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spk01: Good afternoon and welcome to the MIND Medicine first quarter 2023 financial results and corporate update conference call. Currently, all participants are in listen-only mode. This call is being webcast live on the investors and media section of MINDmed's website at mindmed.co and a recording will be available after the call. For opening remarks, I would like to introduce Rob Barrow, CEO of MINDmed. Please go ahead.
spk08: Thank you and good afternoon, everyone.
spk04: Welcome to our first quarter 2023 financial results and corporate update conference call. The press release reporting our financial results is available in the investors and media section of myMEDS website. And our quarterly report on form 10Q for the quarter ended March 31st, 2023 will be filed today with the Securities and Exchange Commission. Joining me today is Sean Greenway, our Chief Financial Officer, Dr. Dan Carlin, our Chief Medical Officer, and Dr. Miri Halperin-Warnley, our executive president. During today's call, we'll be making certain forward-looking statements, including without limitation, statements about the potential, safety, efficacy, and regulatory and clinical progress of our product candidates, financial projections, and our future expectations, plans, partnerships, and prospects. These statements are subject to various risks, such as changes in market conditions, difficulties associated with research and development, and regulatory approval processes that are described in the filings made with the SEC, including the most recent annual report on Form 10-K and quarterly report on Form 10-Q. Forward-looking statements are based on the assumptions, opinions, and estimates of management of the date the statements are made, including the non-occurrence of the risks and the uncertainties that are described in the filings made with the SEC or other significant events occurring outside of IMED's normal course of business. We would caution not to place undue reliance on these forward-working statements, which were made as of today, May 4th, 2023. NIMA disclaims any obligation to update such statements, even if management's views change, except as required by law. I would like to begin by reiterating our deep commitment to advancing our organization and delivering new, life-changing treatment options to the many individuals living with brain health disorders. As we pursue our strategy to bring our lead product candidates to market, we believe we are laying the foundation to create lasting value for our shareholders. In the first few months of 2023, we continue to make steady progress across our pipeline, and we are well positioned to execute on our key priorities and reach multiple milestones throughout this year, including data readouts from our Phase 2B trial of MM120 for the treatment of generalized anxiety disorder, or GAD, as well as from our Phase 2A proof-of-concept trial of repeated low-dose MM120, and Intention Deficit Hyperactivity Disorder, or ADHD. Additionally, we expect to initiate the first clinical trial of MN402 later in the year. Before we dive further into our R&D and financial updates, I'd like to highlight the recently presented positive top-line data from the Phase II double-blind, investigator-initiated trial evaluating lysogyne in the treatment of major depressive disorder, or MDD. This trial was led by Professor Matthias Liechti and Dr. Felix Moeller, our collaborators at University Hospital Basel, or UHB, and the University Hospital of Psychiatry in Switzerland. As a reminder, we have exclusive global rights to data, compounds, and patents associated with the Liechti Lab's research evaluating lysergi and other psychedelic compounds. This includes data from numerous completed and ongoing investigator-initiated trials in both healthy volunteers and patient populations. Our collaboration has been particularly impactful by demonstrating and reinforcing the clinical potential of our drug development pipeline. Top-line data from this investigator-initiated trial demonstrated significant, rapid, durable, and beneficial effects of lysogide, which potentially mitigate symptoms of MDD. Patients in the study received a 100-microgram dose of lysogide on the first dosing day and a 200-microgram dose of lysogide on the second dosing day, which was separated by four weeks. An active small dose of 25 micrograms lysogide was used as a control line. The trial made its primary endpoint at six weeks, which was measured by the change in clinician-rated inventory of depressive symptomatology, or IDSC, scores. Further, the statistically significant improvement was maintained up to 16 weeks, which underscores the potential long-term benefits of lysogide treatment. Data from the secondary endpoints were also encouraging, and the investigational drug was generally well-tolerated. Given the high degree of comorbidity of MDD and GAD, the positive results and clinical activity of lysogide are particularly relevant to our MM120 program. I'm now trying to update on our R&D program, starting with our lead program, MM120, a proprietary, pharmaceutically-optimized form of lysogide detartrate in development for the treatment of GAD and ADHD. GAD is an often debilitating mental health disorder associated with excessive anxiety and persistent worry, which can lead to significant impairment in social, occupational, and other functioning. With very little innovation focused on the treatment of GAD, there's been a noted increase in the incidence and prevalence of individuals diagnosed with GAD in the U.S. and Europe over the past several years. Additionally, the number of patients who are not adequately treated by available therapies is also increasing. This is a result of the low rate of remission and multiple safety and tolerability challenges of SSRIs, SNRIs, antipsychotics, and benzodiazepines. The research we've conducted with patients and healthcare