Good morning. Welcome to the MindMed Conference call and webcast. As a reminder, if you are a covering analyst, please make sure to join the link that was emailed to you this morning by Laura McCormick instead of the public link found on the MindMed's IR site so that you can ask a question when we get to the Q&A portion. In order to ask a question after joining from that link, please click on the Raise Hands button, which can be found on the black bar at the bottom of your screen. You may remove yourself from the queue at any time by lowering your hand. I would now like to turn the call over to Rob Barrow, CEO of MindMed.
Thank you all for being here today. We're very excited to share several updates from our lead program, MM120, which is being developed for the treatment of Generalized Anxiety Disorder, or GAD. During today's call, we will be making certain forward-looking statements. Please take time to review the disclaimer on slide two, which includes important information about these forward-looking statements. I'll start off today by making some introductory remarks. We'll then be joined by Dr. Rakesh Jain, who will be providing a perspective on the unmet need in GAD and our phase II-B trial results. This will be followed by a presentation by our Chief Medical Officer, Dr. Daniel Karlin, who will review a summary of the full top-line results from our phase II-B trial of MM120 and GAD and our ODT pharmacokinetics bridging study. Dr.
François Lilienfeld, our Chief Commercial Officer, will then provide comments on the commercial opportunity for MM120, and we will conclude with summary remarks about the MM120 development plan going forward. As we have advanced the organization over the past several years, we have embraced an unwavering commitment to bold, disciplined, and science-driven leadership, putting patients and their loved ones at the center of everything we do. We aim to rethink the treatment of brain health disorders for the millions of patients in need by executing thoughtful, rigorous science to deliver scalable treatments in areas of major unmet need. The past 12 months have been transformative for MindMed as we've delivered best-in-class execution and outcomes.
Building on our progress, this is a year that we aim to move Lysergide back to the front and center of the brain health pipeline, something that patients in the field at large have been waiting for over 50 years. Behind this critical mission is a team of experienced leadership and drug developers with a proven track record in developing and launching novel products in brain health and other high-impact areas of medicine. Our team has repeatedly set the standard for the field with respect to speed, quality, and efficiency with which we have executed our programs, and we could not be more excited about the path ahead of us. The need and opportunity for MM120 to potentially provide a new best-in-class treatment option for GAD patients could not be greater.
GAD is an indication that has been severely overlooked for the past several decades, resulting in a current prevalence of approximately 10% in U.S. adults, a number that has tripled in the last two decades. Of those suffering from GAD, roughly three-quarters have moderate to severe symptoms, and only a fraction respond to first-line treatments. Given the poor efficacy and limited tolerability of these current therapies, new options are desperately needed. Aiming to meet this and other unmet needs in brain health, our R&D pipeline is comprised of two lead assets: MM120, which we are developing for GAD, and MM402, or R(-)-MDMA, which we are developing to treat core symptoms of autism spectrum disorder. We're excited to be sharing several updates from our MM120 program today.
This includes positive 12-week durability data from our phase II-B trial of MM120 and GAD, and data validating the enhanced product profile for our intended go-to-market formulation of MM120, which utilizes Zydis ODT formulation. Additionally, we are pleased to announce that the FDA has granted breakthrough therapy designation to our MM120 program in GAD, a recognition of both the seriousness of GAD and the potential of MM120 to provide a substantial improvement over currently available therapies. Finally today, our Chief Commercial Officer, Dr. François Lilienfeld, will be providing an update on our planned commercial model and strategy for an efficient and scalable launch, should we ultimately obtain FDA approval for MM120. Results from our phase II-B study of MM120 and GAD delivered and even exceeded our target product profile, demonstrating a significant improvement in all analyzed endpoints for up to 12 weeks after just a single dose.
These results support the fast-acting and durable clinical activity of MM120 and its favorable tolerability profile. Uniquely, the results we achieved were reached with no additional psychotherapeutic intervention beyond studied drug. This strong clinical response especially stands out in the context of current standard of care, which is dominated by serotonin reuptake inhibitors and benzodiazepines. These standards of care are characterized by only modest efficacy, with an average Cohen's d effect size of under 0.4, whereas in our phase II-B study, MM120 demonstrated an effect size of 0.81, 12 weeks after a single dose of 100 micrograms. As I previously mentioned, we are excited and grateful for FDA's recognition of MM120 as a breakthrough therapy in GAD. The benefits of the breakthrough therapy designation are many and are intended to expedite the development and review of breakthrough drugs such as MM120.
Additionally, today we are excited to share results from our PK bridging study of MM120 Zydis ODTs. As we embarked on our development program for MM120, we sought to identify and advance a formulation that is innovative, differentiated, protectable, and has an enhanced pharmaceutical and clinical profile. The results from this PK bridging study delivered on that goal, demonstrating that MM120 Zydis ODTs result in 50% faster onset of action and meaningful improvements in both the overall area under the curve and the area under the curve above target or therapeutic concentrations. We're also excited to be sharing further details of our views, model, and strategy for the commercial opportunity of MM120. In our view, all of the ingredients are in place to enable a successful launch and adoption of MM120, should it ultimately be approved by FDA.
This includes a large market of millions of patients suffering from GAD, a best-in-class profile with strong value proposition, and a commercial model that leverages proven pathways and a large and growing infrastructure for interventional psychiatric care. With that, I'm pleased to introduce Dr. Rakesh Jain. Dr. Jain is a practicing psychiatrist in Austin, Texas, a clinical professor of psychiatry and behavioral sciences at Texas Tech University, and is co-chair of Psych Congress, the largest independent mental health education conference in the U.S. Rakesh, thank you so much for being here with us today.
