Earnings Call Transcript - DFTX Q4 2024

Operator, Operator

Good morning, and welcome to the Mind Medicine Fourth Quarter and Year-End 2024 Financial Results 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. I would like to introduce Stephanie Fagan, Chief Corporate Affairs Officer of MindMed. Please go ahead.

Stephanie Fagan, Chief Corporate Affairs Officer

Thank you, operator, and good morning, everyone. Thank you for joining us for a discussion of MindMed's fourth quarter and year-end 2024 business highlights and financial results. Leading the call today will be Rob Barrow, our Chief Executive Officer, and he will be joined by Dr. Dan Karlin, our Chief Medical Officer. After our prepared remarks, we will open the call for Q&A. An audio recording and webcast replay for today's conference call will also be available online as detailed in the press release announcement for this call. During today's call, we will be making certain forward-looking statements, including without limitation, statements about the potential safety, efficacy, and regulatory and clinical progress of our product candidates, our anticipated cash runway and our future expectations, plans, partnerships and prospects. These statements are subject to various risks such as changes in market conditions and difficulties associated with research and development and regulatory approval processes. These and other risk factors are described in the filings made with the SEC and the applicable Canadian securities regulators, including our annual report on Form 10-K filed today. 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 and the applicable Canadian securities regulators 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, March 6, 2025. MindMed disclaims any obligation to update such statements even if management's views change, except as required by law. With that, let me turn the call over to Rob.

Rob Barrow, Chief Executive Officer

Thank you, Stephanie, and everyone for joining our call today. 2024 marked a year of unparalleled progress for MindMed, underscoring our leadership in advancing new treatments for brain health. We successfully achieved key milestones, positioning us to potentially deliver multiple clinical readouts from our MM120 Phase 3 program in 2026. A year ago, we announced positive results from our Phase 2b study of MM120 in generalized anxiety disorder or GAD, which showed statistically significant and durable improvements in mean Hamilton Anxiety Scale or HAM-A and Clinical Global Impression Severity or CGI-S scores for 12 weeks after a single dose of MM120. We also announced the results of a pharmacokinetic bridging study of our orally dissolving tablet formulation of MM120, our intended commercial formulation, which we are also using in our Phase 3 studies. Additionally, in 2024, we secured a new formulation patent on MM120 ODT, extending our intellectual property protection through at least 2041. Based on the strength of our data and the seriousness of GAD, FDA granted our MM120 GAD program Breakthrough Therapy designation, indicating its potential to represent a substantial improvement over currently available therapies. Our development approach prioritizes designing clean studies that yield clear results and are efficient to operationalize. This is exemplified by our bold decision early in development to study MM120 as a standalone treatment and our streamlined Phase 3 clinical trial designs, which aim to replicate the rapid durable response observed in our Phase 2b study. Our pivotal program in GAD includes two Phase 3 studies, Voyage and Panorama. As we previously announced, we are very excited to have already successfully dosed patients in both studies, and we have seen strong enthusiasm from clinical sites and patients as recruitment has continued to ramp up. These sites include some of the highest-performing enrollers from our Phase 2b study, and we are very encouraged by early enrollment trends. We are also on track to dose participants in Emerge, our first Phase 3 study for the treatment of major depressive disorder or MDD, in the first half of this year. This Phase 3 program closely aligns with our GAD program with a protocol that allows for streamlined and efficient patient enrollment. These two indications, GAD and MDD, affect approximately 51 million adults in the US and represent two of the most significant unmet medical needs in psychiatry. We believe MM120 could offer a differentiated and compelling option in both GAD and MDD, potentially positioning it as a best-in-class and first-in-class treatment option. We aspire to deliver a truly transformative treatment that has the potential to change the trajectory of the ongoing brain health epidemic. In fact, in our research with providers, they have shared their belief that the availability of psychedelics will radically transform treatment for GAD and MDD. Over the past year, we have been dedicated to broadening the awareness and understanding of these disorders and sharing our findings at a number of key medical meetings such as the American Psychiatric Association's Annual Meeting, the International Society for Health Economics and Outcomes Research Annual Meeting and the American College of Neuropsychopharmacology Annual Meeting. We continue to generate evidence that underscores a significant economic and social burden of GAD in the United States, including higher healthcare utilization and costs as well as reduced work productivity. These findings highlight the substantial impact of GAD, which has largely been underappreciated. I couldn't be more thrilled with the progress we've made this past year. As we look forward, 2025 will be a year of execution, focused on our Phase 3 programs in GAD and MDD and preparing for our three pivotal trial readouts in 2026. We have a strong dedicated team in place and continue to build a leading organization with best-in-class execution. Over the past year, we have also strengthened our financial position, having raised approximately $250 million in gross proceeds and gained the support of a number of top institutional investors. We expect our current cash and cash equivalents to provide sufficient funding into 2027, with a cash runway that extends at least 12 months beyond the first Phase 3 topline data readout for MM120 and GAD. Now, let me turn the call over to our Chief Medical Officer, Dr. Dan Karlin, to discuss our clinical development programs in more detail. Dan?

