will look like.
Regarding the plus EBIT.
Sure.
You are right.
We have designed the trial based on our understanding based on proof.
Proof of concept that is their debt and the lithium related agitation patients who were on haloperidol or refractory haloperidol.
And what does is what required repeat them for <unk>.
Use that data we used all our expedience of multiple indications to come up with the doses as we test the doses and we see safety Tolerability and efficacy at that point, we will make a decision do we need to go for the.
And in assessing.
The patients in the lithium ICU patients for agitation. So it will be the ascending dose the that and adaptive trial, we make decisions as we move along so can the data come out early is possible, but currently based on our all of the work we have done in terms of the recruitment rate.
And what doses, we need to do our guidance is Q1 of 2022.
And just a quick follow up so what is clinically meaningful for cows and just I guess the retention maybe it's something we're looking at.
So what is that number because those are the endpoints I'm less familiar with and.
And then are there any with opioid nave patients in the other side effects that you are sort of looking for to not occur during the seven days, they're on the drug and.
Also when you're watching the patients already get you're following them for 10 days.
What is your expectation after the seven days that they go back onto the opioid based drug are you looking to see if they can stay offset dry the seven days of enough for these patients sorry for all of the questions.
None of them.
Those are very good questions.
And the.
I will invite Frank to provide and perspective on what happened what we are trying to achieve for these patients and what happens to them most of the withdrawal symptom free.
Great.
And so Robyn.
Think.
From a side effect profile.
I think what we really care about most is making sure that these patients stay in the study.
I am sure that debt.
They're experiencing a lot of different things and some of them are getting relief from some and others not.
And and so on but the most important thing is that they stay in the study.
In terms of relating sours and cows, it's basically.
Just looking at it versus placebo youre going to get you get a lot of variability and these studies because of the way these patients handle the.
The withdrawal process. So that's also very important but at the end of at the end of the day, what we're trying to achieve here is to get these patients through this withdrawal process and get them onto treatment like naltrexone or things like that where they can begin rehab that to me and to us.
And is probably the most important thing that we could gain with the 501 treatment.
And Robin coming victory of caution in terms of the safety. We will are watching similar kind of parameters, we did and is schizophrenia and bipolar and dementia of what the impact of that on the cardiovascular badger meter and other things because we are doing.
Two of these 12 out of the part for seven to 10 day. So it's the more of let's say of validation of a of more sub chronic range of dosing for the opioid withdrawal symptoms.
Great. Thank you all.
Our next question is from the line of ground <unk> with H C. Wainwright. Please proceed with your questions.
And thanks for taking my question. So just a few kind of technical ones here.
First is for well I was wondering if you could comment on what strategy youre going to take with regard to bringing on actual sales people.
And if youre going to pursue this on the contingent offer basis and if so with what timing you anticipate.
Putting that in place.
Second question is generally speaking on R&D directionality of spending if you could provide us with some commentary on that how do you expect R&D to trend in 2021 relative to 2020.
Because the.
And the profiles of the clinical trials that you're running in 2021 are the <unk>.
From the profiles of the trials that were being run in 2020, but just wanted to get a sense of whether that's going to.
And directly translate into higher R&D spending in 2021 relative to 2020.
Also wanted to clarify the timelines for the results with the 40 microgram dose and demand.
Sure.
And then.
Just wanted to.
Asked about your outlook right now as far as having the one is concerned.
No. The previously we had speculated on the possibility of that.
101, being spun out into a separate entity, but wanted to get a sense of if you.
You would contemplate that when would you contemplate that and what the preponderance of clinical evidence with 701 would you need to see in order to be and are positioned to make a determination as to whether that is likely strategy or not.
I can take on the <unk>.
For the Mega and the proportion as well at 701 question and then I'll pass it back to rail.
Regarding the 40 microgram dose escalation, we will expect data sometime this year.
And we will provide and Duke court.
Timing when the data will be.
The announced for the 40 microgram dose.
And regarding Mexico.
Next question, which is related to the 701.
701 has encouraging.
Antitumor activity. It has 700 patient data from the previous one.
That was done by the previous company before we acquired it is the single agent activity and melanoma and we already had.
Very good evidence that this drug.
Ken kind of.
Some of these call tumors too hard or increase the response rate and the tumor which are refractory to keytruda treatment of nine so <unk>, we will be addressing will be what tumor types of reward one to build the next development plan and where we're going to focus that will occur.
Low us to develop approvable the path for 701 at that point and time once we have the jada and our hands and we will make a decision and.
On what is the best choice partnering.