Thanks so much, Rob, for the very kind introduction. Hello, dear colleagues. As you heard from Rob, I am an academic as well as a practicing psychiatrist, and it's my pleasure to offer you my impressions on GAD because this is one disorder that we simply do not pay enough attention to. As I will show you in a second, that really is a mistake that is worthy of rectification. The first thing for all of us to keep in mind is GAD, Generalized Anxiety Disorder, is actually one of the more chronic disorders that afflicts us human beings. Anxiety, particularly anxiety that's focused on multiple issues and challenges that are long-lasting, really creates a profound negative impact in our patients' and their families' lives. The title here says impact, but the truth is it's impact and unmet needs.
While we have had some innovation in the world of GAD treatment, the last one was all the way in February of 2007. That's simply too long for a disorder that is so prevalent. There is, of course, decades of research on LSD and psychiatric disorders that really does support its unique potential. And as you will see in a minute or two, why I am so very excited about it. In terms of Generalized Anxiety Disorder, it actually is a very high-prevalence disorder. These individuals know they're anxious. Their brain, their body, their mind, everything is negatively affected. There's simply no doubt it's a disorder that affects both the mind and the body: irritability, muscle tension, sleep difficulties, restlessness, fatigue, difficulty concentrating. Oh my goodness, it's quite a laundry list. It's, in fact, the second most common mental disorder among adults in the age group of 18-65.
Here's another major challenge regarding anxiety disorders in that the prevalence has gone up. It's actually tripled in the past two decades. I'm also a child and adolescent psychiatrist, and I'm unhappy to report to you we are seeing very large numbers of young individuals with this condition. It's, of course, very often comorbid with other anxiety disorders and major depressive disorder. Oh gosh, in terms of the negative impact on many aspects of patients' lives, the more severe that Generalized Anxiety Disorder is, greater the negative impact on almost every measure of health. So it's not just that they suffer from an anxiety disorder. They actually have an acute deficit of well-being, a deficit in physical functioning, a deficit in quality of life, and sadly, the presence of significant disability.
Those of us who are wise, be it in the world of psychiatry or just the lay world, would do well by respecting Generalized Anxiety Disorder because it's so impairing at so many different levels. I had mentioned before that it's a chronic condition. It really is a chronic condition. Once GAD takes hold of, it rarely on its own leaves. In fact, it often worsens with time and often precedes additional psychiatric disorders. GAD often then becomes the cause of someone developing major depressive disorder. The psychiatric profession often only looks at the end result and doesn't often think about what precipitated the challenge. This is perhaps one more reason why I am particularly excited about this interest in GAD, because I have found that if I go after GAD well, then I help the patient in the long run.
As the mainstream focus on anxiety disorders returns, thank goodness, patients, however, are quite underserved by current medications, and I should know that. I know that because of my background in research psychiatry. I have actually helped develop benzodiazepines, buspirone, SSRIs, SNRIs in anxiety disorders. I must report to you that the actual output from them, in other words, the effect size of these treatments, are not very good. The government, the U.S. government, has also taken a deep interest in it, and they offer a Grade B recommendation in terms of screening for anxiety in adults, including pregnancy and postpartum people. By the way, this recommendation also applies to children and adolescents. Look, I do think the 21st century in America and the world is the century of anxiety. We are an anxious species.
It behooves us to be aware of that and to offer our patients the very best treatment we can. In terms of what patients with GAD really want and how they're not being served, this slide should highlight for you some of the major shortcomings in the field. It gives me great pain to have to report this publicly to you, that we have not made significant progress in terms of GAD treatment. Our current treatments are very slow. They're not durable. They fade out. You have to take them on a daily basis. Limited response, even if patients are willing to put up with side effects and the slog of taking daily medications, they really don't do well. The side effects are enormous: sexual dysfunction, sedation, weight gain, et cetera.
As you can see from these quotes from patients who suffer from GAD, they are telling us an important story: that there is need for a new treatment paradigm, a new treatment approach. Current treatments aren't not only not very effective, they really have a pretty standard course. The patient, after sometimes many years of waiting, shows up to primary care. Sometimes they're referred to specialty care. I'm afraid all they get is oral daily treatment with medications that are not only very effective, the side effects are considerable. You don't have to just take my word on what I just said. Just look around you. The odds are very high in your family and friend circle. There are people with GAD who are sadly tied down by these daily medications with all the side effects.
It's not a good bargain because they end up not getting the very best of help that we can offer. LSD, it's been around for a while, as you well know, and it's been out in the research world for a long time too. Sure, psychiatry took its eyes off the ball maybe 25, 30 years ago, but this is changing. There were actually 21 studies prior to 1974. They were actually quite good. I have looked at many of them. They may not meet the standards of today's research acumen, but it is important to know that this is not just a new interest of psychiatry. We've been actually looking at it for a while.
But some of the modern-day studies, the Gasser study from 2014, the whole studies from 2022 and 2023, both of them, both of them are asking psychiatry and the community at large to give psychedelics, particularly LSD, a very close look. So with that, I thank you very much for letting me describe to you in just a few words that I, as a practicing psychiatrist who deals with patients and does my very best to help my patients with this condition, I need better treatment options. I truly do. The unmet needs are huge. The patient's suffering is tremendous. The current treatment approaches we're offering our patients truly are suboptimal. With that, I thank you very much for your kind attention, and I'm going to pass the baton on to Dr. Daniel Karlin to continue the conversation. Thank you.
Thanks so much, Rakesh. To reiterate what Rob said, we are extraordinarily pleased to report positive 12-week top-line results from our phase IIB study in GAD that demonstrate a strong and durable effect of MM120 12 weeks after a single dose of the drug without any additional therapeutic intervention. The study met all top-line primary and secondary endpoints with statistical significance, and the results establish a clear dose-response relationship for MM120 in GAD and give us confidence in a go-forward dose. As Rob previously stated, the effect size of a Cohen's d equal to 0.81 at 12 weeks is more than double the estimated effect size of the current standard of care for GAD and was achieved after a single dose of MM120.
