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spk09: Good morning and welcome to the Atai Life Sciences second quarter 2021 financial results and corporate update conference call. Currently, all participants are in a listen-only mode. This call is being broadcast live via the news and events section of the company's website at www.atai.life and is being recorded. For opening remarks, I would like to introduce Greg Weaver, Chief Financial Officer of Atai Life Sciences. Please go ahead.
spk05: Thank you and good morning. Welcome to our second quarter 2021 Attai Life Sciences financial results and corporate update conference call. The press release reporting our financial results is available in the investors and media section of our website at www.attai.life. And our quarterly report on Form 10-Q ended June 30, 2021, will file today with the SEC. Joining me today are Florian Brand, our co-founder and CEO, Dr. Srini Rao, our co-founder and chief scientific officer, and Christian Angemeyer, founder and chairman. During today's call, we'll be making certain forward-looking statements that are intended to be covered by the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. While these statements represent management's current expectations and projections about future results and performance as of today, the TIE's 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 during the call, these statements are subject to various risks that are described in our filings made with the Securities and Exchange Commission, including our final prospectus filed with the SEC on June 21 of 2021. Your caution not to place undue reliance on these forward-looking statements, which speak only as of today, August 16, 2021, and except as may be required by applicable law, a TIE disclaims any obligation to update such statements even if management's views change. I'd now like to turn the call over to Atai's CEO, Florian Brand. Florian?
spk08: Good morning, everyone. Thank you all for joining our first earnings call following our successful completed IPO in NASDAQ in June, where we raised $259 million. We are thrilled by the enthusiastic response to our mission from the investor community, and we intend to use these proceeds to continue advancing our decentralized drug development platform in two ways. First, to by executing on our existing pipeline, and second, by continuing to incubate, acquire, and invest in new programs and enabling technologies. With our unique approach, we aim to become the leading drug development company focused on mental health. We will do so by transforming and advancing the treatments of patients with the ultimate objective to heal mental health disorders so that everyone everywhere can live a more fulfilled life. And now it gives me great pleasure to introduce you to my visionary co-founder and our board chairman, Christian Anamayo. Christian.
spk06: Thank you, everyone. With my co-founders and the entire ATTAI team, I share the common aim of transforming the treatment of mental health disorders and exploring solutions offered by unconventional approaches, including psychedelic compounds. I want to take a few moments to discuss ATTAI's origin and my commitment to ATTAI. In this context, it is important to emphasize that I'm not only part of the founding team, but also made a significant investment in Atai myself. And as many of you know, everything started with my own first psychedelic experience. This experience was, in short, the single most meaningful experience in my entire life. In addition, my friend and our co-founder, Lars Wilde, who suffered greatly from treatment-resistant depression, found healing in psilocybin therapy. Both experiences form the basis for my desire to invest heavily in rigorously researching therapeutic potential of psychedelics for mental health disorders. I hope you leave this call with a real appreciation for both a tight progress to date and what I hope will be an even brighter future to come. While I leave it to Florian and Srini to elaborate on the details of our achieved milestones, I want to emphasize what makes me most proud. Atai is aiming to help solve one of the biggest problems in healthcare, mental health disorders. More than 1 billion people globally suffer from depression, addiction, PTSD, anxiety, and other intractable mental health diseases. And that is just the official number. The unofficial one is most likely significant higher as mental health issues are unfortunately still a stigmatized topic. We have built a well-funded company in the young psychedelics industry and have more than $400 million to continue advancing our 11 programs. We have a rich business development pipeline and are aiming to add more programs over time. All of our drugs, both the psychedelic ones and the non-psychedelic ones, have prior evidence in humans which helps strengthen the indication for the outcome of our trials. Because of our portfolio approach and our extensive pipeline, we expect continuous news flow with 18 R&D catalysts over the next 18 months. Our partnership with Futsuka illustrates big pharma's interest in psychedelics. While we strive to keep control of our assets through phase three, and we are, as you know, well-funded to achieve that goal, We believe that this is just the first step and more pharma partnerships are possible. In short, I'm very convinced that Atai has the potential to become the leading mental health company globally while building value for our shareholders and other stakeholders. Let me now hand it back to our CEO, Florian, who together with our CSO Srinivas and CFO Greg will provide additional updates on our business.
