Mind Medicine (MindMed) Q2 2024 Earnings Call Transcript

Quartr
Provided by Quartr
August 13, 2024

Key Takeaways

  • MindMed completed a constructive end of Phase 2 meeting with the FDA for MM120 ODT in GAD and is on track to initiate its first Phase 3 pivotal trial (VOYAGE) in the second half of 2024, followed by the PANORAMA study in early 2025.
  • The company is expanding its R&D program for MM120 into MDD, planning to launch the registrational EMERGE study in the first half of 2025 with a second trial to follow based on EMERGE findings and further regulatory discussions.
  • In June 2024 MindMed secured a new US patent extending intellectual property protection for MM120 ODT through 2041, bolstering its commercialization runway.
  • MindMed raised approximately $75 million in gross proceeds from an underwritten public offering, which, together with existing cash, extends its cash runway into 2027 and at least 12 months beyond the first Phase 3 GAD readout.
  • Results from the Phase 2b GAD trial showed that a single 100 µg dose of MM120 delivered more than double the effect size of standard of care with a 48% remission rate at 12 weeks and a favorable safety and tolerability profile.
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Earnings Conference Call
Mind Medicine (MindMed) Q2 2024
00:00 / 00:00

There are 10 speakers on the call.

Operator

Good morning, and welcome to the Mymetization Second Quarter 2024 Financial Results and Corporate Update Conference Call. Currently, all participants are in a listen only mode. This call is being webcast live on the Investors and Media section of MindMed's website at mindmed.co, and a recording will be available after the call. I would now like to introduce Rob Ferro, CEO of MindMed. Please go ahead.

Speaker 1

Thank you, and good morning, everyone. Welcome to our Q2 2024 Financial Results and Corporate Update Conference Call. Today, we will be sharing highlights from the Q2 along with the significant progress we've made with plans for our Phase 3 program in generalized anxiety disorder or GAD. Additionally, I'm excited to share further specifics about the expansion of our R and D program for MM120 into major depressive disorder or MDD, both of which are further supported by the financing we announced last week. The press release supporting our financial results and the presentation we will be using on today's call are both available in the Investors and Media section of our website and our quarterly report on Form 10 Q for the quarter ended June 30, 2024 was filed this morning with the Securities and Exchange Commission.

Speaker 1

During today's call and outlined on Slide 2, 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 processing. These and other risk factors are described in the filings made with the SEC, including our annual report on Form 10 ks and our Form 10 Q filed today. Forward looking statements are based on the assumptions, opinions and estimates of management of the date 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 MyMed's normal course of business. You are cautioned not to place undue reliance on these forward looking statements, which are made as of today, August 13, 2024.

Speaker 1

MyoMed disclaims any obligation to update such statements, even if management's views change, except as required by law. Let me begin by taking you through today's agenda on Slide 3. I'll start with our Q2 twenty twenty four business update and then Doctor. Dan Carlin, our Chief Medical Officer, will join to discuss our R and D plans for MM120 oral disintegrating tablet or ODD in GAD and MDD. We are also pleased to be joined by Doctor.

Speaker 1

Reed Robison, Senior Principal Investigator, Cedar Clinical Research and adjunct faculty at the University of Utah. Doctor. Robison is an investigator in our MN-one hundred and twenty clinical development program and will provide his views on our Phase 3 clinical trials. Following Doctor. Robison, I'll discuss our Q2 financial highlights, share our anticipated upcoming milestones and then we'll conclude with a Q and A session, where we will also be joined by Doctor.

Speaker 1

Francois Leventhal, our Chief Commercial Officer to answer your questions. On Slide 4, I'm pleased to share our progress for the quarter and through the first half of the year. In June, we successfully completed a constructive end of Phase 2 meeting with the U. S. Food and Drug Administration, which supports MM120 into pivotal Phase III clinical trials for GAD.

Speaker 1

We are on track to initiate our 1st Phase III trial for MM120 ODT and GAD in the second half of twenty twenty four, which marks a major milestone in our development program. We are also excited to share with you our plans to expand our R and D program for MM120 into MDD with the initiation of the EMERGE study, a registrational clinical trial for MM120 ODT and MDD, which we expect to be initiated in the first half of twenty twenty five. We also expect to conduct a second registrational study in MDD with the study design and timing to be informed by the IMerge study and additional regulatory discussions. The scope and sequencing of our clinical program for MN-one hundred and twenty and MDD is being carefully executed to balance the exciting opportunity represented by MDD, while maintaining a cash runway into 2027. With this approach, we believe our cash runway will be sufficient to support operations for at least 12 months beyond our first Phase 3 readout in GAD.