The statistically and clinically significant 21.9-point improvement on the HAM-A score at week 12, which represents an improvement over placebo that generates a p-value of 0.0025, represents further improvement from our four-week top-line data and is in part driven by a 48% clinical remission rate at week 12. MM120 was well tolerated with no drug-related serious adverse events. The observed AEs were mild to moderate and transient, largely occurring on dosing day, and are consistent with expected effects from the drug class and observations from previous studies. Importantly, there was no suicide-associated safety signal. The 12-week results provide strong evidence of the durability of a single administration of MM120, and we believe it provides additional support for advancing a dose of 100 micrograms of MM120 into phase III development for GAD.
In our Phase IIB study, we employed a standard design consistent with prior studies of approved GAD therapies and included the primary endpoint that supported registration for approved GAD drugs. The study was a randomized, double-blind, placebo-controlled 12-week study of a single administration of MM120 or placebo monotherapy. Participants who enrolled in the study on background pharmacotherapy for GAD were clinically tapered and washed out of all anxiolytic therapies for at least five half-lives after their last dose. The study enrolled 198 patients with GAD who were randomized to one of five treatment arms with a one-to-one allocation across the arms. The primary endpoint was the change in HAM-A from baseline to week four, with secondary outcomes at weeks eight and 12, which, in line with the FDA guidance, were assessed by remote central raters blinded to treatment assignment and visit number.
Participants in the study were required to present with a primary GAD diagnosis and a HAM-A score of 20 or greater at screening and baseline. Eligible participants were randomly assigned to receive a single dose of either 25, 50, 100, or 200 micrograms of MM120 or placebo. Participants were then followed for 12 weeks with outcome measures assessed on day two and weeks one, two, four, eight, and 12. In addition to the HAM-A, the primary outcome measure, additional secondary outcome measures include the Montgomery-Åsberg Depression Rating Scale or MADRS, and the Clinical Global Impressions-Severity or CGIS scale, among others. Our study was designed to demonstrate the drug-only effect of MM120 with no other psychotherapeutic intervention.
The importance of this approach was emphasized by FDA's 2023 draft guidance and, uniquely in the field, allows us to maintain the same delivery protocol between this phase II study and our subsequent phase III studies. More specifically, the participant journey in this study was consistent with other clinical trials in GAD. Before dosing, participants underwent a comprehensive informed consent process and eligibility evaluation. On the day of dosing, participants were continuously monitored for psychological and physiological safety by qualified site staff, and observation was completed when pre-specified readiness criteria were met. To be clear, this study did not include any preparation sessions, assisted therapy, or integration sessions. As a result, we believe this is the most valid assessment of a drug-only effect ever conducted for Lysergide or any other molecule in this drug class. 198 patients were randomized into the study, resulting in approximately 40 patients per study arm.
74% of all randomized participants completed study activities through the end of the study at week 12, with a completion rate of 79% among participants in the two higher dose groups. These strong completion rates were achieved despite participants receiving only a single dose of the study drug and returning to the study sites for follow-up visits despite receiving no additional treatment. Participant demographics and baseline characteristics were generally well balanced across the treatment arms.
Notably, the mean score of approximately 30 on the HAM-A scale indicates that participants in the study suffered from severe GAD, a level of illness supported by mean CGIS scores of approximately five, which corresponds to the scale category of "markedly ill." Looking at the time course of clinical response as measured by the HAM-A, we observed rapid and durable reductions in HAM-A scores through week 12, with clinically and statistically significant reductions in both the 100 and 200 microgram dose groups. In the 100 microgram dose group, we observed a reduction of 21.9 points on the HAM-A at week 12, which represents a 7.7-point improvement over placebo and a p-value of 0.003. A clear clinical dose response was observed across the doses tested, with peak clinical effects plateauing at the 100 microgram dose and generally staying consistent at the 200 microgram dose.
We were also especially encouraged that the study results demonstrated complete maintenance of clinical effect at week 12. Notably, in this study, we observed a robust placebo response that also persisted to week 12 and is of a magnitude consistent with historical studies of GAD treatments, which have also employed an inert placebo. Inert placebo has long been the gold standard in psychiatric studies, despite the broad potential for functional and blinding across many classes of psychoactive drugs. We believe that the placebo response observed in our study reinforces the integrity of the study results. It also reinforces our long-held view that inert placebo is the correct choice of controlled condition in all studies of the psychedelic drug class. The clinical activity of MM120 in GAD is further supported by response and remission rates observed in this study.
The clinical response rate, which is defined as a 50% or greater improvement in the HAM-A score, was 65% in the 100 microgram group at week 12 and increased in a dose-dependent manner up to the 100 microgram dose level. The remission rate, defined as a score of seven or less on the HAM-A, which is indicative of not having clinically significant anxiety, was 48% in the 100 microgram dose group at week 12, meaning that of the participants who received a single dose of 100 micrograms of MM120, approximately one in two were in remission 12 weeks after treatment. The primary analysis of the HAM-A endpoint was conducted using the Multiple Comparisons Procedure-Modeling or MCP-Mod, a sophisticated methodology developed by Novartis, which is highly statistically efficient in establishing and characterizing dose-response relationships.
Using this methodology, the primary endpoint was assessed at week four, and the key secondary endpoint was assessed at week eight. These analyses achieved statistical significance, with multiple dose-response curves being statistically identified to inform future dose selection. As I mentioned, the CGIS was used to assess the overall severity of GAD at multiple time points throughout the study. Because the CGIS is a momentary assessment, it can be validly assessed as soon as the day following treatment, whereas the HAM-A is only valid with a one-week recall period. In the 100 microgram group, statistically and clinically significant improvements in the CGIS were observed as early as day two and were maintained through week 12.