practitioners in the U.S. and Europe tells us that there's a significant demand for a new pharmacological class that could offer faster, more profound, and more durable efficacy responses, as well as favorable safety and tolerability. This is particularly true in the segment of patients who, despite having exhausted all available options, continue to experience intolerable anxiety. Given the need for new treatment options, we are extremely encouraged by the growing data that supports the therapeutic potential of MN120. Patient dosing and enrollment for our Phase IIb trial in GAD is progressing well across our 20 active sites, and we reiterate our expectation of reporting top-line results in late 2023. The trial plans will enroll a total of 200 participants, who will receive a single administration of up to 200 micrograms of MN120 or a placebo. The primary objective of the study is to determine the reduction in anxiety symptoms for up to 12 weeks after a single administration of MN120 across five treatment arms, with a primary endpoint measured at four weeks post-dosing. The results of this trial will guide the dose selection and development strategy for MN120 and GAD, as well as deepen our scientific understanding of its clinical effect and its underlying functional mechanisms of action. As mentioned, we are also evaluating MM120 for ADHD and expect to report top-line data for our Phase 2A trial in late 2023. Our Phase 2A trial is being conducted in collaboration with the University Hospital Basel in Switzerland and Maastricht University in the Netherlands and is designed to evaluate the therapeutic utility of repeated low doses of MM120 in adult patients with ADHD. Notably, this is the first study in which MM120 has been administered outside of the clinical setting. To date, no assays have been reported suggesting the real-world potential of this treatment regimen, as well as demonstrating our ability to deliver MM120 with innovative dose and frequency combinations. In this trial, we expect to enroll a total of 52 participants who will receive a 20-microgram dose of MM120 or placebo twice weekly for six weeks. The primary endpoint to the study are mean change from baseline and ADHD symptoms, and assessed by the AISRF after six weeks of treatment. This proof-of-concept trial is a component of our broader comprehensive NM120 clinical development strategy, which seeks to explore both session-based administration that harnesses perceptual effects of serotonin agonism, and innovative repeat administration regimen that harnesses neuropharmacological effects of recurrent serotonin agonism. The innovation of MM120 and its session-based delivery approach is driven by its mechanism of action as a potent teratonin receptor agonist, which leads to profound sustained psychological effects. We believe MM120 will be delivered as a single-dose pharmacological intervention that will only require occasional administration. We recognize the potential challenges in commercializing a product with such a revolutionary delivery profile and have embarked on robust pre-commercialization plans seeking to educate all external stakeholders of the clinical and economic value of NM120. This is why one of the key priorities we are advancing in 2023 is to develop an innovative market access strategy, document the clinical and socioeconomic burden of GAD and ADHD, and advance the generation of health economics and outcomes research data required to build a superior value proposition for our product candidates. As we progress our pipeline, we look forward to providing greater clarity on the commercial model and path forward for each program to maximize the reach of our novel product candidates. As a reminder, with respect to our intellectual property strategy, our patent portfolio includes 26 pending U.S. applications and 12 pending PCT applications. These include applications covering compositions, dosing, dosage formulations, and methods of treatment, among others, with projected expiration dates beginning in 2041. Additionally, we continue to retain all rights to our product candidates and are aggressively protecting and expanding our intellectual property portfolio as part of our comprehensive market protection strategy. Now I would like to turn to MM402, or RMDMA, which is a synthetic enantiomer of MDMA with potential prosocial effects and a favorable tolerability profile. MM402 is in development for the treatment of core symptoms of autism spectrum disorder, or ASD, which is characterized by atypical social communication and interaction, repetitive patterns of behavior, and restricted interest. Despite its significant and growing prevalence, there are no therapies approved to treat the core symptoms of ASD. MDMA is a synthetic molecule that is often referred to as an empathogen because it is reported to increase feelings of connectedness and compassion. RMDMA is thought to increase levels of serotonin and, to a lesser extent, norepinephrine, and other neurotransmitters in the brain, resulting in feelings of increased sociability and interpersonal emotional warmth. Preclinical studies of RMDMA demonstrate its acute prosocial and pathogenic effects. While its diminished dopaminergic activity suggests that it could exhibit less stimulant activity, neurotoxicity, hyperthermia, and abuse liability risk compared to racemic MDMA or the asthmatic tumor. Our aim for MM402 is to demonstrate its ability to enhance social engagement and interaction rather than having a sedating or blunting effect, which is often a result of currently used off-label medications in the ASD population. Importantly, a late-breaking abstract on a preclinical study of MM402 and a model of ASD has been accepted for presentation at the 2023 American Society of Clinical Psychopharmacology Annual Meeting that is being held in Miami Beach, Florida from May 30th to June 2nd. With even further preclinical evidence to support our approach, we are