Q4 2021 ATAI Life Sciences NV Earnings Call
Currently all participants are in a listen only mode. After the speaker's presentation. There will be an open question and answer session as the live webcast via the news and events section of the company's website at Www Dot <unk> Dot life and is being recorded a replay of the webcast will be available on our website.
Joining me today are Florian brand, Chief Executive Officer, and co founder and Dr. Sweeney round, Chief Scientific Officer and co founder.
The press release announcing our financial results is available on <unk> website.
Please take a moment to read the disclaimer about forward looking statements in the press release.
During today's call we will make certain forward looking statements that are intended to be covered by the safe Harbor provisions of the private Securities Litigation Reform Act of 1095 or forward looking statements.
While these statements represent management's current expectations and projections about future results and performance as high as actual results are subject to many risks and uncertainties that could cause actual results to differ materially from those expectations.
In addition to any risks highlighted in the call. These statements are subject to various risks that are described in our filings with the securities and Exchange Commission.
Cautioned not to place undue reliance on these forward looking statements, which speak only as of today March 32022, and except as may be required by applicable law <unk> disclaims any obligation to update such statements, even if management's views change.
I'll now share a short video from our founder and Chairman Christian Aguilar.
We are in a state of crisis.
Real crisis globally, when it comes to mental health.
Over a billion people that's about one in seven worldwide net with mental health disorder.
And many argue this is unfortunately.
Of the iceberg and that's a real number may be way higher for at least three main reasons.
First this $1 billion is a pre COVID-19 figure.
The pandemic has substantially worse than that.
Global mental health situation, according to leading experts.
Second mental health issues continue to be stigmatized, not everyone, who needs help is coming forward to be diagnosed and treated many unfortunately still suffer in silence.
Luckily this is gradually changing and great work like what we are doing with our philanthropic arm of Thai impact is underway to reduce such stigma.
But as the stigma vanishes I believe the number of diagnosis may increase meaningfully.
And third and generally I personally I believe the wells, we are building with all the technological innovations around us.
It's not good for our mental health.
Constant change misuse of social media Overstimulation all of this is totally toxic for all brain and is taking its toll on all of us.
My personal belief is unfortunately that the number of people globally living with mental health conditions with meaningfully continue to increase in the years to come.
And even those who are receiving help in treatment today arent always getting the help they need.
It is high we believe too many current treatments are one size fits all and one size does not fit all when it comes to mental health.
That's why we are progressing a broad pharmacologically diverse pipeline.
We are developing psychedelic and non psychedelic compounds as well as cutting edge digital therapeutics that show real promise and mental health treatment.
The fact that psychedelics have the potential to massively improved various mental health issues.
Becoming more and more widely accepted yet questions about defensibility, namely patterns and potential commercialization remain.
Regarding patents, we at as high has a broad range of patents.
Cross sell respective portfolio of innovative psychedelics, and obviously non psychedelic therapies as disclosed in our public filings.
Ranging from compositions of matter to methods of treating various indications of interest towards higher.
And of course, we believe that multiple of our compounds may be eligible for data exclusivity.
Don't forget a Thai has been a pioneer in psychedelic medicine.
Given our first mover advantage, we had at the time.
And the team.
And the capital to acquire and or file new patents around those innovative psychedelic therapies. We believe have the potential to be medically viable and which are consistent with our business model.
When it comes to commercialization, we are proactively working with various stakeholders to ultimately enable patients to access our innovative treatments once they are approved.
We have achieved so much and yet this is only the beginning of our incredible journey.
Just as we appreciate today the ground breaking achievements in vaccine development of Madonna and Brian Peg. So the COVID-19 pandemic companies actually now considered to be household names in the future. It is my personal ambition that Ty will be recognized as the driver.
Force in healing mental health disorders globally, and at a tie actually will be synonymous with the solution for this crisis.
I dare to say this with such confidence because of our unique business model.
The compounds that we have historically identified and selected has had prior evidence in humans either because they had been approved in parts of the world as medical solutions use III realistically or have had other anecdotal uses.
I truly believe that as high as one of these rare companies where the stars are aligned.
The mission.
The strategy there.
Our leadership.
<unk> execution.
And the significant unmet need in mental health.
As you hopefully can tell I couldnt be more excited about <unk> future and its potential to play a vital role in solving one of humanity's biggest challenges.
It is imperative to me to be in this journey for the long run to make this world a better place and to play a meaningful role in bringing healing and relief to the millions of people currently suffering from the mental health disorders at highest targeting.
I refused to disappoint them.
And with that I'll hand over to my Amazing leadership team to tell anymore.
Okay.
Good morning, everyone.
It's a pleasure to be here today, and I'm really excited to walk you through our strategy our achievement since January 2021, and through our upcoming R&D milestones this year and beyond.
2021 was a truly transformative year for time, we made important progress across our programs expanded our diverse pipeline with multiple shots on goal and secured approximately 410 million U S dollars and financing.
This allowed us to enter 2022 with $362 million in cash.
Putting us into a very very strong position to work towards our strategic goal.
Achieving clinically meaningful and sustained behavioral change in mental health patients.
To achieve this goal we will focus on three strategic pillars.
One rapid acting insulin insulin to ongoing digital support and three biomarker driven precision mentioned.
Let's turn to the first pillar rapid acting intervention.
This pillar is really about developing our first second and third generation compounds in the most effective and most efficient.
We anticipate these compounds to be highly differentiated to show rapid improvements in mental health disorders.
And we are especially interested in compounds with strong euro plastic properties that open the therapeutic window to initiate behavioral change in patients.
To give you an example in the context of depression.
This first pillar is really about lifting of patient out of depression, and the quick and meaningful way, but then we want these patients to stay on a depression.
And this leads me to our second pillar ongoing digital support.
This pillar is about keeping mental health patients in state of permission and it's grounded and innovative digital care providers patients.
For jewelry and after treatment.
While these tools are especially relevant for the psychedelic assisted therapy that we're developing we see great potential to apply digital support across our entire drug development pipeline.
We believe pairing digital therapeutics with a rapid acting pharmacological agents from pillar, one will allow us to achieve sustained behavioral change in mental health patients.
What works for one patient might not work for another.
As we all know the mental health patient population is highly heterogeneous.
Which brings me to our third strategic pillar biomarker driven precision in general.