Speaker 1

In June, we announced the U. S. Patent and Trademark Office issued a new patent covering the formulation and manufacturing methods of MM120 ODT that extends our intellectual property protection for MM120 ODT through 2,041, providing further runway for potential commercialization. We have also seen continued progress with our 2nd lead program, MM402, which is our proprietary form of the R enantiomer of MDMA. We are currently evaluating MM402 in a Phase 1 single ascending dose trial in healthy adults intended to characterize tolerability, pharmacokinetics and pharmacodynamics.

Speaker 1

We expect the results from this trial will enable further clinical trials to characterize the effects of repeated daily doses of MM402 and the exploration of early signs of efficacy in the autism spectrum disorder population. Lastly, I'm pleased to report that we just completed a successful underwritten public offering, raising approximately $75,000,000 in gross proceeds before deducting transaction fees and other offering related expenses. Based on our current operating plans, we believe that the proceeds from this offering, in addition to our cash and cash equivalents as of June 30, 2024 extends our cash runway into 2027 and at least 12 months beyond our 1st Phase III clinical readout in GAD. Importantly, this funding demonstrates the continued enthusiasm towards our programs and strategy and allows us to rapidly advance MN-one hundred and twenty in both GAD and MDD. Here on Slide 5 is a look at our pipeline of 3 clinical stage programs, including our Phase III trials for MM120 in GAD and MDD.

Speaker 1

As I mentioned, we remain on track to initiate the pivotal Phase III program for MM120 in GAD in the second half of twenty twenty four, and we intend to initiate the 1st registrational study in our newly announced MDD program in the first half of twenty twenty five. As detailed on Slide 6, MM120 has shown significant potential in addressing large unmet needs in brain health disorders. Our Phase 2b trial for MM120 and GAD demonstrated an effect size more than double that of the standard of care and a 48% remission rate 12 weeks after a single dose. We also observed significant rapid and durable effects on conortative depression symptoms in GAD patients. In the U.

Speaker 1

S. Alone, there are 20,000,000 adults with GAD and 31,000,000 adults with MDD. Of these, 13,000,000 18,000,000 are treated annually for GAD and MDD respectively. These two markets represent a substantial opportunity for effective treatment. We believe that if approved, MN-one hundred and twenty could offer patients a differentiating compelling option in both GAD and MDD, which could position it to become the best in class treatment option, targeting 2 of the biggest market opportunities in psychiatry.

Speaker 1

Slide 7 outlines our overall program for MM120 in GAD and MDD, which incorporates constructive feedback from our recently completed end of Phase 2 meeting with FDA. In the coming quarters, we anticipate initiating 3 registrational studies across the GAD and MDD VOYAGE and PANORAMA studies in GAD and the EMERGE study in MDD. The initiation of pivotal studies for NM-one hundred and twenty truly represents a major milestone for Iodine as we strive to become a leader in developing novel treatments to address brain health disorders. Before turning the call over to Dan to go over the details and designs of our Phase 3 studies, I want to take a minute to address our approach to some of the major topics that have come in focus since the FDA Pharmacologic Drug Advisory Committee meeting earlier this year and FDA's recent decision on LICA Therapeutics application for MDMA assisted therapy for PTSD. Our development strategy outlined on Slide 8 is rigorous and thoughtful and continues to be appreciated by regulators, researchers, clinicians and research participants.

Speaker 1

We believe this will ultimately translate into confidence for patients and prescribers. Specifically, we have implemented several strategies to address key methodological considerations in this drug class, including the use of central raters blinded to both treatment assignment and visit number, the inclusion of expectancy and blinding questionnaires, and perhaps most importantly, the elimination of psychotherapeutic intervention in our clinical trials. Additionally, our approach safety monitoring follows well established industry best practices and both through our Phase 3 clinical trials and dedicated clinical pharmacology trials, we intend to fully and robustly characterize the safety of IMM120. Our development of IMM120 has been carefully designed to adhere to the highest clinical and ethical standards in alignment with FDA guidance. We believe that our well designed Phase 2b trial for MM120 and GAD demonstrated compelling tolerability in efficacy data that exceeds today's standard of care.

Speaker 1

Additionally, we continue to publish scientific research backed by the robustness of our clinical data and our increasing body of evidence for MM120's potential as an emerging best in class product candidate, along with the growing unmet need to treat patients suffering from GAD, MDD and other brain health disorders. As we embark on our pivotal development programs for MM120, we remain both appreciative and excited by FDA's commitment to advancing research for the psychedelic drug class. This has been exemplified both through FDA's recent public statements in which they indicated that they continue to encourage research and drug development that will further innovation for psychedelic treatments in addition to the high degree of engagement and partnership that we have experienced in numerous interactions with the FDA over the course of the year. Now, I'd like to turn the call over to Doctor. Dan Carlin, our Chief Medical Officer, to discuss our clinical development programs in detail.