extremely excited to initiate our Phase I clinical trial of NM402 later this year. This trial is intended to characterize the tolerability, pharmacokinetics, and pharmacodynamics of NM402, and we continue to explore all opportunities to generate early signs of efficacy as early as possible in development. We anticipate such data could be generated both in neurotypical healthy volunteers and in otherwise healthy individuals diagnosed with ASD. In parallel, through our research collaboration with University Hospital Basel, in 2022, we initiated and are currently enrolling healthy volunteers in a comparative phase one pharmacokinetics and pharmacodynamic study of R, S, and racemic MDMA. This study is designed to evaluate the tolerability, pharmacokinetics, and acute subjective physiological and endocrine effects of the three molecules. We believe that successful completion will accelerate our understanding of the pharmacological profiles and then forward to as we advance into later stage clinical development. Lastly, moving to our digital medicine update, our drug development strategy is closely complemented by a suite of digital medicine programs that have the potential to facilitate adoption, use, and access to our product candidates. By refining the techniques used to capture, model, and map the autonomic and behavioral outflow and other correlates of neural activity, we can improve the experience of clinicians and the outcomes for patients and the delivery of psychedelics and other perception-altering substances. Our digital medicine programs are oriented toward applications during two primary clinical periods, activities during a treatment session, referred to as intrasession, and activities between treatment sessions, referred to as intersession. Each digital medicine program consists of a platform that contains separate underlying components, some of which we anticipate will be within the scope of FDA's definition of medical devices and others which we anticipate will not be regulated as medical devices. For the medical device products, we intend to engage with the FDA and other international regulatory authorities to receive guidance along the development pathway towards a potential submission for regulatory clearance or approval. The ultimate goal of our digital medicine project is to develop applications that overcome frictional points of care delivery to encourage user adoption across patients, providers, and payers. Overall, we are very pleased with the progress to date. As we advance our key clinical programs and execute on our corporate objectives, we continue to further strengthen the leadership of MindMed. We are very excited by the recent addition of Mark R. Sullivan as our Chief Legal Officer and Corporate Secretary. Mark brings extensive legal and public company life sciences expertise and is a strong addition to our executive team. We believe Mark's experience, insights, and guidance will prove invaluable as we progress to the next stage of MindMed's evolution. I also have to highlight that as we approach our annual meeting in June, we are very excited about the potential of adding Dave Gwiska to our board. Dave brings invaluable insights from his 35 years of experience in the biopharmaceutical industry, including his service as CFO of two S&P 500 pharmaceutical companies, Insight and Celgene. Dave has also previously served on the board of GW Pharmaceuticals before its acquisition by Jazz Pharmaceuticals for $7.2 billion and serves on the board of Cgen, which recently agreed to be acquired by Pfizer for over $43 billion. Dave's nomination represents our ongoing commitment to board refreshment and ensuring we have the optimal mix of experience and perspectives in the boardroom to help the company create value. I believe Dave's involvement is an endorsement of the incredible people and organizations that we have built at MyMed, as well as the potential impact of our products on the millions of individuals suffering from brain health disorders. I'd also like to express the board's gratitude to Bridget Nakes, who notified us that she will not stand for reelection at the annual meeting, for her years of service to the early growth of the organization. Now is the time to radically transform how we treat brain health disorders, and we are deeply committed to realizing that potential for change. With that, I will now turn the call over to our CFO, Sean Greenway, to discuss our financial results. Sean? Thanks, Rob, and thank you all for joining us today. We will now turn to our financial results for the first quarter ended March 31st, 2023. As of March 31st, 2023, our cash and cash equivalents total $129.4 million compared to $142.1 million as of December 31st, 2022. We believe that our current cash and cash equivalents on hand positions us to accelerate our preparation for moving quickly into our pivotal studies for our lead program, MM120, and will be sufficient to meet our operating requirements beyond our key development milestones in 2023 and into the first half of 2025. Our net cash used in operating activities was $13.3 million for the quarter ended March 31st, 2023, compared to $12.9 million in the quarter end March 31st, 2022. Research and development expenses were $12.6 million for the quarter ended March 31, 2023, compared to $10.2 million for the quarter end March 31, 2022, an increase of $2.4 million. The increase was primarily due to increases of $2.9 million in expenses related to clinical research for the MM120 GAD study, $0.9 million in expenses related to our MM402 program and $0.2 million in internal personnel costs as a result of increasing research and development capabilities, which were offset by a decrease of $0.7 million in expenses related to our MM110 program and a decrease of $0.9 million in expenses in connection with various external RID collaborations. General and administrative expenses were $8.3 million for the quarter end March 31, 