When it comes to <unk>. There is no one size fits all approach. So this pillar is about identifying patient subtypes, using biological and digital biomarkers to treat patients with a therapy that is right for them at the right moment in time.
We believe this will reduce the need for trial and error and gift each patients the best chance of receiving the treatment that works for her.
Each of these pillars hasnt true disruptive potentials on its own.
But it is by combining them that we can really unleash their full potential.
Allowing its truly forwards from intel's patients by achieving clinically meaningful and sustained behavioral change.
And we have already laid the groundwork for all three pillars. For example by building out our digital data and biomarker teams and we will continue to be highly active in all of these three pillars.
That said our focus for the next few years will remain on pillar, one rapid acting intervention generating value by executing and further expanding our drug development programs and by further strengthening the robust patent portfolio of our compounds.
Let's now have a closer look at our achievements in our first pillar since January 2021, and then look ahead, what we can expect over the next two years.
Since January 2021, we launched eight new programs, including three programs dedicated through drug discovery.
This brings our total number of drug discovery and development programs to 30 as of today. It goes without saying that we intend to stay highly active in business development. This year and also beyond.
From an R&D perspective, we also achieved many meaningful milestones in 2021.
Allow me to highlight just a few of them.
We saw a positive phase III data for <unk> 360.
The result of this groundbreaking trial in treatment resistant depression, or CRD led us to increase our stake in Columbus pathways to 22, 8%.
We also shared positive phase Iia proof of mechanism data for all our was seven <unk>.
This compound is being developed to treat cognitive impairment associated with schizophrenia, a condition that today has no approved treatment options.
And then the September 2021, we initiated the phase Iia proof of concept trial with <unk> 101 and PRD.
We anticipate top line data from this trial by the end of this year.
And we also recently received IND clearance from the FDA to run our first clinical study with this compound in the United States.
So as you can tell we made a lot of progress here and as we look ahead to the upcoming two years, we are anticipating at least 14 R&D catalysts.
Alongside these exciting R&D milestones, we saw further validation of our approach to capture the value of our programs.
In March 2021, we were thrilled to announce a collaboration with Otsuka pharmaceuticals.
Significant licensing deal for <unk> hundred one represents the first major partnership between a biopharmaceutical company developing psychedelics and large pharma.
When it comes to capturing the value or monetizing our programs, we have a high degree of Optionality.
And with the IPO of combos pathways and the licensing deal with Otsuka.
Already successfully demonstrated some of the ways in which we intend to capture value in the future.
We will decide the best and most viable option of capturing value, including self commercialization for each of our assets on a case by case basis.
Before handing over to <unk>, Let me give you an update on the Oracle and profit impact.
Impact that we announced in October 2021.
Since then the toy impact has launched the Thai Felicia on at MGH, a center for the neuroscience of psychedelics.
We also made sizable donations to Max and towards humanitarian support in Ukraine with a special focus on mental health.
We believe that these philanthropic efforts are strongly aligned with our vision of healing mental health disorders for everyone everywhere.
Our Chief Scientific Officer, Sweeney will now walk you through a more detailed update on our pipeline.
Thanks Lauren.
Christian in Florida mentioned, we're in a truly exciting time here at a time.
Since the start of 2021, we've added five new drug development programs and three new technologies to our portfolio.
We completed two important trials last year, and we're rapidly advancing the rest of our growing pipeline towards the clinic.
And as shown on this slide our pipeline targets, many important indications and dental zone, including cognitive impairment associated with schizophrenia.
Treatment resistant depression, generalized anxiety disorder post traumatic stress disorder and opioid use disorder.
The advancement of our deep pipeline will result in many clinical readouts across this year and next.
2022, we're eagerly anticipating data from our ongoing phase Iia proof of concept trial of <unk> hundred one.
This is a potentially groundbreaking at home rapid acting therapy for CRD.
Later this year, we intend to conclude the phase one comparative bioavailability study to bridge from the IV formulations in a subcutaneous formulation of <unk> hundred one.
We believe that this formulation will be key to supporting.
Yes.
We expect continued clinical advancement in our other programs, we have a phase one trial readout and a phase Iia trial initiation for <unk> seven.
We have initiated a phase one trial of <unk> and we also anticipate phase one trial initiations that impact file for radio Andrew next year.
In total we expect to obtain six phase II in four phase one trial readouts across 2023 and 24, that's an amazing number of milestones. They are legally short period of time.
The second program on the list is targeting cognitive impairment associated with schizophrenia or CIM.
Schizophrenia is a leading cause of disability worldwide, primarily due to the mark and essentially ubiquitous cognitive impairments that are associated with this condition there.
There are no treatments currently approved for <unk>.
Our platform company, we're cognizant of life Sciences is developing Aro <unk> southern a Gaba glutamate and cholinergic receptor modulator for the treatment of the stability and condition.
Arnold almost seven has been tested in nine third party clinical trials to date with pro cognitive effects observed in two phase one trials and one phase II trial.
Data from our previously conducted phase one trial are shown here.
This study involved the scopolamine chairman's widely used clinical model.
These impairments.
Some of the deficits and used by this jones, including attention as shown on the left and verbal memory shown on the right where improves by the co administration of our own level of southern.
The beneficial effects were present only at 30 milligram dose as highlighted by the circles on the two graphs.
Benefits were absent in higher doses consistent with an inverted U shaped dose response curve.
Importantly, this pro cognitive effects associated with illustrations on quantitative EEG, while QE Qi <unk>.
Specifically with some of that <unk> <unk> induced a relative spectral shifts from lower to higher frequencies, thus, providing a biomarker for target engagement.
More recently, a large phase II trial was conducted in 181 patients with diabetic peripheral neuropathic pain. The results of which are shown here. This condition is often associated with sub clinical cognitive impairments due to the impact of long standing diabetes on brain vascular churn.
Again, we saw pro cognitive events, notably in the domain of verbal memory.
The benefit was seen in both immediate and delayed recon is shown on the left and right hand side some constraints.
These results were consistent with the results of the previous phase one trial I mentioned previously.
As you can see on the graphs the benefit was seen only at the lower dose level again, consistent with an inverted U shaped dose response curve.
Building on these studies in December of last year.
