Mind Medicine (MindMed) Inc (MNMD) 2024 Q1 法說會逐字稿

Good day, and thank you for standing by.

Welcome to the MindMed Q1 2024 Earnings Conference Call.

At this time, all participants are in a listen-only mode.

After the speakers' presentation, there will be a question-and-answer session.

(Operator Instructions) Please be advised that today's conference is being recorded.

I would now like to hand the conference over to your first speaker today, Rob Barrow, CEO of MindMed.

Please go ahead.

Thank you, and good afternoon, everyone.

Welcome to our first quarter 2024 financial results and corporate update conference call.

The press release reporting our financial results is available in the Investors and Media section of our website, and our quarterly report on Form 10-Q for the quarter ended March 31, 2024, is being filed today with the Securities and Exchange Commission.

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, including our annual report on Form 10-K and our Form 10-Q being 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 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 8, 2024.

MindMed disclaims any obligation to update such statements, even if management's views change, except as required by law.

Joining me on today's call are Dr. Daniel Karlin, our Chief Medical Officer; and Dr. Francois Lilienthal, our Chief Commercial Officer.

Earlier today, we announced the transition of Schond Greenway, who as of May 3rd is no longer serving as our Chief Financial Officer.

On behalf of the Board and the company, I want to thank Schond for all of his hard work and dedication to our mission over the past two years and wish him the best of luck in his future endeavors.

We've retained an executive search firm to assist in identifying a new Chief Financial Officer to support the next phase of MindMed's growth and evolution.

Moving back to our first quarter results.

We are excited to be providing this financial and business update during this important period for MindMed.

It's been a fantastic start to the year and a highly productive quarter for MindMed, which was highlighted with the positive 12-week data from our Phase 2b clinical trial for MM120 in the treatment of Generalized Anxiety Disorder, or GAD.

Alongside the data, we were thrilled to announce that FDA designated MM120 as Breakthrough Therapy in the treatment of GAD.

This designation is reserved for therapies that are intended to treat a serious or life-threatening condition, and for which preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies.

We believe receiving this FDA designation in the positive Phase 2b trial data, we shared reinforces MM120's potential as an emerging best-in-class product compared to today's standard-of-care.

On the heels of the MM120 data in March, we completed a successful oversubscribed underwritten offering and concurrent private placement, raising approximately $175 million in gross proceeds before deducting transaction fees and other offering-related expenses.

Participants in the offering included some of the most respected Blue-Chip Institutional Healthcare investors, which we believe further validate the great work that we have been able to achieve over the past year.

Most importantly, this financing puts MindMed in its strongest financial position ever and we expect that it will fund the company through important development milestones for MM120 and other programs in our pipeline.

Finally, we announced several scientific posters and presentations that we have shared at various medical meetings.

In April, we presented posters at the European Psychiatric Association's 2024 Congress in Budapest, Hungary, and then Anxiety & Depression Association of America 2024 Conference in Boston.

This month, we presented detailed results of the American Psychiatric Association's 2024 Congress and at the International Society for Pharmacoeconomics and Outcomes Research.

These poster presentations cover data from our Phase 2b trial of MM120 and GAD, as well as studies related to the epidemiology and growing burden of GAD, which we believe remains underappreciated.

Additionally, our collaborators from University Hospital Basel will be sharing one year follow-up results from a Phase 2 Investigator-Initiated study of Lysergide in the treatment of anxiety disorders at a Society of Biological Psychiatry 2024 annual meeting being held May 9th through 11th in Austin, Texas.

Overall, increasing our visibility at these key scientific meetings represents an important strategic initiative for MindMed in 2024 as we look to expand awareness of our work and build MindMed's profile within the scientific community.

Our progress comes at a crucial time with an urgent need for better treatments to address the epidemic of brain health disorders, a situation that has grown significantly worse over the past several years.

In our lead indication, GAD for example, a recent mental health prevalence study that was prepared for the Substance Abuse and Mental Health Services Administration, found that 10% of US adults report having symptoms consistent with a GAD diagnosis, making it the second most common mental health disorder among adults 18 to 65 years old.

In comparison to historical studies of the prevalence of GAD, the condition appears to have tripled in the last two decades alone.

Our MM120 program in GAD has seen extraordinary progress over the past year, culminating in the four-week data from our Phase 2b trial that we announced in December 2023 and the subsequent positive 12-week follow-up data that we shared in March.

Results have exceeded our target product profile for MM120, demonstrating a significant improvement in all analyzed endpoints for up to 12 weeks after just a single dose and without any additional therapeutic intervention.

