Mind Medicine (MindMed) Inc. Price & Performance (MNMD)

These statements are subject to various risks such as changes in market conditions and difficulties associated and regulatory approval processes. These and other risk factors are described in the filings made with the SEC the applicable Canadian securities regulators. Including our annual report on Form 10 ks 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 MyMed'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. MineMed disclaims any obligation to update such statements even if management views change except as required by law. With that, let me turn the call over to Rob.

Thank you, Stephanie. And everyone for joining our call today. 2024 marked a year of unparalleled progress for Mind Med underscoring our leadership in advancing new treatments for brain health. We successfully achieved key milestones positioning us and to deliver multiple clinical readouts from our MM120 Phase three program in 2026. A year ago, we announced positive results from our Phase 2b study at MM120 in generalizing GAD which showed statistically significant and durable improvements in Mean Hamilton Anxiety Scale or HAM A in Clinical Global Impression Severity or CGIS scores for twelve 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 two studies. Additionally, in 2024, we secured a new through at least 02/1941. Based on the strength of our data and the seriousness of GAD, FDA granted our MM120 GAD program breakthrough therapy designation indicating its potential 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 three 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 three studies, Voyage and Panorama. As we previously announced, are very excited to have already successfully dosed patients in both studies and we have seen strong enthusiasm from clinical sites and patients recruitment has continued to ramp up. These sites include some of the highest performing enrollers from our Phase 2b study We are very encouraged by early enrollment trends. We are also on track to dose participants in IMerge our first Phase three study for the treatment of major depressive disorder or MDD.

The first half of this year. This Phase three program closely aligns with our JAD program with a protocol that allows for streamlined and efficient patient enrollment. These two indications, GAD and MDD, affect approximately fifty one million adults in The U. S. And represent two of the most significant unmet medical needs in psychiatry. We believe MM120 could offer a differentiated and compelling 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 ZEISSYIA's orders and sharing our findings Mind 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's Annual Meeting. We continue to generate evidence that underscores the significant economic and social burden of GAD in The United States including higher healthcare utilization and costs as well as reduced work These findings highlight the substantial impact of GAD, which is largely 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 three 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 $250,000,000 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 twelve months beyond the first Phase three top line data readout for MM120 and GAD. Now let me turn the call over to our Chief Medical Officer, Doctor. Dan Carlin, discuss our clinical development programs in more detail. [indiscernible] Thanks, Rob. As Rob just mentioned, we have already dosed participants in both of our pivotal Phase three clinical studies for GAD. Voyage and Panorama. We are highly encouraged by the early enrollment trend and continue to expect top line readouts from VOYAGE in the first half of twenty twenty six and Panorama the second half of twenty twenty six.

Each study consists of two parts, Part A, a twelve week randomized double blind placebo controlled parallel group study assessing the efficacy and safety of MM120 versus placebo [indiscernible] a forty 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 one hundred micrograms or placebo while in Panorama we expect to enroll approximately two fifty participants who will be randomized two to one Mind two to receive MM120 100 meter fifty micrograms or placebo, As Rob mentioned, we have taken an intentional and thoughtful approach to our development which has been informed by our team's deep experience in developing novel psychiatric 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 three studies in GAD closely resemble the design and three 2b study In both Voyage and Panorama, the primary endpoint is the change from base [indiscernible] in the Hamei 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 fifty micrograms did not demonstrate a meaningful clinical response. We believe this evidence strongly supports our view that the endothelitica effect of MM120 cannot be attributable to functional unblinding Mind thus the measured effect reliably represents a true drug effect.

These trials were designed to have 90% power to detect a five point improvement over placebo based on certain statistical assumptions. Where in the Phase 2b trial, we observed an almost eight point improvement for MM120 over placebo at week twelve. We are using an adaptive design in our Phase three 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 MA 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 FM-one 20 and 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 twenty twenty six.

Just like in our GAD program, we anticipate that our MDD program will consist of two pivotal clinical studies. Our first study, [indiscernible] Part A, a twelve 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 of forty week extension period during which participants will be eligible for open label treatment with MM-one hundred and twenty subject to meeting eligibility requirements.