2023. essentially flat compared to the same quarter a year ago. Our net loss for the three months ended March 31st, 2023 was $24.8 million compared to $18.5 million for the same period in 2022. Lastly, I wish to reiterate that we are continuing to execute on a very efficient operation in terms of quarterly cash burn and headcount when compared to our peers in the space. As we have highlighted during our prior business update conference calls, We intend to continue to be thoughtful with our cash while also focusing and prioritizing our support for our most precious research and development activities directed toward our key value drivers. More specifically, we will review our discretionary expenses on a constant basis to ensure that we are seeking to capture value from operational efficiencies where we can. I will now turn the call back to Rob who will provide some closing comments. Thank you, Sean. We remain laser-focused on driving our key programs forward, which includes advancing our MM120 product candidate in GAD and ADHD to Phase II clinical readouts later this year, as well as initiating our first clinical trial of MM482. Additionally, our early R&D activities are progressing, and our collaboration with the University Hospital Basel continues to offer the opportunity to generate early clinical evidence to inform our pipeline's progression. I also want to extend my sincere appreciation and gratitude for the foundational work that has brought us closer to advancing novel treatments for brain health disorders. In particular, I would like to thank our highly talented and deeply committed team here at MindMed, our investors, and the many people who have been supportive along the way, including our research participants and their families. We are working tirelessly to deliver on our mission of transforming the treatment landscape for the many individuals living with brain health disorders who are underserved by today's available therapies. Finally, I'd like to remind everyone that the purpose of today's call is to discuss our first quarter updates and the progress of our business, and we will not be addressing matters related to our annual meeting. We encourage all of our shareholders to review our definitive proxy statement that has been filed with the SEC on CDAR and to visit www.protectmymed.com for updates pertaining to our proxy campaign. With that, I'd like to thank you all again for joining today, and I'm happy to take questions.
spk01: Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press star followed by one on your touchtone phone. You will hear a three-tone prompt acknowledging your request and your questions will be polled in the order they are received. Should you wish to decline from the polling process, please press star followed by two. If you are using a speakerphone, please lift the handset before pressing any keys. One moment please for your first question. Your first question comes from Charles Duncan, Cantor Fitzgerald. Charles, please go ahead.
spk07: Okay. Yes. Good afternoon, Rob, Sean. Thanks for taking my questions. And also, thanks for all of the clinical trial design details, particularly for 120 and ADHD and 402. That was helpful. I do have a couple of questions, though, regarding MM120 in GAD. I'm wondering, with a sample size of, call it 200, five arms, so about 40 per arm, I'm wondering if you could frame what you would like to see out of that study in terms of some of the effect sizes, and if you anticipate a full kind of dose response Or would it be really bookended by placebo versus the highest dose? So tell us what you think would be good out of that 420 or out of that 120 study in GAD. Thanks.
spk04: Thanks, Charles. Thanks for the question and for joining us today. With respect to the size and design of the Phase 2B study, so as you mentioned, 200 patients were anticipating rolling across the five treatment arms, which for everyone's, as a reminder, is doses of 25, 50, 100, or 200 micrograms for a placebo. Patients receive a single dose and then are followed for 12 weeks. The study was designed in such a way where the statistical methodology we're using really gives us power across the entire spectrum. So we benefit from the response across the treatment segment. That methodology was developed at Novartis, and it's something that Ultimately, it's a two-part statistical test, one that tests whether or not there is any treatment response at all, and the second part of the test is we nominate candidate profiles, which would reflect exactly what you're getting to in terms of the type of dose response, the magnitude, effectively the slope and the shape of that dose response curve. In terms of the maximum magnitude we anticipate seeing, we've really designed the study so that we can characterized the effect size and power of Phase III program, but our expectation was really set to demonstrate just anything at or above the standard of care. The standardized effect size for most available angiolytics is around 0.3 to 0.5, whether you look at SRIs or benzodiazepines. And so even if we saw a response of that magnitude, we would anticipate seeing a significant outcome. That said, we certainly want to see an improvement over the standard of care and believe there's an opportunity to do exactly that. So in terms of our expectations, we do want to fully characterize response across the doses, both acutely and in terms of durability. I think it's particularly important to emphasize that by looking at multiple doses that we believe would be at or above or within the therapeutic window, that actually gives us important insights, both in terms of the magnitude and durability of response at those different doses and the sub-therapeutic doses as we anticipated. So the design has been, again, to robustly power and detect the difference, but also to make sure we're characterizing adequately the acute and durable response to power and design our Phase III program.