We believe these results demonstrate the fast acting and durable clinical activity of MM120, along with its favorable tolerability profile.

In the context of currently available therapies for GAD, these data represent a major step forward in a field that has suffered from practically no innovation in the past 20 years.

The Cohen's d standardized effect size of 0.81 in the 100 microgram dose group at 12 weeks is more than double the estimated effect size of the current standard-of-care for GAD, which are estimated to have effect sizes below 0.4 on average.

We believe this result can wholly be attributed with the standalone effect of MM120, as the trial was conducted in the absence of any other therapeutic intervention.

We also reported results from our MM120 PK Bridging trial, evaluating the MM120 orally dissolving tablet or ODT formulation that delivered upon our clinical aspirations for the new product formulation.

The ODT formulation provides numerous benefits including extending MM120's intellectual property profile, as well as product performance benefits such as enhanced bioavailability and increased area under the curve, a therapeutic concentrations that further differentiates MM120's clinical profile.

Overall, the characteristics of the ODT formulation demonstrated in the PK Bridging trial offer what we believe is compelling evidence for its differentiated clinical profile and supports our decision to progress the ODT formulation into Phase 3 development.

With this exciting progress, we believe we've successfully achieved the goals of Phase 2 development for MM120 and expect to advance MM120 into pivotal Phase 3 clinical trials for GAD.

We anticipate having an End-of-Phase 2 meeting with FDA in the second quarter of 2024 to align on the scope of our Phase 3 development program and to initiate our Phase 3 clinical program in the second half of 2024.

Additionally, based on the promising data we have observed for MM120 and indications beyond GAD, such as depression, we are actively evaluating additional clinical indications and believe the overall development program for MM120 may represent the best-in-class treatment for GAD and beyond.

As we build momentum in development of MM120, we are also strategically enhancing our focus towards commercial planning.

As you may recall from our Analyst Day in March, market research shows strong enthusiasm for MM120 with 74% of surveyed healthcare practitioners, indicating that FDA approved psychedelic treatments will change their approach treating anxiety and depression.

This positive sentiment aligns with the success of Johnson & Johnson's SPRAVATO or intranasal esketamine, which is rapidly approaching blockbuster status.

SPRAVATO's impact extends beyond its own use case, as it has helped pave the way for the interventional psychiatry model.

This established model includes well-defined patient care reimbursement pathways, REMS documentation processes, and logistics infrastructure, all of which we believe can be readily leveraged for MM120 is successful in clinical trials and ultimately approved by the FDA and marketed.

Our second lead program is MM402, which is the R-enantiomer of MDMA.

We believe MM402 holds promise for its potential prosocial effects and favorable tolerability profile versus racemic MDMA, or the S(+)-enantiomer.

The focus of our MM402 program is to develop a regularly administered product that treats the core symptoms of Autism Spectrum Disorder or ASD, in particular social communication difficulties.

Remarkably, despite the significant and increasing prevalence of ASD, there are currently no approved therapies specifically targeted at its core symptoms.

With robust preclinical evidence supporting our approach, we have initiated our first clinical trial of MM402, a single ascending dose trial in adult healthy volunteers in the fourth quarter of 2023.

This Phase 1 trial is intended to characterize tolerability, pharmacokinetics, and pharmacodynamics of the MM402 and will enable further clinical studies to characterize the effects of repeated daily doses of MM402 and the exploration of early signs of efficacy in the ASD population.

Concurrently, our collaborators at UHB conducted a comparative Phase 1 pharmacokinetics and pharmacodynamic trial of R/S-racemic MDMA, with data anticipated in the second quarter of 2024.

We believe that the results from this trial will expand and expedite our understanding of MN402's pharmacological profile as we progress into later stage clinical development.

We will now turn to our financial results for the quarter ended March 31, 2024.

As of March 31, 2024, the company had cash and cash equivalents totaling $252.3 million compared to $99.7 million as of December 31, 2023.

We believe that our cash and cash equivalent will be sufficient to fund our operations into 2026 based on our current operating plan.

For the quarter ended March 31, 2024, net cash used in operating activities was $16.6 million compared to $13.3 million for the same period in 2023.

Research and development expenses were $11.7 million for the quarter ended March 31, 2024, compared to $12.6 million for the same period in 2023, representing a decrease of $0.9 million.

This decrease was primarily due to decreases of $0.6 million in expenses related to our MM402 program, a decrease of $0.5 million in expenses related to preclinical activities, partially offset by an increase of $0.3 million in internal personnel costs as a result of increasing research and development capacities.