Speaker 1

Dan?

Speaker 2

Thank you, Rob. Turning to Slide 10. We believe the MM120 has the potential to address large unmet needs in major brain health disorders based on the compelling results we shared from our Phase 2 trial for MM120 and GAD. In this trial, we observed a rapid onset of effect with a 1.8 point reduction in clinical global impression severity or CGIS within 24 hours in participants treated with 100 micrograms, which was highly statistically significant with a p value less than 0.0001. The response was durable, showing a 21.9 point improvement in the Hamilton Anxiety Scale or HAMA at week 12 in participants treated with 100 micrograms.

Speaker 2

This further improvement from week 4 indicates potential long lasting effects. Importantly, the magnitude of response in participants given MM120 was such that 48% of participants who received 100 micrograms remained in remission at week 12. This high remission rate is particularly encouraging for a chronic condition like GAD. The treatment also demonstrated a favorable safety and tolerability profile with most adverse events limited to the dosing day, which is crucial for patient acceptance and adherence. Finally, these results were achieved with no additional therapy, highlighting the potential for MM120 as a standalone treatment for GAD.

Speaker 2

These outcomes support our Phase 3 program in GAD. I'll now discuss our Phase 3 development plan for MM120 and GAD Slide 11. As Rob mentioned, in June, we completed a highly collaborative and constructive end of Phase 2 meeting with FDA, reaching alignment on our Phase 3 pivotal trials. This program will consist of 2 pivotal clinical trials, the Voyage study and the PANORAMA study. Each trial consists of 2 parts.

Speaker 2

Part A will be a 12 week randomized double blind placebo controlled parallel group study assessing the efficacy and safety of MM120 ODT versus placebo. Part B of each trial will be an open label 40 week extension study designed to provide important long term data on the durability and potential retreatment profile for MM120. Voyage is anticipated to enroll approximately 200 participants who will be randomized 1 to 1 to receive MM120 ODT100 micrograms or placebo. Panorama is anticipated to enroll approximately 240 participants who will be randomized 5 to 2 to 5 to receive MM120 ODT100 micrograms, MM120 ODT 50 micrograms or placebo. In accordance with FDA guidance and our regulatory discussions to date, our clinical program for MM120 continues to utilize complementary study designs across our Phase II and III studies to address key methodological issues such as functional unblinding.

Speaker 2

In this regard, in the PANORAMA study, we are including a 50 microgram arm to confound participants' ability to accurately assess the dose condition to which they have been randomized. We believe that this approach builds on the evidence from our Phase 2b study in which we demonstrated that despite functional unblinding at all tested doses of MM120, the lower doses 25 50 micrograms did not demonstrate a meaningful clinical response, supporting our view that the anxiolytic response to MM120 is independent of functional unblinding. While we previously observed an almost 8 point improvement for ML120 over placebo at week 12, both Voyage and Panorama have been designed to have 90% power to detect a 5 point improvement over placebo based on certain statistical assumptions. Additionally, in both studies, we will use an adaptive design with an interim blinded sample size re estimation, which allows for an increase in sample size of up to 50% in each study. This approach allows us to adjust for variability and nuisance parameters with the goal of maintaining statistical power and enhancing the interpretability of our results.

Speaker 2

Key elements such as inclusion and exclusion criteria will largely mirror our successful Phase 2b trial in GAD and both Phase 3 studies will recruit adults aged 18 to 74 with a diagnosis of GAD and a HAMA score of 20 or greater. During Part B of the Phase 3 studies, investigators will closely monitor patients using electronic patient reported outcomes, central rater assessed HAMA and clinician administered scales. Participants will be eligible for retreatment with MM120 ODT 100 micrograms if their HammA score reaches 16 or higher with up to 4 treatments available through Part B. Importantly, the design allows an assessment of the durability of the treatment effect, the need for and response to retreatment and long term safety. Key outcomes from Part B would include time to retreatment or inefficacy.

Speaker 2

We will also assess safety data on repeated treatments, average treatments per year and response to retreatment. This information will be valuable in understanding the longer term dynamics of MM120 ODT treatment in GAD patients. Overall, both VOYAGE and PANORAMA are designed to be consistent with our successful Phase 2b trial, including using the Ham A as our primary outcome measure with the primary endpoint for the Phase 3 programs being changed from baseline to week 12, which is consistent with the durability we observed in Phase 2. Based on the data we collected in Phase 2, we have also agreed with FDA to a reduction in treatment session duration from a minimum of 12 hours to 8 hours. This is operationally advantageous in our research program and enhances MM120's practicality in real world settings.

