Full Year 2023 Mind Medicine (MindMed) Inc Earnings Call

[music].

Operator: Good morning, and welcome to the Mind Medicine Full Year 2023 Financial Results and Corporate Update conference call. Currently, all participants are in 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.

Okay.

Good morning, and welcome to the mine Medicine full year 2023 financial results and corporate update conference call.

Currently all participants are in listen only mode. This call is being webcast live on the investors and media section of the mine next website at <unk> Dot com.

And a recording will be available after the call.

Rob Barrow: For opening remarks, I would like to introduce Rob Barrow, CEO of MindMed. Please go ahead. Thank you and good morning, everyone. Welcome to our full year 2023 financial results and corporate update conference call. The press release reporting our financial results is available in the Investors and Media section of our website, and our annual report on Form 10-K for the year ended December 31, 2023 is being filed today with the Securities and Exchange Commission. During today's call, we will be making certain forward-looking statements, including, without limitation, statements about the potential safety, efficacy, and regulatory and clinical progress of our product candidates, our anticipated cash runway, and our future expectations, plans These statements are subject to various risks, such as changes in market conditions and difficulties associated with research and development and regulatory approval processes that are described in the filings made with the SEC, including our annual report on Form 10-K being filed today.

For opening remarks, I would like to introduce Rob burrow CEO of mind, Matt. Please go ahead.

Okay.

Thank you and good morning, everyone welcome to our full year 2023 financial results and corporate update conference call.

Press release reporting our financial results is available in the investors and media section of our website and our annual report on Form 10-K for the year ended December 31, 2023 is being filed today with the Securities and Exchange Commission.

During today's call, we will be making certain forward looking statements, including without limitation statements about the potential safety efficacy and regulatory and clinical progress of our product candidates, our anticipated cash runway and our future expectations plans partnerships and prospect.

These statements are subject to various risks such as changes in market conditions difficulties associated with research and development and regulatory approval processes that are described in our filings made with the SEC, including our annual report on Form 10-K being filed today.

Rob Barrow: Forward-looking statements are based on the assumptions, opinions, and estimates of management at the date the statements are made, including the non-occurrence of the risks and uncertainties that are described in the filings made with the SEC or other significant events occurring outside of MiMed's normal course of business. Please use caution not to place undue reliance on these forward-looking statements, which are made as of today, February 28th, 2024. MindMed disclaims any obligation to update such statements, even if management's views change, except as required by law.

Forward looking statements are based on the assumptions opinions and estimates of management at the date. The statements were made including the non occurrence of the risks and uncertainties that are described in our filings made with the SEC or other significant events occurring outside of mine that's normal course of business.

You are cautioned not to place undue reliance on these forward looking statements, which are made as of today February 28 2024.

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

Rob Barrow: Joining me on today's call are Sean Greenway, our Chief Financial Officer, and Dr. Daniel Carlin, our Chief Medical Officer. We are excited to be providing this financial and business update during this important period for Mindville. 2023 was a highly productive year for MindMed, which included positive phase 2b results for MN120 in the treatment of patients with generalized anxiety disorder, or GAD. We believe that the initial data we shared validates our scientific understanding of MN120's mechanism of action and shows the potential for an emerging best-in-class product profile compared to today's standards.

Joining me on today's call are Sean Greenway, our Chief Financial Officer, and Dr. Daniel Carlson, our Chief Medical Officer.

We are excited to be providing this financial and business update during this important period remind matt.

2023 was a highly productive year for my bed, which included with positive phase <unk> results for and then 120 and the treatment of patients with generalized anxiety disorder or <unk>.

We believe that the initial data we shared validates our scientific understanding it and then 100 twenty's mechanism of action and shows the potential for an emerging best in class product profile compared to today's standard of care.

Rob Barrow: On March 7th, we will be hosting a virtual investor event during which we look forward to sharing top-line 12-week data from our Phase 2B study of MN120 and GAD, as well as KOL perspectives on the generalized anxiety disorder market, the data, and our initial views on a commercial opportunity. In addition, we anticipate sharing results from our Phase I Pharmacokinetics Bridging Trial to support the differentiated product profile of our MM120 Orally Dissolving Tablet, or ODT formulation, and its advancement into pivotal clinical trials in GAD. We are excited about this upcoming event and hope most of you will be able to join us.

On March 10th we will be hosting a virtual investor event during which we look forward to sharing top line 12 week data from our phase <unk> study it and then 120th JD as well as Kols perspectives on the generalized anxiety disorder market the data in our initial views on the commercial opportunity.

In addition, we anticipate sharing results from our phase one pharmacokinetic bridging trial to support the differentiated product profile of <unk>, and then 128 orally dissolving tablet or ODT formulation and its advancement into pivotal clinical trials.

Yeah.

We are excited about this upcoming event and hope most of you will be able to join US. Please keep an eye out for additional information.