Dan Karlin, Chief Medical Officer

Thanks, Rob. As Rob just mentioned, we have already dosed participants in both of our pivotal Phase 3 clinical studies for GAD, Voyage and Panorama. We are highly encouraged by the early enrollment trends and continue to expect topline readouts from Voyage in the first half of 2026 and Panorama in the second half of 2026. Each study consists of two parts. Part A, a 12-week randomized, double-blind placebo-controlled parallel group study assessing the efficacy and safety of MM120 versus placebo, and Part B, a 40-week extension period with opportunities for open-label treatment designed to provide important long-term data on the durability and response patterns with MM120. In Voyage, we expect to enroll approximately 200 participants who will be randomized one-to-one to receive MM120, 100 micrograms or placebo, while in Panorama, we expect to enroll approximately 250 participants who will be randomized two-to-one to receive MM120, 100 micrograms, 50 micrograms or placebo. As Rob mentioned, we have taken an intentional and thoughtful approach to our development strategy, which has been informed by our team's deep experience in developing novel psychiatric therapies and through close collaboration with FDA. Our protocols are designed with operational input from sites and participants and specific attention to enabling enrollment so that we are able to rapidly recruit a representative sample of participants. Our Phase 3 studies in GAD closely resemble the design and execution used in our Phase 2b study. In both Voyage and Panorama, the primary endpoint is the change from baseline to week 12 in the HAM-A, which was the outcome measure used for the approval of the currently available GAD therapies. These trials incorporate important methods such as the use of central raters who are blinded to both treatment assignment and visit number, questionnaires to assess potential expectancy bias, and in the case of Panorama, multiple control arms, including a lower dose control that is perceivable and was previously tested. This approach builds on our Phase 2b data where we demonstrated that despite functional unblinding of participants at all tested doses, the lower doses, including 50 micrograms, did not demonstrate a meaningful clinical response. We believe this evidence strongly supports our view that the anxiolytic effect with MM120 cannot be attributable to functional unblinding and thus the measured effect reliably represents a true drug effect. These trials were designed to have 90% power to detect a 5-point improvement over placebo based on certain statistical assumptions, whereas in the Phase 2b trial, we observed an almost 8-point improvement for MM120 over placebo at week 12. We are using an adaptive design in our Phase 3 studies that includes an interim blinded sample size re-estimation, which allows for increased enrollment of up to 50% in each trial. This approach helps to adjust for any unexpected variability in nuisance parameters, specifically dropout rates and pooled variance of HAM-A response, maintaining statistical power and enhancing the interpretability of our results if needed. Key elements such as inclusion and exclusion criteria will largely mirror our successful Phase 2b study of MM120 in GAD, incorporating exclusion criteria around the recency or total use of psychedelics to ensure a representative sample is recruited. We also conduct comprehensive safety assessments and labs before and after the administration of MM120 and ensure the collection of all adverse events. Turning to our MDD program with MM120. We remain on track to dose our first participant in the first half of 2025 with data expected in the second half of 2026. Just like in our GAD program, we anticipate that our MDD program will consist of two pivotal clinical studies. Our first study, Emerge, will be comprised of two parts. Part A, a 12-week randomized double-blind placebo-controlled parallel group study assessing the efficacy and safety of a single dose of MM120 versus placebo. And Part B, a 40-week extension period during which participants will be eligible for open-label treatment with MM120 subject to meeting eligibility requirements. In Emerge, we plan to enroll at least 140 participants with a primary diagnosis of MDD randomized one-to-one to receive MM120, 100 micrograms or placebo. The primary endpoint in Emerge is the change from baseline in Montgomery-Åsberg Depression Rating Scale Score or MADRS at week six between MM120, 100 micrograms and placebo. The design and timing of the second MDD trial will be informed by the progress from Emerge and additional regulatory discussions. With that, I'll turn the call back over to Rob to discuss our fourth quarter and year-end financial results. Rob?