Speaker 2

We will continue to collect data on monitoring times and safe parameters for determining the appropriate timing for ending sessions using structured, intentionally designed criteria to determine the time course and resolution of drug effects that could require monitoring. We are happy to say that we remain on track and expect to initiate our 1st Phase III trial, VOIAGE, in GAD this year. Turning to Slide 12, as Rob stated earlier, we are also excited to announce the expansion of our R and D program for MM120 into MDD. Data from our Phase 2 GAD study led to our decision to pursue MDD as an additional indication for MM120, given the demonstrated potential for antidepressant effects. In the 100 microgram dose group, we observed an 18.7 point improvement from baseline in the Montgomery Aspert Depression Rating Scale or MADRS score at week 12.

Speaker 2

This represented a 6.4 point advantage over placebo, which was statistically significant with a p value less than 0.01. These results are particularly encouraging given that the study wasn't powered for this endpoint and that baseline MADRS scores were lower than we would expect in patients experiencing a major depressive episode, which appeared to create a ceiling effect on the response to MM120. Slide 13 represents the Phase 3 development program for MM120 and MDD, which we expect will consist of 2 pivotal clinical trials. Our first trial, the EMERGE study, like our pivotal trials in GAD, will be comprised of 2 parts. Part A, which is a 12 week randomized double blind placebo controlled parallel group study assessing the efficacy and safety of a single dose of MM120 ODT versus placebo.

Speaker 2

And Part B, which is a 40 week extension study during which participants will be eligible for open label treatment with MM120 ODT subject to certain conditions for retreatment eligibility. IMerge is anticipated to enroll at least 140 participants randomized one to 1 to receive MM120 ODT 100 micrograms or placebo. The primary endpoint in IMerge will be the change from baseline in MATTRIS score at week 6 between MM120 ODT100 micrograms and placebo. We expect to conduct a second registrational trial in MDD in the future with the design and timing to be informed by the EMERGE study and additional regulatory discussions. As Rob mentioned earlier, our planned execution of the MM120 program and MDD will balance this exciting opportunity across 2 pivotal programs with our continued operational and financial diligence.

Speaker 2

With that, I am happy to introduce Doctor. Reid Robison, who will provide his perspective on our Phase 3 trials.

Speaker 3

Thanks, Dan. I'm very excited about the Phase 3 development programs that you just shared. As I believe they stand to make a significant impact in the field of psychiatry. I've been personally thrilled with the results I've seen so far from MindMed's MM120 development program. The GAB Phase 2b results are truly impressive with MM120 exhibiting rapid and robust efficacy sustained 12 weeks after a single dose.

Speaker 3

Equally impressive is the change in MADRS score from baseline to week 12 in the Phase 2b GAD trial participants showing improvement in comorbid depressive symptoms. For people suffering from GAD, including with comorbid depression, these trials offer a beacon of hope. And I've seen firsthand how debilitating both conditions are severely impacting quality of life. Given that current standards of care falling short of meeting our patients' needs, it is vital that we develop and bring to market new effective treatment options. Three things stand out about the Phase 3 development programs that are important from an investigator and physician perspective that I want to share with you today.

Speaker 3

First, the Phase 3 programs are operationally efficient. 2nd, they enhance our ability to recruit patients. And third, the Phase 2 and 3 trials are similar in design, suggesting a high degree of read through as possible. All of this will make our execution of these trials more seamless. I'll break all three attributes down further.

Speaker 3

From an operational perspective, the key design elements of both Phase 3 programs make them efficient to run. This operational ease is crucial as it allows my team to manage the trials effectively while maintaining scientific rigor. In the GAD trials, reducing treatment session monitoring from 12 to 8 hours is an example of this, making delivery of MM120 more practically feasible, mirroring how I would expect to treat patients if MM120 is approved. Another significant advantage of these trials is our ability to efficiently recruit and enroll patients. While the GAD program will start earlier than the MDD program, having both programs run concurrently, we can tailor recruitment efforts to match specific diagnoses.

Speaker 3

GAD and MDD have overlapping symptoms. And this approach improves our ability to put patients in whichever program is appropriate for their clinical presentation, thereby accelerating enrollment. Lastly, the design of these trials directly builds on MindMed's Phase 2b GAD trial results. This continuity enables us to build on existing data, enhancing the ability to validate prior findings and the efficacy and safety of MM120 ODT with a high degree of consistency. In addition, the 12 week primary endpoint for the Phase 3 trials in GAD should provide evidence on durability, which I believe is of utmost importance to physicians and patients.

