Definium Therapeutics, Inc. Q2 FY2024 Earnings Call

Good morning, and welcome to the Mind Medicine 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 Barrow, CEO of MindMed. Please go ahead.

Thank you, and good morning, everyone. Welcome to our second quarter 2024 financial results and corporate update conference call. Today, we will be sharing highlights from the second quarter 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&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 reporting 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. 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 processes. These and other risk factors are described in the filings made with the SEC, including our annual report on Form 10-K and our Form 10-Q filed today. Forward-looking statements are based on the assumptions, opinions and estimates of management of the date the statements are made, including the non-occurrence of the risks and uncertainties that are described in the filings made with the SEC, or other significant events occurring outside of MindMed's normal course of business. You are cautioned not to place undue reliance on these forward-looking statements, which are made as of today, August 13, 2024. MindMed 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 2024 business update and then Dr. Dan Karlin, our Chief Medical Officer will join to discuss our R&D plans for MM120 oral disintegrating tablet, or ODT in GAD and MDD. We are also pleased to be joined by Dr. Reid Robison, Senior Principal Investigator, Cedar Clinical Research and Adjunct Faculty at the University of Utah. Dr. Robison is an investigator in our MM120 clinical development program and will provide his views on our Phase 3 clinical trials. Following Dr. Robison, I'll discuss our second quarter financial highlights, share our anticipated upcoming milestones, and then we'll conclude with the Q&A session where we will also be joined by Dr. Francois Lilienthal, our Chief Commercial Officer to answer your questions. On Slide 4, I'm pleased to share our progress for the quarter and for 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 the advancement of MM120 into pivotal Phase 3 clinical trials for GAD. We are on track to initiate our first Phase 3 trial for MM120 ODT in GAD in the second half of 2024, which marks a major milestone in our development program. We are also excited to share with you our plans to expand our R&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 2025. We also expect to conduct a second registrational study in MDD with the study design and timing to be informed by the Emerge Study and additional regulatory discussions. The scope and sequencing of our clinical program for MM120 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. 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 2041, providing further runway for potential commercialization. We have also seen continued progress with our second 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. 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 million 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 first Phase 3 clinical readout in GAD. Importantly, this funding demonstrates the continued enthusiasm towards our programs and strategy and allows us to rapidly advance MM120 in both GAD and MDD. Here on Slide 5 is a look at our pipeline of three clinical stage programs, including our Phase 3 trials for MM120 in GAD and MDD. As I mentioned, we remain on track to initiate the pivotal Phase 3 program for MM120 in GAD in the second half of 2024, and we intend to initiate the first registrational study in our newly announced MDD program in the first half of 2025. 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 in 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 comorbid depression symptoms in GAD patients. In the U.S. alone, there are 20 million adults with GAD and 31 million adults with MDD. Of these, 13 million and 18 million are treated annually for GAD and MDD, respectively. These two markets represent a substantial opportunity for effective treatments. We believe that, if approved, MM120 could offer patients a differentiating and compelling option in both GAD and MDD, which could position it to become a best-in-class treatment option targeting two of the biggest market opportunities in psychiatry. 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 three registrational studies across the GAD and MDD programs, including the Voyage and Panorama studies in GAD and the Emerge Study in MDD. The initiation of pivotal studies for MM120 truly represents a major milestone for MindMed, 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 study, 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 Lykos 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. 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 to safety monitoring follows well established industry best practices. Through our Phase 3 clinical trials and dedicated clinical pharmacology trials, we intend to fully and robustly characterize the safety of MM120. Our development of MM120 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 in GAD demonstrated compelling tolerability and efficacy data that exceeds today's standard of care. 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 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 Dr. Dan Karlin, our Chief Medical Officer to discuss our clinical development programs in detail. Dan?