Rob Barrow, Chief Executive Officer

Thanks, Dan. Turning to our financial results for the year ended December 31, 2024, we ended the year with cash and cash equivalents totaling $273.7 million compared to $99.7 million as of December 31, 2023. Overall, we believe that our cash and cash equivalents as of December 31, 2024 will be sufficient to fund our operations into 2027 and at least 12 months beyond the top-line data readout for our first Phase 3 trial of MM120 in GAD. Research and development expenses were $21.8 million for the three months ended December 31, 2024, compared to $11.5 million for the three months ended December 31, 2023, an increase of $10.3 million. R&D expenses were $65.3 million for the year ended December 31, 2024 compared to $52.1 million for the year ended December 31, 2023, an increase of $13.2 million. The increase was primarily due to expenses related to our pivotal MM120 programs, Phase 1 MM402 program, and an increase of internal personnel costs, partially offset by a decrease in expenses related to preclinical activities. We anticipate R&D expenses to ramp up in 2025 due to the costs associated with running three pivotal Phase 3 studies. General and administrative expenses were $10.7 million for the three months ended December 31, 2024, and were the same for the three months ended December 31, 2023. G&A expenses were $38.6 million for the year ended December 31, 2024, compared to $41.7 million for the year ended December 31, 2023, a decrease of $3.1 million. The decrease was primarily attributable to reduced professional services fees and expenses partially offset by increased stock-based compensation expense and costs associated with pre-commercial activities. The company's net loss for the three months ended December 31, 2024, was $34.7 million compared to $23.8 million for the same period in 2023, an increase of $10.9 million. The company's net loss for the year ended December 31, 2024, was $108.6 million compared to $95.7 million for the same period in 2023, an increase of $12.9 million. The increase was primarily attributed to research and development expenses associated with our MM120 and MM402 programs. In closing, I'm incredibly proud of the progress we have made over the past year at MindMed. We believe MM120 is uniquely positioned to potentially offer a novel and highly differentiated treatment option for people living with brain health disorders. None of our progress would have been possible without the dedication of our exceptional team. I want to thank them for their continued efforts and commitment to our mission. With that, I'd like to thank you all again for joining us today, and the team and I are happy to take your questions.

Operator, Operator

Our first question comes from Marc Goodman with Leerink. Your line is open.

Madhu Yennawar, Analyst (for Marc Goodman, Leerink)

Hi, this is Madhu on the line for Marc. I think some people we speak with are trying to get a better understanding of which GAD patients would be likely to want to use MM120 over other available options once it could be eventually approved. So I'm curious, would this be for patients who strictly don't respond to other available therapies or patients past a certain severity level? If you could share any insights that you have on that, maybe from market research or just in terms of the patients that are looking to enroll in these studies, that would be great. Thank you.