General and administrative expenses were $10.5 million for the quarter ended March 31, 2024, compared to $8.3 million for the same period in 2023, an increase of $2.2 million.

The increase was primarily attributable to increased stock-based compensation expense of $1.1 million and an increase of $0.7 million in personnel-related expenses due to an increase in headcount to support the growth of our business.

Company's net loss for the quarter ended March 31, 2024 was $54.4 million, compared to $24.8 million for the same period in 2023.

This increase was primarily due to changes in the fair value of the 2022 US Dollar Financing Warrants of $27.7 million.

In conclusion, this is a very exciting time for MindMed.

We believe the data on MM120 and GAD that we shared validates our scientific understanding of MM120's mechanism of action and shows the potential for an emerging best-in-class product profile compared to today's standard-of-care.

We are excited to be on the cusp of moving forward into Phase 3 with this program, which we currently expect in the second half of the year following our anticipated End-of-Phase 2 meeting with FDA.

Before concluding our call, I want to extend my sincere appreciation and gratitude for the critical work and unmatched execution that has brought MindMed ever closer to realizing our mission.

I would like to thank our highly talented and deeply committed team, our research collaborators and clinical investigator teams, our investors, and the many other individuals who have been supportive, including especially our patients and their families.

We are working tirelessly to deliver on the therapeutic potential of our pipeline and to transform the treatment landscape for the many individuals living with brain health disorders.

With that, I'd like to thank you all again for joining us today and I'm happy to take any questions.

Thank you so much.

At this time, we will conduct the question-and-answer session.

(Operator Instructions) Rudy Li, Leerink Partners.

Thanks for taking my question.

Congrats on the progress.

So Lykos just announced that the FDA is hosting an AdCom meeting for its MDMA therapy in PTSD.

So can you maybe talk about the implications to MM120 and just curious what are the key topics that you are looking at for this AdCom meeting?

Thanks.

Yes.

Thanks so much, Rudy.

I'll start it off, and then certainly invite Dr. Karlin to comment as well.

We certainly I think as a shield and we as a company expected Advisory Committee for any first [entering a] drug class, I think it's important to draw a clear distinction between the mechanism of action that the methods of how MDMA is administered in Lykos clinical program for PTSD and the distinct way in which MM120 is being developed and studied.

But generally, we would expect there to be an Advisory Committee for novel treatments such as this.

So I think there's been some commentary publicly and trying to read into this.

I don't think there's much to be read into in all of us across the board and if you don't expected this to be occurring.

In terms of subject matter, certainly we would be following very closely and looking to understand points of interest for the Advisory Committee and we've seen the ICER report on Lykos program.

We have intentionally from day one designed our program to answer many of the key questions that have been presented in our field and that are covered in FDA's guidance.

And feel very confident that we will continue to demonstrate some best-in-class scientific rigor and approach to addressing those questions.

But certainly we'll follow the areas of interest from the Advisory Committee members and look forward to hopefully a successful outcome for Lykos and MDMA.

Thanks.

Super helpful.

Thanks, Rudy.

Brian Abrahams, RBC Capital Markets.

Hi.

Good afternoon.

Thanks for taking my questions.

At the recent APA presentation, you showed some trends over time in both HAM-A and PGIS.

And it looked like, directionally they were similar, but maybe there were some subtle differences there.

I was wondering if you could talk about that.

And just I guess how that's impacting what your base case is here for the durability of the administration based on both this and other evolving data?

And then secondarily, I think, the matter has changed here.

I think really underscores what could be potential antidepressive effects.

And so I know you sort of alluded to it a little bit in the prepared remarks.

But I'd be curious to hear what -- more specifically what some of the factors that you guys are going to be considering in determining whether or not to move this forward in a major depressive disorder or other depression indications.

And I guess how you're thinking about what the potential indications might be there?

Thanks.

Perfect.

Thanks so much, Brian.

I'll turn it over to Dan to talk about your first question.

Then I'll maybe address the second one.

Dan?

Yes.

Absolutely, and thanks so much for the question.

So when we look across all of the different measured data that we've shown publicly so far, what we see is directional agreement and to a very large extent, magnitude agreement as well.

So in general, each of these different scales gives us confidence in the different domains that they pick up, that the effect we're seeing is real, is not an artifact of one particular scale or one particular method of administering a scale.

