Definium Therapeutics, Inc. Q1 FY2023 Earnings Call

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.

Thank you and good afternoon, everyone. 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 MindMed's website and our quarterly report on Form 10-Q for the quarter ended March 31, 2023, will be filed today with the Securities and Exchange Commission. Joining me today is Schond Greenway, our Chief Financial Officer; Dr. Dan Karlin, our Chief Medical Officer; and Dr. Miri Halperin Wernli, 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 at the date the statements are made, including the non-occurrence of the risks and uncertainties that are described in the filings made with the SEC or other significant events occurring outside of MindMed's normal course of business. You are cautioned not to place undue reliance on these forward-looking statements which are made as of today, May 4, 2023. MindMed 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 MM-120 for the treatment of generalized anxiety disorder or GAD, as well as from our Phase 2a proof-of-concept trial of repeated low dose MM-120 in attention-deficit hyperactivity disorder or ADHD. Additionally, we expect to initiate the first clinical trial of MM-402 later in the year. Before we dive further into our R&D and financial updates, I would like to highlight the recently presented positive top line data from the Phase 2 double-blind investigator-initiated trial evaluating lysergide in the treatment of major depressive disorder or MDD. This trial was led by Prof. Matthias Liechti and Dr. Felix Mueller, 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 Labs research evaluating lysergide 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 lysergide and its potential to mitigate symptoms of MDD. Patients in this study received a 100 microgram dose of lysergide on the first dosing day and a 200 microgram dose of lysergide on the second dosing day, which was separated by four weeks. An active small dose of 25 micrograms lysergide was used as a control arm. The trial's primary endpoint at six weeks was measured by the change in clinician-rated Inventory of Depressive Symptomatology or IDS-C scores. Further, the statistical significance was maintained up to 16 weeks, which underscores the potential long-term benefits of lysergide treatment. Data from the secondary endpoints were also encouraging and the investigational drug was similarly well tolerated. Given the high degree of comorbidity of MDD and GAD, the positive results in clinical activity of lysergide are particularly relevant to our MM-120 program. I'm now going to provide updates on our R&D program, starting with our lead program, MM-120, a proprietary pharmaceutically optimized form of lysergide D-tartrate 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 MM-120. Patient dosing and enrollment for our Phase 2b 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 to enroll a total of 200 participants who will receive a single administration of up to 200 micrograms of MM-120 or placebo. The primary objective of the study is to determine the reduction in anxiety symptoms for up to 12 weeks after the first administration of MM-120 across five treatment arms. The primary endpoint is measured at four weeks post-dosing. The results of this trial will guide dose selection and development strategy for MM-120 in GAD as well as deepen our scientific understanding of its clinical effects and its underlying functional mechanisms of action. As mentioned, we are also evaluating MM-120 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 MM-120 in adult patients with ADHD. Notably, this is the first study in which MM-120 has been administered outside of the clinical setting. To date, no SAEs have been reported suggesting the real-world potential of this treatment regimen, as well as demonstrating our ability to deliver MM-120 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 MM-120 or placebo twice weekly for six weeks. The primary endpoints to the study are mean change from baseline in ADHD symptoms as assessed by the AISRS after six weeks of treatment. This proof-of-concept trial is a component of our broader comprehensive MM-120 clinical development strategy, which seeks to explore both session-based administration that harnesses perceptual effects of serotonin agonism, and an innovative repeat administration regimen that harnesses the neuropharmacological effects of recurrent serotonin agonism. The innovation of MM-120 and its session-based delivery approach is driven by its mechanism of action as a potent serotonin receptor agonist, which leads to profound sustained psychological effects. We believe MM-120 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 a robust pre-commercialization plan seeking to educate all external stakeholders of the clinical and economic value of MM-120. 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’ve progressed 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’d like to turn to MM-402 or R(-)-MDMA, which is a synthetic enantiomer of MDMA with potential prosocial effects and a favorable tolerability profile. MM-402 is in development for the treatment of core symptoms of Autism Spectrum Disorder or ASD, which is characterized by atypical social communication and interactions, repetitive patterns of behavior and restrictive interests. Despite its significant and growing prevalence, there are no therapies approved to treat the core symptoms of ASD. MDMA is a synthetic molecule enantiomer referred to as entactogen because it is reported to increase feelings of connectedness and compassion. R(-)-MDMA is thought to increase levels of serotonin and to a lesser extent, norepinephrine and other neurotransmitters in the brain resulting in feelings of increased social ability and interpersonal emotional warmth. Preclinical studies of R(-)-MDMA demonstrated acute prosocial and entactogenic effects while its diminished dopaminergic activity suggested it could exhibit less stimulant activity, neurotoxicity, hyperthermia and abuse liability risk compared to racemic MDMA or the S-enantiomer. Our aim for MM-402 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 the preclinical study of MM-402 in a model of ASD has been accepted for presentation at the 2023 American Society of Clinical Psychopharmacology Annual Meeting to be held in Miami Beach, Florida from May 30 to June 2. With further preclinical evidence to support our approach, we are extremely excited to initiate our Phase 1 clinical trial of MM-402 later this year. This trial is intended to characterize tolerability, pharmacokinetics, and pharmacodynamics of MM-402, 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 1 pharmacokinetics and pharmacodynamic study of R(-)-MDMA 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 profile of MM-402 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 as a potential to facilitate adoption, use and access to our product candidates. We're refining the techniques used to capture, model, and map the autonomic and behavioral outflow and other correlates of neural activity to improve the experience of clinicians, 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 intra-session, and activities between treatment sessions referred to as inter-session. Each digital medicine program consists of a platform that contains separate underlying components, some of which we anticipate will be within the scope of the 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 projects is to develop applications that overcome friction points of care delivery to encourage user adoption across patients, providers, and payers. Overall, we are very pleased with the progress today. 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 will be a strong addition to our executive team. We believe Mark’s experience and insight and guidance will prove valuable as we progress to the next stage of MindMed's evolution. I would also like to highlight that as we approach our Annual Meeting in June, we are very excited by the potential of adding Dave Gryska 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, Incyte 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 Seagen, 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 MindMed, 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 Brigid Makes, who notified us that she will not stand for reelection at the Annual Meeting and we thank her for her years of service during 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, Schond Greenway to discuss our financial results. Schond?