spk07: Okay. So that's helpful, Rob. So we should not consider that this is a pivotal program or pivotal study and judge its outcome based on that, but that, you know, whether or not it's viable to help you move forward into phase three, correct?
spk04: That's correct. It would be very much premature to consider this a pivotal study. It's certainly an important part. We've even seen presentation by representatives at FDA at recent conferences, particularly at ECNP, a few weeks ago about the importance of demonstrating dose response. And again, I think we, as a sector studying this drug class, really need full comprehensive information and data sets before we go into a pivotal program that is going to be very efficient, very clean design as we anticipated today. So it has been the study, the phase two study has been designed to give important insights in that design, characterize the response in this population, which has not been done at this scale, at this magnitude. And really, no studies to date that we're aware of have looked at a comprehensive exploration of dose response. So that is the intent of this study. And ultimately, we believe that will give us both additional support for our ultimate clinical package that will be submitted as an NDA, but also would help us be very efficient with our phase three design.
spk07: Very good. And then one quick perspective builder on the recent CPT codes. CPT-3 codes. I'm wondering if you could provide your perspective on how you think the AMA's recent, I guess, approval of first step approval to establishing CPT code to enable really intermittent therapy that involves both a drug and a therapist, if you have a perspective on that and how that may actually reduce the risk of not only approval, but commercialization of these types of drugs. Thanks.
spk04: Thanks, Charles. I'll turn it over to Dan Carlin, our chief medical officer, to respond to that one.
spk03: Hi, Charles. Dan here. It's a really important question, obviously something we've been paying a lot of attention to at level three codes are used for experimental and new services that have not yet been cleared or approved. There's a substantial body of evidence behind them yet. Now we think this is an important step in the right direction and we applaud Compass and NAPCS for the collaboration on getting to that point. But we also know that while that code is specific to psychedelic services in general, it's a little more applied to everybody across the board. In many cases, for existing parallel services such as ketamine administration, while there is an existing HS-CPS level two code or a G code specific to those services, many if not most commercial insurers are actually being billed for services like this under existing level one codes. So there are a number of paths to coding success and obviously some official recognition from the ANA and in the CPT is important. It's only one sort of leg on the process to having a fully robust coding system that will cover all forms of third party payers, including government and non-governmental commercial payers.
spk07: That's helpful. Thanks for the added color, Dan. Thanks for taking my question. Thanks, John.
spk01: Thank you. Your next question comes from Brian Abrahams, RBC Capital Markets. Brian, please go ahead.
spk05: Hey there. Good afternoon. Thanks for taking my questions. Two for me. I guess first off on MM120. As you think about how you might interpret the upcoming phase two data, I'm curious your latest thoughts on how to find the best dosing window and dose levels that are going to maximize the benefit-risk profile. And I guess I'm curious if multiple doses are effective, would you move forward with two doses or more in phase three? And I guess how might you think about steering which dose might be appropriate for which patient and balancing efficacy with safety?
spk04: Yeah, thanks so much for the question, Brian. You know, it would be a little bit premature to say specifically, and obviously we have Many thoughts about how we generally think about safety and efficacy and the balance of benefit and risk as we design a phase three program. What I would say is that we are very much intent on being extremely efficient and clean in our study design and want to make sure that we have as direct of a path and as efficient of a program as possible. So as we look to the data from this study, It is important to note one of the things that's particularly exciting about the drugs we're working on, and 120 in particular, is that the acute administration seems to drive both an acute and durable response. And because of that, it does offer some advantages potentially in terms of the risk profile. So we wouldn't expect sort of physiological risk to persist like it would if you were taking a daily medication. So we'll certainly be monitoring outcomes, both efficacy and safety, for the duration of the 12 weeks. We want to make sure that whatever dose we select to move forward into phase three is both responsive in terms of efficacy, but also is well-tolerated and we anticipate would be safe as we get into a larger part of the development program. With all that said, too, I think it's really important to note that based on the historical effect sizes, including effects as we've seen from investigator-initiated studies, while they're preliminary, right, being evidence for approval necessarily, those effect sizes are quite large. And so we would anticipate that even if we were to choose a dose that was better tolerated, let's say, just theoretically, or had a similar sort of response, we would be able to have a high degree of confidence, I think, based on the historical effect sizes, if we're ultimately able to replicate that, that the size in the Phase III program would be adequate and would give us plenty of patients to be able to demonstrate a statistical difference if we see a clinically meaningful response as we anticipate.