Rob Barrow, Chief Executive Officer

Yeah. Thanks so much, Madhu. I'll turn it over to Dan in just a second. I think at a very high level, certainly the indication we're pursuing, which is the broad label for all generalized anxiety disorder patients, would enable access much more broadly than if we had a severely restricted criteria on the label. Certainly, there are a pair of dynamics that come into play and we've had really encouraging signs in that research just based on the relative lack of treatments for GAD in a long time since any new treatments have been introduced and the overall severity of that population. But maybe, Dan, if you want to add some clarity there as well.

Dan Karlin, Chief Medical Officer

Yeah, absolutely. I think there's a really interesting point there, which is that the sorts of patients who would be interested in accessing the drug are a really broad swath of the population. For folks with diagnosed GAD, tolerability and efficacy of existing drugs like SSRIs is pretty unsatisfactory. SSRIs have never been particularly effective against anxiety cluster symptoms, either in GAD or MDD. So what we see both in market research, but also in who presents to enroll in our studies is that there are people with severe GAD, there are people with moderate GAD, there are people who have had prior treatments, including SSRIs or psychotherapy. There are people who haven't had those treatments before either because they didn't want them or because their GAD wasn't recognized. So we see there being both broad appeal and, of course, based on the efficacy we've seen in Phase 2b, the ability to really help a broad swath of patients. Now, the realistic nature of a payer-supported commercial market is that there are likely to be step-therapy requirements. So what you see often with new treatments in the class, even new treatments that have a mechanism that's similar to existing treatments or the same as existing treatments, is a requirement to have been failed by one or more existing treatments. But, given the efficacy that we're seeing, given the appeal of having a single treatment with no lingering adverse events, we think that the demand side will be quite high.

Operator, Operator

Thank you. Our next question comes from Gavin Clark-Gartner with Evercore ISI. Your line is open.

Gavin Clark-Gartner, Analyst (Evercore ISI)

Hey, guys. Congrats on the progress, and thanks for taking the questions. First, I just wanted to ask, are you planning to give more granular enrollment updates for both of the GAD trials over the course of this year? Or is the next update that we should expect enrollment completion?

Rob Barrow, Chief Executive Officer

Yeah. Thanks so much, Gavin. We haven't yet provided exact guidance. I think we would expect to follow a similar pattern as industry standard and as we did in our Phase 2 study where, as we approached the end of enrollment, we were able to announce that. But certainly, as we have any material updates, we would be disclosing those.

Gavin Clark-Gartner, Analyst (Evercore ISI)

Got it. That makes sense. And then separately, just on the sample size re-estimation analysis, I wanted to confirm that there is no alpha spending, no futility criteria, and also ask what you think the likelihood of the trial being upsized a little bit is and when this analysis roughly may occur?

Rob Barrow, Chief Executive Officer

Yeah, great question. The sample size re-estimation is designed as a no-alpha-spend, blinded re-estimation. And as Dan mentioned, it's only based on the nuisance parameters, the dropout rate and the pooled variance of HAM-A outcomes. So we can't provide exact timing for when that would occur other than upon the completion of about half the patients — about 100 patients who make it through week 12 is when we anticipate running that analysis. But certainly no futility, no alpha spending, and it's really just to ensure that power is maintained if any of those nuisance parameters are outside of our estimates. Now, the estimates we have, we feel quite confident in, based on a long history of historical norms in this population and also analyzing the data from our Phase 2 clinical trial. So we feel quite confident in the assumptions we've made at baseline, but it just adds an additional layer of protection in the event there is some kind of surprise on either the variance or on the dropout rate.

Gavin Clark-Gartner, Analyst (Evercore ISI)

Very helpful. Thank you.

Operator, Operator

Thank you. Our next question comes from Brian Abrahams with RBC Capital Markets. Your line is open.

Nevin, Analyst (for Brian Abrahams, RBC Capital Markets)

Hi, everyone. This is Nevin for Brian. Thank you for taking our questions. With the Voyage and Panorama studies underway, I was wondering if you could provide any more color on what you're seeing in the early rates of enrollment — are they tracking in line with or better or worse than the prior Phase 2 trial? And then, given the recent more enthusiasm for psychedelic clinical trials in general, are you seeing similar types of patients enrolling in the pivotal trials as you did in the Phase 2? I'm wondering if perhaps the increased awareness of psychedelics among the patient population could change or potentially impact the expectancy bias among that group.