spk08: Thank you, Christian. Allow me now to provide a few introductory comments, then Trini will review highlights from our drug development pipeline, and Greg will provide the quarterly financial report followed by the Q&A. For people not yet familiar with our company, let me briefly give you an overview of Atai Life Sciences. We founded Atai three years ago as a response to the significant unmet need that we witnessed firsthand ourselves with friends and family members suffering from mental health disorders. As you know, we operate our business in a decentralized model and utilize enabling technologies such as digital therapeutics. This allows us to support and accelerate the development of compounds in our companies. And these are all companies we have either acquired, controlling, or significant interest in or incubated de novo. We have a disciplined program selection process that is focused on differentiated mental health opportunities and aimed at increasing the clinical probability of success. On an asset level, we are focused on developing compounds with prior evidence in humans. Combined with our unique portfolio approach, which is designed to avoid binary risk, the entire pipeline can be both innovative and diversified. The process also incorporates a milestone-based approach to capital allocation. We have already demonstrated our ability to capture value this year by partnering with other world-class organizations focused on mental health. One example of this is Perceptions Licensing Deal with Otsuka, an industry leader in innovative mental health therapies. This deal represents the first major partnership between a biopharmaceutical company developing psychedelics and large pharma. In only three years, we have aggressively built a pipeline of 11 development programs and six enabling technologies. We believe that several of our target indications have a potential market opportunity of at least $1 billion in annual sales each, once approved. Outside of our current focus indications, we see in significant untapped business opportunities around indication expansion with an additional estimated market potential of $18 billion by 2026. We intend to invest in these indications for our most promising compounds to optimize our portfolio and maximize shareholder value. Looking forward, it is important to highlight the density of our new slopes. We have 18 R&D catalysts over the next 18 months, a result of our portfolio approach and our extensive pipeline. The two most imminent upcoming milestones are, first, Compass Pathways, that is expected to provide top-line results on their Phase IIb study in Q4 of this year, and second, Recognify Life Sciences, that has initiated a Phase II trial and expects to have data by the end of the year. In addition, we plan to initiate Perceptions Phase II trials for TRD, and Demarex Phase 1-2 OUD trial still in this quarter. Additionally, we plan to initiate three Phase 2 trials and four Phase 1 trials next year. With a very strong cash position, we are well equipped to maintain our leadership in developing treatments for mental health disorders. I will now turn the call over to Srini for a more detailed update on the Atai pipeline.
spk11: Thanks, Florian. As Florian has highlighted, we have a broad array of exciting assets in or nearing the clinic. On this call, I will focus on the programs with the most near-term visibility and highlight upcoming milestones, starting with perception neuroscience. The lead compound for perception is TCN101, a formulation of R-ketamine. R-ketamine is a glutamatergic modulator being developed as a rapid-acting antidepressant with non-dissociative properties and the potential for at-home use. This is in contrast to S-ketamine, marketed as Fervato, which must be administered only in the clinic. In preclinical models, R-ketamine has demonstrated higher potency, greater durability, and lower abuse potential compared to S-ketamine. The recently published results of an open-label, seven-subject trial in patients with treatment-resistant depression, or TRD, using IVR-ketamine supported the hypothesis that R-ketamine may be efficacious at sub-dissociative doses in contrast to S-ketamine. As we've mentioned before, we're excited about these potential aspects of differentiation particularly from the perspective of the scalability and commercial potential for a product delivered at home. In February 2021, Perception announced positive Phase I results demonstrating the safety and tolerability of PCN101 in 58 subjects treated at doses of up to 150 milligrams IV. The compound was well tolerated, and there were no serious adverse effects reported. Additionally, The pharmacokinetics of PCN-101 in plasma were found to be approximately dose proportional. Notably, the study demonstrated that PCN-101 required substantially higher doses to induce perceptual changes compared to ketamine. Importantly, we anticipate initiating our phase 2A trial of PCN-101 in Q3 2021. This randomized double-blind placebo-controlled trial testing an IV formulation of our ketamine will be conducted across 13 sites in Europe and aims to enroll 93 patients diagnosed with TRD. We anticipate the study running through late 2022. In parallel, we intend to conclude a phase one bioequivalent study to bridge from the IV formulation to a subcutaneous formulation of PCN101, one that we believe will support at-home use. Next, Recognify Life Sciences is developing RL007, an orally available cholinergic, glutamatergic, and GABA-B receptor modulator. In aggregate, RL007's complex pharmacology is thought to alter the excitatory-inhibitory balance