In IMerge, we plan to enroll at least 140 participants with a primary diagnosis of MDD randomized one to one to receive MM120 Mind hundred micrograms or [indiscernible] The primary endpoint in IMerge is the change from baseline in month Montgomery Asper Depression Rating Scale score [indiscernible] at week six and placebo The design and timing of the second MDD trial will be informed by the progress from IMerge and additional regulatory discussion. With that, I'll turn the call back over to Rob to discuss our fourth quarter and year end financial results. [indiscernible] Thanks, Dan. Turning to our financial results for the year ended 12/31/2024.

We ended the year with cash and cash equivalents totaling $273,700,000 compared to $99,700,000 as of 12/31/2023. Overall, we believe that our cash and cash equivalents as of 12/31/2024 will be sufficient to fund our operations into 2027 and at least twelve months beyond the top line data readout for our first Phase three trials Mind M120 and GAD. Research and development expenses were $21,800,000 for the three months ended 12/31/2024, compared to $11,500,000 for the three months ended '23, an increase of $10,300,000 R and D expenses were $65,300,000 for the year ended 12/31/2024, compared to $52,100,000 for the year ended 12/31/2023. An increase of $13,200,000 The increase was primarily due to expenses related to our Pivotal MM120 programs, Phase one MM-four zero two program and an increase of internal personnel costs partially offset by a decrease in expenses related to preclinical activities. We anticipate R and D expenses to ramp up in 2025 due to the costs associated with running three pivotal Phase three studies. General and administrative expenses were $10,700,000 for the three months ended 12/31/2024, and were the same for the three months ended 12/31/2023. G and A expenses were $38,600,000 for the year ended 12/31/2024, compared to $41,700,000 for the year ended 12/31/2023, decrease of $3,100,000 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 $34,700,000 compared to $23,800,000 for the same period in 2023, an increase of $10,900,000 Company's net loss for the year ended 12/31/2024 was $108,600,000 compared to $95,700,000 for the same period in 2023, an increase of $12,900,000 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 Mind 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.

Our first question comes from Mark Goodman with Leerink.

Hi.

This is Madhu on the line for Mark. 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. And so just curious, would this be 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 patients that are looking to enroll in these studies, that would be great.

Yes. Thanks so much, Mario. And I'll turn it over to Dan in just a second. I think at a very high level, Certainly, indication we're pursuing, which is a 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 pair dynamics that come into play Mind we've had really encouraging signs in that research just based on the relative lack of treatments for GAD and the long time 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.

Yes, absolutely. And I think that there's a really interesting point there, which is that the sorts of patients who would be interested in accessing the drug is a really broad swath of the population. For folks with diagnosed GED, tolerability and efficacy of existing drugs like SRIs Is pretty unsatisfactory SRIs have never been particularly effective against anxiety cluster symptoms either in GAD or MDD. So what we see both in research, but also 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 SRIs 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 brought 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 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 existing treatments or the same as existing treatments is a requirement to have been failed by one or more existing treatments.

But given the the efficacy that we're seeing, given the appeal of having a single stream with no lingering adverse events we think that the demand side will be quite high.

Thank you.

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

Hey guys. Congrats on the progress Mind thanks for taking the questions. [indiscernible] 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? Thanks so much, Kevin.

We haven't yet provided the exact guidance. I think we would expect to follow a similar as industry standards Mind as we did in our Phase two study, where we as we approach the end of enrollment, we were able to announce that. But certainly as we have any material updates, we would be disclosing those Got it. That makes sense. And separately, just on the sample size re estimation analysis, I wanted to confirm that there's no alpha use, no futility criteria Mind also ask what you think the likelihood of the trial being upsized a little bit is Mind when this analysis Yes, great question. The way the same size of your estimation is designed is a no alpha Mind blinded re estimation Mind the damage is only based on the nuisance parameters, the dropout rate, and the pooled variance of of the standard early pooled variance of HMA 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, you make it through week 12. Is when we anticipate to run that analysis But certainly no futility, no spend of alpha and it's really just to ensure that power is maintained if any of those nuisance parameters are are outside of our estimates.

Now the estimates we have, we feel quite confident in based on a long history of historical norms Mind this population and also analyzing the data from our Phase two clinical trial. So we feel quite confident in the assumptions we've made at base but it just adds an additional layer of protection in the event there is some kind of surprise either the variance or on dropout rate. Very helpful.

Thank you.