Thanks, Rob, and thank you all for joining us today. We will now turn to our financial results for the first quarter ended March 31, 2023. As of March 31, 2023, our cash and cash equivalents totaled $129.4 million compared to $142.1 million as of December 31, 2022. We believe that our current cash and cash equivalents on hand position us to accelerate our preparation for moving quickly into our pivotal studies for our lead program MM-120 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 31, 2023 compared to $12.9 million in the quarter ended March 31, 2022. Research and development expenses were $12.6 million for the quarter ended March 31, 2023 compared to $10.2 million for the quarter ended 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 MM-120 GAD study, $0.9 million in expenses related to our MM-402 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 MM-110 program and a decrease of $0.9 million of expenses in connection with various external R&D collaborations. General and administrative expenses were $8.3 million for the quarter ended March 31, 2023, essentially flat compared to the same quarter a year ago. Our net loss for the three months ended March 31, 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 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 resource, our 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, Schond. We remain laser focused on driving our key programs forward, which includes advancing our MM-120 product candidate in GAD and ADHD to Phase 2 clinical readouts later this year, as well as initiating our first clinical trial of MM-402. Additionally, our early R&D activities are progressing and our collaboration with 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’re 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 filed with the SEC and on SEDAR and visit www.protectmindmed.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.

Thank you. Ladies and gentlemen, we will now begin the question-and-answer session. Your first question comes from Charles Duncan of Cantor Fitzgerald. Charles, please go ahead.

Okay. Yes, good afternoon, Rob, Schond, thanks for taking my questions. And also thanks for all of the clinical trial design details, particularly for MM-120 in GAD, the ADHD study and MM-402 — that was helpful. I do have a couple of questions though regarding MM-120 in GAD. I’m wondering with a sample size of, call it, 200 across 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 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 MM-120 study in GAD. Thanks.

Thanks, Charles. Thanks for the question and for joining us today. With respect to the size and design of the Phase 2b study, as you mentioned, 200 patients we're anticipating enrolling across the five treatment arms, which for everyone’s reference is placebo, 25, 50, 100 and 200 micrograms. Patients receive a single dose and then are followed for 12 weeks. This 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 ultimately it's a two-part statistical test: one that would test whether or not there is any treatment response at all, and the second part of the test is where 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 that we anticipate seeing, we’ve really designed the study so that we can characterize the effect size and power a Phase 3 program. But our expectation was really set to demonstrate something at or above the standard of care. So the standardized effect size for most available anxiolytics is around 0.3 to 0.5, whether you look at SSRIs 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 the 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 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 anticipate. 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 3 program.