We announced the successful outcome of our phase Iia proof of mechanism study of oral <unk> seven conducted in patients with <unk>.
The results of this trial are summarized here in this 32 patient single arm single Blind study <unk> seven demonstrated clinically meaningful pro cognitive effects.
As you can see there are dose dependent improvements on several of the cognitive measures that we assess.
This is evident on the symbol coatings us a broad measure of cognitive function the correlate highly with the matrix consensus continent battery tools for.
The beneficial effects were most pronounced at the 20 and 40 milligram doses and started to wane at 80 milligrams. These.
These data are consistent with the inverted U shaped dose response seen in earlier studies.
Additionally, the trial show changes to EG, there were consistent with our previous results seen in the phase one trial involving the <unk> challenge.
Based on these exciting results, we have decided to move into a larger randomized placebo controlled phase Iia proof of concept trial.
This trial will be powered to show improvements on cognitive measures.
We plan to initiate the study later this year.
Next I want to focus on our potential therapies with treatment resistant depression with CRD.
Depression effects 300 million people globally and ranked as the second leading cause of disability worldwide.
While current treatments are effective for certain patients a significant percentage of patients either respond inadequately will leave us with.
A third of patients are classified as being treatment resistant.
This is likely partly due to the heterogeneity of the <unk> patient population.
Let's first discuss compass pathways and its development candidate comp <unk>, our proprietary formulation of psilocybin.
As Soren mentioned, we consider the phase <unk> trial to be a resounding success.
Spending 233 patients 22 sites in seven languages. This was the largest most logistically complex and most robust psilocybin trial ever conducted.
The results of this randomized double blind dose controlled trial demonstrated that <unk> hundred 60, when co administered with psychological support resulted in a rapid and durable improvement in depression symptoms.
When compared to the one milligram dose a single administration of <unk> 25 milligrams of <unk> hundred 60, <unk> achieved a six six point reduction from baseline to week three on the Montgomery Hasbro's depression rating scale, where mattress.
This is a remarkable improvement.
Most recent approvals were based on the Madras change of four or less.
With a P value of less than 0.001, the primary endpoint was robustly men.
The compound was generally well tolerated with over 90% of treatment emergent adverse events classified as being either mild or moderate in severity.
Looking forward Compass is scheduled to have an end of phase two meeting with the FDA in late April .
They anticipate kicking off the phase III trial later this year.
Perception neurosciences developing PCN 101, the formulation of our academy for the treatment of TRP.
Mark Ketamine is a glutamatergic modulator being developed as a rapid acting antidepressant with non associated properties, meaning it has the potential for at home use.
Our phase one study of IV archiving and was completed in September 2020.
The agent was well tolerated over the dose range explored and no serious or unexpected adverse events were observed.
Following the successful results in September 2021, we initiated a phase Iia proof of concept trial of IV in the IV <unk> hundred one in patients with CRD.
This double blind placebo controlled trial consists of three parallel loans of 31 subjects each.
Subjects will receive a single dose of placebo or one of two doses of our academy.
Depressive symptomatology will be assess over the subsequent 14 days using the mattress.
The trial is currently active across sites in Europe , and U S sites will be launching soon.
Data from this important study are anticipated by the end of this year.
Concrete results of this trial could be game changing for patients as current rapid therapies require administration and clinical setting.
This comes with significant burdens for both patient and provider.
In January of this year, we announced the clearance of our investigational new drug application by the FDA.
This clearance support the conduct of our phase one DDI study, which we intend to complete this year.
We also anticipate completing our phase one relative bio availability study this year.
As I mentioned previously this trial is designed to bridge. The currently these formulation to subcutaneous one.
This formulation will be key to supporting the potential of at home use.
In addition to these clinical programs, we have two preclinical programs focused on tid entering the clinic this year.
Our platform company <unk> life Sciences is developing <unk>.
A formulation of <unk> dimethyltryptamine more DMT.
In addition, our platform company <unk> life Sciences is adopting rls on one this is a formulation of <unk> a pharmacologically unique psychedelic coupon.
We plan to initiate both phase one trials with these compounds later this year.
So we have a total of four exciting CRD drug candidates in our pipeline.
Together these represent a range of pharmacologically unique treatment options for TRT heterogeneous indication with an urgent need for innovation.
Turning to anxiety, let's talk about <unk> 907, which we are developing a gaba therapeutics for the treatment of anxiety disorders.
Designing disorders are the most prevalent with mental health disorders.
It's estimated that approximately one third of people are diagnosed with an anxiety disorder at some point in their lives.
<unk> 907 is a <unk> form of that apart.
The compound was first approved in France, and $19 79 for the treatment of anxiety.
<unk> <unk> is a <unk> agonist, increasing the production of neuro steroids like analog <unk> one.
And a Fox news rapid acting <unk> benzodiazepine, but without significant sedation cognitive impairment for ataxia.
A recent analysis of post marketing surveillance data encompassing over 14 million prescriptions has demonstrated endotoxin. Unlike benzodiazepine is not associated with abuse or dependence.
In June 2021, we initiated a randomized double blind placebo controlled phase <unk> trial of <unk> 91, seven is.
As outlined at the bottom of the slide this study of the single and multiple ascending dose trial.
It's focusing on the safety Tolerability PK and pharmacodynamics of <unk> seven.
Based upon the mechanism of action of this compound we are using Q E. G has a target engagement biomarker looking for increased relative spectral powered the beta band.
Such changes haven't demonstrated with IBM pregnant women and related compounds.
They were also noted in our phase one trial and better balancing the week inducted in 2019.
We've completed the single ascending dose element in the phase one trial to the multiple ascending dose component is ongoing.
Top line for the entirety of the trial are expected by the middle of 2022.
We anticipate initiating a phase iia proof of concept trial later this year.
We're excited at the prospect of <unk> 907, combining the best characteristics benzodiazepine NSS Ryan's potentially offering patients with anxiety, a new and much improved treatment option.
Next we'll move on to opioid use disorder <unk>, a major health challenge, particularly here within the U S.
Both of our OUP focused compounds are presently in phase one clinical trials now.
<unk>, we are developing <unk>, an oral formulation of <unk>, which is a naturally occurring <unk> compound.
In September we dosed the first subjects in phase one component of a combined phase one <unk> trial.
This trial is designed to assess the safety tolerability PK and efficacy of <unk>.