Speaker 3

I'm looking forward to getting these Phase 3 trials started. They have the potential to pave the way for significant advancements in treating GAD and MDD. And I'm eager to see the results of MyoMed can move forward with the development of MM120 and make a meaningful impact on patients' lives. And with that, I'll turn the call back over to Rob. Thank you, Doctor.

Speaker 3

Robison. We're excited to get started and grateful to

Speaker 1

be aligned on our pivotal programs with clinicians like you. I'll now turn to our financial results for the quarter ended June 30, 2024, which are highlighted on Slide 15. As of June 30, 2024, the company had cash and cash equivalents totaling $243,100,000 compared to $99,700,000 as of December 31, 2023. We believe that our cash and cash equivalents as of June 30, 2024, combined with the proceeds from our recently closed financing will be sufficient to fund our operations into 2027. Based on our current operating plan and anticipated R and D milestones, we expect this cash runway to extend at least 12 months beyond the top line data readout for our 1st Phase 3 trial of MN-one hundred and twenty in GAD.

Speaker 1

For the 6 months ended June 30, 2024, net cash used in operating activities was $36,600,000 compared to $27,200,000 for the same period in 2023. Research and development expenses were $14,700,000 for the quarter ended June 30, 2024, compared to $14,800,000 for the same period in 2023, representing a decrease of $100,000 The decrease is primarily due to decreases of $500,000 in expenses related to our MM120 GAD program and a decrease of $2,000,000 in expenses related to preclinical activities, partially offset by an increase of $1,000,000 in internal personnel costs as a result of increasing research and development capacity and an increase of $1,400,000 in expenses related to our MM402 program. We do anticipate R and D expenses to ramp up in the second half of this year and in 2025 as we get the Phase III studies in GAD and MDD up and running. General and administrative expenses were $9,800,000 for the quarter ended June 30, 2024, compared to $14,400,000 for the same period in 2023, a decrease of $4,600,000 The decrease was primarily attributable to professional services fees and expenses during the 3 months ended June 30, 2023. Relating to the proxy contest in connection with our 2023 Annual General Meeting of Shareholders, partially offset by increased stock based compensation expense.

Speaker 1

The company's net loss for the quarter ended June 30, 2024 was $5,900,000 compared to $29,100,000 for the same period in 2023. The decrease was primarily due to changes in the fair value of 2022 U. S. Dollar financing warrants of $15,000,000 This is an exciting time for us at Mymed with many key catalysts coming up over the next couple of years, as you can see highlighted on Slide 16. We anticipate initiating Voyage, our first Phase 3 trial in GAD in the second half of twenty twenty four and PANORAMA, our second Phase 3 trial in GAD in the first half of twenty twenty five.

Speaker 1

We also expect to initiate EMERGE, our 1st Phase 3 clinical trial in MDD in the first half of twenty twenty five. We're projecting top line Part A readouts for these pivotal trials, starting with Voyage in the first half of twenty twenty six and then Panorama and Emerge in the second half of twenty twenty six. These anticipated milestones represent significant value inflection points for our company could potentially bring us closer to providing novel and highly differentiated treatment options for patients with GAD and MDD. We believe that the evidence generated to date on MM120 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 standards of care. We are excited to advance With strong muscle protection and IP strategies and a With strong market protection and IP strategies and a cash runway into 2027 12 months beyond our first Phase 3 readout, we are well positioned to execute on our strategy.

Speaker 1

As we conclude, I want to extend my sincere appreciation and gratitude for the critical work and careful execution that has brought MyoMed 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 supported, 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 today. The team and I are happy to take any questions.

Speaker 4

Thank

Speaker 5

Our first question comes from the line of Charles Duncan with Cantor. Your line is now open.

Speaker 6

Hi. This is Elaine Chien on for Charles. Thank you for taking our questions. This is a 2 parter. For the first question, is the open label 100 microgram dose to help maintain response or remission rates versus having patients continue the 50 microgram dose in the 40 week follow-up?

Speaker 6

And for my second question, is the reduction of the treatment session duration to 8 hours from 12 hours? What information enabled this decision to be agreed by the FDA? And what requirements for patient care following the 8 hour treatment session? What requirements will be implemented? Thank you.

Speaker 1

Yes. Thanks so much, Lane. To the first question, so when we're designing the Phase 3 program, continuing patients on, I think 2 things are worth pointing out with the open label Part B portion of the study, I should say the extension Part B of the study. First is that we've been really thoughtful about how we analyze and think about the extension phase in the study because until patients actually receive open label treatment in that Part B of the study, they remained in a blinded status, until someone had actually received an open label drug. While it's an extension study with open label opportunities for treatment, they haven't actually received anything, which is unusual here.