Of course, CGIA collected by a blinded-rater is going reflect slightly different things than PGI, that maybe more determined by a patient's individual experience in the treatment.

But particularly the fact that we're seeing week-12 slight degradation on the PGI doesn't give us any concerns about the robust activity of the drug, particularly since we're seeing such strong significance across the clinician rated measures.

Rob, do you want to speak to that or just you want me to?

Yes.

Absolutely.

Thanks so much Dan.

And I would just note too on that first point, Brian, that obviously the Hamilton Anxiety Scale is the gold standard for any sort of anxiety approval.

So that's where we're going to be focused and our dialogue with FDA.

Again, look, while we talked about the pairwise comparisons here, we have to remember that it was a large 200 patient study.

We had robust power and statistical conclusions on the HAM-A.

So then we're looking at secondary endpoints and looking at pairwise comparisons, we're talking about around 40 patients per arm in the Phase 2 study.

So that has progressed and look at the numerical changes even those would be likely to be statistically significant if we saw the same effects in a larger population.

In terms of the depression indication, something we've alluded to and spoken about before publicly, which is that we're actively assessing additional indications.

I think as we look at the landscape in psychiatry and really look at the promise of this drug class and the kind of magnitude that we believe we can achieve in terms of really changing the direction of what we've talked about a lot is the epidemic of brain health or mental health in this country.

Depression, anxiety have such a strong overlap and interplay and looking at major depressive disorder and other related indications makes quite a bit of sense, of course, as we think about how -- getting the drug in the hands of clinicians and making sure it has the opportunity for the broadest impact and broadest uptake.

So we'll provide guidance at the right point in time if and when we come to a determination on the exact indication and clinical development plans for any subsequent clinical indications.

But obviously with the major scores, it'd be -- it's hard to overlook the magnitude of response we saw on the potential antidepressant effects in our Phase 2 study, building that on top of prior study from our colleagues showing a 16-week durable effect in major depressive disorder.

There's obviously we think an opportunity there and something that we'll be looking at very closely and giving further guidance on the future.

Got it.

Thanks so much.

Charles Duncan, Cantor.

Hi.

This is Elaine on for Charles.

Thank you for taking my questions.

Just going back to your presentation at APA, I'm just curious, what feedback did you receive with the KOLs?

Was the 12V durability the most important, and also what was the perception towards the improvement in matters?

And I have a follow-up on 402?

Thanks so much, Elaine.

Yes, I'll turn it over to Dan to address that one as well.

Yes.

Thanks, Elaine.

We get feedback of all different types and certainly different folks are focused on different aspects of the efficacy.

I think for clinicians who are on the ground treating people with GAD, the rapidity of effects.

So the fact that we saw strong clinically significant and statistically significant changes on scales that are measurable as soon as day two was particularly notable.

And then, of course the durability as you suggested, there are folks who look at this and take those two in combination to say that it really does look like we are eliciting a rapid and durable drug effect, which is unlike other tools that folks have available to them.

So across the board, very warmly received and folks are appropriately excited to see these data.

Okay.

Got it.

Thank you.

And for 402 pending favorable PK profile and tolerability from the Phase 1 trial, what do you envision 402’s target product profile to be for ASD?

Yes.

At a high level certainly with no approved therapies to treat core symptoms of autism spectrum disorder, the ultimate goal here is to have a regularly administered treatment that would aid in the core symptoms and social communication deficits in autism.

The analogy we like to draw often is the equivalent of how psycho stimulants are used to treat ADHD, such that while the drug is having its pharmacological effects with psychostimulants, patients are able to better focus and have better -- and better participate in occupations.

And the same would apply obviously through different mechanisms in targeting a different disorder.

But in autism, the social communication deficit, the core of autism and that the FDA patient workshops have described as the target for pharmacological intervention in autism are social communication deficit.

The very things that for racemic MDMA and we believe potentially R-MDMA will aid in as well.

So the ultimate product profile would be regularly administered product that would aid in an individual's social communication, abilities and would allow them to more readily participate in their daily occupation.

Got it.

Very helpful.

Thank you for taking our questions.

Thanks, Elaine.

Francois Brisebois.

Hi.

This is Dan on for Frank.

Thanks for taking our questions.

Firstly with regard to the planned Phase 3, could you give us some color on how you were thinking about the design of that study?

Any similarities or differences to the Phase 2b and specifically, does the Zydis ODT formulations PK impact the Phase 3 design in anyway?

Yes.

Thanks so much, Dan.