We expect to obtain safety data from the phase one portion of this trial later this year. There is also we're eagerly anticipating.
Our second <unk> focused company tours is developing <unk> 101.
<unk> form of <unk>.
This compound which is the active moiety and prana is considered atypical opioid receptor modulator that is not to be safer and better tolerated than classical opioids.
Our phase one single ascending dose trial of <unk> hundred one was initiated earlier this year with the first subject dose this loan.
This study is expected to readout by the end of this year.
By the end of the year, we will have 10 compounds in phase one or phase. Two this is a remarkable achievement for a company that is only three five years now.
Onto our discovery stage programs.
In the past year, we've added two new subsidiaries shifted <unk> targeting and fee development.
These two companies are focused on bioprospecting and medicinal chemistry, respectively.
The supplement the AI based computational chemistry approach of Anthea genetics, a company, which we founded in 2019.
Taken together these three discovery platforms, each incorporating a unique approach means that a tie boasts one of the most robust discovery engine and CNS.
These platforms will be crucial to the expansion of our pipeline with therapies that are even more innovative in the years to come.
Our digital therapeutics with DTA and data efforts are key elements to achieving clinically meaningful and sustained behavioral changes in patients.
Gtx and multimodal data collection and analysis are integral elements of our strategy concerning ongoing digital support and precision metal zone.
We are focused on digital therapeutics to improve the safety efficacy and scalability of our compounds with.
With Ciber, we're developing brain computer interface space digital therapeutics to ultimately provide a digital guide to support psychedelic administration.
With Introspect digital therapeutics, we're developing personalized app based treatments to improve patient outcomes.
In March 2021, Introspect launched a user acceptability trial for participants that we're undergoing Kevin therapy.
Finally, our data analytics platform synthesize the digital biological and phenotypic data to allow for better characterization of patients in our target indications.
Analysis of these data may not offer the generation of novel Biomarkers ultimately supporting our goal of precision mental health.
We have come a very long way in our first year as a public company and I'm immensely proud of all of that we have achieved we have an extremely robust pipeline cutting edge discovery platforms and highly innovative digital and data products.
These programs put us in a particularly strong position to achieve our upcoming clinical milestones. The announcement, we made a meaningful difference in the lives of patients with mental health disorders.
With that I will now turn the call over to Greg for an overview of our financial highlights Greg.
2021 was a pivotal year for <unk> to put us in a strong financial foundation to support our ongoing growth in pursuit of our mission.
Our year end 2021 cash balance of $362 3 million represents a cash runway for approximately two years.
The operations into 2024 inclusive of our ongoing business development activities.
During 2021, we raised net proceeds of $410 million from our June NASDAQ IPO the series D and other financing activities and we received $28 million from the Otsuka license and collaboration agreement in Q2 of 2021.
During the year, we made important strategic investments in our platform companies totaling $82 million.
Notably $52 5 billion of encompass pathways $14 9 million in <unk>, our oral drug delivery formulation company and.
And $10 $6 million and Gaba and supported their pursuit of innovative treatments for anxiety disorders.
Our full year 2021, total operating expenses were $156 2 million with R&D expense of $48 million in G&A expense of $92 8 million.
Noncash stock compensation expenses for the full year 2021 were $63 $4 million with $19 4 million recorded the R&D and $44 million to G&A.
Our R&D expenses for 2021 represented an increase of $36 6 million over 2020.
Driven by increased <unk> expenses related to advancements in R&D programs and increased R&D personnel costs.
Included in R&D personnel costs was an increase of $19 1 million of share based compensation expense.
The acquisition of in process R&D expense recorded was $15 5 million for the 12 months ended 2021 related to our investments and took the <unk> <unk> bio and neuro nasal.
Compared to $12 million for the prior 12 months ended December 2020.
G&A expense for 2021 increased by 12 million over last year, driven primarily by G&A personnel costs professional consulting fees and other G&A costs related to supporting platform growth and public company requirements.
These increases were partially offset by a decrease in G&A share based compensation expense of $22 9 million.
And looking forward, we expect R&D and G&A operating expenses to increase year on year as.
As we initiate multiple clinical trials across the pipeline and we make the necessary investments in our chairman and infrastructure to support the continued growth of our research and development efforts.
And closing important to understand that we are well capitalized well organized and built for the long term with substantial cash resources.
To fund our operations through numerous value, creating clinical development catalyst this year and next.
Thank you I'll now hand, the call back to Florida.
Thanks, Greg.
I'd like to thank our employees for their ongoing dedication to advancing our vision and to our investors who actively support our work.
We're incredibly proud of our strong execution in 2021, delivering on advancing our programs validating our business model through key collaborations and further expanding our diverse pipeline.
This ongoing positive momentum positions a tie for an even more exciting future.
We anticipate 10 of our programs to be an active human trials by the end of the year with at least seven clinical readouts in the next two years.
With that we are very happy to take your questions.
Hello, Good morning, and welcome to a timeline sciences fourth quarter and year end 2021 for new and resign.
Jefferies.
Hey, guys. Thanks, Thanks for the updates appreciate it first question is on the <unk> 917.
<unk> program is data coming up mid 2022, so I'm just curious what would be what would drive a no go decision for you guys. What's a deal breaker in Europe in that phase one data set.
Andrew Thanks for the question.
I think the most important thing there will be some sort of safety and tolerability concerns and thats going to be the key points.
Not surprisingly as we've mentioned, we're pushing the doses and looking at <unk> and other things, but the most important thing is going to be safety and tolerability.
Okay understood and then second my follow up question is <unk> 101.
At the end of the day do you think this <unk>.
Drug is completely free of the unwanted side effects that we see with Academy and our <unk> Academy and if not then can you maybe share. Some examples where there has been an approved drug that does cause subtle hallucinations association, but it's still use at home.
Yes, good question so.
The doses that we've tax based on the phase one trial, where associated very minimal.
Either no associated effects are very minerals associate of FX. So thats actually how we made the decision around those doses.
So of course, we need to validate our mutual firm that in a patient population. So obviously, that's going to be important an important objective of the phase two.
In terms of compounds that have some sort of associated with psychedelic effect.
One example that I'd like to provide us with <unk> or <unk>.
This is a compound that was approved for obesity. So obviously, a very widespread condition.