spk05: That's really helpful. Thanks, Rob. And then I guess secondarily, with regards to the 402 program, you mentioned the study that's going to be looking at racemic MDMA and the enantiomers in healthy volunteers in collaboration with UHB. I was wondering if you could elaborate a little bit more on that study, what specifically you're going to be looking for in terms of the, to better understand the pharmacology, the parameters you'll be exploring, and when we might report data there. And I'll hop back into the queue. Thanks.
spk04: Yeah, thanks so much for that. So in terms of the study design, it's two different doses of RMDMA, so 125 and 250 milligrams, a single dose of SMDMA, and a single dose of racemic MDMA. And this is an inpatient. All the patients would be crossed over and receive these different treatments. And as you can see, 125 milligrams of S and the Semic MDMA that's being administered here. So in terms of the outcomes that we're looking to, largely they're the pharmacodynamic outcomes. So overall drug effect in terms of intensity and duration that we're conducting is one of the primary outcome measures, or I should say Dr. Leakey's lab is conducting the five dimensions of altered states of consciousness, the 5DASC scale. It's also a functional perceptual activity of the two enantiomers and racemic MDMA. So we'll be looking at a number of autonomic effects, of mood effects, of course, characterizing pharmacokinetics and looking at other endocrine effects, levels of oxytocin, prolactin, cortisol, vasopressin. So many of the have been implicated in the activity of our oral racemic MDMA to characterize that response with two different doses and ultimately seek to inform how we advance our own phase one program and further into endoclinic in phase two and beyond.
spk05: Got it. Thanks so much.
spk01: Thank you. Your next question comes from Francois Brisbois, Oppenheimer. Francois, please go ahead.
spk06: Hi, thanks for taking the question. Congrats on the progress here. Just a couple here. In terms of the recent hospital basal study that you mentioned there, just to maybe if you can remind us just the differences here. So multiple doses, the comparison is not to a true placebo and, you know, obviously a different indication, although similar comorbidities. And then, you know, so maybe just talk about the differences and how, you know, this could be a read-through. towards your study, and any thoughts on patients, you know, keeping them on SSRIs versus winding them off and what they can do. Thank you.
spk04: Great. Thanks so much, Frank. So, in terms of study design, this is an investigator-initiated study looking at the impact in patients with major depressive disorder. Patients in the active arm received two different doses that were separated by a month. First was a 100-microgram dose. The second was a 200-microgram dose, which again was separated by four weeks. The control group in this study was administered a 25-microgram dose at both of the treatment days, at both of the dosing sessions. So it was not an inert placebo, but we still did see a statistical and clinically meaningful differentiation between the response to those two doses. So we saw a 3.6-point improvement in the IDSC dose. score, which is the inventory of depression symptomatology score six weeks after administration of the first treatment session for the low-dose arm. And we also saw a 12.9-point improvement on the IDSC and the higher-dose 100 and the 200-microgram dose arm. Those effects remained durable up to 16 weeks, and we saw a number of encouraging secondary endpoints in the study. So overall, I think we view it as particularly impactful and important given the relevance to depression, which is, of course, an area and indication where there's a huge growth in incidence and prevalence, and one where we've also seen historical evidence of activity of LSD or lysogyne. But it's also particularly important to note that there's a high degree of comorbidity between generalized anxiety disorder and major depressive disorder, both in terms of diagnostic overlap, which we think is incredibly high, but also the number of patients the prevalence of diagnoses in the overlap in the population. So we think it's both relevant to our GAD program, but also opens up an opportunity. We've seen historically strong, consistent responses in many studies and hundreds of patients with lysogide and anxiety and depression and other neurotic illness. And so this seems as consistent with the data we reported in anxiety back in 2022, again, demonstrating a strong statistically significant response after acute administration is what anyone would hope to see in a depression study and something, again, we think is particularly important, both in anxiety and opens up the door to potentially having other indications in the future.
spk06: Okay, great. And can you remind me if the, were the patients on, you know, SSRIs or whatever they were on or were they waned off in this trial?
spk04: Some additional details about the specifics there will be forthcoming as the full publication is released. But generally, to comment broadly about your question, we don't have modern data to fully characterize the difference in either pharmacokinetics or pharmacodynamics, which I think would be particularly of more interest with concomitant administration of SSRIs and a molecule like MM120. But historical data has suggested that there may be an alteration of the PD profile, but we haven't seen any evidence where that would be alarming or a safety signal. So something we are certainly monitoring and know others and academic researchers have been interested in that differentiation response. And certainly as we progress in development, we're going to be looking at very closely.