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

Hi, everyone. This is Nevin on for Brian. Thank you for taking our questions. So 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 [indiscernible] And then I guess among those who just given that recent more enthusiasm for psychedelic clinical trials in [indiscernible] Are you seeing similar types of patients enrolling in the GAD trial in the pivotal trials as you did in the Phase And I'm wondering if perhaps the increased awareness of psychedelics among patient population could change or potentially impact the expected expectancy bias Yes. Thanks so much, Devin. So we can't provide Specific numbers enrollment. As Dan mentioned, we've been really highly encouraged by the enthusiasm from providers, from patients, from the early enrollment trends Mind [indiscernible] quite confident as a result Mind the progress we're making Mind both of the studies. To your latter question, again, we wouldn't provide specifics on demographics, but the inclusionexclusion criteria and the population we're pursuing are very, very close to identical almost to the Phase 2b trial.

And so the expectation Mind 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 population and representative one And then the final point, While we certainly have seen growing interest, I think I don't know that we could say that that has had a direct impact in any measurable way on expecting I mean, I think population level or group level trends certainly are one thing, but I think you have to remember for an individual person, for a patient who's been suffering for 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 unsatisfied or not getting the level of response from currently available therapies, and therefore come into clinical trials without 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 just by the nature of it being Okay.

Thank you. And then a quick follow-up as well. I know you had mentioned that the inclusion exclusion criteria were similar across Panorama and Voyage. Looking at the Clin trials listing for both of them, I see that The exclusion criteria for Voyage specifically mentioned bipolar disorder, but Panorama does not. Is there any particular reason for that?

No, the inclusion criteria have been consistent across both studies in that respect.

Okay.

Thank you.

Thank you. Our next question comes from Charles Duncan with Cantor. Your line is open. Hey, good morning, Rob and Dan.

Congrats on the design and operationalizing these Phase three Thanks for taking the question. I had another question about enrollment [indiscernible] a broad swath of patients to be interest [indiscernible] types of severity or treatment experience that are presenting. And then with regard to experience with LSD or psychedelics in the past, what What is happening in terms of the enrollment for the patients in Voyage and Panorama? Thanks.

Thanks, Charles. I'll turn it over to Dan to answer both those Yes. 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 three, what we were able to see in the Phase two study, again with like what Ram said, nearly identical inclusion and exclusion about two thirds of patients with treatment experience who've been failed by prior treatments, about one third who hadn't treated ten percent to fifteen percent with a fairly recent diagnosis of GAD.

We know in the population there are almost twice as many people walking around with symptoms of moderate to severe GATs 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 Mind obviously that diagnosis gets made Mind folks who have had the disease for some time You'll recall in Phase two, we saw a mean HMA of 30 just about thirty. So that puts people well into the severe category and no reason to think that we would particularly different in this study. [indiscernible] 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 three, no reason to think things would be looking all that different Okay.

And then let me ask you a quick for a little bit of a nuance on Panorama. I like that you're using a dose that doesn't appear effective to remove expectation bias, but for unblinding, excuse me, Were you surprised at how sharp the dose response curve was 50 versus 100. And do you anticipate that 50 really to have an a no effect Mind to remove the reduce the function on Mind. Yes. Thanks so much for the question, Charles.

Yes, two key features there Mind I'll talk on the dose response aspect first, which is that Certainly, the design in the Phase two Mind, the primary analysis was one that is aimed at defining a dose response where we pre specified response curves Mind statistically showed that the data from the Phase two study matched multiple of those candidate dose response curves. So I'd say that the data certainly [indiscernible] the potential and the assumption we made going into the Phase two study I think it was quite stark as you mentioned, the fact that in the primary in Phase two at week four, there was less than a point improvement over placebo at the microgram level and there was a seven point five seven point six unit improvement over placebo for the one hundred microgram dose. So while we weren't surprised by the overall shape of the curve, it is Mind quite stark contrast that the difference Mind response between fifty and one hundred micrograms Mind the data that's been generated to Dayton if you recall, really, the only data in the field to look at a a comprehensive dose response across a full [indiscernible] Now on the second point, it's really important to stress and we think that the field in many instances has conflated some of the issues that are at play with why we take these additional methodological steps.