The compound was a five is a <unk> agonist that has five H Q2 way activity.
You took four five ex the normal dose the normal daily dose you actually got a pretty <unk>.
Psychedelic effect and Thats actually reflected in the clinical trial section of the label. So I think there is precedence is all about therapeutic index.
Perfect. Thank you.
Of course.
Thanks, Andrew and our next question will come from Mena.
<unk> at Citi.
Okay.
Yes.
And thank you for taking my question.
So I was wondering if you could talk a little bit about Anthony are lagging.
You can talk a little bit about <unk> 101 kind of following up on the last question just around.
I know you said that you recently got your R&D cleared by the FDA for this program. If you can talk a little bit about how the FAA failing about potentially studying <unk> hundred one in an at home setting in a later stage study and kind of what they would require.
From this initial study.
<unk>.
In order to fill up the data.
Yes.
Thanks for the question and so it's not going to come as a big surprise. It is ultimately going to end up being a review issue right. So.
They're not going to really opine until there's actual data.
It's hard to fault their position on this so in general what would you anticipate will you require I think the therapeutic index is going to ultimately be an important element. This is schedule of cars and the academy as scheduled as well some scheduled three compound.
And there are plenty of at home schedule III compounds are events, even scheduled to come down so I don't anticipate that being a major issue of course, the other elements of this formulation, we want to make sure that we can control the use of this compound and that's one of the reasons that we actually are moving forward with subcutaneous.
There are devices that allow us to.
Really tightly control administration of using that rather than a distraction.
Got it and then maybe back off the top a little bit about the differentiation for.
The program that <unk> I'm, just curious if you could talk a little about the formulation higher thinking about administering at eight.
Eight months.
And slowly so our primary formulation there is an oral transmit puzzled zone. So we're developing this in conjunction with Intel's zones and the reason we're doing this is that you can really tightly controlling almost engineer that formed the release profile using an alternative proposal film.
So what we want to accomplish here is a T. Max of say five to 10 minutes somewhere in that ballpark, we want to wrap up the entire psychedelic effects over the course of maybe 45 minutes or so the rationale here is to fit into the estate as ketamine treatment paradigm, but with respect to that form with respect to that release profile. We wanted to be 100 jumper.
On the upswing. So this is in contrast to say in a relational approaches and we don't we're not entirely sure whether there's a direct how the duration of psychedelic effects.
Impact long term efficacy in terms of stability long term.
Having.
Something on the order of an hour.
It seems to make sense versus something that's sponsored by 10 minutes and of course, that's logistically a lot easier to deal with and something that say five or six hours.
Thank you.
<unk>.
Thanks Nina.
Our next question will come from Charles Duncan of Cantor Fitzgerald.
Okay.
Yes.
Okay.
Okay Ken.
Can you guys hear me.
Perfectly fine high chance, Okay Super.
Florian <unk> team so congratulations on all the progress in.
In the last year and thank you for the very thorough overview that was helpful reminder.
Had a couple of questions regarding the pipeline.
There has been some discussion about <unk> 101.
And <unk> it.
Proof of concept.
Data and CRD later on this year.
I guess I'm wondering how could you define good versus great results and is there a potential for exceeding S catamenia activity or duration of of that activity.
So let me take the first the last question first so if you think about the preclinical data.
Multiple experiments that have been done there was a greater magnitude of efficacy seen with our academy versus us to the mean.
And equally importantly, there was a longer duration of activity that we've seen.
Now in clinical settings as anecdotal data that suggests that maybe racemic ketamine is a little bit more efficacious than US Academy. So you take this all together and there is a potential for a better therapeutic coming for better efficacy and a longer duration of efficacy with our academy versus F. Kennedy.
So going back to the first question in terms of what is what's a win of course, we won't hit our primary endpoint.
Surprise so.
Seeing a substantial and statistically significant improvement on the Madras is going to be key but equally equally important is the therapeutic index as I alluded to earlier right. So we want to be a good multiple.
Between the efficacious dose in the therapeutics and the therapeutic dose we've sort of pre selected that rises to 60 milligram dose to high dose that we're looking at is indeed, essentially announced <unk> associated it's right on the costs and of course, there may be differences between healthy volunteers and patients with 30 milligram dose.
Is quite substantially different in both healthy volunteers and then.
Hopefully in patients as well.
Okay. That's helpful. And then one quick question on <unk>.
<unk> seven <unk>.
You mentioned moving forward in a phase Iia and you also mentioned the complex of fire. If you will of an inverted U shaped dose response curve. So have you disclosed the dosing that you plan to pursue and the duration of that study.
So.
Right. There is an inverted U shaped curve, we saw the most robust benefits.
If you take it all in aggregate quantitative EEG symptomatic improvement we saw the best efficacy in a 20% to 40 range. So it'll be somewhere in that ballpark I mean that shouldn't be a great surprise based on the proof of mechanism study.
<unk> and all these other items were in the process of <unk>.
Working out now we have had multiple meetings and kind of finalizing our trial design there and of course as that becomes the declarer we will.
Obviously publicly disclose them.
Final question first soaring more of a big picture kind of strategy question.
You fast forward say, yes, let's say three years or even two years. What do you think this type of call will involve will it be primarily discussion of different pharmacological agents that are moving forward into late stage development or will it also.
Include increased visibility on the J J develops her tits. Thank.
Thank you.
Thanks, Joe.
Very short answer is both.
He will be.
Said earlier, we will be laser focus on the very first pillar.
Rapid acting interventions, our drug development pipeline, and we will anticipate that.
Large share also lease calls will be abolished docks, but while we progressing guard trial and we anticipate that we will have this year. The first time, our digital therapeutic combined with our compound in the clinical trial or in multiple ones that we of course were also more and more talk in detail about the combination products.
Going forward so.
Lots of R&D catalysts coming up.
<unk>.
Now looking forward to the next years to discuss the progress very good look forward. Thank you.
Thanks Charles.
Our next question will come from Ritu brawl at Cowen.
Okay.
Okay.
Yes.
Okay.
Hi, guys. Thanks for taking the question.
Maybe we'll start with a high level for Florian flooring, you had mentioned as one of your pillars going forward youre going to two biomarker driven.
Precision mental health strategy.
<unk> strategy.
Biomarkers in.