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 rather whether or not it’s viable to help you move forward into Phase 3, correct?

That’s correct. It would be very much premature to consider this a pivotal study. Now, it’s certainly an important part and we’ve even seen presentations 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 and have a very clean design as we anticipate today. So the 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 or 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 as we submit an NDA, but also would help us be very efficient with our Phase 3 design.

Very good. And then one quick perspective builder on the recent CPT codes, CPT III codes, I’m wondering if you could provide your perspective on how you think the AMA’s recent step toward establishing CPT codes to enable intermittent therapy that involves both a drug and a therapist might affect commercialization and reimbursement for these types of therapies? How may that reduce the risk for approval or commercialization of these types of drugs? Thanks.

Thanks, Charles. I’ll turn it over to Dan, our Chief Medical Officer to respond on that one.

Hi, Charles, Dan here. It is a really important question, obviously something we’ve been paying a lot of attention to as progress has been made on that CPT code. As folks listening will know, the Level III codes are used for experimental and new services that have not yet been cleared, approved or have a substantial body of evidence behind them. Now we think this is an important step in the right direction, and we applaud the organizations that collaborated 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 broadly applied across the board. In many cases, for existing parallel services such as S-ketamine administration, while there is an existing HCPCS Level II code or G code specific to those services, many if not most commercial insurers are actually being billed for services like this under existing Level I codes. So there are a number of paths to coding success and obviously some official recognition from the AMA and in the CPT is important. It’s only one leg in 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.

That’s helpful. Thanks, Dan. Thanks for taking my questions.

Thanks, Charles.

Thank you. Your next question comes from Brian Abrahams, RBC Capital Markets. Brian, please go ahead.

Hey there, good afternoon. Thanks for taking my questions. Two for me, I guess first off, on MM-120. As you think about how you might interpret the upcoming Phase 2 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 3? And how might you think about steering which dose might be appropriate for which patient and balancing efficacy with safety?

Yes. Thanks so much for the question, Brian. It’d 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 3 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 particularly exciting about the drugs we’re working on, and MM-120 in particular, is that the acute administration seems to drive both an acute and durable response. Because of that, it does offer some advantages potentially in terms of the risk profile. So we wouldn’t expect physiological risk to persist like what you'd see with a daily medication. 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 in Phase 3 is both effective in terms of efficacy and also well tolerated, and we anticipate it 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 the effects as we’ve seen from investigator-initiated studies, while they’re preliminary, those effect sizes are quite large. And so we would anticipate that even if we were to choose a dose that is better tolerated or had a similar response, we would be able to have a high degree of confidence, I think, based on the historical effect if we’re also able to replicate that, that the size of the Phase 3 program would be adequate and it would give us plenty of patients to be able to demonstrate a statistical difference if we see a clinically meaningful response as we anticipate.

That’s really helpful. Thanks Rob. And then second, regarding the MM-402 program. You mentioned the study that’s looking at racemic MDMA and R(-)-MDMA 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 to better understand the pharmacology, the parameters you’ll be exploring and when we might report data there? I’ll hop back in the queue. Thanks.

Yes. Thanks so much. So in terms of the study design, it's two different doses of MDMA: 125 milligrams and 250 milligrams, a single dose of S-MDMA and a single dose of racemic MDMA. This is inpatient, and all the participants will be crossed over and receive these different treatments. In the 125 milligrams of S and the racemic MDMA are being administered here. In terms of the outcomes that we’re looking at, largely the pharmacodynamic outcomes: overall drug effect in terms of intensity and duration. One of the primary outcome measures is the 5-Dimensional Altered States of Consciousness or 5D-ASC scale. It's also investigating functional perceptual activity of the R(-)-MDMA and racemic MDMA. So we look at a number of autonomic effects, mood effects, of course characterizing pharmacokinetics and looking at other endocrine effects, levels of oxytocin, prolactin, cortisol, vasopressin — many of the pathways that have been implicated in the activity of racemic MDMA — to characterize that response with two different doses and ultimately seek to inform how we advance our own Phase 1 program and further into Phase 2 and beyond.