So in terms of planned Phase 3 studies, obviously we're going to reserve sort of final determination of the protocols until as we have our End-of-Phase 2 meeting and reach and complete alignment with the agency on the path forward to those pivotal studies.

But given our interactions to date, we certainly feel we have a high degree of understanding of the right approach there.

And by-and-large, that the Phase 3 clinical trials will be extremely similar, it’s not virtually identical to our Phase 2 clinical trial design, with the exception that we intend to go forward with for purposes of the statistical comparison to the overall design, comparing a 100 microgram ODTs, as you mentioned to a placebo.

The ODT formulation in and of itself has no impact on the design of the Phase 3 program.

We were really encouraged by the PK Bridging results and from what we've seen in that study, both quantitatively and the results we report, but also qualitatively in report talking to the investigators in that Phase 1 study.

But believe that it certainly going forward with a 100 microgram dose, it is optimal in our view and we're particularly encouraged about the prospects as we go into that clinical trial.

So really no impact in terms of study design, but even higher conviction about the clinical potential in that formulation.

Thanks.

That's helpful.

Just one quick one, the new epidemiological data that was presented at APA, could you talk about the GAD-7 screening tool, how that's potentially if that's being used in the next trials and any learnings regarding the market opportunity in GAD based on that new data?

Thanks.

Yes.

I'll mention it first and then turn it back over to Dan to talk perhaps about clinical utility of that -- of the GAD-7.

We certainly are going to be using the GAD-7 and the open label portion of our Phase 3 program to screen patients for potential re-treatment.

So after our 12-week double-blind period, patients will have the opportunity to roll it over into a nine-month open label study where they'll be screened and then if symptoms of GAD are present, didn't have the opportunity for re-treatment.

I think one of the things we've observed in all the epidemiological data and the disease burden in our pharmacoeconomic research is that one of the most costly patient populations are patients who have GAD symptoms, but haven't yet received a diagnosis of GAD and also patients who have received diagnosis of GAD and have severe disease.

As it turns out, the vast majority of patients with GAD have moderate to severe disease.

And in part because the treatments we have available today are not particularly well suited to treating anxiety.

But certainly we'll be looking at GAD-7, our Phase 3 program.

And given the underdiagnosis of GAD, we believe both the tool will become an important tool in the toolbox of finding these patients out in the real world, but also there's a really massive opportunity that's been underappreciated by payers, by providers, and certainly by patients who go many years without a diagnosis.

And that USPSTF's recommendation for using the GAD-7 for screening going forward, really all of this provides kind of a tailwind for what we expect to be the pickup of the overall prevalence of GAD and ultimately a larger population of patients we hope to be able to help.

Dan, I'll turn it over to you if you have anything to add on the clinical utility of the GAD-7.

Yes.

So I mean, what we learned from this epidemiological work was that as we assumed, this is an underdiagnosed condition.

So despite its high diagnosed prevalence, in this particular study, just over 23% of respondents had a positive screen on the GAD-7 and just over 80% of those folks didn't have a diagnosis, had never been diagnosed with GAD.

We learned a bit about the healthcare utilization of these folks who are walking around, likely with GAD, but with undiagnosed GAD.

And obviously there's a tremendous impact on individual wellbeing, individual distress, but also on healthcare costs and cost to employers as well.

What all this adds up to is that it's further evidence in support of the USPSTF recommendations from the past year that folks really ought to be screened.

So the GAD-7 is the equivalent essentially for anxiety disorders of the PHQ-9 for depressive disorders.

PHQ-9 has been used more and more frequently over the past 30 years to 25-ish years to pick up depressive disorders that somewhat to the expensive anxiety disorders.

And so we are strongly supportive of screening for anxiety disorders in primary care settings and other healthcare settings.

What ends up being reflected in the data about the current environment is that folks who weren't diagnosed tend to be younger.

So that in the end, what is likely happening is that people develop anxiety symptoms in their 20s or early 30s.

And then go 10, 15, 20 years walking around in distress without getting a diagnosis and as a result of not being diagnosed, not being able to be treated.

And so we continue to believe that people will benefit from early screening and intervention that gets to the disorder and gets to treatment earlier in the course of illness before comorbidities and other impacts of the illness accumulate.

Thank you.

That's very helpful.

Thanks for taking my questions.

(Operator Instructions) Sumant Kulkarni, Canaccord Genuity, LLC.

Gentlemen, thanks for taking my question of.

So what are your latest thoughts on potentially developing MM. 1,000 for depression?