Rob Barrow, Chief Executive Officer

Yeah, thanks so much, Nevin. We can't provide specific enrollment numbers, and we're really highly encouraged by the enthusiasm from providers, from patients, and by the early enrollment trends, and are quite confident as a result in the progress we're making in both of the studies. To your latter question, again, we wouldn't provide specifics on demographics, but the inclusion/exclusion criteria and the population we're pursuing are very, very close to — almost identical to — the Phase 2b trial. And so certainly the expectation and all of the extensive screening that we do to ensure that we get the right patients in these studies, we feel quite confident that we're getting a similar and representative population. On the final point, while we certainly have seen growing interest, I don't know that we could say that that has had a direct impact in any measurable way on expectancy. And I think population-level or group-level trends are one thing, but for an individual person, for a patient who's been suffering through GAD for, in many cases, years or decades, people enroll in late-stage trials with inevitable expectancy, regardless of the treatment that is being studied, simply for the reason that most of those patients either are unsatisfied or not getting the level of response from currently available therapies and therefore come into clinical trials with the hope that something new will potentially help them. And so while they may be randomized to get placebo or an inactive dose of drug in these studies, we certainly expect, like with any clinical trial, there's going to be a degree of expectancy just by the nature of it being an experimental drug that we're studying.

Nevin, Analyst (for Brian Abrahams, RBC Capital Markets)

Okay, thank you. And then a quick follow up as well. I know you had mentioned that the inclusion/exclusion criteria were similar across both Panorama and Voyage. But looking at the clinicaltrials listing for both of them, I see that exclusion criteria for Voyage specifically mentioned bipolar disorder, but Panorama does not. Is there any particular reason for that?

Rob Barrow, Chief Executive Officer

No, the inclusion/exclusion criteria are consistent across both studies in that respect.

Operator, Operator

Thank you. Our next question comes from Charles Duncan with Cantor. Your line is open.

Charles Duncan, Analyst (Cantor)

Hey, good morning, Rob and Dan. Congrats on the design and operationalizing these Phase 3s. Thanks for taking the question. I had another question about enrollment criteria. I think Dan mentioned that he expected a broad swath of patients to be interested in the study. But I guess I'm wondering, are you seeing any types of severity or treatment experience that are presenting? And then with regard to experience with LSD or psychedelics in the past, what is happening in terms of the enrollment for the patients in Voyage and Panorama? Thanks.

Rob Barrow, Chief Executive Officer

Thanks, Charles. I'll turn it over to Dan to answer both of those.

Dan Karlin, Chief Medical Officer

Yeah, consistent with what we believe to be a representative sample of people who seek treatment for GAD in general, what we're seeing — again, while we can't really comment on live enrollment in Phase 3 — what we were able to see in the Phase 2 study, with nearly identical inclusion/exclusion, was about two-thirds of patients with treatment experience who'd been failed by prior treatments, about one-third who hadn't been treated, and 10% to 15% with a fairly recent diagnosis of GAD. We know in the population that there are almost twice as many people walking around with symptoms of moderate to severe GAD who have never been diagnosed with it on a population level. So when new treatments become available or new studies are launched, additional attention is paid to a diagnosis, and obviously that diagnosis gets made in folks who have had the disease for some time. You'll recall in Phase 2, we saw a mean HAM-A of just about 30, which puts people well into the severe category. There's no reason to think that we would be particularly different in this study. So, when we think about that, the breadth of the appeal of the treatment and the degree to which people aren't served by what's available, that's, again, while we can't comment exactly on Phase 3, there's no reason to think things would be all that different.