Thank you, Rob. Turning to Slide 10. We believe 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 in GAD. In this trial, we observed a rapid onset of effect with a 1.8 point reduction in Clinical Global Impression Severity, or CGI-S, 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 HAM-A, at week 12 in participants treated with 100 micrograms. This further improvement from week four 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. These outcomes support our Phase 3 program in GAD. I'll now discuss our Phase 3 development plan for MM120 in GAD on 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 two pivotal clinical trials, the Voyage study and the Panorama study. Each trial consists of two parts. 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 1:1 to receive MM120 ODT 100 micrograms or placebo. Panorama is anticipated to enroll approximately 240 participants who will be randomized 5:2:5 to receive MM120 ODT 100 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 2 and 3 studies to address key methodological issues such as functional and blinding. 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 across active doses, the lower doses, 25 micrograms and 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 MM120 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 in nuisance parameters with the goal of maintaining statistical power and enhancing the interpretability of our results. 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 HAM-A score of 20 or greater. During Part B of the Phase 3 studies, investigators will closely monitor patients using electronic patient reported outcomes, centrally rated HAM-A, and clinician administered scales. Participants will be eligible for retreatment with MM120 ODT 100 micrograms if their HAM-A score reaches 16 or higher, with up to four 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 will include time to retreatment or inefficacy. 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 change 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. We will continue to collect data on monitoring times and safety 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 first Phase 3 trial Voyage in GAD this year. Turning to Slide 12. As Rob stated earlier, we are also excited to announce the expansion of our R&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-Asberg Depression Rating Scale, or MADRS, score at week 12. 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 two pivotal clinical trials. Our first trial, the Emerge Study, like our pivotal trials in GAD, will be comprised of two 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; 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. Emerge is anticipated to enroll at least 140 participants, randomized 1:1 to receive MM120 ODT 100 micrograms or placebo. The primary endpoint in Emerge will be the change from baseline in MADRS score at week six between MM120 ODT 100 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 in MDD will balance this exciting opportunity across two pivotal programs with our continued operational and financial diligence. With that, I am happy to introduce Dr. Reid Robison, who will provide his perspective on our Phase 3 trials.

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 GAD Phase 2b results are truly impressive, with MM120 exhibiting rapid and robust efficacy sustained 12 weeks after a single dose. Equally impressive is the change in MADRS score from baseline to week 12 in the Phase 2b GAD trial, with participants showing improvement in comorbid depressive symptoms. For people suffering from GAD, including those with comorbid depression, these trials offer a beacon of hope, and I've seen firsthand how debilitating both conditions are and how they severely impact quality of life. Given that current standards of care are 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. First, the Phase 3 programs are operationally efficient. Second, 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. 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. GAD and MDD have overlapping symptoms, and this approach improves our ability to place 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. 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 so MindMed 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, Dr. Robison. We're excited to get started and grateful to 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 $243.1 million, compared to $99.7 million 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&D milestones, we expect this cash runway to extend at least 12 months beyond the top line data readout for our first Phase 3 trial of MM120 in GAD. For the six months ended June 30, 2024, net cash used in operating activities was $36.6 million, compared to $27.2 million for the same period in 2023. Research and development expenses were $14.7 million for the quarter ended June 30, 2024, compared to $14.8 million for the same period in 2023, representing a decrease of $0.1 million. The decrease is primarily due to decreases of $0.5 million in expenses related to our MM120 GAD program and a decrease of $2 million in expenses related to preclinical activities, partially offset by an increase of $1 million in internal personnel costs as a result of increasing research and development capacity and an increase of $1.4 million in expenses related to our MM402 program. We do anticipate R&D expenses to ramp up in the second half of this year and in 2025 as we get the Phase 3 studies in GAD and MDD up and running. General and administrative expenses were $9.8 million for the quarter ended June 30, 2024, compared to $14.4 million for the same period in 2023, a decrease of $4.6 million. The decrease was primarily attributable to professional services fees and expenses during the three 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. The company's net loss for the quarter ended June 30, 2024 was $5.9 million, compared to $29.1 million 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 million. This is an exciting time for us at MindMed 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 2024 and Panorama, our second Phase 3 trial in GAD in the first half of 2025. We also expect to initiate Emerge, our first Phase 3 clinical trial in MDD in the first half of 2025. We're projecting top line Part A readouts for these pivotal trials starting with Voyage in the first half of 2026 and then Panorama and Emerge in the second half of 2026. These anticipated milestones represent significant value inflection points for our company, and 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 our pipeline and to be on the cusp of moving forward with our pivotal development programs for MM120 in both GAD and MDD. With strong market protection and IP strategies and a cash runway into 2027 and 12 months beyond our first Phase 3 readout, we are well positioned to execute on our strategy. As we conclude, I want to extend my sincere appreciation and gratitude for the critical work and careful execution that has brought MindMed ever closer to realizing our mission. I would like to thank our highly talented and deeply committed team, our research collaborators and clinical investigator teams, our investors and the many other individuals who have been supportive, 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. And the team and I are happy to take any questions.