And would that be a program that the organization is ready to run simultaneously with the pivotal program and GLD and other things you're doing on for oh two, are you focusing on JV with undivided attention until you get more clarity on trial results there?

Yes.

Thanks so much, Sumant.

Yes, no, as mentioned earlier, we've certainly are taking a very hard look at the market dynamics and the opportunity in a depression and related indications.

We have built the company really from the ground up over the past three years and have done so all along the way with the ability to -- with an eye, of course, to executing on pivotal development programs, but also with the ability to take on multiple programs far beyond what's currently in our pipeline.

So the infrastructure and our team and our ability to execute and operationalize multiple programs, the pipeline has been something we've been working towards and been doing over the past several years.

And so we certainly believe and expect that we'll be in a position to execute on multiple clinical indications potentially in parallel.

Now, we never lose focus on our furthest along asset, the furthest along program, which is of course, MM120 and GAD.

But even as we've conceived of operationalizing other indications like for instance potentially in depression, there are many operational efficiencies and quite a bit of overlap.

So we'll be in a position to give further guidance if and when we decide to launch a program in a second indication with 120.

But based on our team's abilities and based on certainly the existing evidence, I believe there's opportunity in depression and a number of other indications in brain health.

Correct.

And as a follow-up, as you plan to hold your End-of-Phase 2 meeting with the FDA, where do you think the most potential for differences between what you might propose versus the FDA's potential outlook might be?

Yes.

I wouldn't want to speak for the agency.

I think, we obviously try to go into any sort of regulatory interaction and we very much have appreciated and it's easily said, but it's very much true and I've had the privilege of working with the agency and position on this drug class over the past five or so years.

And we know they've been extremely thoughtful, extremely productive, and there's always nuance in any drug development program.

But we certainly listen to the conversation, the dialogue we've had in the past follow the guidance and try to make logical, rational, scientific arguments for when there's any sort of particular view that needs to be discussed or hashed out.

So I'd be reluctant to sit to speak for FDA and say where we would expect there to be some particular points of discussion.

But by and large, we think we view FDA as very much as a partner in this and have had a very constructive dialogue date and expect that to continue as going into Phase 2.

Got it.

Thank you.

Elemer Piros, Rodman.

Yes.

Good afternoon.

Rob, I'd like to talk a little bit, if you wouldn't mind addressing how heavily pretreated the Phase 2b population was.

And in the commercial setting once we get there, where do you see MM120 being used, especially considering that there is a large population that is undiagnosed without treatment?

Where would MM120 fit in based on your Phase 2b trial, your Phase 3 design once you agree with the FDA et cetera?

Yes.

Thanks so much, Elemer.

So I'll take the second part of the question first, which is to say, when we conceive of where MM120 could fit in the real world in clinical practice.

I think as a field, there's been some of a constraining of views on the opportunity in a concept that these therapies could only be reserved for the most severe patients who have failed everything else.

And what we're really seeing over and over in the clinical data is that there seems to be a sort of trajectory change.

And so GAD in particular, what we observe is that patients who go undiagnosed and/or have severe GAD end up spending years going to the doctor having other related comorbidities.

And they have a huge impact on their quality of life and also huge impact on the healthcare system.

Now, where the value also comes from, we talk about reimbursement, and we talked about the burden on the healthcare system from a financial point of view are in those patients who go undiagnosed, who have severe GAD, but walk around not knowing that they have severe GAD.

And so we actually see the opportunity is far more expansive than simply that the patients who have failed everything else.

Now, that is not to say that we expect and we're going to be marketing as a first line therapy per se.

We obviously are going to be focused in our commercial activities and certainly believe there's enormous value to be gained by focusing on the patients who have severe -- failed prior treatments and who have severe disease.

But we certainly believe there's a likelihood that patients who are not at the end of their treatment portion and failed everything else could potentially benefit.

And that really also aligns with the data we've been able to generate now.

We see a nice mix that is largely representative of the real world population in our clinical trials.

And so certainly a significant portion of the patients have prior treatments and have failed numerous prior treatments.

When we look at slices of the data, we don't see a meaningful difference between response regardless of treatment history, which again, I think in depression there's a much better definition of treatment resistance and focus on only this last line patients.

But in GAD, it's somewhat of a different dynamic that we think is more favorable both from a business standpoint and from a clinical impact standpoint.

Yes.

And do you think that there is a difference between the journey of a patient, newly diagnosed than try different sort of medications in with primary diagnosis is depression as opposed to GAD?

And if you could address what sort of physicians one versus the other would see before they get some significant help, if ever?