Rob Barrow, Chief Executive Officer

Thanks so much for the question, Charles. I think there are two key features here; I'll speak first to the dose-response aspect. Certainly, the design in the Phase 2 study's primary analysis was aimed at defining a dose response where we pre-specified response curves and statistically showed that the data from the Phase 2 study matched multiple candidate dose response curves. So I'd say that the data matched the potential assumptions we made going into the Phase 2 study. I think it was quite stark, as you mentioned, the fact that in the Phase 2 at week four, there was less than a point improvement over placebo at the 50 microgram level and there was a 7.5 to 7.6 unit improvement over placebo for the 100 microgram dose. So while we weren't surprised by the overall shape of the curve, it is in quite stark contrast — the difference in clinical response between 50 and 100 micrograms — and the data that has been generated to date. If you recall, there's really only sparse data in the field to look at a comprehensive dose response across a full range. On the second point, it's really important to stress that the field has in many instances conflated some of the issues at play with why we take additional methodological steps. We talked before about potential expectancy, which we certainly expect to be the case in any clinical trial. And with any treatment where there is a clear discernible acute effect, there's the risk that that functional activity could unblind patients, and unblinding is effectively a binary variable — you're either blinded or not. What we saw in the Phase 2 data was that patients across dose levels were functionally unblinded at a high rate, yet we still saw a dose response between the two levels. The intent of including a 50 microgram dose is twofold. It's important that the dose level be as close to the acute perceptual effects as the clinically active dose of interest, 100 micrograms. Otherwise, it doesn't have similar functional activity and it doesn't aid in the functional blinding that we're pursuing. But fundamentally, we're trying to sever the tie between an expectancy bias and any impact on biasing clinical outcomes. We do that through many mechanisms, one of which is using centralized raters, but by having that 50 microgram dose level what we're able to do is effectively, through the consent process, inform patients that whether or not they feel perceptual effects on the day of dosing, they may be receiving a real dose of drug or they may be receiving a dose that previously has been shown not to be clinically active. So just because a patient feels something does not mean they can assume they are receiving a dose that will make them clinically better. This is one of the best steps any study has taken in psychiatry to try to enhance validity and minimize bias in these outcomes. We feel stronger about the validity of the data that we'll be able to generate in these studies because of these additional design elements.

Charles Duncan, Analyst (Cantor)

That's helpful, Rob. One quick last question, then going back to an earlier question, I think the ISI person asked regarding the adaptive design, what dropout rate are you assuming could happen so that we can kind of gauge how it's going over the course of the trial?

Rob Barrow, Chief Executive Officer

We assume a pooled standard deviation of 10 units and a dropout rate of about 15%.

Operator, Operator

Thank you. Our next question comes from Francois Brisebois with Oppenheimer. Your line is open.

Analyst (Oppenheimer), Analyst (Oppenheimer)

Hi, this is Dan on for Frank. Thanks for taking our question. Given all this regulatory scrutiny in this space, is the upcoming PTSD advisory committee something you're looking to learn from to inform your own development, or is this different enough that you don't expect a direct impact?

Rob Barrow, Chief Executive Officer

Thanks so much, Dan. We're always looking at advisory committee outcomes, particularly neuropsychopharmacology advisory committees, to understand the dynamics. Given the difference in the population and our development plans, we are focused on execution of our studies. We'll certainly be watching and observing, but we don't see a direct impact on our program at this time.

Operator, Operator

Thank you. Our next question comes from Joel Beatty with Baird. Your line is open.

Joel Beatty, Analyst (Baird)

Hi, congrats on the progress and thanks for taking the question. For the Phase 3 trials in GAD, how much of a risk is there that some of those patients during the 12-week randomized phase go on to take another therapy? And if that does happen, might it happen more in the placebo patients than the treatment patients? If that situation occurs, how does that get handled by the statistical plan?

Rob Barrow, Chief Executive Officer

Yeah, thanks, Joel. We have a high degree of confidence in our sites and go to great lengths to ensure that all patients adhere to the trial protocol, which as a monotherapy trial includes taking no other therapies during the randomized period and really throughout the duration of the study. So we monitor that very closely, and if patients do violate that criterion, it is addressed in the statistical analysis plan. We are prepared today to go through the specifics of that plan and have a great collaboration with FDA on our development and statistical analysis plan for both of the Phase 3 studies. We certainly monitor very closely and try to ensure adherence to the protocol at every site and have had great success historically in our engagement with these sites so far.