On average, participants improved on the CGIS from "markedly ill" to a level between "borderline" and "mildly ill." In practical terms, this is a highly clinically meaningful improvement and aligns both in magnitude and direction with the rapidity and durability of the observed effects measured by the HAM-A. In addition to anxiety symptoms, participants were assessed on the Montgomery-Åsberg Depression Rating Scale or MADRS for the effect of MM120 on comorbid depressive symptoms. GAD has a substantial diagnostic and symptomatic overlap with depressive illnesses and, consistent with the general population of GAD patients, participants presented with comorbid depression symptoms, with average baseline MADRS scores in the mid-20s. In both higher dose groups, a statistically significant and clinically meaningful separation from placebo at all time points, with a p-value of less than 0.01 at week 12.
MM120 was safe and well tolerated in the study, with 99% of adverse events rated mild or moderate. Only one serious adverse event in the study occurred in the 50-microgram dose group 98 days after dosing and was deemed unrelated to the treatment. Additionally, there were relatively few withdrawals from the study due to adverse events. Importantly, we saw no signal of increased suicidality from the treatment. There were no incidents of suicidal or self-injurious behavior, and there were no more than two participants per arm with suicidal ideation, which in all cases was mild to moderate. Events coded as adverse effects on the day of dosing, when the vast majority of AEs occurred, as seen here indicated by DD, were consistent with the pharmacodynamic effects of MM120.
These included illusion, hallucination, and euphoric mood, as well as nausea and headache, all of which were expected with our understanding of the drug's mechanism of action. These adverse effects were not dose-limiting. I will now discuss our MM120 PK bridging study that enables us to confidently bring our ODT formulation into phase III development and as our intended go-to-market formulation if MM120 should ultimately be approved. The transition to Zydis ODT formulation offers numerous product performance, clinical, and intellectual property benefits. Importantly, this formulation yields durable shelf-life stability for an otherwise unstable molecule. We are also pleased to report that our PK bridging study for MM120 Zydis ODT also delivered on our clinical aspirations for the new formulation.
Our goal with the MM120 ODT formulation was to reduce the time between drug ingestion and reaching a target concentration of greater than 1 nanogram per milliliter, which is associated with acute perceptual effects thought to produce the clinical improvements observed in the phase IIb study that I just described. This PK bridging study was a standard crossover design in which each of the 29 healthy participants was randomized one-to-one to receive MM120 100 micrograms in the capsule formulation used in MMED-008 or the new Zydis ODT formulation. Following a 2-week washout period, each participant was administered the other formulation. A total of 24 participants completed dosing using both formulations.
The overall PK curves generated from this study demonstrate a favorable profile of the MM120 ODT formulation, with a shorter TMAX, similar CMAX, higher overall AUC, and, most importantly, a higher AUC at target concentrations greater than 1 nanogram per milliliter. Zooming in on the early phase of the PK curve, we see that the absorption characteristics of the MM120 ODT formulation allow us to reach the 1 nanogram per milliliter threshold approximately 50% faster. This is a key differentiator, as the time spent between drug ingestion and reaching a clinically active concentration of the drug is minimized, making the most efficient use of patients' and clinicians' valuable time. Looking at overall bioavailability, we see that the ODT formulation produced a 17% greater bioavailability and notably can drive a substantially higher area under the curve without markedly changing the CMAX.
Perhaps most importantly, the ODT formulation shows a 23% increased AUC when the concentration of the drug is above the one nanogram per milliliter target. Even so, the MM120 ODT formulation did not increase the duration of perceptual effects of MM120. In summary, the characteristics of the ODT formulation demonstrated in this PK bridging study offer compelling evidence for its differentiated clinical profile and support its progression into phase III development. I will now turn the call over to Dr. Francois Lilienfeld, our Chief Commercial Officer, to discuss the commercial opportunity for MM120 in GAD. François?
Thank you, Dan. I'm honored to be here to be leading a talented team that together has launched multiple blockbuster drugs across many therapeutic areas.
When our team considers the commercial potential of MM120, we feel strongly that the key factors are in place to enable a scalable, efficient launch and uptake to help the millions of patients in need of novel treatments in generalized anxiety disorder. Generalized anxiety disorder, or GAD, is a large and growing problem in the U.S., with millions of patients receiving inadequate efficacy, intolerable side effects, or choosing not to remain on treatment. We are entering into a large market with significant unmet need, an established reimbursement framework, and a large and growing infrastructure. Our best-in-class profile with MM120 creates a strong value proposition for all stakeholders and, we believe, makes for a compelling commercial opportunity.
Importantly, in line with Dan's emphasis on the standalone effects of MM120 that have been demonstrated in phase 2, we believe our care delivery model, which does not rely on psychotherapy, preparation, integration, or other intensive non-drug intervention, could enable broader accessibility and a wider range of providers and delivery sites to potentially adopt MM120 compared to others in our drug class. We recently conducted primary research with psychiatric healthcare practitioners to understand their enthusiasm and receptivity for the potential of the psychedelic drug class. What we found was staggering. A full 74% of healthcare practitioners indicated that the availability of FDA-approved psychedelic treatments will change how they approach anxiety and depression, and 62% indicated the belief that FDA-approved psychedelic treatments will radically transform the treatment of anxiety and depression. These effects were even more pronounced when focusing on healthcare practitioners that are providers of Johnson & Johnson SPRAVATO.