in the brain to produce pro-cognitive effects. We're developing this compound for the treatment of cognitive impairment associated with schizophrenia, or CIAS, which is a challenging indication with significant unmet need as no drug therapies are presently approved for this condition. In April 2021, Recognify initiated a 32-patient phase 2A proof of mechanism study for RL007 after receiving IND clearance from the FDA to commence U.S. clinical development for the treatment of CIAS. The exploratory study is designed to evaluate the effects of RL007 on safety, tolerability, and quantitative electroencephalogram, or QEEG-based measures that are viewed as biomarkers for cognition. More specifically, the objective of the trial is to extend the results of a previous study involving a scopolamine challenge in healthy volunteers. In addition to observed improvements in verbal memory, RL007 administration resulted in a spectral shift on QEEG from a lower frequency theta band to higher frequency alpha and beta band oscillations. Further, we're investigating the effects of RL007 on several evoked potential measures. including mismatch negativity and P300, the latter in response to an auditory oddball task. Ultimately, we're looking for a confluence of data consistent with pro-cognitive effects when all cohorts in the Phase IIa trial are analyzed. Such top-line data, which are anticipated by the end of the year, will allow us to progress confidently into the proof-of-concept study. The latter will be a double-blind placebo-controlled trial focused on more traditional cognitive endpoints including subsets of the matrix battery. Next, GABA Therapeutics' primary program is GRX917, an oral formulation of a deuterated version of etafoxine, the latter a compound that has a long history of prescription use in France and other countries for treating anxiety disorders. Mechanistically, etafoxine and GRX917 have been found to increase the production of neurosteroids, including allopregnanolone. an IV formulation of which was approved in the United States in 2019 for the treatment of postpartum depression. This mechanism of action is thought to underlie etafoxine's rapid onset of anxiolytic activity that is similar to that observed with benzodiazepines, but without the sedation, cognitive impairment, or abuse independence risks associated with its class of compounds. Further, etafoxine has an extensive safety database, which we believe will greatly de-risk the future development of GRX917. Like etafoxine, we hypothesize that GRX917 will provide rapid anxiolytic activity with improved tolerability compared to current treatments for anxiety, and the deuteration is intended to enable less frequent dosing and or lower doses with GRX917 than etafoxine. In June 2021, we initiated a randomized double-blind placebo-controlled phase one trial in Australia, which will ultimately enroll approximately 76 healthy adults. The study is a single ascending dose, multiple ascending dose design, looking at safety and tolerability, pharmacokinetics, as well as pharmacodynamics using QEEG. Based upon the mechanism of action of GRX917, we're using the QEEG as a target engagement biomarker. looking for increased relative spectral power in the beta band. Such changes have been demonstrated with IVL or pregnenolone and related compounds, and were also noted in a 2019 phase one trial of Advoxine that we conducted. Top line data for the GRX917 phase one trial are expected early in 2022. Moving to Demorex IB, we are developing DMX1002, an oral formulation of Ibogaine, the latter a naturally occurring psychedelic product, as a potential disease-modifying treatment for opioid use disorder. We anticipate initiating the phase one component of an exploratory phase one slash two-way trial of DMX1002 in recreational drug users and healthy volunteers in the UK in the third quarter of 2021. To that end, we recently received approval from the UK Medicines and Healthcare Products Regulatory Agency, or MHRA, to commence subject enrollment. The phase 1 slash 2A trial is designed to assess safety, tolerability, pharmacokinetics, and efficacy, and the results will inform future studies in patients with opioid use disorder. We expect to obtain safety data from the phase 1 element of this trial in early 2022. We have an extensive early stage pipeline that will be entering the clinic in 2022, and we'll provide a deeper update on these programs and associated milestones as we approach next year. Further, it should be noted that the digital therapeutics being developed at Introspect are currently undergoing user acceptability testing at Academy and Clinic in San Diego. We anticipate rolling out the Introspect technology in our Viridia and Rivixia Phase I trials and Demarex Phase II trials starting next year. Finally, a brief mention of COMPASS Pathways and its compound, COMP360, which is a proprietary formulation of synthetic psilocybin, a 5-HT2A receptor agonist being developed as an oral rapid-acting antidepressant, is in order. In June 2021, COMPASS announced completion of dosing in the Phase IIb clinical trial of COMP360 in a total of 233 patients diagnosed with TRD. This randomized, double-blind, dose-ranging study investigating the safety and efficacy of psilocybin is the largest industry-funded clinical trial of psilocybin conducted to date. Getting to this stage in this trial is a major achievement, and the Compass team should be commended for their incredible work. We look forward to the top-line data of this trial later this year. I will now turn over the call to Greg for an overview of our financial highlights.