Operator, Operator

Thank you. Our next question comes from Rudy Li with Chardan. Your line is open.

Rudy Li, Analyst (Chardan)

Hi, thanks for taking my question. I have a question regarding the MDD indication given the competitive landscape for psychedelics. How important is the MDD indication for MM120 to compete with other psychedelic products? And when should we expect updates on the timing and the design of the second MDD study? Thank you.

Rob Barrow, Chief Executive Officer

Thanks, Rudy. Overall, when looking at the development plan for MM120, we see a broad and massive market and opportunity to help many millions of patients. Having the broadest label fully enables us to market to a broader population and help as many patients as possible. In psychiatry, having a label that covers both GAD and MDD means that a patient presenting with either cluster of symptoms would be an on-label candidate for the product. As we look around the landscape, many other therapies focus primarily on treatment-resistant depression; our strategic difference is pursuing these two large indications to maximize patient impact and set us apart. That perspective informed our selection of GAD, where there have been few new therapies in the past 20 years, and our plans to go after both large populations.

Operator, Operator

Thank you. Our next question comes from Sumant Kulkarni with Canaccord Genuity. Your line is open.

Sumant Kulkarni, Analyst (Canaccord Genuity)

Good morning. Nice to see the progress and thanks for taking my questions. I have two. First, given you have Breakthrough Therapy designation for MM120 that potentially allows for more back-and-forth with the FDA, could you give us any details on when you had your last interaction with the agency and if any of the changes that are currently affecting government agencies have impacted your interactions in any way?

Rob Barrow, Chief Executive Officer

Thanks, Sumant. With Breakthrough Therapy designation, we do have frequent interactions with the agency on various topics, including the clinical Phase 3 program, clinical pharmacology, CMC and other aspects that are important to ensure the quality and adequacy of our data to support a submission. We think highly of FDA as a strong partner and, especially after receiving Breakthrough Therapy designation, we've brought on an experienced regulatory team with strong prior interactions with the division. We've been encouraged by the level of engagement and clarity we've received and feel a high degree of alignment in our approach with the expectations we're hearing. Regarding the disruptions in Washington, fortunately at this stage our interactions with FDA have not been changed; the division of psychiatry has continued to be constructive and engaged with us.

Sumant Kulkarni, Analyst (Canaccord Genuity)

Got it. Thanks. Second, if we fast forward to a time when other psychedelic agents that involve shorter times in the clinic might become competitors at the time MM120 is approved, what would be the key points in favor of MM120 versus, for example, a deuterated DMT, knowing we haven't seen Phase 2 data on that molecule yet?

Rob Barrow, Chief Executive Officer

Look, with tens of millions of patients we might be able to treat across the indications we're pursuing, there is room for multiple modalities. Some of the things we're encouraged by are both the magnitude and the durability we've seen in large, well-controlled studies where we are exceeding placebo by more than double the standard of care. That's not something we've seen broadly across the field. There are also practical site economics that come into play — a treatment that requires very high throughput can be problematic for sites. Clinics that deliver Spravato, for example, have to turn over the room multiple times a day, which can be an administrative burden and inefficient economically. So while there are assumptions about duration of various products, we've been highly convinced about our approach and what it will mean for sites of care and patient access.

Operator, Operator

Thank you. Our next question comes from Patrick Trucchio with HC Wainwright & Company. Your line is open.

Patrick Trucchio, Analyst (HC Wainwright & Company)

Thanks. Good morning. A couple of follow-up questions. With the Phase 3 trial in anxiety, the primary endpoint is HAM-A. Which secondary endpoints — things like function or quality of life — could be important from both a regulatory and payer perspective? Secondly, I'm curious if you can discuss some of the HEOR work that's been conducted and what further research you plan to support MM120 after a potential approval. Lastly, the Phase 2b trial showed about an 8-point improvement on HAM-A relative to placebo. How did the learnings from that trial lead to the powering for the Phase 3 studies in GAD, and how are Phase 2b learnings influencing the Phase 3 trial in MDD?