In psychiatry and Neuropsychiatry are you thinking genomic biomarkers are you thinking.
EEG based Biomarkers and other electrophysiology Biomarkers, how should we think about that and then I have some more detailed questions on the programs.
Sure.
In general, we think about biological Biomarkers and digital Biomarkers digital Phoenix royalty so there.
<unk> can vary a little bit into detail on the biology biological ones may have actually one program running with Si product slate looks at minimal ohmic profiling.
Patients, which we believe is very exciting and then on the digital side.
There is very interesting in each of research going on.
On behavioral Biomarkers.
Noise.
Typing behavior et cetera, so that allows us by using our digital therapeutics hopefully in the future to better characterize patients. So it's really both biological biomarkers and digital Biomarkers and screening I don't know if you want to deep dive a little bit into the meta below mix.
Angola.
Sure. Yes, just briefly the byproduct is really focused on that looking at particular markers of mitochondrial metabolism, essentially and there is an association with mitochondrial metabolism and certain subsets of the pricing. So this is unique right. This is a very clear biologically underpinned form of depression.
And so we wanted to test this hypothesis, so addressable mitochondrial dysfunction non psychedelic clearly very different and see if we can improve mood and us in that particular subset.
Great and then a quick follow up on that.
<unk> seen as you think about the data that's coming out is it mid year.
And acute EEG beta band shift how should we be looking at that the magnitude of that shifts versus say the other gathered patents in development. So you've got a Gaba plus Sheraton <unk> component to the mechanisms do you need are you going to show.
Or do you need as much of a beta band shift for this trend to have equal efficacy as other cap attempts.
Yes, that's a great question. So we don't necessarily anticipate the same magnitude of shift and is a very simple reason for that rights of this compound is increase in production. There is there is a scene insights specificity of regional specificity in the brain to that this isn't a distinction to an agonist right.
Whether it's a pam or a direct agonist you typically see a much larger pharmacodynamic effects of such compounds.
So again don't necessarily anticipate I mean, we will see how it all plays out right. We're doing a lot more dose ranging with 907 and we could do it at a boxing match.
That's not necessarily an expectation.
Got it Okay, and then getting back to one 101, almost housekeeping question on the safety side.
Are you monitoring heart rate and blood pressure.
Perfect S ketamine.
And do you have any instant youll have less sort of a hemodynamic factor heart rate effect then.
<unk> and <unk>.
With that does that factor in Q.
<unk> jumps at home.
Absolutely. So yes, we are of course going to monitor blood pressure et cetera in our trial.
As for whether that will affect at home use the answer is probably yes at the moment. It is really difficult to say whether or not there is any benefit.
Versus us economy right. So these loans are not that big there of course healthy volunteers, it's a little bit different.
It was IV right. So Ivy is also going to be elevated from where ultimately we are going to go forward with subcutaneous. So we're going to be doing a bond relative bioavailability study a little later this year. So we should have results by the end of this year, that's going to be the ROE that's going to be the real key in terms of what the blood pressure profile looks like and of course, taking that and putting it into into patients.
Can be the most definitive.
Thanks.
Yes.
Thank you.
Our next question will be bringing on Judah frommer from credit Suisse.
Okay.
Okay.
Okay.
Yes, hi, guys. Thanks for taking my questions and all the details. So far first just following upon on 101 that sub Q formulation can you remind us of the timing relative to trial data for the bridging study and how tightly those will be recorded and then all.
I mean sure you kind of talk about we will go forward with sub Q.
Is there any.
Potential engineering are.
Stumbling block that you could foresee.
<unk> off sub Q formulation and is there a world where we're only IV or is just a matter of time until we get to some scale.
So answering a lot of beds I mean, clearly IV is not consistent with that on mute. So we will develop I mean sub Q is really the best from our perspective. It gives us the most robust and least variable pharmacokinetic profile compared to say intranasal. So that's what we're really interested in sub Q in general subcutaneous is not necessarily.
The bulk of the formats of Formula right I mean, the Grand scheme of things you do have to worry about local tolerability. We've we've addressed all of those issues at this point at least pre clinically and of course, we have to demonstrate that in humans, but theres lots of optionality there.
In terms of the timeline, yes, we anticipate both results towards the end of this year.
Okay. That's helpful. And then just moving back to the precision biomarker discussion how should we think about kind of the overall strategy with Biomarkers is it more for patient enrichment is it coming up in conversations with regulators. Obviously, you know, it's a relatively new area.
Kind of a precision approach to drug development. So curious if that factors into those and then anything that can be integrated into <unk>.
Potentially.
Tim and excellent services exclusivity from a biomarker perspective.
<unk> absolutely.
Whether it's <unk>.
Expanding on that.
Companion diagnostic type of approach I mean, absolutely it's going to be in the level of course, we are going to have IP around the right. So that would that would be obviously fantastic why are we doing it while we know that <unk> really heterogeneous right. The phenotypes of final common pathway for probably a whole bunch of underlying pathophysiology.
So that May explain why you have streamers is comprised and why do you have a third or half of patients that don't respond presumably some of it is this underlying pathophysiology.
So that's why we want to address we want to be able to increase the effects size right. What is the magnitude of the change on the Madras as an example decrease variability again tying into effect size.
So there will be an enrichment element potentially leading smaller trials, but of course ultimately something that may very well end up in the label.
Okay. That's really helpful. And then lastly, maybe for Greg can you just help us with kind of cash priorities over maybe the next year or two you know R&D is there any way to force rank. The programs that you have anticipated over the next year in terms of our capital need and then business development.
How dynamic cargos those levers are.
Thanks Julien.
Yeah, we look at the.
For the year, just transpired, but it's been a remarkable one for our financial footing for the company between the success of $410 million coming in between the IPO of the series B and in a position of two years of runway with $362 million at year end bonuses sufficient budget to manage all of our clinical and preclinical programs.
We've heard about today, along with the headroom for us.
Investing in additional BD is oriented and screen you had mentioned on the call.
From a financial strategy perspective.
Mr. CFO here pretty proud of what we've done and the heavy lift to get to this point over the last two years and grateful for our firearms to you on our investors know the team that we built just pretty remarkable and I think investors can look at this as a really solid foundation of footing here on the financial side.