spk05: Thank you, Srini, and hello, everyone. As Florian mentioned, in June we completed our upsized IPO of 17.25 million shares, raising gross proceeds of 259 million, including the full green shoe exercise. Cash and equivalents totaled 453.6 million as of June 30, compared to 97.2 million as of December 31, 2020. The six-month increase of 356.4 million is attributable to the IPO net proceeds of 231.6 million plus $168.6 million from Series C and Series D common stock issuances, $20 million of licensed revenue proceeds, and $4 million proceeds from the sale of investments and conversion of convertible notes. Offsetting were cash payments of $32 million for investments in platform companies and $35.8 million in net operating expenses in the first half of 2021. So our operating use of cash for the six months ended June 30, 2021 was $14.6 million, which includes the positive effect of the $20 million in license revenue proceeds received from Perception's license and collaboration agreement with Otsuka Pharmaceuticals. Operating costs and expenses in the first half of 21 were as follows. Research and development expenses of $16 million and $21.6 million for the three and six months ended June 30, 2021, as compared to $2.9 and $5 million for the same prior year periods. The increase of $13.1 and $16.6 million, respectively, were attributable to personnel costs, including stock-based compensation expense, and increased CRO expenses related to advancements in our R&D programs. And we also recorded acquisition of in-process R&D expense of $8 million and $9 million for the three and six months ended June 30, relating to our investments in Neuronasal and Inaris Bio. Moving to G&A expenses, for the three and six months ended June 30, 2021, were 37.3 million and 46.6 million as compared to 2.9 and 4.4 in the same prior year periods. The increases of 34.4 and 42.2 million respectively were attributable to personnel costs, including stock-based expense, professional fees, and other costs related to support our platform growth, and public company requirements. Total stock-based compensation expense for the three and six months ended June 30 was $37.5 and $37.7 million, respectively, as compared to $41,000 and $82,000 for the comparable prior year periods. This reflects the recognition of expense related to the achievement of the IPO performance-based partial vesting conditions. The year-to-date R&D portion was $9 million, and G&A portion was $28.7 million for your modeling. I'd like to draw your attention to two one-time items in our first half results. First, with Compass Pathways, where in the second quarter we booked a gain of $16.9 million relating to our investment in Compass's May follow-on equity round. But Ty participated and purchased 140,000 shares for $5 million, and We now own 19.4% of Compass. And the licensing revenue of $19.9 million recorded from Perception's license and collaboration agreement with Otsuka Pharmaceuticals. I'd compliment the management team at Perception and everyone involved at a tie on this deal. And also point out that the strategic intent is to drive additional non-dilutive licensing transactions in the future. I'll now hand the call back to Florian.
spk08: Thank you, Greg and Trini. I would like to thank the entire TIE team, as well as our supportive investors, and their contributions to all we've achieved this year. Looking ahead, we are energized to drive in an important and catalyst-rich 2021 and 2022 with additional clinical readouts, trial initiations, and business development. This is an incredibly exciting time for TIE, and we will continue to provide updates on our program as they advance. Before we will take questions, I would like to highlight the following five key takeaways on our progress to date and roadmap forward. Number one, with our strong balance sheet and broad portfolio, we have solidified our leadership position as an innovative drug developer within mental health. Number two, by design, our company is structured to maximize the probability of success in drug development through a combination of basically three elements. a unique portfolio approach, a focus on developing compounds with prior evidence in humans, and a milestone-based approach to capital allocation. Number three, our differentiated model has been validated by our attraction to date, where we are the only biopharma company developing psychedelics that has entered into a drug development collaboration with large pharma. Number four, Etai has accelerating momentum, with 18 near-term catalysts, including phase two data readouts by year end from Recognify and Compass Pathways. Number five, we continue to drive our business development activities by incubating, acquiring, and investing in complementary compounds and enabling technologies. With that, we are happy to take questions.
spk09: Thank you. Ladies and gentlemen, at this time, we will be conducting a question and answer session. If you'd like to ask a question, you may press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key. Our first question comes from the line of Charles Duncan with Cantor Fitzgerald. Please proceed with your questions.
spk04: Yes, good morning Florian and team. First of all, thanks for taking the question and thanks for all the details in outlining the 12 and 18, call it week and month plan. So had a quick question on RL007 Phase 2A in CIAS. I guess I'm wondering if you could provide a little bit more detail on the enrollment criteria regarding call it symptom presentation as well as concomitant medications and perhaps frame a useful result for informing the next steps out of that study with regard to dosing and duration?
spk11: Absolutely, Charles, and thanks for the question. Generally speaking, of course, they have to meet the criteria of schizophrenia with a cognitive impairment That is, I believe, one sigma below normal. And in terms of concomitant meds, I mean, they're allowed to have that. We are limiting it to aripiprazole and one other related compound, and that's really about it, just to keep the population as homogeneous as possible. In terms of a meaningful outcome, I mean, as you'll recall, what we're trying to do here is extend the results of the previous phase one study, which was a scopolamine challenge study. And in that trial, they found two things. First, they found improvements in verbal memory. And they also found, you know, concomitantly with that, changes on quantitative EEG. Specifically, they found alterations in the spectral profile pre and post drug. And it was really shifting from lower frequencies to higher frequencies. And generally speaking, such higher frequencies are associated with improved cognition. Folks with schizophrenia, particularly those with prominent cognitive impairments, do have some degree of suppression of higher frequencies. They tend to be, you know, they tend to run at lower frequencies. So the very first thing that we're looking at is a replication of the quantitative EEG spectral shift. So that's going to be the first thing. And then we'd like to extend from there to some of the evoked potential measures that we're looking at, mismatch negativity and P300. I mean, you know, but broadly speaking, a win would be around some of the spectral shift. That's kind of the key here. Obviously, concomitant improvements in evoked potentials would be great, and we are doing cognitive assessments as well. Obviously, this is a very small study. We aren't expecting much, but if we find some proportionality or concordance with the EEG shifts, then that, of course, would be a big win as well.