spk06: Okay, great. And then in terms of the R&D day that you mentioned, which will be in the second quarter, is that where you plan on sharing more information? details about your commercialization plans for each product, or is that kind of at a later time?
spk04: I think as we think about an R&D day in the second quarter, one of the key things we would like to highlight is an update on the progress of the clinical trial, of our overall programmatic approach. We'll speak much more to the intellectual property and market protection strategy, and they got some important insights that should make a very clear story to anyone who's been looking at market protection and the ability to protect a novel asset. So that will be one area of focus. We'll obviously dig into and have some key opinion leaders talking about generalized anxiety disorder as an indication and where the treatment might fit in the overall landscape. And then we'll also have an opportunity to present some individuals who have actively done clinical trials and research with LSD with the drug class generally and provide some insights into the commercial viability in that way. I think certainly as we progress and reach a phase two readout and are getting to an end of phase two program, total clarity on what the path to our late stage program looks like, we'll be in a position at that point to speak a little bit more about market access and the overall commercialization strategy. But certainly at our investor day coming up in the second quarter, we'll be giving a lot more insight into the status of the programs and I think greater clarity on some of the elements of our ultimate product that we try to take to market and our overall approach there.
spk06: Okay, great. Thank you very much.
spk04: Thanks, Frank.
spk01: Thank you. Your next question comes from Elmer Piros, EF Hutton. Elmer, please go ahead.
spk02: Yes, good afternoon. What I'd like to verify, Rob, is 20 clinical sites that you previously identified Is this the final number for the GAD trial?
spk04: So the 20 clinical sites was certainly the number of sites that, as we noted earlier in the year, were brought online and were fully recruiting at the beginning of the year. And we've seen a lot of interest from a number of sites and a number of highly experienced sites. And as we think about site engagement and bringing sites online, they can both be driven by an individual study, but also programmatically, right? So we have an opportunity to engage with sites that might be great sites in a later stage phase three program. So we're actively engaged with a number of discussions and a number of different avenues to make sure we can be as efficient as possible getting into that pivotal program. But certainly 20 sites is where we started and Coney actually in one patient.
spk02: Yeah. And at the end of the year, would we, Shall we expect primary endpoint information, so efficacy at four weeks, or maybe some latter time points, eight weeks and 12 weeks, as you have those as secondary endpoints?
spk04: We certainly anticipate reading out, at least as a top-line readout, the four-week data, which is the primary endpoint of the study. So we're getting greater clarity as we progress and give an update on the study in the future, but our expectation when we speak to top line results would be at least reading out the primary endpoint.
spk02: Yeah. And I just found this company called MindBio who is doing or plan to do a microdosing LSD trial in MDD. Do you think that they would have freedom to operate if they continue to pursue that indication with
spk04: Well, again, in terms of intellectual property, certainly in a research setting, there's a carve-out for doing research. So anything of that nature wouldn't come into play until much later down the road. But where we are positioned in the program and the kind of support we've had, the team we've built, the efficiency we will have demonstrated as we get the readout by the end of this year, I think will make it very clear where everyone stands in the market and who's likely to be first to market with any sort of LSD product.
spk02: I see. And just last two small questions here. Do you have a cutoff value for the HEM-A score at baseline in the GAD trial or minimum severity?
spk04: We do. I'll turn it over to Dr. Carlin again.
spk03: I don't believe that we publicly disclosed that minimum cutoff score at the current just to maintain trial integrity. So, yes, we do have a score, but in general, just for integrity purposes, I don't believe that it's publicly disclosed.
spk04: Yes. I'll just expand on that real quickly. If we point you to our investor presentations published on our website, the minimum score we require to be enrolled in the trial as an entry criterion is a Hamilton anxiety score of 20 or greater.
spk02: 20 or greater. Okay, thanks for clarifying that. And do you expect a good portion of the patients to have depression as a comorbidity in this study?
spk04: Based on the overall, you know, population, the comorbidity of GAD and major depressive disorder, we certainly anticipate that the patients would have comorbid diagnosis with depression. What's critically important is to have a GAD as a primary diagnosis. But it would not be a representative population if you had an indication such as GAD. There wasn't some comorbid depression in the study.
spk02: But you are not examining efficacy based on reduction in depressive symptoms.
spk04: Oh, we absolutely are. As secondary outcome measures, we're absolutely looking at response on standard depression scales and would use that as another important insight into the potential response to depression.