Speaker 1

It certainly wouldn't be the case in the case of an open label extension of a daily medicine. The selection of 100 micrograms is because it is the clinical dose of interest relying on our Phase 2b results. We believe 100 microgram dose is our go forward dose and our modeling from the Phase 2b results and the MCP mod analysis we conducted there suggests that it is the dose to take forward and the efficacious dose we should be studying. Whereas the 50 microgram dose is there simply as a functional mask as an additional control to aid in addressing the concept of functional unblinding. That's the rationale.

Speaker 1

Not interested in 50 micrograms as a clinical dose to take forward or to be submitted at this time. The intent is to characterize what happens in a more real world like setting where patients would have the opportunity for retreatment upon the reemergence or the continued inefficacy after the initial phase of the study. In terms of Part B of your question or the second part of your question, we presented data. So from very early on, I know this has been a point of discussion since the advisory committee earlier this year. We have been very intentional about designing structured criteria for when patients would be allowed to end their monitoring session.

Speaker 1

In Phase 2, we went to the extreme of conservatism and used the DSM-five definition of hallucinogen intoxication. So patients had to be cleared by meeting effectively no signs of hallucinogen intoxication. As we've continued our regulatory discussions and our thinking is further evolved and been informed by the data, we have refined that checklist to be much more modeled around what we'd expect to be representative of a real world REMS like checklist for reusing patients after a dosing session. So we presented data, we collected a time course of those assessments in our Phase 2b study to characterize exactly the sort of temporal curve of when patients would be able to be part of a clinical dosing session and use those data to present to FDA and make the argument that shorter duration of monitoring is appropriate. And as we go forward in the Phase 3, Dan mentioned that the minimum required duration of monitoring in the Phase 3 will be 8 hours, but we'll also be assessing the readiness for departure from a dosing session as early as hour 5, so that we'll be able to characterize again that response starting earlier than even the required monitoring here.

Speaker 1

We also make goal that we believe that in a real world setting and when we think about labeling and RIMs, there should be a required monitoring period if there is one that's at the far left tail of the spectrum. Physician discretion should be able to be employed. And so minimizing the fixed duration of required monitoring is something that is of interest to us that we're continuing to build a structured case around to ensure that we have data in hand to make the data informed arguments to the agency.

Speaker 6

That's very helpful. Thank you so much for taking all of our questions.

Speaker 5

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

Speaker 7

Hi, good morning. Thanks for taking my question and really appreciate all the detail on the trial designs. Two questions from me. I guess first off, can you elaborate on the degree of follow-up and retreatment data that is going that you think will be required prior to filing and potential approval in GAD? Is there a bar for the durability that you need to demonstrate beyond 12 weeks and or a certain proportion of patients who will need to be retreated?

Speaker 7

And then I had a follow-up.

Speaker 1

Yes. Thanks so much, Brian. So our expectation is that because we are limited in the extent of randomized control period of studies, we run into pragmatic and ethical issues if we keep patients with severe anxiety on no background treatment after a single placebo intervention, for instance, beyond 12 weeks. So we run into a sort of limitation on how long we can do randomized controlled parallel group study. So in that because of that, we've aligned around a 12 week duration and even FDA's guidance talks about a 12 week duration to establish the response.

Speaker 1

We believe those data are sufficient to demonstrate the durability and that in terms of initial application, we would use the extension phase of the study to inform the characteristics, the dynamics of retreatment that would be informative in labeling. But we certainly are focused on our primary endpoint and our end of Phase 2 meeting really had good discussion with the agency and we believe reached alignment around that 12 week primary endpoint being the most important outcome in the study to demonstrate that durability of response after a single treatment.

Speaker 7

Okay, got it. And then how much dose dependence will you need to demonstrate between 50 and 100 micrograms in order to address potential regulatory questions about functional unblinding? Do you need to show a statistical separation between those two arms or just a trend? Thanks. I'll hop back in the queue.

Speaker 1

Yes. This is a great and really interesting question and one that we have both thought about extensively and internally as we designed our Phase 3 program and discussed extensively with the agency. Our view is that the 15 microgram control is simply there as a control. It is not of statistical interest to us. Our Phase 2 study was intentionally designed to establish dose response.

Speaker 1

That was the primary analysis of the Phase 2 study, which we did with high degree of statistical significance. And as part of the MCT mod analysis, we come away with characterization of what we believe is the minimum clinically effective dose to achieve kind of clinical outcomes we're pursuing. That coupled with the reality that in our Phase 2 study, we saw a high degree of functional unbinding or unmasking across all active doses of drug, but that only the 2 high doses achieved a clinical response. Our belief is that 100 microgram is the go forward dose and that any other dose groups we include are not there to reestablish the dose response. They're there to try to confound patient expectancy.