As you mentioned like and some strategic options and we will work with our board whatever is best for our shareholders. We would explore that option. So it's a work in progress State June and we will provide an update as we get to learn ourselves about the data and as we build our strategy one.
We have made.
Clear is that we are and the company becoming of focus neuroscience company from AI and all the way to drug discovery development and now we have integrated commercialization. So we are of very unique.
Capability to be able to come up with the drug under one roof and be able to commercialize. So we want to continue to build on that capability. So with that I will pass it onto <unk>. So he can address your question on the commercial thing sure. Thanks, Shlomo Hello, Ron.
The sales force build strategy.
Is.
Is in place.
As we've talked about previously we intend to build our own hospital based sales force of 75 to 100 representatives that.
That number will be informed as we complete the ongoing project.
Project to design and size and structure of that sales force, but 75 to 100, certainly is as a reasonable a reasonable assumption at this point.
And we will track the NDA review over the course of the year, starting with the day 74 letter.
And then obviously well know not only if the filing has been accepted but we'll know our <unk> that will that will obviously continue to.
To support the build if we're successful there.
We are building the commercial infrastructure today, we will have that ready for September and the event, we do receive a priority review.
And then the the lever that would need to be pulled down. It's just the hiring of the sales reps, we will monitor that well have the mid cycle review meeting et cetera.
The.
The track, where we're at but our goal is to hire that sales force type of it ready and the fourth quarter to be trained and then under our base case assumption to have them ready to launch in Q1, or we will just move that earlier, if we get positive news on the priority review.
Okay and just.
Two quick clarify Qatari points there.
Are you, saying that you would meaningfully accelerate the sales force activities.
When you get to the mid cycle review point or when you are and kind of draft labeling discussions with the FDA and just wanted to clarify that sure no debt.
For the clarification and then we will just track.
I mean, our plan is to to recruit and hire and the fourth quarter. So that the sales organization can complete its training will be trained and everything except obviously of the product label, which would come at approval and then we will complete the training then and then we'll have our launch.
For the drug is approved so yeah, no I was just referring to tracking progress you don't know until you know at the very end. So I didn't want to represent and any of the way that the mid cycle will give us any guarantee its just track questions from the FDA et cetera.
And you anticipate that there is likely to be rich talent pool to choose from as and when Youre looking to make those hiring decisions and does that a reasonable assumption.
That is my reasonable assumptions and so yes.
Okay, and then just wanted to circle back on the R&D directionality of spending in 2021 relative to 2020, how we should be thinking about that.
And on debt.
Our major trial that we'll be initiating it and.
Dementia phase II trial.
Those have the bigger the spend but our trials even if we look at I would say they named it one and two which was two phase III trials with 750 patients the.
R&D spend was quite limited to complete the trial.
So I would say the phase III trial for dementia will be something of that order and tons of our expense per patient cost can be 15th of June.
And then per patient costs for that basically we use and building our assumptions and depending on where we end up with the opioid withdrawal. After our data release comes and what the late stage plan is that we'll add it to our planning for 2021 'twenty two so at this point and time I think.
We are not providing any granular guidance, but our overall guidance is that our cash is in a good position to achieve all of these milestones and in 2000 during the one and get well into 2022.
Okay, and then just one minor technical question on the liquidity trial I was wondering if you could clarify when you look at the secondary end point, which was classified as the earliest time at which of two point drop as seen in rats. After five of one administration.
Would you.
And considered to be.
Uh huh.
The good outcome on that the secondary endpoints and.
Can you explain kind of the relationship between the secondary endpoint and the primary endpoint in other words and the secondary endpoint only of real importance of the primary endpoint of wasn't met our how are you thinking about the relationship between the primary and secondary.
So I will.
Right now for this.
Thank you for the question. So yes, so the primary endpoint for.
Adding to all the experts is very significant which is the drop of breath of to where the patient is not to some of the line.
And the secondary endpoint is how quick it go so and as you may understand in and IC.
We want to make sure that we call appropriately the patients as soon as possible and because we saw excellent results with variety of planning too.
With the statistically significant.
I mean period.
20 minutes so.
That will be also very good and then.
And we talked about this with all of our expertise.
To your second point is of course.
We intend to meet our primary endpoint and that is why we have all of the escalation of the Joseph a.
And then we can we kind of triangulate that also with how soon that can be done, but also with the duration of.
And the effects.
Yes, so basically.
The way we should be thinking about this is it's very possible that you could see a two point drop and the ramp significantly earlier than two hours and that's what the secondary endpoint is designed to capture right.
That is correct that is correct and this is this we have the precedence of France or any of the one and two and even and tranquility and Thats great.
Thank you.
Youre welcome.