Yes.

I'll turn that over to Dan to maybe address initially and happy to extend on that.

Dan?

Yes.

Happy to try to address.

And I think it's a really good question about the patient journey.

I think what we have to remember when we think about the differences between MDD and GAD is that while they are very much overlapping diagnoses, MDD is episodic, it's a cyclical illness with periods of depression interspersed with periods of euthymia or normal mood.

And so folks falling into a state change going from their sort of usual state into a depressed state, maybe more likely to seek care earlier in the course of the illness.

And what we're seeing as we dive deeper and deeper into the epidemiology of anxiety disorders and GAD is that the insidious nature of the onset of GAD may lead folks to be seeking care later to sort of to acclimate to this new way of feeling.

And even though they're in distress, not necessarily see it as a target that they would want to raise with a clinician.

With both of these conditions, the patient journey very often starts with primary care.

Folks have more contact with their primary care doctors if they're not regularly seeing a psychiatrist, or other psychiatry provider.

And often first line treatments are given at the level of primary care, again, partly due to availability of specialty psychiatric providers, who can prescribe.

So things like SRIs, as a starting point have moved toward primary care for both depression and anxiety or depressive and anxiety disorders as folks show themselves to either be more severe or to be more resistant to treatment to not sustain benefit or to have intolerable side effects with first line treatments is generally when folks enter the psychiatric care system.

But what we know is that these patterns are driven by treatment availability.

It was the commonality that the frequent prescribing, the familiarity with SRIs that brought them into the primary care setting in a way that previous antidepressants maybe weren't as comfortable for primary care doctors, [MAYs] and things like tricyclic, which are more difficult to prescribe.

And so while we can reflect on the current patterns of care, journeys of care where people are getting what sorts of care.

The availability of different treatments changes those patterns.

And so while -- we absolutely think about how things happen today, we're also very much oriented toward creating a world that is built to an extent around what we're able to bring to bear on these disorders.

Then just a little follow-up here, if you don't mind.

So some people believe that a psychedelic medicine treatment would only be prescribed by a specialist.

I'm not sure, because after all, whether you're a general practitioner or a specialist, you are not going to administer these therapies.

They are going to be administered at specialized centers, so you're not going to be necessarily directly involved in the actual treatment.

Do you agree or disagree with this line of thought?

I think there are parts of that that we absolutely agree with another parts we might push back on a bit.

So that the sorts of prescribers who are comfortable prescribing any given medication will have everything to do with the sorts of data we're able to generate around efficacy and safety in appropriate patient populations, appropriate assessments for pre-prescribing.

And in many cases, perhaps the prescriber, the prescribing healthcare provider will be affiliated with or possibly even involved with the actual administration of medicine, possibly with the help of lower level providers.

There are many cases we can imagine where the prescriber and the ultimate session monitor may not even be affiliated with one another that they can be identified individually and that while what we've seen for interventional psychiatry today is largely centered around specialized centers.

This has to do as much with the need for physiological monitoring and medical certification as it does with actual safety and appropriateness of location.

We didn’t see physiological liability in Phase 2b which we believe will begin to open up the possibility that we can build the body of evidence that the types of places where MM120 can be safely administrated might be significantly broader than specialized centers.

So very much considering a range of options where who could be the potential prescribers and who could be the potential session monitors.

Yes.

Thank you very much.

Dan, I'm going to add one comment on top of that, Elemer, which is that I think one of the things we repeatedly want to make sure is fully appreciated is the scale of the potential opportunity here.

And the fact that just because treatment practices today with the tools in the toolbox of practitioners, right?

We live in a world where only SRIs primarily are administered, and they're often doled out first at primary care.

It’s easy for observers of that market to start to say, well, that's the only way it can be done.

And really what we're talking about is a sort of transformational change both at a patient level because of the magnitude and the durability of response we're able to generate.

But also at a level of medical practice where we can actually start to think about having these new tools really reshape the ability to have meaningful impact on patients.

And so doing, opening up the potential opportunity such that this isn't relegated to a very last line of treatment where no one can access it because they have to have gone to a psychiatrist for five years before they're eligible.

We see that as too constrained of a view here and believe that there's a need for a much larger opportunity or need for a much larger view of how we can have a meaningful impact.

Yes.

May I just add one other aspect, and I'm sure that a specialist, a psychiatrist spent a lot of time to manage the side effects or manage titrating those drugs or replacing with another one.

We don't have this issue with MM120.

Do we?

That's exactly right.