Got it. Thanks so much.

Thank you. Your next question comes from Francois Brisebois, Oppenheimer. Francois, please go ahead.

Thanks for taking my question. Congrats on the progress here. Just a couple here. In terms of the recent University Hospital Basel study that you mentioned, maybe if you can remind us of the differences here. So multiple doses comparison is not to a true placebo and obviously a different indication, although similar comorbidities. Maybe just talk about the differences and how this could be a read-through towards your study? And any thoughts on patients, keeping them on SSRIs versus tapering them off for the trial? Thank you.

Great. Thanks so much, Francois. 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. The 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 on both dosing days. So it was not an inert placebo, but we still did see a statistical and clinically meaningful differentiation between the response to those doses. We saw a 3.6-point improvement in the IDS-C 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 IDS-C in the higher dose, 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, we view it as particularly impactful and important given the relevance to depression, which is of course an area where there’s a huge incidence and prevalence and one where we’ve also seen historical evidence of activity of lysergide. It's also particularly important to note that there’s a high degree of comorbidity between generalized anxiety and major depressive disorder, both in terms of diagnostic overlap and prevalence. 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 lysergide in anxiety and depression and other neurotic illness. This is consistent with the data we reported in anxiety back in 2022, again demonstrating a strong statistically significant response after acute administration. What anyone hopes to see in a depression study is something that is consistent and durable, and again, we think it’s particularly important both for anxiety and possibly for other indications in the future.

Okay. And can you remind me if the patients were on SSRIs or were they washed off for this trial?

Yes. 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 with concomitant administration of SSRIs and a molecule like MM-120. Historical data has suggested that there may be an alteration of the PD profile, but we haven’t seen any evidence that would be alarming or indicate a safety signal. This is something we are certainly monitoring and know others and academic researchers have been interested in that differentiation of response and as we progress in development we will be looking at that very closely.

Okay, great. And in terms of the R&D Day you mentioned would still be in the second quarter, is that where you plan on sharing more details about your commercialization plans for each product? Or is that kind of at a later time?

I think for our 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 trials and our overall programmatic approach. We’ll speak more to the intellectual property and market protection strategy, which should make a very clear story to anyone who’s been looking at market protection and the ability to protect a novel asset. We will have key opinion leaders talking about generalized anxiety disorder as an indication and where treatment might fit in the overall landscape. We’ll also present individuals who have been actively finding clinical trials and research with LSD and the drug class generally, and provide some insights into the commercial viability. Certainly as we progress and reach a Phase 2 readout and are getting into a Phase 3 program, we’ll be in a position at that point to speak more about market access and the overall commercialization strategy. But at our Investor Day coming up in the second quarter we will give a lot more insight into the status of the programs and I think greater clarity on elements of our ultimate product and our overall approach.

Okay, great. Thank you very much.

Thank you. Your next question comes from Elemer Piros, EF Hutton. Elemer, please go ahead.

Yes, good afternoon. What I’d like to verify, Rob, is the 20 clinical sites that you previously identified. Is this the final number for the GAD trial?

So the 20 clinical sites was the number of sites that, as we noted earlier in the year, were brought online and are fully recruiting at the beginning of the year. We’ve seen a lot of interest from a number of highly experienced sites. As we think about site engagement and bringing sites online, this can be driven both by an individual study but also programmatically. We have an opportunity to engage with sites that might be great sites in a later stage Phase 3 program. So we’re actively engaged in discussions across multiple 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 they are currently enrolling patients.

And at the end of the year, should we expect primary endpoint information? So efficacy at four weeks or maybe some later time points, eight weeks and 12 weeks as you have those as secondary endpoints?

We certainly anticipate reading out at least the four-week data, which is the primary endpoint in the study, as a top line readout by the end of the year. We’ll provide greater clarity as the study progresses and give an update on timing in the future, but our expectation when we speak to top line results is that we’d be reading out the primary endpoint.

I also found a company called MindBio who is planning 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?

In terms of intellectual property, in a research setting there is typically a carve out for doing research, so that wouldn’t come into play until much later down the road. But given where we are positioned in the program and the kind of support we’ve had, the team we’ve built, and the efficiency we will have demonstrated as we get the readout by the end of this year, we think we’ll 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.