spk04: Okay. Thank you. One additional pipeline question, then a quick follow-up for Greg. Regarding the Comp 360 results that could come towards the end of this year, you know, clearly we've spoken to Compass Management about this, but we'd like to hear your perspective on what you'd like to see out of the trial in terms of, call it three-week effect sizes and response rates, as well as longer-term durability. given that this is the largest controlled trial of psilocybin to date and given that it represents a new paradigm relative to the current standard of care?
spk11: Okay, Charles, I think you said Greg, but I'm willing to take that. Of course, Greg, if you want to chime in, please do so. You know, with respect to the psilocybin study, I mean, clearly one of the things that we're looking at is, you know, the key, of course, is their primary endpoint at three weeks. That certainly shows a rapidity of onset, as well as some degree of durability. Of course, with the promise, I mean, part of the promise of psilocybin is an extended duration of, you know, of efficacy, of driving someone into remission. As such, we're certainly going to be watching the data from there on out, right? This trial does go out to 12 weeks post-dose. And so we'll be obviously looking at that. You know, it's powered certainly to, you know, for the primary endpoint at three weeks. And, you know, obviously these data will, of course, inform subsequent studies. I mean, clearly responder data, responder remission data over the subsequent weeks will be really quite key for, you know, understanding and interpreting the results from this trial. Does that answer your question?
spk04: Yes, it does, and it was for you. My follow-up for Greg was relative to OPEX over the course of, say, the 6 to 12 months, not looking really for guidance, but, say, just a range. How do you see the income statement over the course of the next year or so?
spk05: Thanks, Charles. Greg here. Good question, because inside the first half numbers, you've got some in-process R&D and some spike in the non-cash stock comp. But if you strip it out, the OpEx in the first half is running about 18.25, and I think we're going to see personnel costs growing as we continue to support the platform companies and build out the capabilities internally. And as the pipeline moves to a more clinical stage, we'll have additional R&D spend likely to grow there to support that activity as well. As a range, you know, it'll be north of where we are now, maybe 25 to 30 range per quarter as we go forward would be directionally okay.
spk04: That makes sense. Thank you for taking my questions.
spk05: You bet. Thanks, Jeff.
spk09: Our next question comes from the line of Ritu Barrow with Cowan. Please proceed with your question.
spk02: Good morning, guys. Thanks for taking the question. My first question is on perception and 101. Can you review for us the dose and the dosing paradigm and treatment duration that you're using in the upcoming Phase 2a that you plan to start in Q3? And when we do get the data in 2022, I guess, what are the most important scales that we should be looking to for depression efficacy, but as well as the degree of disassociation versus S-ketamine? And then I've got a follow-up.
spk11: No problem. I'll start with that one then. So in terms of dosing, we haven't really guided on that at this point. What I can say is that you know, based on the phase one, we have some latitude on dosing. And we are certainly, you know, going with doses that are sub-dissociative based on the phase one result. So that's essentially what we're doing there. In terms of endpoints, obviously the madras is going to be kind of key here. Oh, you also talked about dosing frequency. So this trial is a single dose. It's a single IV administration of the compound. And clearly, we're following the depressive symptomatology out to 14 days of primaries at 24 hours, consistent with other ketamine studies. The results of this trial will give us some indication of the dosing frequency or the re-dosing frequency, which we do anticipate will be required here, not unlike S-ketamine or ketamine proper. You know, there's preclinical data suggesting greater durability of effect. So that's really what's driving, you know, driving this hypothesis that we might be able to dose less frequently than ascadamine, which, of course, is twice a week for four weeks. So, you know, so that's kind of the long and short of it in terms of the dosing. In terms of endpoints, madras obviously is a key endpoint here. In terms of dissociative slash psychedelic effects, there's really two things that we're focused on. Obviously, CADS is something that's widely used in the industry, and we certainly are including that. I'd say that CADS is perhaps not the best suited for this. We are also doing the 5D ASC here, and that will give us a lot more granularity on the sort of psychedelic type effects that one may, you know, that we're seeing with the compound.
spk02: Got it. And then my next question is on the Demorex Phase 1-2 study that you're planning on starting in Q3. Srini, you mentioned the safety in PK. Are you doing any special cardiovascular monitoring around the IB study? And then again, since this is recreational drug users, what sort of efficacy data Could you glean out of it and when?