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

Hi. This is Elaine Kim on for Charles. Thank you for taking our questions. This is a two-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? And for my second question, regarding 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 will be implemented? Thank you.

Yeah. Thanks so much, Elaine. To the first question, when we're designing the Phase 3 program and considering the open label Part B portion of the study, there are two things worth pointing out. First, until patients actually receive open label treatment in Part B, they remain in a blinded status; although Part B is structured as an extension with open label opportunities, until someone has actually received open label drug they have not received anything in practice. Second, the selection of 100 micrograms is because it is the clinical dose of interest. Relying on our Phase 2b results and our MCP-Mod modeling, we believe 100 micrograms is the go-forward dose and the efficacious dose we should be studying. The 50 microgram dose is included simply as a functional mask, an additional control to aid in addressing the concept of functional unblinding; we are not taking the 50 microgram dose forward as a clinical dose at this time. The intent of Part B is to characterize what happens in a more real-world-like setting where patients have the opportunity for retreatment upon reemergence of symptoms or lack of continued efficacy after the initial phase of the study. Regarding the second part of your question, we presented data from Phase 2 that characterized the time course of assessments used to determine readiness for release from monitoring. In Phase 2 we used a conservative approach modeled on definitions of intoxication; as our regulatory discussions progressed and were informed by the data, we refined that checklist to more closely align with a real-world clinical checklist for releasing patients after a dosing session. We used the Phase 2b time course data to make the argument to FDA that a shorter duration of monitoring is appropriate. For Phase 3, the minimum required monitoring duration will be 8 hours, but we will also assess readiness for departure as early as hour five so we can characterize the potential to release patients earlier. Ultimately, physician discretion should play a role and minimizing a fixed required monitoring duration, where supported by data, is an objective for us as we build the evidence base.

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

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

Hi. Good morning. Thanks for taking my question, and really appreciate all the detail on the trial designs. Two questions from me. First, can you elaborate on the degree of follow-up and retreatment data 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? And then I had a follow up.

Yes. Thanks so much, Brian. Our expectation is that because we are limited in how long we can ethically and pragmatically keep patients with severe anxiety untreated after a single placebo intervention, we've aligned around a 12 week randomized, controlled period. FDA guidance also references 12 weeks to establish response. We believe those data are sufficient to demonstrate durability for the primary application. The extension phase, Part B, will inform the characteristics and dynamics of retreatment and that information would be informative for labeling. Our End-of-Phase 2 meeting included good discussion with the agency and we believe we reached alignment around the 12 week primary endpoint being the most important outcome to demonstrate durability of response after a single treatment.

Okay. Got it. And then, how much dose dependence will you need to demonstrate between 50 and 100 micrograms in order to address the 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.

This is a great question and one we've thought about extensively. Our view is that the 50 microgram control is included as a control to help confound participant expectancy; it is not a statistical comparison of primary interest. Our Phase 2 study was intentionally designed to establish dose response and produced a high degree of statistical significance for dose response. Given the Phase 2b results, and the MCP-Mod analysis, we characterized a minimum clinically effective dose. In Phase 2 we observed a high degree of functional unblinding across active doses, but only the higher doses achieved a clinical response. We believe that 100 micrograms is the go-forward clinical dose. The 50 microgram arm is included to aid functional blinding and address expectancy bias, not to be a formal statistical comparator for the label. Our primary regulatory comparisons will be 100 micrograms versus placebo, which is the standard approach for drug approvals in GAD and MDD. The 50 microgram arm helps strengthen the overall design and robustness of the 100 microgram effect across different study allocations.

That's really helpful. Thanks so much.

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

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 2b can be used as one of the pivotal trials or do you still need both Phase 3 trials to file an NDA? And quickly, as a follow-up to Brian's question: with the first Phase 3 GAD starting in the second half of the year, what will be the rate limiting step for filing considering the 40-week extension trial? Thanks.