We also sought to understand these healthcare practitioners' impression of MM120. When presented with a profile of MM120 in GAD, a vast majority, over 85%, were impressed with the clinical activity of MM120, including in particular its rapid onset and durability of activity. Based on these results, we believe that there is a clear desire for the future adoption of novel treatments such as MM120 in psychiatry. Focusing on the commercial model that we believe can deliver on this desire, there is a large and rapidly expanding infrastructure of interventional psychiatry providers around the U.S. that are both well-equipped and especially enthusiastic about the potential of MM120. As we conceive our commercial model, it is likely to leverage a similar interventional psychiatry model that has been established by Johnson & Johnson for SPRAVATO, or intranasal esketamine, over the last 5 years. U.S.
Net sales in 2023 for SPRAVATO, which is approved for treatment-resistant depression and MDD with acute suicidal ideation or behavior, exceeded $600 million and are projected by Johnson & Johnson to surpass $1 billion in annual sales in coming years. SPRAVATO treatment requires patients to come in for up to 56 sessions over the course of a year. In each session, the medication is self-administered by the patient, who is required to be monitored for at least two hours before they are released to go home. With the rapidly advancing uptake of this model, there are now more than 3,500 clinics and offices that have been certified for the delivery of SPRAVATO under the SPRAVATO REMS. While we believe there is an even broader infrastructure for MM120, the seamless transition for these clinics to one day provide MM120 makes for a compelling and efficient initial target.
Importantly, in this interventional psychiatry model, the pathways for patient care, reimbursement, REMS documentation, and logistics are well established and could be leveraged for MM120 if it is approved and marketed. Here is how this model works. Patients are evaluated by healthcare practitioners with prescribing rights, often a psychiatrist, and, if appropriate, are prescribed the treatment. The medicine is distributed by a specialty pharmacy, and the treatment is then administered by the patient at the start of the treatment session that takes place in the clinic or office. The patient is monitored by licensed healthcare providers for the entire duration of the session before being safely released. We feel it is important to point out that in real-world practice, the healthcare practitioners who monitor treatment sessions are often quite different from the prescribing healthcare practitioners, and monitors most often have lesser degrees of training or qualification than the prescriber.
For each of these steps in the process, prescription, drug, and monitoring, stakeholders are reimbursed by payers utilizing well-established processes and pathways. Digging into these dynamics further, each of the three stakeholders in this model receives reimbursement from payers using established CPT codes. Notably, each step in the process is reimbursed differently with a unique economic driver. Evaluation and prescribing are commonly reimbursed on a per-visit basis. Drug costs are reimbursed as a pharmacy benefit based on established prices, rebates, and discounts, and session delivery is reimbursed on an hourly basis to the clinics monitoring a patient. In the case of SPRAVATO, the list price of the drug is between $25,000-$62,000 a year. In addition to the drug cost, payers reimburse patient monitoring time on an hourly basis at a cost that can total up to $17,000 per year.
We expect to be utilizing a similar model for care provision and reimbursement, and given the economic drivers and profile of MM120, we believe the reimbursement and value proposition is compelling. While we look to the commercial model established by SPRAVATO, there are a number of attributes of MM120 that could make it even more attractive for providers and patients, and ultimately more easily scalable. These differences are both clinical and logistical in nature. If the three-month durability results from our phase IIb are ultimately supported in pivotal studies, this could enable four or fewer treatment sessions per year on average, compared to up to 56 treatment sessions for SPRAVATO. For patients, this means only a few visits to the clinic instead of having to be driven to and from the clinic and kept under observation every single week.
For providers, this could also mean a lower administrative burden to submit documentation to insurance or a REMS program. Also, given the potential duration of monitoring for MM120, the care delivery model would only require providers to treat one patient per room per day to obtain reimbursement for that time, while the same provider would have to see four patients back to back to back to back in order to achieve the same hours of reimbursement for SPRAVATO. While conceptually the potential advantages of MM120 over a shorter duration drug are clear to us, we wanted to test whether current SPRAVATO providers would react. Here again, the response was overwhelming. 80% of current SPRAVATO providers thought that MM120 would be easier to arrange than SPRAVATO, and over 75% of these providers believed that MM120 would be more economically attractive for them compared to SPRAVATO.
These responses further support our view of the direct applicability of the SPRAVATO infrastructure and commercial model to the path forward for MM120. As we advance toward commercialization, leveraging this established infrastructure will be a priority for our potential launch. With the potentially advantageous delivery dynamics and profile of MM120, it is perhaps no surprise that 92% of these SPRAVATO providers indicated that they would be likely to refer a patient for MM120, and 84% of these providers indicated that they would be likely to prescribe and administer MM120 in their clinic if it becomes FDA-approved and is marketed. Of course, an important element to enable scale, value, and adoption is payer reimbursement. Generally, payer perspectives on the potential value of MM120 are positive, and we believe there is a clear path to reimbursement.
GAD patients represent a large burden on payers, and the clinical profile of MM120 would offer a predictable, compliant, and efficient allocation of payer resources. Current treatments for GAD often take weeks to work, frequently fail, and people stop taking them due to tolerability issues, which creates significant waste for payers. Their customers, large employers, are increasingly interested in better managing GAD and brain health. In this regard, it is important to understand that GAD has a major impact on employers by driving employee disengagement and work productivity loss, even when employees affected by GAD are on currently available treatments. In fact, on average, an employee with severe GAD misses 46 workdays per year and often drives significant incremental disability costs. Our hope is that by helping patients suffering from GAD, the benefits would be multitude and will extend far beyond the individual.
As we continue advancing our commercial strategy, our approach will focus on these three key imperatives. First, we will seek to engage and educate providers and patients about GAD and MM120. Second, we will seek to continue accruing evidence and highlighting the value proposition to patients, healthcare practitioners, payers, and employers who are frustrated with the state of GAD care today. And third, we intend to engage and work with the current infrastructure to integrate MM120 while pointing out its potential advantages versus competitors. While we understand that at a surface level, the commercial pathway for a novel treatment like MM120 may seem unique, we believe that all the ingredients are in place to enable a scalable, accessible, and valuable commercial opportunity. Most importantly, by doing so, we aim to reach the millions of individuals who are suffering from GAD and need new treatment options.