spk11: Yeah. So in terms of cardiovascular safety, of course, there is a signal depending on the publication for QT prolongation in this population. I mean, I think there are some confounds of existing data. There were certainly multiple dosing experiments that had been done. The concentration of Ibogaine wasn't necessarily clear. So that's something that we're looking at very closely. We are doing Holter. We're doing repeated ECG endpoints as well in sort of standard fashion here. We would like to see, of course, that there's a dose range that we can get to that is relatively devoid of QT prolongation. So that's really the focus here. In terms of efficacy in the phase one element, I mean, we're, you know, the focus on the efficacy endpoints are really in the phase two piece, which is those individuals that are undergoing medically assisted detox. So, you know, looking at their withdrawal and then looking at long-term remission, if you will, is really what we're focusing on there rather than within the phase one component of the trial.
spk02: Got it. Thanks for taking the questions.
spk11: No problem.
spk09: Our next question comes from the line of Brian Abrahams with RBC Capital Markets. Please proceed with your question.
spk03: Hey, guys. Thank you so much for taking my questions and congrats on all the progress. Maybe just starting with the PCN 101, I was wondering if you could talk about the status of the subcutaneous formulation. You mentioned that would be moving into a bridging study in your opening comments. Just wondering, I guess, where that stands, what, if any, gating factors there are to starting that study, and what your target volume would be for that administration.
spk11: I think a lot of the details here are not public. I mean, the long and short of it is that the formulation is under development. And of course, you know, there's the formulation itself and then compatibility with the device, the subcutaneous injector. So all that work is ongoing. The BE study, as you're familiar, is relatively straightforward and very quick, right? I mean, it's basically comparative IV versus subcutaneous injectors. And as we mentioned in the opening remarks, we are looking to get the data from that contemporaneously, roughly with the phase two results. So that's ongoing currently. In terms of volume, the standard volume here for subcutaneous is keeping it under two milliliters. And obviously we'd like to keep it significantly under two milliliters. And that's obviously what we're pursuing with our formulation.
spk03: Great, thanks. And then you also have recently announced Revixia launch to develop Selenorin A. Just a couple of questions there. I guess first off, I'm curious on the digital therapeutic element there, which you talked about a little bit in your opening remarks, and your vision for integrating that to help assist with dosing therapy and monitoring, how that might provide an administration advantage. Secondarily, you also pointed out that you don't interact with 5-HT2A, which could potentially enable, I guess, additivity to SSRIs. So I'm curious if you could also speak to how you envision the future program in terms of combination potential, both with SSRIs as well as with other TRD programs in your pipeline. Thanks.
spk11: Yeah, I think that that's with salvinorin, that's really the key point. I mean, clearly the compound is psychedelic. It has many properties in terms of the psychedelic experience that overlap with classical psychedelics, as well as with some aspects of ketamine as well. So very interesting compound, certainly some, you know, in this case, more anecdotal data around antidepressant efficacy and Very curious pharmacology overall. It's a kappa agonist. Many such kappa agonists, well, they tend to be a little more on the partial agonist side like pentazosine and things that are related to that, but they tend to be more dysphoric. So this is really quite an interesting compound. And because of its opioid receptor pharmacology, you know, certainly the potential exists to be used concurrently with SSRIs, SNRIs, et cetera. So that's what really, you know, that's what really is kind of the value add here, something that we're obviously very, you know, very keen to pursue. More broadly, as we've discussed, you know, clearly depression is multifactorial, and different patient populations may have different, you know, underlying pathophysiologies driving that, certainly in subsets aspects of opioid dysfunction. So perhaps this is better suited to that population. So that's, that's certainly why we're interested in this compound and pursuing it. In terms of the digital therapeutics, I mean, obviously this is a somewhat broader point. You know, we mentioned several times that the redose frequency is not necessarily clear from the outset and it's going to vary undoubtedly by patient. So again, You know, regardless of the compound, there'll be a subset that don't respond. There'll be a subset that have a very long term remission. And we envision the digital therapeutics not only to support the patient, both pre and post psychedelic in terms of, you know, pre psychedelic, of course, pre psychedelic administration, you know, expectation setting and the preparatory work and then post. you know, providing psychosocial therapy, not unlike a reset-O from PEAR, but also tracking symptoms and, you know, giving the physician, the treating physician, input as to when the patient should be redosed. And again, this is more broad. This is certainly something that we're looking at with Viridia with its DMT program, as well as Rivixia with its salvinorin-A program, as well as others. Does that answer your question? Yes, that's really helpful.
spk03: Thanks, Randy.
spk09: No problem. Our next question comes from the line of Judah Fromer with Credit Suisse. Please proceed with your question.