Rob Barrow, Chief Executive Officer

Thanks, Patrick. For secondary outcomes in the Phase 3 program, we are certainly looking at a number of measures. One that is of interest is CGI, which measures overall disease severity and patient functioning; that's important to us at the HAM-A primary time point. Regarding HEOR, we've done extensive research, some of which we've presented in posters and publications. That work covers everything from prevalence to the impact on quality of life and economic parameters like workplace productivity, absenteeism and presenteeism. Over the past decades diagnostic and treatment patterns have shifted, and our work has focused on the prevalence and the economic burden of GAD. We have a strong market access and HEOR team continuing this work to make arguments for the value of a product. We see value coming through when you consider the magnitude of remission after a single administration that is durable for many months — the health economics become favorable for such a treatment. On your last point, the Phase 2 showed about a 7.7 unit improvement for the 100 microgram dose. Notably, that was an improvement over about a 14-point placebo response, which is larger than historical averages in GAD, where placebo was closer to about 10 units. We powered the Phase 3 studies at 90% to detect a 5-point improvement over placebo, which we view as a conservative assumption. Also, Phase 2 had five arms, four of which were active doses; the Phase 3 studies are configured differently, which based on trial methodology research can reduce placebo response. We also have the sample size re-estimation to protect power during study conduct. So we've been conservative and feel confident in the powering and the probability of success given a meaningful treatment effect.

Patrick Trucchio, Analyst (HC Wainwright & Company)

That's really helpful. One additional question: how are you measuring long-term durability of MM120 in Part B of the studies? Do you need that data to submit for approval, or could you submit with the 12-week data?

Rob Barrow, Chief Executive Officer

Good question. We're not in a position today to specify exactly what would be required for submission, but historically for depression and anxiety drugs the durability requirement for approval has often been in the range of 4 to 12 weeks, which is encouraging. In our trials we characterize durability beyond 12 weeks in the 40-week extension period with the opportunity for open-label treatment. Until a patient actually takes open-label product in that extension period, they remain blinded and we do not unblind on a per-patient basis until the overall study is complete. We can look at group-level analyses after 12 weeks without affecting study integrity. For durability, we can use measures like Kaplan-Meier curves to assess the durability of response after a single treatment at baseline. We expect differences in time to relapse or to open-label treatment between those randomized to MM120 and those randomized to placebo, and we are tracking patterns of subsequent treatment and durability of response after re-treatment as well.

Operator, Operator

Thank you. Our next question comes from Michael Okunewitch with Maxim Group. Your line is open.

Michael Okunewitch, Analyst (Maxim Group)

Hey, guys. Thank you so much for taking my questions today, and congrats on all the progress you've made. I have one quick question on runway and capital use. You've done a fantastic job managing your balance sheet so far. You have two Phase 3s ongoing and a third launching in major depression. The conventional wisdom suggests you would need a confirmatory study in MDD as well. Would you expect a confirmatory MDD study to be launched concurrently with your other programs? Is this something you considered in your current runway projections?

Rob Barrow, Chief Executive Officer

Thanks, Michael. We certainly consider all of our development plans across our programs in our financial projections and guidance for cash and runway. Our approach in MDD is such that we are planning a second study, but we have not disclosed exact timing. The design and timing will be informed by Emerge's progress and regulatory interactions. We remain financially prudent and mindful of operational efficiencies in how we start and run studies. Our current projections reflect our planned development activities across programs.

Michael Okunewitch, Analyst (Maxim Group)

All right, thank you very much. And once again, congrats on all the progress.

Operator, Operator

This concludes the question-and-answer session, and you may now disconnect. Thank you for your participation. Everyone, have a great day.