spk02: Yeah, wonderful. Thank you very much for both of you.
spk04: Thanks, Elmer.
spk01: Thank you. Your next question comes from Patrick Truccio, HC Wainwright. Patrick, please go ahead.
spk00: Thanks. Good evening. Just I'm wondering, as you look at the broader space of sponsors exploring psychoactive agents, how do you view the differentiation of MM120 relative to some of these shorter acting compounds like psilocybin or 5-MeO-DMT? Do you see the advantages primarily on the efficacy and potential duration of remission, or is there also potential to separate on safety and tolerability profile as well?
spk04: Yeah, thanks for the question, Patrick. So when we look at the history of research of this drug class, as a drug developer, you want to see drugs that have a likelihood of demonstrating a benefit-risk ratio. profile that ultimately gets you to an application and approval. And LSD is the most characterized drug in the entire class. There's certainly been a lot of discussion about shorter acting molecules. What we know from the real world, I think it's important to highlight that there's a fairly large expanded access or compassionate use program that's ongoing in Switzerland. And our collaboration, both with Dr. Leakey at UHB and more broadly with many of the psychiatrists in Switzerland, has given us some real insights. These providers are able to utilize psilocybin or LSD, and in many instances when we have discussions about the preference, they choose to use LSD. They also have indicated on multiple occasions that the actual conduct of administration sessions, whether it's LSD or psilocybin, occurs for approximately the same duration. That's going to obviously vary by the individual, but we thought it was a particularly important insight that in practice in the real world where this is being done regularly and has been done for several years, there isn't a significant differentiation between those two molecules. Now, some of the ultra-shorter acting molecules such as DMT or 5-Neo-DMT, these are certainly molecules that work on serotonin system, but what we need to characterize is both the acute and durable response. That's what we certainly have seen more from historical data of LSD and gives us an extraordinary degree of excitement around the potential of our product candidates.
spk00: Can you talk more about the health economic outcome research that you referred to earlier and understanding that there's still more planning here to be done? I'm wondering what would this potentially look like prior to the launch and how big of a differentiator would it be for MM120 if you had this type of data at the time of or soon after a potential launch?
spk04: Yeah, so I wouldn't want to speak too much of the specifics at this point, but we are actively engaged both with Francois Lillenthal, our chief commercial officer who's had an incredible career in commercial launches, including most recently at Merck before coming over to MindMed, to demonstrate the value proposition and make sure we have a path for commercialization, for market access, for reimbursement, and also our digital medicine programs, which give us an extraordinary opportunity to gather such data and engage in longer-term observational studies, both of patients with the disorders we are seeking to treat, but also more specifically in some particular areas of research interest to us, both internally and through some of our collaboration. So we'll certainly be sharing more as we progress and as we get to have more clarity and or share more clarity, I should say, on the commercialization pathway and our ultimate plans. We'll give additional insights in terms of our approach to HUR data generation and also the implications for market access, pricing, reimbursement, and such.
spk00: That's helpful. Just one last one from me. Can you talk about just broader strategic priorities as it relates to business development and Specifically, how do you think about potential partnership activity following the Phase II readouts for MM120 later this year?
spk04: Yeah, we've certainly seen quite a bit of interest in our program and our readout. And at any time where we would advance to a point where we reach a disclosure threshold, we would certainly do so. But at this point, we haven't, we do not have any business development or licensing or partnership agreements for subsequent development of the program. But again, we've seen a high degree of engagement and excitement, both in terms of the serotonin system as a target, which is one of the best characterized systems in all psychiatry, but also in particular in our program and our approach, the ability to generate the kind of robust data and the consistency with which we're approaching our clinical development program. Our phase two study design and the way we've operationalized the study is exactly how we anticipate progressing into the phase three program. And we think that gives us a great opportunity to transition out without changing any of the variables that are important in terms of conduct of the study and hopefully could impact safety or effectiveness. So we've seen a lot of excitement across the board and we'll keep any of our options open as we progress.
spk01: That's helpful. Thank you very much. Thank you. Ladies and gentlemen, as a reminder, should you have a question, please press star 1 on your touch-tone phone. There are no further questions at this time. I will now turn it back for closing remarks.
spk04: Thank you, Operator, and thanks everyone again for joining us today. We're extremely pleased with where we've come so far this year and are incredibly encouraged by moving very quickly to a data readout in late 2023 for our lead program and getting our second lead program, MM402, into the clinic later this year. Thanks, everyone, again, for joining us, and I look forward to sharing future updates.
spk01: Thank you. Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines.
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