I will now turn the call back over to Rob for summary comments on the MM120 development. Rob.
To conclude today, I would like to discuss the path forward for MM120 and GAD. We've now achieved the goals of our phase II development program, which included establishing the dose-response relationship for MM120 and demonstrating rapid and durable clinical activity in GAD. We believe the data support dose selection and advancement of MM120 into phase III development, and are excited to kick off our program later this year. In terms of our development pathway, we intend to conduct two phase III pivotal clinical trials, which are in planning. This program is expected to include both 12-week randomized placebo-controlled primary efficacy study designs and long-term open-label extension studies to characterize retreatment parameters. In terms of our phase III clinical design, we expect the design to be largely consistent with our phase II study design, which we believe may de-risk our approach given the robust results already shown in phase II.
We intend to hold our end-of-phase II meeting with the FDA in the first half of this year and will be initiating our phase III program in the second half of the year. We anticipate presenting full data from our phase IIb study in a peer-reviewed publication and at a scientific meeting later this year. We're also currently evaluating additional clinical indications for MM120 and are excited to provide further updates in the future. I'd like to thank you all again for joining us here today. I'm thrilled by the progress we have made at MindMed over the past several years, and I'm excited to share in all that is ahead as we seek to deliver on the therapeutic potential of our pipeline and provide new options to the millions of patients suffering from brain health disorders. With that, I'd like to open up to any questions.
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Hey guys, thanks so much for taking my question. A lot to ask, but I'll keep it to one and hop back in the queue for any additional ones. Maybe just on the commercial side, you outlined some of the similarities and differences versus a SPRAVATO administration. I was wondering if you could maybe elaborate a little bit more on what you think the SPRAVATO centers will need to do to accommodate the different needs and monitoring requirements for a drug like 120, including sort of fewer patients being monitored for longer sessions, and whether reimbursement is strictly focused on monitoring hours versus maybe then to some degree on the number of patients coming through the rooms each day. Thanks.
Yeah, thanks so much, Brian. I'll turn that one over to Dan to start there, and maybe François wants to expand from there.
Yeah, so one of the things that's required for SPRAVATO specifically is physiological monitoring. And we actually don't anticipate that we're going to need to have a physiological monitoring requirement. So that in certain ways reduces the burden on these clinics. The sorts of people who can be involved in the monitoring for MM120 ought to have fewer medical requirements. And as we're working through plans for phase III and beyond, coming to agreement with the FDA on exactly what it is that we're monitoring for and what level of practitioners are required to do that. So in many ways, the setups that exist both in SPRAVATO clinics but also in the broader psychotherapeutic milieu are pretty appropriate as they are for what we anticipate to be the monitoring requirements for our product.
That's really helpful. Thank you.
Our next question will come from François with Oppenheimer. You may now unmute your audio and ask your question.
Hi, thanks for taking the question. Just a quick one. In terms of and I don't know if Rakesh is available to answer here as well, but I was wondering in the real world here, obviously in the trial, there's a washout period, but how do we think it's going to work out for patients in terms of getting totally off SSRIs, or is this something that you wouldn't expect that necessarily at first and then down the road could happen? I'm just wondering your thoughts on the real-world translatability of totally washing out patients. Thank you.
Yeah, thanks so much, Franç . I'll turn that over to Dr. Jain, if you're there.
Yeah, I'm certainly here. Hey, François, good morning to you and a great question, my friend. Really, it's a good question because many of these patients are on medications, but not all of them. You'd be surprised how many aren't taking an SSRI, SNR, or a benzodiazepine. Look, it is never easy to ask a patient to continue taking a medication that isn't effective. So asking a patient that, "Hey, here's a safe and effective way to taper down because we have a trial of a medication coming up," I don't think it's going to be challenging. I do that all day long. I would say 80%-90% of the clinical visits I have with patients are transitioning patients from one to another medication.
De-prescribing, which is what you're talking about, François, is a skill set we in the psychiatry world have developed quite well over the last decade or so. Thanks for your question, sir.
Thanks for that question. It's Dan. The other thing I think that's worth pointing out is that while for the sake of trial integrity, we're washing folks out of background therapy, there is emerging evidence in the field that background therapy doesn't interfere with the therapeutic action of drugs in the class. Now, we haven't built that body of evidence yet, but there's no reason to think that in the real world we would necessarily have to insist on a pre-dose washout. So in the real world, folks who respond well to treatment could then subsequently stop other medicines that they didn't need to be on any longer because they were in a state of state remission.
Our next question will come from Charles with Cantor Fitzgerald. You may now unmute your audio and ask your question.
Yes, good morning. Thank you for taking our questions and for hosting this very informative webcast. Congrats on the data. I did have a question for Dr. Jane. And just to build some perspective, I'm wondering really if you think this is practice-changing or incremental, and do you see the durability at three months as sufficient, or would you like to see six-month durability, or is that not really important at all? And then finally, which patients in your practice would you target? How would you incorporate this into your practice in terms of deciding the type of patients to administer the agent to? Thanks.
Thanks, Charles. Yeah, Rakesh, please go ahead.
Wow, Charles asks three great questions, three great questions. Let me take them in order. First of all, is it game-changing? Charles, this is my 31st year in psychiatry, and I have sort of gotten jaded over the last 20, 30 years in seeing just incremental or sometimes side-moving interventions, but this isn't one of them. This is a biggie. It's a biggie not just because it was a one-time administration of a medication. That in itself is quite remarkable, but it's the effect size. Now, I've been doing clinical trials and clinical practice for decades, and we simply don't have interventions, Charles, that exceed a 0.4, a 0.5. And here we have a 0.8. But it's not just that. About half the people were in remissions. If you look at numbers needed to treat, which is a very important proxy for a drug's effectiveness, it's only two.