Is it right to think about later stage program doesn't most expensive or are there any kind of a phase <unk> you'd highlight as being more expensive than a kind of a typical phase one drug trial.
Okay.
A general rule.
Things get a bit more expensive as you move through the phase of the clinical development from experience wheelhouse.
I think that the.
Situation specific allocation of capital across the platform.
This is this is something we take a close look at will be very responsible and thoughtful about how we how we allocate the capital. So we get both drive these programs forward and live within our means and so I would answer it that way.
More to come thanks.
Yes very quickly.
I think what we basically do is a very continuous.
Graham review, where we thoughtfully look at the capital deployed.
And basically new data coming out and I think the example of <unk>, where we increased our stake based on the strong data that came out as a very good example of how we make capital allocation decisions.
<unk>.
Yes across all our pipeline. So that's a really continuous process, where we over over again review programs and make the decisions for in general resource of locations.
For many programs not only provide capital, but also our deep domain expertise and people that work on all those programs.
Great. Thanks, Chris.
Thank you for our next question, we have Brian Abrahams from RBC capital markets.
Okay.
Okay.
Okay.
Okay.
Hey, guys. Thanks for taking my questions. Congrats on all the progress and really appreciate the comprehensive overview of the pipeline.
Maybe starting off with.
Comp 360 <unk>.
Which you alluded to the proof of the positive proof of concept data, we'd seen for Christmas item.
Which you obviously have a stake in the success out but.
I'm also wondering sort of recognizing that your own psychedelic compounds all her and different profiles in terms of the administration and on half life, but.
I guess I'm wondering if there is any.
Generalizable learnings you can take away from that 360 dataset.
Help inform your future trial design conduct what you might be looking for going forward for your proof of concept studies as those programs mature.
Yes. So the trial was essentially the same sort of thing that we're doing with our economy and we're doing a single administration data at a single administration. It's early to understand in a robust fashion for the duration of efficacy is so that was again really critical and we are doing as we move forward in <unk>.
The things we are anticipating readouts, just like we're anticipating readouts for our Academy.
So I don't think theres anything that's not going to be too shocking.
When we introduce those factors of re dosing into the archiving, obviously is going to be the national IV is not particularly great for that.
For DMT and others will be we're still working on when those get introducing incentives, but I think the most important thing there was re dosing that's going to drive the one that's been.
To drive long term efficacy, that's what's going to drive these folks and their emission which of course is really what we're after here.
That's really helpful and then maybe on.
<unk> 17.
I know the sad Mad studies are still ongoing so the data is still very preliminary but I guess I'm curious if you could maybe just characterize your overall level of confidence on that program based on what you're seeing both pre clinically and clinically so far in terms of the ability for the deteriorated.
<unk> two <unk>.
Comparable or even better PK characteristics, and maybe but maintained.
But the pharmacologic effects of about approximately.
First of all we're very enthusiastic about this program for the.
The main reason of this compound at advancing the parent if you will has been on an untold millions of people at this point right. So there is.
The review on safety was over 14 million scripts, but it's been a program and that was only in France. It's been approved and I think in over 30 countries. At this point, so lots and lots of experience lots and lots and lots of use.
Across a range of anxiety disorders.
Pre clinically we know that this compound and.
<unk> at generated at Fox near the same effect in terms of increasing the production of non steroids, so pretty confident on that.
In terms of the phase one and.
It's obviously.
Too early to say, we did this add theres. Some interim analysis really we want to get the totality of the trial done before.
<unk> and talking about the results.
Okay, Great now that makes it a lot of Samsung and then maybe one more on me if I could and this was of agricultural.
Florian and Greg It seems like there is.
Fair amount of capital earmarked for potential additional business development.
Can you talk a little bit more specifically about the types of assets or.
Technologies that you might be looking for.
Would they be more along the psychedelic side, our non psychedelics or are you looking more for enabling technologies to augment some update.
The pharmaceuticals that are that are in the pipeline might even consider branching into other disease areas that are within neuroscience and neuroscience, perhaps adjacent to mental health.
Sure.
Hey, Greg maybe let me let me go first menu chime in so ultimately we're very much agnostic when it comes to color modalities are the ways that we can improve.
Yes, mental health disorders, and ultimately help patients.
Our specific focus on psychedelics ordinance liabilities or <unk>. So we are basically organizing our activities along the three strategic pillars that we discussed earlier, so rapid intervention, where we see strong new pumps big effects that we can use to kind of capitalize behavioral change and then we are very excited about the digital therapeutics that we have in development.
Currently.
Basically both hardware and software to help along the patient journey.
The last one being precision mental health as we've discussed and we see great potential and the greater use of capital in all those three pillars and also a great ROI for.
Shareholders ultimately, we believe that the drug development pipeline itself there is.
We can expand bear even further within the scope that we have right now in neuroscience.
Basically what.
It's interesting cross through indication perspective, and everything that we add should be very complementary.
We wouldn't add fifth a fixed five ht drag.
<unk> agonist, most likely but look at uncorrelated.
In terms of toy risk profile.
And that is roughly a summary of how we think about deploying capital.
Great. Thanks, so much.
Thanks, Luke footnote there just to echo that I think it tip from financial point of view, there's Roman these plants here and our strategy to add to this family of companies.
The screening process that we go through and it's pretty robust and what you'd expect in terms of screening for a strong IP.
Market potential.
Value add for shareholders, so that would be the key takeaways.
Thanks again.
Thank you and for our next question, we have Patrick <unk> from H C. Wainwright.
Hi, good morning, and good afternoon.
Two questions. The first one is just with with at least 14 drug development, enabling technology catalysts over the next few years can you tell us which update or updates you believe are underappreciated or perhaps not as widely understood and what the expectations are around those updates.
Do you want to take that one.
If I can start volume can jump in.
As we just talked about Gaba is really exciting its got a lot of previous use history.
It sometimes might get a little bit of short first I think it's.
It's really been a phase one trial design when we kicking off the phase two a little bit later.
<unk>.
AMC.
Lots of interesting work, that's being done on DMT.
Really unique profile with our formulation and builds extensively on the data that's been generated with campus already. So I think these are the couple of these are some of the things that.
Are of Great interest to me certainly in terms of moving forward.
Some of the digital integration I think is going to be very exciting as EMEA a lot of news around that as we move forward as well.