I'll say, I mean, obviously Dan is practicing psychiatrist.

That said, when we talk to KOLs, one of the things that we hear over and over again is the excitement around a drug with a high degree in relative terms of clinical remission that we're able to achieve.

And the fact that those results are driven by both the rapidity and durability of effects such that patient walks in the door with SRIs as you mentioned, Elemer, patient is going to be given the drug and is going to take a number of weeks before the next expected clinical benefit.

And over that time is when we see the adverse events, the side effects of the drug already occurring.

But here what we're seeing is such a rapid response that a follow-up within a couple of days is largely indicative of where the patient at least in our study so far, is going to be months later.

And in large part, if they achieve remission, they seem to stay in remission.

And so that kind of clinical clarity early in the treatment course is something that has high desirability from providers and something that we’ve been very excited to see in our data.

Yes.

But you forgot to mention the headache the next morning.

Well, there's lots of things that are worse for you that give you a headache the next morning.

So we feel very comfortable with the physiological profile.

Thank you.

Thanks, Elemer.

Patrick Trucchio, H.C. Wainwright & Company.

Thanks.

Good afternoon.

I have a couple of follow-up questions.

The first is on the new epidemiological data presented APA.

Just in terms of the potential impact on commercialization of MM120 and GAD, I'm wondering if you can talk about the prospect or possibility of having this validated GAD-7 screening tool more widely deployed in the real world healthcare setting as part of this potential commercialization.

Secondly, if this data itself is helpful or can be built upon as part of health economic outcomes research, or is there some other use for it that could be beneficial for the potential launch of MM120?

And then separately, just there's some UHB data upcoming.

So I was wondering first if you can give us an idea of potential read-through regarding durability of treatment we should expect from the Phase 2 UHB data being presented to Society of Biological Psychiatry and whether or not findings in that study could impact discussions with the FDA regarding the MM120 Phase 3 program and what way could that data maybe helpful to you?

And then separately regarding MM402, can you talk about the potential read-through from the UHB Phase 1 trial to your program and how you think about next steps for MM402 and ASD assuming a positive outcome from your SAD study?

Yes.

Thanks so much, Patrick.

So I'll try to take these one by one.

So certainly in terms of the prevalence, all that we've been talking about the underdiagnosis of GAD.

The fact that there is a tool that can we believe validly pick up GAD that is yet to be diagnosed.

The fact that that is now being recommended for implementation and is not been fully implemented suggest to us that really what we're seeing in terms of current epidemiological data is just the tip of the iceberg.

The market is actually much, much larger than we're seeing in the statistics today or from the last several years.

That obviously has a huge impact from a health and societal level, but from a market opportunity, of course, means that the market maybe orders of magnitude larger than we're expecting based on current epidemiological data.

And that aligns with certainly what we hear and hear from clinical practitioners that we absolutely actively are working on HEOR, health economics research to quantify the scale and the scope of the impact that we can ultimately see here.

And to demonstrate the value proposition to all of the key stakeholders who are going to need to be aligned to enable the broad uptake of our product.

So something we're actively engaged in, have a really talented group that's working on that.

Potential read-through of the UHB study.

Certainly as we look back over the past couple of years, we initially had investigator-initiated data on lysergide, again, different dose and regimen.

But that demonstrated the durable effects out to really about six months after treatment for patients who got LSD or lysergide first.

And in this study we now have follow-up even further with those patients.

So as we've conceived of the Phase 2 result that we were able to achieve, we've also seen largely in terms of HAM-A symptoms -- HAM-A scores a sort of flat lining where we didn't see a regression back to baseline or worsening of symptoms on average over time.

And so if we ultimately are seeing those effects granted in investigator-initiated smaller studies, but if those effects that are shown to be durable for many months longer, I think (inaudible) think it bodes well for the potential of what we'll be able to demonstrate as we go forward into to longer studies like our open label study that's planned for Phase 3.

And similarly within MM402, of course, it's very difficult to have read-through from a healthy volunteer population into a disordered population in terms of results from a Phase 1 study.

But certainly the understanding will have in terms of some of the mechanisms underlying the activity of MM402, the demonstration of tolerability and sort of AE profile that we'll be able to report out and observe within MM402 up the doses of 250 milligrams and will be certainly encouraging for us.

And it won't be informative as we continue to design our program.

But again, it's hard to -- we don't want to overextend the interpretation of healthy volunteer data, when we talk about going into to Phase 2 and later research.

That's helpful.

Thank you very much.

Thanks, Patrick.

Thank you.

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