So, we talked before about potential expectancy, which we certainly expect to be the case in any clinical trial. And with any treatment, universally the truth for psychiatric drugs. But for any treatment, where there is a clear discernible acute effect there's a risk that that functional activity could unbind the patients. And unbinding importantly is a binary variable. There's not a a continuous degree. You can't be twenty percent unblinded or eighty percent unblinded, you're either blinded or not. And so what we saw in the Phase two data was that all patients across the dose levels effectively were unblinded eighty eight percent or more across all those levels. Functioning unblinded Mind we saw that start dose response [indiscernible] really the intent of including a fifty microgram dose is twofold. It's really important that dose level is as close to the acute perceptual effects as the clinically active or the dose of interest that we're studying one hundred micrograms Otherwise, it doesn't have similar functional activity and it doesn't really aid in the functional blinding that we're pursuing. Really what we're trying to do fundamentally is sever the tie between an expectancy bias and an impact on biasing the clinical outcomes.

And we do that through many mechanisms, one of which is using Mind and centralized raters. But by having that dose that fifty microgram dose level, what we're able to do is effectively through the consent process inform patients that whether or not they feel effect of the drawing of acute perceptual effect on the day of dosing, they may be receiving a real dose of dry eye that may be receiving a dose that previously has been shown not to be clinically active. So just because a patient assumes that Just because they feel something on the other day of testing, they can't assume that they're getting a dose of drug that's going to make them better. And really that's great of a link as any study has ever been asked to go in psychiatry to try to enhance validity and minimize the bias of these outcomes because like with other approved JAD therapies like Xanax for instance, there's a acute perceptual effect that just hasn't been looked at Mind past. And so we feel even stronger about the validity of the data that we'll be able to generate in these studies because of these additional analyses and the additional to design almost we've included in the Phase III program.

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 is the dropout rate that you are assuming could happen so that we can kind of gauge how it's it's going over the course of the trial.

And we assume the pooled standard deviation of 10 units and a dropout rate of about 15%.

Okay. Thanks. Very helpful.

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

Hi, this is Dan on for Frank. Thanks for taking our question. Thanks for all the color around the enrollment as well as as we about the outcomes here.

Just a quick one from us. Given all this regulatory scrutiny in this space, is the upcoming PTSD adcom, is this something you're looking to learn from to inform your own development or is this the indications are different? So Yes. Thanks so much. We're always looking at all the cons, particularly neuropsychopharmacology advisory committees just to understand the dynamic of those. But given the difference Mind the population Mind In our development plans, we certainly are focused on execution of our studies Mind we'll certainly be watching and observing, but don't know that we see a direct impact Thank you.

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

Congrats on the progress Mind thanks for taking the question. The question is on for the Phase three trials in GAD, how much of a risk is there that some of those patients during the twelve week randomized phase go on to take another therapy And then if that does happen, then it might happen more so in the placebo patients. And then if that situation were to occur, how does that get handled by the stats plan? Thank you. Yes. Thanks so much, Joel.

We certainly 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 includes as a monotherapy includes taking no other pharmacotherapies during the twelve week randomized period and really throughout the duration of the study. So we monitor that very closely and and for patients who do violate that criteria. Is addressed in the statistical analysis plan. I don't know that we are prepared today to go through the specifics of that plan Mind had a great collaboration with FDA and development of our Cisco analysis plan for both of the Phase three studies. So But we certainly monitor it very closely Mind try to ensure adherence to the protocol at every site and had great success historically in our engagement with these sites so far.

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

Thanks for taking my question.

I have a question regarding the MDD indication. Given the competitive landscape, Thank you, Dennis. How important is MDD indication for MM120 to compete with other academic products And when should we expect updates on the timing and the design of the second MDD study? [indiscernible] Thanks so much, Rudy.

Our overall, I think, looking focusing on overall development plan for MM120, we just see such a broad and massive market Mind opportunity to help potentially millions of patients and having the broadest label certainly enables us to hopefully if the drugs approved market to that broader population and hopefully gain access and ensure that we can help as many of those patients as possible. So when we think of psychiatry, we think of some of the major neurotic illness in psychiatry having a label that covers both GAD and NDD effectively means that a patient coming in the door with either cluster of symptoms would be on label candidate for the product. And as we look around the landscape with many other therapies focus exclusively or primarily on treatment resistant depression. It's just a strategic difference in how we've approached the opportunity and what we think of in terms of the expansiveness of both the market and and patient opportunity, how broad of an impact we can have. And that's informed everything from the selection of GAD where there's been so few therapies in the last twenty years Mind overall there's far fewer treatments available for dry eye disorder.

Than for MDD. But also in our plans to go after these really significant Mind large populations we're not in our view be able to set us apart Mind maximizing the patients we can help.

Very helpful.