I'll have to treat two people in order to drive one person into full remission. I'll have to treat almost just one and a half people to drive somebody into response with one of the most chronic diseases. So the immediate answer to your first question, which is, is it a game-changer? I actually think when I first saw this data, in my mind, I said, "Psychiatry and anxiety disorder treatment will never be the same again." That's not hyperbole. I think it's going to be true. The second point you raised about was durability. Of course, the longer you can see durability, it is valuable. But let me share this with you. GAD is so refractory and so very prone to being present and recurring.
If I can see data at 12 weeks, I can tell you with some confidence how things will be at month four, month six, month nine, month 12. So I'm actually quite satisfied with 3 months because someone who has GAD at three months, if they're in remission or in response status, they are doing quite well. Your third question, which was, "Which type of patient will I be selecting in?" The obvious answer is not complete, actually. It's not going to be just the GAD patient. It's going to be the GAD patient who is motivated. It's the GAD patient who has almost certainly a significant number of comorbidities. I hope you were paying very close attention to Dan's presentation when he showed it wasn't just anxiety that improved. It really was also the very often significant presence of depressive symptoms that also improved.
By the way, don't miss out on the following point I'm about to make, which is the Clinical Global Impressions-Severity. That is how we clinicians practice. The average person I'm talking about the average person at week 12 was kissing a two. A two is borderline illness. That doesn't happen in psychiatry very much. So the type of patient, I think, will be a pretty broad-based patient who is motivated, who is willing to accept the fact that these might be enduring changes, and a clinician who's willing to engage with such a patient. So I hope I answered all three of your questions, Charles.
Absolutely, you did. I appreciate that. Do you have a perspective on the 20% non-completors? Is that more than or in line or less than you would have anticipated? Thank you for taking my questions.
Yes. I also paid close attention to that number. We think of GAD as a homogeneous condition, right? If you've got a migraine, you've got a migraine. But the truth is, with GAD, there's a huge variability in the kinds of people and the approaches they take. So that number actually was less than I had anticipated. Please also keep in mind, there was no psychotherapy component to this particular trial. Now, while this study is a big deal, obviously, to MindMed, I cannot tell you how big a deal that is to my community. The 55,000 people I represent at psychiatry, our major shortcoming in the world of psychiatry isn't just medications aren't effective. We don't have access to therapists. We don't have access to people who are trained in how to deliver cognitive behavioral therapy.
So the fact that this worked even without any significant therapy, Charles, that's a really, really big deal. That 20%, it does not bother me. That's just the way it tends to be in real life.
Thank you, Dr. Jane. Congrats, Rob and team, on the results.
You're welcome, sir.
Our next question will come from Sumant with Canaccord Genuity. You may now unmute your line and ask your question.
Good morning. Very nice to see these 12-week data, and thanks for taking my question. This question is for Dr. Jane and Dr. Karlin. If MM120 were to eventually be approved, from a practicing psychiatrist's perspective, what do you think the key impediments, if any, might be to widespread patient use of a potentially game-changing product such as MM120 in the GAD context?
Thanks so much, Sumant. Rakesh, maybe I'll point this one to you as well, and then Dan can expand on it. Anything more to this?
Oh, sure . Yeah, there are challenges. Let's not be unrealistic about it. The first challenge is going to be my community, which hasn't had a "real psychedelic" as a treatment option for the last, what, 70 years? Before that, we had lots of studies, as I showed you earlier, Sumant, but we didn't have an indication. But here's the good news. And I think we should give a lot of credit to the last five years of cultural change in thinking, which is the acceptance that psychedelics and, of course, MM120 is a major class A psychedelic don't just change the mind, but they change the brain that drives the mind. That is now fairly well established. And as a result, my community, if shown data like this, is going to be quite persuaded. And of course, this is a phase 2 data.
We will need two phase III datasets. The other thing that I think we should appreciate is SPRAVATO has really tilled the ground. All of a sudden, psychiatry's initial option was just daily medications, and SPRAVATO came in and showed us it is possible to give a medication intermittently, though, of course, quite frequently, but still intermittently. And the SPRAVATO centers have really learned the art of how to create time and space for patients and to allow for them, without psychotherapy, to improve. So Sumant, I actually think once we have the phase III data with MM120, my community is actually, for the most part, going to turn towards the medication and this therapy option rather than act as a barrier. But I would love to hear what you have to say, Dan.
Thanks, Rakesh. It's a really excellent question because it gets us thinking about something that psychiatry has accepted in a world where we didn't have highly effective treatments, which is that when folks presented in distress, they were often relegated to the oldest and least effective medicines rather than getting early access to the most effective treatments. With the advent of treatments that seem to be able to put people into true early, rapid disease remission, psychiatry. It will be incumbent on us to reorient psychiatry towards alleviating distress as effectively and early as possible before the pathways, the neural pathways that get activated by being in distress get overtrodden, and patterns of life emerge from that distress.
So, while I agree entirely with everything Rakesh said and the enthusiasm for these treatments in psychiatry among psychiatrists of all generations, new residents entering the field in part because they see these things coming down the pipeline, but the larger reorientation toward early, highly efficacious treatment, and a lot of that will have to be based on the recognition that, in fact, healthcare savings and productivity increases from early treatment offset the potential higher initial cost.
Thank you.
Our next question will come from Patrick with H.C. Wainwright. Please unmute your line and ask your question.
Hi, good morning, and congrats on the data updates today and the progress on MM120. Just during the presentation, it was mentioned that there are more than 3,500 certified delivery clinics for SPRAVATO. I'm wondering if you can tell us what it would take to have MM120 certified for delivery at all of these clinics, and how soon would you anticipate that MM120 could be certified at these clinics for GAD following a potential FDA approval?