Maybe just to add to this I think as you mentioned with more than 14 catalysts coming up.
Often the.
The focus tends to be on the more advanced compounds, but I think what is exciting about the tie is really kind of this diverse pipeline with diverse pharmacology and the richness and useful that you mentioned, but really provides a nice continuous drumbeat for investors and so it's really the totality that is often overlooked because so much was going on that.
I would like to highlight here.
And then just regarding the end of phase II meeting per campus in April I'm wondering what is hybrid considered to be the ideal outcome from that meeting and separately I'm wondering how do we think about comp 360 relative to the CRD programs. So the tie is running.
<unk> hundred one <unk>, one and specifically is there a place in the depression treatment paradigm for all of these treatments either.
Or and clinic settings.
So with regards to the end of phase II meeting, obviously clearance to move forward into phase III in agreement on what the Phase III program looks like is going to be keg right. So thats. What we are that's a win win.
And for Us.
In terms of what how these different <unk>.
That's going to fit together psilocybin is furthest along it's a fantastic asset we've got a great result, as we've talked about with the phase II trial, a phase <unk> trial. So that of course is one of the key anchors. We always I always like to think about that would be one anchor and <unk> being the other.
The DMT asset that I was talking about is sort of the second generation of sunstone right.
Optimize phonogram, we've optimized formulation.
We've optimized duration of effect.
So that's that's sort of the next thing obviously, a number of years behind <unk> nine it's going into phase one we.
We have other kind of Arcata mean, Reits our academy in a totally different <unk> profile. It's glutamatergic, it's not <unk> <unk>, probably will pick up a different subset of <unk> patients. It's at home, which of course is a major plant differentiation probably increases the total addressable market as well and then finally thousand Rnas.
<unk> unique pharmacologically psychedelic psychedelic like it's got some very interesting properties in terms of its subjective effects.
Our hypothesis is that I'll pick up a different subset of CRD population and of course all of these to also have label expansion opportunities and they may also be non overlapping.
Yes, just just one last one if I may just on <unk> 100 to the phase one trial I'm wondering if you can tell us how the doses were selected for this phase one trial and in determining the maximum tolerated dose can you tell us what date is expected to be collected and released later this year and what you need to see to give increased.
Confidence, but the <unk>.
Safety profile and Tolerability can support advancing this program.
So most of the data around IV game in aggregate in terms of efficacy is using doses that are sort of in the $7 eight and above range right. So we just started low to understand the compound so understanding both the PK of <unk> as well.
All of this major metabolite, nor I became so that's where we started three and then six nine and 12. So nine obviously is a dose that is certainly consistent with previous work that's been done without again so.
So in terms of what we're looking for of course is subject to the fact general safety and Tolerability, but not surprisingly looking at cardiovascular.
And our parameters are so.
There is literature that suggests that there are no qt prolonging effects of I've again.
Not again, where we're fully cognizant of that but we want to.
Characterize that characterize it in the context of this patient population in the context of in clinic treatment met.
In medically supervised treatment in a condition that has significant morbidity and mortality. So that's.
That's the sort of balancing act that were looking at.
And that's what we'll be reporting out on.
That's helpful. Thank you very much.
Thanks, I think well have time for one more question from <unk> Kulkarni at.
Canaccord Genuity.
Okay.
Okay.
Good morning, Thanks for taking my questions nice to see on your progress.
Question on the pipeline on <unk> 100 to one of the specific <unk> that are leading to the safety data now coming later this year versus earlier and the second is actually a two part strategy question Kristian mentioned two things. One is your first mover advantage in second year commendable goal of becoming a household name for treating mental health on the first mover advantage what are the key.
Gating factors from bringing the entirety of compass in house, given the significant first mover advantage that company and just currently and in the household name component.
Is that several of your current ups might require clinical infrastructure to administer what are your latest thoughts on perhaps starting from dry runs on that side, mainly in clinics or is that something that is not a ton in price plans.
So let me touch on the <unk> one the IV again.
Questions and then I'll turn it over to Florian for some of the other to answer some of the others. So.
I had mentioned what the the key variables are with respect to what we're looking for in the phase one we're looking for subjective effects that are consistent with some sort of a history right. So this psychedelic narrow phrenic type.
Experience, which seems to have an important.
Thanks very important practices.
So that's the first thing and then it's all about risk benefit and is there is a cardiovascular the changes on Qt for example are those.
Are those acceptable for the context that I provided so that's really where we're going to be looking for will be picking a dose from the phase one.
And then we're moving forward that moving it forward into the phase III Regina double blind placebo controlled two arm.
I'm looking at your own control or urine confirmed absence or leased homes reduction going forward.
Yes, I'm happy to take the first or the second part of your crisis since I mean in terms of first mover advantage.
We were starting out in 2017 with Comverse 2018.
Hi.
Had a chance to look at many many components early on where and when psychedelic medicine was not as.
As permanently discussed and the Neuropsychopharmacology and also among investors. So we had a good chance to look at all components that we believe based on all the data have a commercial potential.
And also a solid <unk> for profitability.
So that was basically what we are excited and also of course the science. So the scientific data came out.
And that's how we basically assembled our pipeline on the psychedelic side, but as you know we also are very active in the loan psychedelic component on the digital therapeutics sites.
On the crush surround clinics I mean, we believe that.
Our strength.
The one and also our deep domain expertise in CNS is really drug development in CNS Thats, where our core expertise lies and that's why we also intend to focus going forward that doesn't mean that we're not.
Entertaining discussions with infrastructure providers I think that is key.
To be very early to think about scaling those therapies also how our digital therapeutics coming into this so we will be very much.
Thinking about how to best scale those therapies in a safe and responsible way, but as of now we don't envision too yes.
Yes, two to move towards brick and mortar or running clinics.
Thank you.
Thank you all for your questions and Windows that we didn't have time to get to as we are approaching the end of our allotted time.
I'd like to turn the call back over to <unk> for any closing remarks.
Sure. Thank you Colin and thanks, everyone for listening in and for all your questions 2021, as we've discussed was truly transformative for <unk>.
And I'm deeply thankful for that.
Lists for dialing in all of our team for the great efforts over.
Over the last years and also to our investors to be an integral part of our journey, so far and I'm really excited about what's yet to come.
Yes.