Thank you. Our next question comes from Sumant Kulkarni with Canaccord Genuity.

Your line is open.

Good morning. Nice to see the progress Mind thanks for taking my questions. I have two. The first one is, given you have breakthrough therapy designation for MM120, the 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? Yes. Thanks so much, Sumein.

As you mentioned, with breakthrough therapy designation, we do have frequent interactions with the agency Mind on various topics including clinical Phase three program, but also clinical pharmacology and CMC and other aspects development program that are just as important to ensure the quality and the adequacy of our data support submission, hopefully an approval. We think very highly look at FDA has strong partners With us from the outside of our program, but especially as we've received a breakthrough therapy designation over the past year and brought on a an incredible regulatory team who's just successfully interacted with the division extensively in the approval of Kobensi Accurit Therapeutics, so we've been really encouraged by the level of engagement and the thoughtfulness and the thoroughness with which the division and the agency more broadly has engaged with our program and feel a high degree of alignment and consistency in our in our approach with the expectations that we're hearing. So we've been really encouraged Mind certainly there's been lot of coverage of the disruption in Washington and all that's happening there. Fortunately, at this stage, our interactions with FDA have not been changed in any way and we've continued to I think watching the division of psychiatry really go out of their way Mind and go to great lengths to to be constructive and highly engaged with us.

Got it. Thanks. And if we also if we fast forward to a time when other psychedelic agents that involve shorter times in the clinic might become competitors at a time when MM120 is approved as well.

What would the key point be in favor of MM120 versus a deuterated DMT, for example, with the knowledge that we haven't really seen Phase two data on that molecule [indiscernible] [indiscernible] with fifteen million patients that we might be able to treat with both the indications we're going after, There are more than enough patients for many new treatment modalities, but some of the things we've been really encouraged by are both the the magnitude and the durability in large and well controlled well conducted studies where we are exceeding a robust placebo by more than double the standard of care. That's not something we've seen broadly with the field. And there's also in our market research, there's some site economics that play into this where a treatment that requires a high degree of patient throughput can be problematic for these sites of care. I mean, look at clinics that deliver SPRAVATO and and many of these clinics have to turn over the room four or five times a day which they're being reimbursed on an hourly rate in many instances. [indiscernible] becomes a huge administrative burden and quite inefficient economically for these sites. So Well, I think at face there have been some assumptions made about the duration of various products, we have been at every turn really encouraged Mind highly convicted about our approach and what that will mean for sites of care and patient access. [indiscernible] Thank you.

And our next question comes from Patrick Truce with H. C. Wainwright and Company. Your line is open.

Thanks. Good morning. A couple of follow-up questions from me. So So clearly with the Phase three trial in anxiety, it's primary endpoint is Ham A. I'm just wondering which secondary endpoints things like function or quality of life could be in important from both a regulatory as well as a payer perspective. Secondly, I'm curious if you can discuss some of the HEOR health economic outcome research that's been conducted Mind what further research that you plan to conduct in order to further after it's potentially approved. And then just lastly, I think the Phase 2b trial, I think, showed an eight point improvement on the HAM A relative to placebo. I'm just curious how the learnings from that trial kind of led to the powering for the Phase three studies in GAD, but as well I'm wondering I know that data was collected on the MADRIS and how learnings from the Phase 2b trial are influencing the Phase three trial Mind MDD? [indiscernible] Yes. Thanks so much, Patrick. So To your first question, we're certainly looking at a number of additional secondary outcome measures in the Phase three program. One that is of interest to us is CGI.

Which is overall disease severity and patient functioning score. And so that is one that we're quite interested in. And The time points we're interested in for the MAA, the primary outcome measure In terms of the HER research, we've done extensive research several of those studies, which we've now presented pro posters and are our advancing publications for. So that covers everything from I think when you look at GAD, there's been such a focus shift in the last twenty to thirty years away from anxiety, which for a long time is a predominant focus of psychiatry. There's been such a shift to major depressive disorder. We all remember the everyone worries But depression is a chemical imbalance in your brain as your commercial from the 1990s with the advent and introduction of SRIs that led to a pretty massive diagnostic drift and for tools for depression being rolled out pretty substantially. So over that time, the burden and the prevalence of GAD has grown and now affects as Dan mentioned when we look at the broad epidemiological data and the research we've done, there's a significant portion of the population that is walking around with moderate or severe symptoms of generalized anxiety disorder that is never been diagnosed Mind presumably just think that's how life is.