spk10: Yeah, hi. Thanks for taking the question. Maybe we want a little bit more high level on this space as it kind of continues to evolve. I think there probably are a couple narratives developing here where I think some companies in this space are assuming that we'll need a bit of a change in treatment landscape and maybe a real estate or kind of treatment location change in terms of how patients are dosed with psychedelics. It does seem like your team is looking more to leverage the existing infrastructure in the mental health industry. Can you talk about thoughts about doing that as you move compounds through the clinic and if there is any need to effectively kind of reinvent the treatment landscape here.
spk11: Yeah, I'll let Florian take part of that.
spk01: Go ahead. Yep. Well, thanks. Yeah, I have a two-hour thinking around that.
spk08: So we are certainly R&D focused, and that's our DNA, and that's what we are doing right now. It's really focused on executing the trials. And in terms of how we, and I think you correctly summarized it, we intend to leverage the existing infrastructure that existed pre-J&J's approval with Pravata, and that's Pravata or J&J is currently also building out to administer the inpatient Pravata treatments. So we intend to leverage the existing infrastructure and certainly observe and be closely involved in this ecosystem, but primarily focus on the development and execution of our drug development pipelines. And I think there, and Tuni can allude to how our therapies fit in, in what way in terms of treatment duration in a second. But here, key for us is to optimize, in general, the time of the therapist. especially also through the digital therapeutics that Srini already pointed out, as well as optimizing the duration of the treatment in its entirety. So here really slotting things into an existing infrastructure to really optimize for scale and to reach as many patients as possible. in a thoughtful way. And Srini, maybe you have some things to add, especially on how to slide into the existing infrastructure.
spk11: Yeah, I mean, I think you hit upon the main points, right? So the real question is scalability. And it's been mentioned a number of times by other players that there are limits to the number of therapists, et cetera, that one can train. Particularly for those that the for those compounds require sitter etc. So the entire approach with both the solvent RNA program the DMT program is to create an overall profile of psychedelic effect that mimics in some way as ketamine so really having something that you know has a psychedelic effect that lasts less than an hour we're really targeting sort of the 30 to 45 minute range and allows us to potentially leverage the S-ketamine infrastructure. And I believe J&J has over 3,000 clinics at this point. With such a short duration of action, our hypothesis, and it is that, is that we don't require the heavy lift of a traditional sitter in this context. Of course, we'll find out relatively soon enough. But certainly there's no real sitter, if you will, in the context of esketamine. So we do believe that there is utility in supporting the patient, as I mentioned, both pre and post the psychedelic effect. And of course, that requires therapy as well. If you have access to therapists, Godspeed, go for it. But certainly the digital therapeutic is going to provide a baseline level of therapy and a standardized therapy, which I think will be quite beneficial What we didn't get into is our work with cyber, which is actually hardware. And that hardware will provide aspects, if you will, of a digital guide. So, you know, the idea here is really to get the patient into the appropriate mindset. I mean, these folks are very suggestible during the psychedelic effect. And you can kind of drive where things go with the appropriate, you know, discussion, you know, where their minds are at prior to the psychedelic effect. So relaxing the patient may be beneficial, so that's where the with digital therapeutics, though, of course, this is going to work with hardware-based digital therapeutics, feedback-based digital therapeutics, but this is something that will be an active area of research for us.
spk10: Okay, that's helpful. Thanks. And then a quick follow-up on something I think we heard Greg say tied to the Atsuka Club. Is it more tied to psychedelics and big pharma kind of validating their approach there? Just maybe a little bit more color on that comment.
spk08: Sure. I think the executive partnership indicates, I guess, a validation from our perspective of our ability to capture value. So we have been executing for a while, but in March demonstrated also that we captured the value that we generated. It's one potential avenue and something that we want to build on as Greg mentioned and as you also pointed out. So here we intend as part of our strategy to continue the dialogue and potentially also enter into more agreements with strong strategic partners. That's kind of one avenue. Of course, we generally optimize for success, meaning that we get all our compounds to approval, especially given the broad set of enabling technologies that we have that are especially relevant for the psychedelic-assisted therapies, as Srini just alluded to. Here we think we have a competitive advantage and will nevertheless be very open and entrepreneurial when it comes to potential interest from other very strong strategic players. So we'll always evaluate on a case-by-case basis to ensure we optimize here for shareholder value. Great, thank you.
spk09: Our next question comes from the line of Esther Hong with Barenberg. Please proceed with your question.
spk12: Hi, good morning, and congratulations on all the progress. So first question, wanted to ask about PCN 101's or ketamine for TRD. Regarding dissociative effects or lack of, is there any difference in patients who may be more susceptible to potential dissociative effects, or is it pretty clear that it depends on dose strength, in this case, very high doses? And then I've got a follow-up. Thanks.