Our next question is from the line of Eddie Hickman with Guggenheim Securities. Please proceed with your questions.
Hey, guys. Thanks for taking my question and I'm on for yacht and this morning, so given the recent debt backed by Acadia.
And the increase.
And worry for the investors on the lack of clarity of that.
Companies are getting from the FDA regulatory front. So could you just give us a sense of what your baseline proposition will be for the dementia study and what the size and scope and how many studies you need and that'll give us comfort.
If you see success down the line and then on the schizophrenia and bipolar can you give us any update on the pricing now that you filed.
The index.
Thanks, Eddie for discussion and this has been my level of address your first question.
About the.
Acadia and the FDA.
No.
And our indication dementia related agitation is the.
Acute.
And it is like and a two hour endpoint, it's very different situation and.
And also if you look at our data from our tranquility effect size is very large even with smaller number of patients VIP aggregate, the dose dependent and responses safety and Tolerability soybean.
Of our interactions with the EBITDA based on such a strong tranquility data that we have and how the hand and efficacy on multiple and foreign <unk>.
And we'll design are a real portfolio as a trial, which could be of the order of something like <unk>.
And we'll learn need anything more than that at least the Brexit single time, and we will have a conversation with the FDA. If one phase III trial is the vision or <unk> of one trial is the vision and additional safety data base needs to be expanded all of all of those questions will be addressed in our.
And of Phase two meeting.
That's the bulk of other than the other phase II meeting Q2, once we get that agreement with the FDA on the <unk>.
A number of trials trial design there.
As well as on the endpoint and then we will be in a position to initiate and develop a plan for our phase III trial and also thinking through this what would be required to get the NDA and the dementia patients as you know and.
Last two decades, almost that has not been the new drugs that have.
And being approved or helping these patients the unmet need is very high and we've been very encouraged with all our interactions with the EBITDA you can imagine we of multiple interactions around the five indications. So we are very pleased so far with all of our interactions and then we are very confident with us.
Strong data we have for the acute treatment of agitation from the tranquility trial, we will have productive conversations with FDA to double of the.
And next stage of the plan.
Your second question.
Bill do you want to address the sure. So Eddie your question was on pricing.
For the initial launch indications.
Obviously pricing pricing work will be ongoing over the course of the year, we wouldn't announce the price until we get an approval because our process involves gaining insights.
From payers and in this case hospital pharmacist and <unk> for any of our members.
PMT Committee members.
And we began that process I'll say that the.
And the unmet need is certainly recognized by.
Those individuals.
And the profile of the 501 is well received and.
And so we will continue to gain insights from the market are Paramount payer MSL team will be deployed shortly and so they'll begin to have conversations and get more insight into the reaction and the potential opportunity for <unk> for 501, initially and the hospital setting, but the value proposition, we believe will be of <unk>.
And given the clinical data and and also we've talked about this and other context, but even the hospital pharmacist et cetera recognize the opportunities that may exist, if patients can be more efficiently treated and the emergency department setting and so that'll be something we'll be exploring.
As the process.
Continues to put together a solid value proposition.
Do you think it will be priced at the single film or is the reason to believe and in that setting the price does like leading multiple doses over the course of some of ours.
So our current thinking is it would be priced on the per film basis.
The current thinking so that of patient needed a single film it could be obviously used in that context, if they needed more than one film which is not.
Unlikely you could happen each of them would be would be billed separately.
Okay. Thanks.
And then just one quickly on the PTSD and you can you give us any color on sort of size dose and timing of.
The study.
The Isd like done.
And like Yale is pursuing that and we don't like to comment on those things, but these trials are designed to efficiently to test that whether we can explore and fiber one potential and homecare setting.
Okay. Thank you.
Our next question is from the line of Colin Bristow with UBS. Please proceed with your question.
Hey, guys. This is Richard.
And again for calling a couple of questions from us.
So I wanted to get some more clarity regarding the 40 Mcg dose at the for dementia, especially with how that relates to the at home study.
Would that be included in the pivotal phase three trial, only if you're able to get into the at home setting now or would that be sort of a separate study and the future.
And then another question from US is that regarding the.
The 65 year older patients for schizophrenia and bipolar disorder.
What do you expect that label scenarios, so that would there be of warning regarding debt population or would there be any usage of difference in terms of the.
The dose level or the frequency.
Just wanted to get some idea on that thank you.
So we just submitted the NDA, we haven't had any conversation with the EBITDA, but the data that we have and hand and subgroup analysis. We have done we don't expect debt will be our label will be any different for the younger generation of the elderly patients and is schizo and schizophrenia and bipolar.