Speaker 1

There's been a good degree of confusion, I think, in the field about what methodological things like an intermediate control group are there to do. And there's been a lot of confusion about the differences and similarities between expectancy, bias, functional and blinding in these studies. Our view is that 50 micrograms is a dose that overlaps with 100 micrograms, the dose of clinical interest in terms of its perceptual effects, such that patients coming into the study would if the story we'll ultimately be trying to develop here is that when a patient comes into the study with obviously a degree of expectancy because patients only enroll in clinical trials if they expect something to happen. We'll be able to inform patients that if they feel the effects of a drug during a treatment session, they may be receiving a dose that is the active dose of drug or they may be receiving a dose that they will feel with a similar effect, but that has been shown in previous studies to not be clinically active. And so we're trying to mitigate the expectancy bias.

Speaker 1

The reality is that after a patient receives a dose, whether it be placebo 50 micrograms or 100 micrograms, they will have the new knowledge of the feelings of the effect of that drug. And we fundamentally believe that the feeling of the drug is the mechanism of the drug as is very often the case in psychiatry. And so we do not intend or believe it is necessary to analyze statistically the 50 microgram dose. Our intent is to compare 100 micrograms versus placebo, which has been the regulatory standard for virtually all approved drugs, but certainly all approved drugs for GAD and for MDD. And again, that 50 microgram control then is simply there as an additional aid in functional blinding and to prove out the robustness of the 100 microgram dose effect across 3 different study designs and 3 different allocations.

Speaker 7

That's really helpful. Thanks so much.

Speaker 5

Thank you. Our next question comes from the line of Rudy Lee with Leerink Partners. Your line is now open.

Speaker 4

Hi, thanks for taking my question. Congrats on the progress. Regarding the regulatory pathway in GAD, did you confirm with the FDA that the Phase IIb can be used as one of the pivotal trials? Or do you still need both Phase III trials to file the NDA? And quickly just a follow-up to Brian's question.

Speaker 4

With the 1st Phase 3 JAD starting in the second half of the year, what will be the rate limiting steps for filing considering the 40 week open label retention trial? Thanks.

Speaker 1

Yes. Thanks so much, Rudy. In terms of regulatory pathway, the Phase 2b study that we conducted is not a pivotal study. We intend to file with 2 Phase 3 studies, which are planned, the Voyage and PANORAMA studies. Secondly, in terms of the rate limiting, of course, we have come away with end of Phase 2 with a high degree of alignment.

Speaker 1

Always there's the caveat that many of the final decisions about what is going to be required for an NDA are reserved for discussions in a pre NDA meeting. But I believe at this stage is that the completion of the Part A of the Voyage and Panorama studies is the rate limiting factor to demonstrate 2 adequate well controlled studies that demonstrate the safety and efficacy of the drug. And that while we have an ongoing clinical pharmacology program and we'll have Part B of the studies that will be informative in that process, we believe a data cut from Part B of our Phase III studies would be adequate to enable submission.

Speaker 4

Got it. Very helpful. Thanks.

Speaker 5

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

Speaker 8

Hi, this is Dan on for Frank. Thanks for taking our questions. I guess related to some other questions that have been going on. Could you talk a little bit more about the end of Phase 2 meeting, especially considering the Lycos adcom, whether there were any issues or concerns that were raised during the meeting? And thanks for all the color around the strategies that you've taken, but was there any surprises during the meeting?

Speaker 8

Anything you want to add there?

Speaker 1

Yes. Thanks so much for the question, Dan. Our End of Phase 2, we got fortunate in the sequencing of the regulatory events that have happened this year. So we had our End of Phase 2 meeting very shortly after the Likos Advisory Committee, which we thought was a great benefit because it allowed us to integrate the thinking and feedback and obviously the public conversation from the Likos AdCom into our discussions with the agency and something that we greatly value to us to be able to learn from other happenings in the field to make sure we're pursuing a strategy we're really confident in. So we had a great discussion with the agency.

Speaker 1

I think we came away with a higher degree of alignment. There are no surprises. There's certainly a shared dialogue around trying to solve complex issues. I think we're incredibly appreciative of the agency in terms of their willingness to engage in those conversations, their willingness to be pragmatic and to with the plan we have designed, we will have a strong case to be made both to the agency and to any commentators or observers or whether that be an advisory committee or in peer reviewed publications and the broader narratives that we can go over the compelling argument for both the value proposition and the safety and efficacy of the drug that would allow us to then proceed to a submission. So no surprises.

Speaker 1

I would say that we had a very constructive dialogue and came away with a clear path forward.