Yeah, thanks so much, Patrick. It's a bit premature to say definitively. The timeline is going to be a function of ultimately what the labeling and REMS and requirements agree to with FDA, and the drugs ultimately approve. So a little bit premature to say exactly, but certainly from a logistical standpoint, from a sort of infrastructure standpoint, we see very little standing in the way. I mean, largely, SPRAVATO clinics that we know well and go out and visit, and many of which conduct clinical research in our field, have very minimal differences between the rooms that are used to treat patients with SPRAVATO and the rooms that are used in research for our drug class or our drug. Ultimately, we see a very direct path to sort of transitioning and being ready for the adoption.
We're not talking about a significant capital investment at a site level if all you have to do is buy a nice lamp and a rug. Really, I think there's a really practical implementation here that should be quite scalable, quite efficiently. But again, the specific requirements are going to be subject to all that is agreed upon on labeling and REMS.
Rob, if I may just offer a quick thought, entirely agree with you, my friend. This process is going to be quite straightforward. I think our colleagues online should appreciate to become a REMS-certified center for SPRAVATO is actually one of the easiest things psychiatry has ever encountered. It's a straightforward process. Every SPRAVATO center, by default, already has the space, already has the equipment. By the way, equipment really means a bed, or it means a reclining bed, and eyeshades, and music. They're already quite used to that delivery methodology. You're right. We don't know what the FDA will say ultimately. But from my community's perspective, the 55,000 that I represent, we're not going to have logistic challenges.
Great. Thank you so much.
You're welcome, Patrick.
Our next question will come from Brian with RBC. You may now unmute your line and ask your question.
Hi, thanks for taking my follow-ups. Just a couple of questions on the data I wanted to follow up on. First, can you remind us of the way you imputed for non-completors in both the response and remission calculations and then the mean HAM-A change curves? And then secondly, on the ODT, can you talk a little bit more about the implication of the steeper exposure curve, why you don't see differences in duration of hallucinogenic experience given the longer AUC above the target concentrations? Maybe a little bit more granularity on the AEs. Sounds like lower GI AEs, but any more detail versus the capsule would be helpful. And then the degree of subject-to-subject consistency of exposure for the ODT versus the capsule, how similar or different was that? Thanks.
Perfect. Yeah, thanks so much, Brian. So why don't we start with the second question first? So as we dug into the data from the ODT bridging study, really where what we do see, as you noted, is a quite stark difference in the rate of absorption and the time to get to the onset of action of the drug. And that ultimately is what is driving the difference in AUC, right? After the absorption phase, we don't see a dramatic difference in any meaningful way. In fact, those curves are almost and statistically are quite overlapping from the time we get to CMAX and beyond. In the absorption phase, because of the more rapid absorption, we do get patients to CMAX faster. And that's, again, what was driving the vast majority, if not all, of the difference in AUC.
So from an overall AUC standpoint, again, it is getting patients to that peak faster in terms of exposure, and then effectively, they stay at that peak for longer. So when we actually look at some of the qualitative feedback we had from the study as well, there was really positive feedback about the overall nature of the ODT formulation compared to the capsule formulation. In terms of adverse events, aside from, say, potentially some reduced GI burden, what we didn't see, we didn't really see any drastic differences in terms of perceptual effects. And really, everything else was largely consistent, which is represented by the fact that even in the phase II-B study where we reported the specific AEs today, most of those are just pharmacodynamics of the drug.
The action of the drug during a treatment session is really the vast number of and all of the AEs that occur in the study. Last part of that, in terms of subject-to-subject variability, there certainly is a good degree of variability, a number of factors between individuals. What we see definitely is a difference in terms of elimination, in terms of the clearance of the drug. And we're still, of course, in the development program, starting and continuing to explore exactly what may be driving those inter-individual differences in terms of metabolism and things of that nature. But I don't have a definitive answer for the cause yet, but there certainly is a degree of variability, which importantly sets the ODT apart because it makes it quite difficult to reliably get patients to have bioequivalents.
From a competitive standpoint, we think about years down the road, it creates an additional hurdle, just pragmatically, for a potential generic applicant to try to replicate formulation and demonstrate bioequivalence. As to your first question about imputation, that varied by the type of analysis that was being conducted. The primary analysis was an MMRM with imputation based on intercurrent events such as patients failing treatment or needing to return to their standard of care. In those instances, patients were imputed, regardless of their treatment assignment. They were imputed based on as if they had been in the placebo arm. If they were missing at random, they were imputed based as if they would have been in the group that they were assigned to and treated. It was a mixed imputation via an MMRM that ultimately drives responses.
What I can say, and again, it varied by the different types of analysis we conducted, we did do extensive sensitivity analyses. Regardless of the methods of imputation or ultimately the statistical approach we took, we ended up with the same conclusions. We didn't see any sensitivity to the statistical methodology that would have changed the outcomes of the study.
Got it. Thanks so much.
Thanks, Brian.
We have time for one more question. Our question comes from Sumant with Canaccord Genuity. Please unmute your line and ask your question.
Thanks for the follow-up question. Clearly, these data suggest solid durability in the trial, but do you have any initial thoughts on whether retreatment might work as well once initial treatment wears off and whether the same dose might be optimal for retreatment as well?
Yeah, thanks, Sumant. It's a great question and something that we, as we advance into phase III development, will certainly be exploring. Our intention, as we described earlier, was to, following a 12-week randomized controlled phase of the phase III studies, to roll patients over into an open-label extension study to explore exactly that question, to characterize the interval between retreatments and ultimately the response upon retreatment. That's a question of great interest to us. And the exact timing of when we'll have that answer, of course, will be driven by phase III program. And in relation to regulatory timelines, something will be discussed with the FDA in phase II.
Thank you.