Coming back to your question about the 40 microgram dose.
And the Optionality that is being bid once we have data and our hand.
Currently our focus.
Laser focus is on initiating efficacy trial and.
And the Lf setting, where we had the tranquility data and we had the.
Very positive data with multiple doses now so we're going to stay and focused on that and.
And communities everything is almost considered as the homecare and say I think and we may not have any restriction on the label for using and the home care setting. What we are preparing is supervised setting and for nursing home and the need to prove anything else in the home care setting and we need to expand the labor line.
Debt fund and dine and our after the end of phase two meeting.
And understanding what the requirements are and whether one trial or two trials, then we will be able to make choices and decisions. What is the smart phase III trial design that we can deploy having the optionality that we will have and our hand, which is very clear 30, and 60 and then what.
And we learned from the 40 and then we will be in a position to expand on that plan. Once we had the meeting with the FDA and we are initiating our phase III trial.
Colin did it answer your question.
Yeah. So just another follow up on that so you're 40, MTG data and they come after your initiation of the phase III.
Just wanted to see like how that how the timing of going to influence.
What are you going to be including in the phase III are you going to be doing three doses are you going to do two and maybe at the 40.
Later on.
Current thinking is the two doses of good and the LSA and setting with <unk> and <unk> both of the.
Effective and safe and tolerable and there is sufficient.
The difference in their PK profile, so there's no need to add any third dose for.
For the additional insights will help us determine if in future, we need to design and any trial, which could be involving a lower dose and the mid dose then we could use that particularly for the home care setting. So that is just the optionality and it also.
Builds up to what already data, we have and our hand in terms of the number of patients who presented to the FDA.
We don't have a specific plan for T dose.
Doses, and we don't see any need for that.
Got it thank you.
Our next question is from the line of Samir and Sony with Rx Securities. Please proceed with your question.
Thanks for taking my questions Congrats phone and completion of the filing.
Just got a couple of XT and once really of points of interest more than anything else, but I was wondering why you chose 40 micrograms is the extra cohort the data.
And as opposed to the midpoint, which would've been 45 micrograms.
And then the second question is just on the and.
The release trial.
Assuming we see positive data or are you assuming debt, we will need of phase T. D. What would it go for a phase III trial, thanks very much.
So let me address the Krish.
Christian.
And the lead trial once we of the data then for you to make a decision and of choice.
And that we can go to the phase III and what do we need to convince the EBITDA. If we see any GAAP then we may do some bridging study, but at this point and time.
Data from the five cohorts should be able to inform us of what our phase III program that should look like and what do we need to present to the FDA.
Unless mds for some information.
In terms of the question about the part D.
Think we know 30, and 60 odd effective and like and efficacious.
The 45 would it be in fact, the Walter and 40 of the effective also based on our PK PD modeling and prediction, where we will be with.
And back to school and all of that.
So we chose for the because it gives us more flexibility and.
And I have been saying that in and homecare setting with the lower doses and thats exactly what the thinking that it is separated and upfront and 60 and it is has that like an all or the efficacy. So it will provide more flexibility as we expand our margin and dementia. There is no other reason for the year.
<unk> would be effective so that's why the joys of made after doing very detailed peak of beauty morning.
Thanks very much.
Thank you. Our next question is from the line of Smart Kulkarni with Canaccord. Please proceed with your question.
Thanks for the follow up so five of one gets closer and closer to the market and as you think about expanding the franchise and agitation and especially as you go into some kind of extending how are you thinking about the potential for that with the Lexus and our tolerance of debt.
And we know that IV Dex is a very different dosing ballgame vs. Sublingual thin, but net of any limiting maximum number of doses of the <unk> per month or per year to two.
The facilities, the agitation on and acute disease.
So the.
I am not aware of any limitation, but we are aware that we need to no debt and if you look at most of the some of the alpha.
And <unk> that have been used they have been used chronically. So we don't expect that it will be a issue, but it's a good question to keep it.
And it if we had going for chronic agitation with 501, then we will need to demonstrate that.
Thank you.
Thank you at this time, we've reached the end of the question and answer session and I will now turn the call back over to the low <unk> for closing remarks.
Before we conclude I want to thank everybody for joining US today 2000 joined day was a great year for buyer of XL as we continued to execute and milestones across our program. This momentum positions us for it and exciting year ahead.
We plan to expand the commercial potential of <unk> 501, and grow our pipeline and blowing our proprietary neuroscience. The AG platform to create long term value for our shareholders. Please reach out to us if you of any additional questions.
Thank you. This concludes today's conference you may disconnect your lines at this time and we thank you for your participation.