spk11: Yeah, that's a really interesting question. I mean, I think the short answer is we don't really know in terms of patient subsets. Obviously, It's something that we're looking into. You know, we have a couple of different avenues to be looking into that, including some of the digital aspects as well as some of the more metabolomic aspects. So that's something that is of great interest. Right now, we're focused on dose, to be honest with you.
spk12: Okay, got it. And then wanted to ask about GRX917, deuterated edifoxine for generalized anxiety disorder. Can you speak more about the non-deuterated etafoxine use in France and specifically the safety profile? Where is it used in the treatment paradigm? Any additional details from its history of use in France? Thanks.
spk11: Yeah, absolutely. So this is obviously a really old approval. So this was approved in 1979 in France. And there were some sort of reciprocal approvals in other small territories, but nothing in any of the major territories. And when it came out, it was viewed as a benzo light, but it was pretty obvious that its profile was quite different. At that time in the late 70s, early 80s, you know, this was kind of the heyday of benzodiazepines and people attributed the sort of drunken feeling, if you will, of a benzodiazepine with efficacy. So there was a bias against the compound right off the bat. And You know, it is something that has sold, you know, a significant amount that's used in particularly vulnerable patient populations, the elderly, et cetera, where there's certainly been a lot of use. And, you know, there was a publication a couple years ago that spoke to the safety. This was from the safety database in France. I think it was about 13 million exposures. and looking at overall safety. And, you know, the compound is very well tolerated, very limited effects in terms of, you know, reported adverse effects. Certainly compared to other compounds, I mean, compared to benzo, it was quite clean. Even compared to SSRIs, you know, the profile was very favorable. Specifically, no data suggesting that there's any kind of addictive properties or, you know, dependence issues with this compound.
spk12: Got it. Thanks.
spk11: Absolutely.
spk09: Our next question comes from the line of Nathan Weinstein with Aegis Capital. Please proceed with your question.
spk07: Good morning, everyone, and thanks so much for taking my question. Just a quick one on the pipeline for KUR101. Would you consider a broader indication set beyond OUD, just given the range of traditional uses that the compound has had?
spk11: Yeah, it's a good question. So, you know, I tend to view opioid use disorder as kind of a spectrum. And, you know, in many situations, particularly with iatrogenic opioid use disorder, it starts with the treatment of acute pain. And it's interesting, there was a study that was done, a large cross-sectional study that suggested that 6%-ish of patients that received a prescription for a acute opioid, you know, in other words, a short duration opioid, if they took it, we're still taking an opioid a year later. So that's really kind of terrifying. And obviously things have clamped down significantly over the course of subsequent years. But regardless, there is a need for a compound that has a better tolerability profile than a traditional opioid. So You know, that is something that we're looking at. Again, there's a spectrum from treatment of pain, both acutely and chronically, all the way to opioid use disorder. And that's something that we're going to be investigating with this compound. And to your point, this is basically where Kratom is currently used, right? So if you look at the boards, as it were, like the Reddit and other places, as well as some of the publications, It really is used as a treatment for pain, particularly in those individuals that require more analgesia than non-scheduled compounds but can't tolerate an opioid. And it's also used to mitigate withdrawal symptoms. So that spectrum is what we're focusing on as we develop this compound.
spk07: Great, thanks. And just one follow-up. Obviously, one of the beautiful things about ITAI is the multitude of different programs and the different APIs. So just curious whether the procurement of drug substance for any of the programs had been a logistical challenge or if you foresee it being so in the future.
spk11: I mean, there have been no specific logistical challenge. I mean, certainly a lot of ours are synthetic. There are three that are, you know, semi-synthetic or purified extracts. And that, you know, that's Ibogaine and deuterated mitragynine as well as salvinorin A. We have good supply agreements for those products. So it hasn't really been an issue and we don't anticipate it being an issue. We are, you know, in general, we'd like to minimize the amount of stuff that's coming from plants for a range of reasons, you know, including environmental impacts. So we are looking at alternative routes to producing the drug substance. But, you know, something that will be that, you know, that's for a future discussion.
spk07: Great. Thanks so much.
spk09: There are no further questions in the queue. I'd like to hand the call back to management for closing remarks.
spk08: Great. Thank you everyone for dialing in today and for all the questions that you had for us. Thanks also for everyone at the entire team and all our investors that brought us here where we are today. And I'm very, very looking forward to the future, what is yet to come. very exciting times. And with that, I would like to thank you all and wish you a very successful week. Thank you, everyone.
spk09: Ladies and gentlemen, this does conclude today's teleconference. Thank you for your participation. You may disconnect your lines at this time and have a wonderful day.
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