Speaker 8

Great. And just as a quick follow-up, the dose relationship being going after 50 micrograms and 100 micrograms, does the FDA generally agree with that approach that demonstrating a dose relationship just address the expectancy bias or functional blinding issue?

Speaker 1

I think I understand your question. So we presented our view and our logic and our strategy at our end of Phase 2 meeting and in our Phase 3 protocols, and we're certainly confident in the path forward in our plans to address these issues. I think it's really important to for us to highlight the reality that this is a very common issue in psychiatry. While there's been a sort of spotlight shown on the matter of expectancy and functional unblinding. This is how psychiatry drugs work, particularly for mood and anxiety disorders.

Speaker 1

2 milligrams of Xanax is fully functionally unblinded. And based on historical research, even SRIs have something like a 70% incidence of patients being able to correctly guess that they're on an SRI. It's only that under 5% of historical studies of SRI that actually asked the question or appeared to look. So while this is being scrutinized in our field, it's not unusual. And in that, we believe that we should follow the well established precedents for evidence required to establish the safety and efficacy of drugs, which is demonstrating statistically and clinically significant improvement over a placebo.

Speaker 1

That's what our program is designed around. And while we include many, many aspects to try to mitigate and address the questions around expectancy and functional and blinding, we have alignment, we believe, with the agency on the path forward. Again, this is just something that is not all that new, even though it's been highly talked about over the last couple of months.

Speaker 8

Great. Thanks for taking all questions.

Speaker 1

Thanks, Dan.

Speaker 5

Thank you. Our next question comes from the line of Joel Beatty with R. W. Baird. Your line is now open.

Speaker 7

Good morning. This is Christopher Chen on for Joel. Thanks for taking our question. In terms of 120, I know your primary focus is the domestic market, but have you started at all analyzing ex U. S.

Speaker 7

Opportunities? And if so, how would you characterize that analysis? Thank you.

Speaker 1

Yes. Thanks so much, Christopher. We have started to analyze ex U. S. Markets and engage in certainly some dialogue about those opportunities.

Speaker 1

We do not at this time intend to develop a sales force or launch the drug most ex U. S. Markets, our focus would be on the U. S. Markets, and we're certainly open to engaging and discussing collaborations and partnerships ex U.

Speaker 1

S. When it makes sense about potential commercialization in those markets. But obviously, the dynamics of, for instance, launching a drug in Europe and the pricing and various considerations there would be, we think, a lower return on investment than our focus on launching the drug in the U. S. Primarily.

Speaker 4

Thank you.

Speaker 5

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

Speaker 9

Good morning. Thanks for taking my questions. Do you have any specific targets for prior use of LSD or other psychedelics as inclusion criteria in your Phase 3 trials? And in the open label portions of your studies, how do you ensure integrity is maintained to make sure that any potential durability of effect is more purely attributable to MM120 versus other treatments or therapy?

Speaker 1

Yes. Thanks so much, Sumant. I'll turn that over to Dan Carlin to address that one.

Speaker 2

Yes. So thanks, Sumant. For prior psychedelic or LSD exposure, we have explicit exclusion criteria related to recent use and any heavy use over a number of years preceding enrollment. So while we don't specify beyond that from an inclusion exclusion perspective, we certainly want to be sure that we're getting folks who aren't currently using or recent heavy users. We also will in Phase 3 track use history of course.

Speaker 2

And what we found in Phase 2 was in essence with these criteria because we're moving into Phase 3 very much with inclusion exclusion mirroring Phase 2. What we found was about a 15% to 20% historical usage in the population we ended up enrolling, which interestingly aligns almost exactly with epidemiological findings on use in the general population. So as ever, we want to get a population that is representative of the overall GAD population as possible. And we think we did that in Phase 2 and we'll continue to do that in Phase 3. As far as data integrity attribution of efficacy, The extension phase that we discussed and that Rob expanded on a bit in the prior question is really going to be run very much the same way that the blinded phase is run.

Speaker 2

So that in all of our studies, we wash people out of background therapy. If folks are engaging in psychotherapy outside of

Speaker 1

the trial, that has to

Speaker 2

be sort of stable and unchanging for a period of time, both before and through the trial. And we'll continue to enforce those same restrictions on outside treatment, other treatments, newly added psychotherapy through the entire extension phase. So while we do give folks the opportunity to get either dosed for the first time if they started in a placebo arm or a control arm, the expectation is that the only treatment that they're receiving, the only newer change treatment that they're receiving and the only pharmacological treatment that they're receiving through the entire extension phases is MM120.

Speaker 1

Thank you.

Speaker 5

Thank you. And I'm currently showing no further questions in the queue. This does conclude today's conference call. Thank you all for joining and you may now disconnect.

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