Thanks, Rudy. The Phase 2b study is not considered a pivotal study. We intend to file using two Phase 3 studies, the Voyage and Panorama trials. Regarding the rate limiting step, while we achieved a high degree of alignment at the End-of-Phase 2 meeting, final decisions for NDA requirements will be confirmed at a pre-NDA meeting. Our belief at this stage is that completion of Part A of Voyage and Panorama—i.e., two well-controlled studies demonstrating safety and efficacy—will be the rate limiting factor. While Part B provides informative longer term data, we believe a data cut from Part B could be adequate to enable submission alongside the primary data from Part A.

Got it. Very helpful. Thanks.

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

Hi. This is Dan on for Frank. Thanks for taking our questions. Could you talk a little bit more about the End-of-Phase 2 meeting, especially considering the Lykos Advisory Committee, 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 were there any surprises during the meeting? Anything you want to add there?

Yes. Thanks for the question, Dan. We were fortunate in the sequencing of regulatory events this year. Our End-of-Phase 2 meeting occurred shortly after the Lykos Advisory Committee, which we thought was beneficial because it allowed us to integrate the thinking and public discussion from that advisory committee into our discussions with FDA. We had a great discussion with the agency and came away with a high degree of alignment; there were no surprises. There was constructive dialogue about complex issues and we appreciated the agency’s willingness to be pragmatic and engage in ways that do not slow development. Our view coming out of that meeting is that our planned program provides a strong case to the agency and to external observers through scientific publications and peer-reviewed evidence that will support the value proposition, safety, and efficacy of MM120 and allow us to proceed toward submission. So no surprises—just a constructive and clear path forward.

Great. And just as a quick follow-up, the dose relationship—going after 50 microgram and 100 microgram—does the FDA generally agree with that approach to demonstrate a dose relationship and to address expectancy bias or functional blinding issues?

I think I understood your question. We presented our rationale and strategy at the End-of-Phase 2 meeting and in our Phase 3 protocols and are confident in the path forward. It is important to note that functional unblinding and expectancy are not unique to this field; many psychiatric drugs produce perceptible effects and historical precedents exist for regulatory approval based on statistically and clinically significant improvement over placebo. Our program is designed to follow those precedents while including multiple complementary measures—central raters, expectancy and blinding questionnaires, a lower-dose arm to aid functional blinding, and other design elements—to address these methodological concerns. We have alignment with FDA on our overall approach and believe this path is consistent with established standards for demonstrating safety and efficacy.

Great. Thanks for taking our questions.

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

Good morning. This is Christopher Chen on for Joel. Thanks for taking our question. In terms of MM120, I know your primary focus is the domestic market, but have you started at all analyzing ex-U.S. opportunities? And if so, how would you characterize that analysis? Thank you.

Thanks, Christopher. We have started to analyze ex-U.S. markets and engaged in dialogue about those opportunities. At this time, we do not intend to develop a sales force or launch the drug in most ex-U.S. markets; our primary focus will be the U.S. We are open to collaborations or partnerships for ex-U.S. commercialization when it makes strategic sense. Launch dynamics, pricing, and other considerations in markets like Europe would lead us to prioritize the U.S. market first given expected returns on investment.

Thank you.

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

Good morning. Thanks for taking my questions. Do you have any specific targets for prior use of LSD or other psychedelic 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?

Thanks, Sumant. I'll turn that over to Dan Karlin to address the specifics.

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. While we do not specify additional thresholds beyond those exclusion criteria, we want to ensure we are not enrolling people who are current users or recent heavy users. In Phase 2b we tracked lifetime and prior use history and found about a 15% to 20% historical usage rate in the population we enrolled, which aligns with epidemiological data in the general population. We aim to enroll a population representative of the overall GAD population, and we'll carry that approach into Phase 3. Regarding data integrity and attributing durability of effect to MM120, the extension phase will be conducted similarly to the blinded phase. Background psychotherapy, if present, must be stable and unchanging for a defined period before and during the trial, and we will enforce the same restrictions in the extension phase. Outside treatments or newly added psychotherapy during the extension will be restricted. While participants who were on placebo will have the opportunity to receive MM120 in Part B, the expectation is that the only new or changed pharmacological treatment participants receive through the extension phase will be MM120.

Thank you.

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.