Okay. And just two small questions here. Do you have a cutoff value for the HAM-A score at baseline in the GAD trial or minimum severity?

I’ll turn that one over to Dr. Karlin.

I don’t believe that we publicly disclosed the minimum cutoff score at the current time just to maintain trial integrity. We do have the score defined in the protocol, but for integrity purposes we haven't publicly disclosed it. I’ll expand on that briefly: if you refer to our investor presentation, which was published on our website, the minimum score we require to be enrolled in the trial as an entry criterion is a Hamilton Anxiety Rating Scale or HAM-A score of 20 or greater.

20 or greater. Okay. Thanks for clarifying that. Do you expect a good portion of the patients to have depression as a comorbidity in this study?

Based on the overall population and the comorbidity of GAD and major depressive disorder, we certainly anticipate that many patients will have comorbid depression. What’s critically important is to have GAD as a primary diagnosis, but it would not be a representative population if there were no comorbid depression in the study. Yes, as secondary outcome measures, we’re absolutely looking at response on standard depression scales and would use that as another important insight into potential response in depression.

Yes, wonderful. Thank you very much for both of you.

Thanks, Elemer.

Thank you. Your next question comes from Patrick Trucchio, H.C. Wainwright. Patrick, please go ahead.

Thanks. Good evening. As you look at the broader space of sponsors exploring psychoactive agents, how do you view the differentiation of MM-120 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 a potential to separate on safety and tolerability profile as well?

Yes. Thanks for the question, Patrick. When we look at the history of research in this drug class, as a drug developer you want to see drugs that have a likelihood of demonstrating a favorable benefit-risk profile that ultimately gets you to approval. 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 is that there's a fairly large expanded access or compassionate use program that's ongoing in Switzerland. Our collaboration with Dr. Liechti at UHB and conversations with psychiatrists in Switzerland have given us some real insights. These providers are able to utilize psilocybin or LSD, and in many instances, when asked about preference, they choose to use LSD. They have also indicated on multiple occasions that the actual conduct of administration sessions, whether it's LSD or psilocybin, occurs for approximately the same duration — it varies by individual, of course — but in practice, where this is being done regularly, there isn't a significant differentiation between those two molecules. Some of the ultra-short-acting molecules such as DMT or 5-MeO-DMT are certainly interesting and work on serotonin systems, but what we need to characterize is both the acute and durable response, and that's what we have more historical data on with LSD, which gives us great confidence in the potential of our product candidates.

Can you talk more about the health economic outcomes research that you referred to earlier? I understand there's still more planning here to be done. I'm wondering what this would potentially look like prior to launch and how big of a differentiator it would be for MM-120 if you have this type of data at the time of or soon after a potential launch?

I certainly don't want to speak too much to specifics at this point, but we are actively engaged both with François Lilienthal, our Chief Commercial Officer, who's had an extensive career in commercial launches, including most recently at Merck before coming to MindMed, to demonstrate the value proposition and make sure we have a path for commercialization, market access and reimbursement. Our digital medicine programs 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 and more specific areas of research interest. We'll be sharing more as we progress and as we get greater clarity on the commercialization pathway; we'll be in a position to speak more about our plans for data generation and the implications for market access, pricing and reimbursement.

That's helpful. One last question: can you discuss broader strategic priorities as it relates to business development? Specifically, how do you think about potential partnership activity following the Phase 2 readouts for MM-120 later this year?

Yes. We've seen quite a bit of interest in our program. At any time where we are advanced to the point where we reach the disclosure threshold, we will disclose partnerships. At this point, we do not have any business development or licensing agreements for subsequent development programs. That said, there has been engagement and excitement both about the serotonin system as a target, which is one of the best-characterized systems in psychiatry, and about our program and approach. The way we have designed and operationalized our Phase 2 study gives us a clear path into Phase 3 without changing variables that could impact safety or effectiveness. So there's a lot of potential and we'll keep our options open as we progress.

That’s helpful. Thank you very much.

Thank you. There are no further questions at this time. I will now turn it back for closing remarks.

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, MM-402, in the clinic later this year. Thanks, everyone again, for joining us, and we look forward to sharing future updates.

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.