It's how human experiences. And so a lot of our work so far is focused on that prevalence and also on the impact on quality of life and on economic parameters like workplace productivity, absenteeism, presenteeism, the overall economic burden on these patients. And we have an incredible market access and HUR team that is continuing this work and that allows us to also trying to make arguments for the value of a product Mind we really see that value come through overwhelmingly when we look at the magnitude of remission that we can achieve after a single administration that is durable for many months, the math becomes really remarkably favorable in terms of the health economics for a treatment such as this. On your last point, so as you mentioned, seven point seven unit improvement over placebo for the one hundred microgram dose in Phase two. Mind I think it's notable there that that was an improvement over about a 14 placebo response. About around 40% larger than the historical average in GAD. Most SRI studies had a placebo response of about 10 units. Now We've assumed, as Dan mentioned, 90% power [indiscernible] based on a five point improvement over placebo I think that's a fairly conservative assumption, especially when you consider that the Phase two study included five arm, four of which were a dose of active drug, And in the Phase three studies, we are doing a head to head or a three arm study where based on a broad body of research Mind the clinical trial methodologies, we would expect that to potentially reduce the placebo response.

So we've been quite conservative and we also have the sample size re estimation to make sure we don't lose that power in this study conduct. But certainly feel quite confident in the strength of that powering in the probability of having a successful study if we a clinically meaningful response of placebo?

Right. That's really helpful. And if I could just one additional question Just I'm wondering how you're measuring the long term durability of MM120 in Part B of the studies? And do you need that data in order to be able to submit for approval? Or could you submit with the I think the twelve week data, would that be sufficient?

Yes, great question. I mean, we're not in a position today to speak to what would be acceptable for the application. But certainly, if you look back at historical precedents for depression and anxiety drugs, the outside of durability has been required for almost all products has been So the anxiety has been between four and twelve weeks of activity. So that's quite encouraging that we have such a long and extensive precedence there. In terms of characterizing the durability response, we're looking at beyond the twelve weeks and in the nine months extension period with the opportunity for open label treatment. So a few things there. One is that until a patient and importantly until a patient actually takes the open label product in that extension period they're still Mind. Right? They aren't told at the end of twelve weeks what treatment assignment Mind we don't at any point in the trial until everything is completely done, where we'd be unwinding on a per patient basis. Now we can do Importantly, group level on blinding and primary analysis once we get through twelve weeks because that has no impact on the study. But for patients who continue into the extension phase, until they take open label drug, they remain blinded.

And so could look at things like a capital Meyer curve for the durability of response after a single treatment at baseline and presumably will be a higher rate of relapse or inefficacy for patients who never respond in the placebo arm and there is likely we would expect to be a longer period before an open label treatment is administered for patients who receive M124 before they versus placebo at first dose. And so we're looking at a number of characteristics there, both to [indiscernible] beyond twelve weeks after a single treatment Mind then the use patterns and the durability Mind subsequent response if patients do administer an open label treatment in the follow-up period?

Great. Thanks so much.

Thank you. Our next question comes from Michael Okunovich Hey, guys. Thank you so much for taking my questions today Mind congrats all the progress you've made. [indiscernible] one quick question here on runway and capital use. You guys have done a fantastic job managing your balance sheet so far. You do have two Phase IIIs ongoing and a third launching in major depression And the conventional wisdom there would suggest you would need a confirmatory study in MDD as well.

So would you expect a confirmatory in MDD to be lost concurrently with your other programs? And is this something you consider in your current runway [indiscernible] Yes. Thanks so much, Michael. We certainly Consider all of our development plans across all of our programs in our financial productions and guidance for cash and runway.

Our approach in major depressive disorder is such that as we said, we're not in position to comment on the exact precise timing or design of the second study in MDD today, we have had constructive progress in our overall planning for our program and our assets Mind certainly excited to share that data at a future point in time. And that will be informed by some of the progress in our ongoing Phase three studies Mind regulatory interactions. Certainly one of the attributes in our execution of our program is the ability to continue sites and efficiently keep them going in terms of screening and enrollment. So we're certainly mindful of the operational of when we start studies, but also being financially prudent and responsible managing our cash expenses over the the conduct of our Phase III program. All right.

Thank you very much. And once again, congrats on all the progress Thank you. This concludes [indiscernible]