Rob Barrow: Please keep an eye out for additional information. Looking further into 2024, we'll be working closely with the FDA to finalize our Phase III development program for MM120 and GAD and expect to hold our end-of-Phase II meeting with the FDA in the first half of the year. This is intended to enable the initiation of our Phase III clinical program in the second half. In addition, this year, we anticipate sharing one-year follow-up results from a study of lysorgye and anxiety disorders, which was conducted by our collaborators at University Hospital Boston. Our progress comes at a crucial time with an urgent unmet need for better treatments to address the ongoing epidemic of brain health disorders, a situation that has grown significantly worse over the past several years. In our lead indication, GAD, for example, a recent mental health prevalence study that was prepared for the Substance Abuse and Mental Health Services Administration found that 10% of U.S. adults report having symptoms consistent with a GAD diagnosis, making it the second most common mental health disorder among adults 18 to 65 years old.

Looking further into 2024 will be working closely with the FDA to finalize our phase III development program for <unk>, and then 120th JD and expect to hold our in the phase II meeting with the FDA in the first half of the year.

This is intended to enable the initiation of our phase III clinical program in the second half of the year.

In addition, this year, we anticipate sharing one year follow up results from a study of lighter Jive and anxiety disorders, which was conducted by our collaborators at University Hospital Basel.

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

Our lead indication for.

For example, our recent mental health prevalent study that was prepared for the substance abuse and mental health services administration.

The 10% of U S. Adults report, having symptoms consistent with the J D diagnosis, making it the second most common mental health disorder. Among adults 18 to 65 years old.

Rob Barrow: In comparison to historical studies of the prevalence of GAD, the condition appears to have tripled in the last two decades alone. This growth in prevalence and focus of anxiety disorders has unfortunately not been matched by innovative treatments, with the treatment landscape remaining dominated by SRIs, benzodiazepines, and, in more limited cases, antipsychotics. In fact, the last original approved marketing application that was focused on the treatment of JAD was obtained for Cymbalta in 2004. While each of these medicines has gone on to become blockbuster products driving significant value to the innovators, the ethics of these products have been limited, and in many instances, intolerable side effects, such as sexual dysfunction and weight gain, have led to noncompliance and discontinuation of treatment, which we believe has created a significant Seeking to address these growing issues, our R&D pipeline is focused on two lead product candidates, MM120, or Lysergide Detartrate, and MM402, or R-MDMA. Additionally, through a broad collaboration with researchers at University Hospital Baselund, so it's We are exploring the potential of several assets to potentially expand our development pipeline as our LEAD programs continue to progress.

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

This growth in prevalence and focus of anxiety disorders is unfortunately, not been matched by innovative treatments.

Treatment landscape remaining dominated by Ssris, benzodiazepine and more limited cases and types of products.

In fact, the last original approved marketing application was focused on the treatment of J D was obtained for Cymbalta in 2004.

While each of these medicines have gone onto become blockbuster products driving significant value to the innovators. The efficacy of these products has been limited and in many instances intolerable side effects, such as sexual dysfunction weight gain Atlantic noncompliance and discontinuation of treatment, which we believe has created a significant need in the market for novel treatment options.

Seeking to address these growing issues. Our R&D pipeline is focused on two lead product candidates, and then 120, <unk> and <unk> or our MD&A.

Additionally, through a broad collaboration with researchers at University Hospital, Basel, Switzerland, we're exploring the potential of several assets to potentially expand our development pipeline is our lead programs continued to progress.

Across these development programs are utilizing two different delivery paradigm.

120 in <unk>, we are pursuing a session based delivery approach in which the product candidate is administered under ongoing healthcare supervision.

Rob Barrow: Across these development programs, we're utilizing two different delivery approaches. For MM120 and GAD, we are pursuing a session-based delivery approach in which the product candidate is administered under ongoing healthcare supervision. Meanwhile, separately for MM402 and ASD, we are pursuing a standard outpatient drug delivery approach in which we anticipate the product candidate being administered on a daily basis at home. Our MM120 program in GAD has seen extraordinary progress over the past year, culminating in the four-week data from our Phase 2B trial that we announced in December 2023. The trial met its primary end point with statistical and clinically meaningful reductions in HAM-A scores four weeks after a single administration of MN120. We observed the largest clinical activity in the 100-microgram dose group with an observed effect size of 0.88.

Separately and then for our ASD, we are pursuing a standard outpatient drug delivery approach in which we envisioned the product candidate being administered on a daily at home basis.

And then 120 program and JD has an extraordinary progress over the past year, culminating in the four week data from our phase <unk> trial that we announced in December 2023.

The trial met its primary endpoint with statistical and clinically meaningful reductions in <unk> score is four weeks after a single administration of an ever more in 'twenty.

We observed the largest clinical activity in the 100 microgram dose group and observed effect size of 0.88.

On an absolute basis. This represents a 21 three point improvement score from baseline to week, four and was seven six points better than placebo with an associated P value of 0.0004.

And this group we also observed a 78% clinical response rate, 50% clinical remission rate at four weeks being at four weeks. After a single dose and then went to 20 half of the participants no longer showed clinically significant anxiety.

Rob Barrow: On an absolute basis, this represents a 21.3 point improvement in HAM-A score from baseline to week 4 and was 7.6 points better than placebo with an associated p-value of 0.0004. In this group, we also observed a 78% clinical response rate and a 50% clinical remission rate at four weeks, meaning that four weeks after a single dose of MN121, half of the participants no longer showed clinically significant anxiety, and 78% of participants achieved a 50% or greater reduction in HAM-A score. Additionally, we observed clinically and statistically significant improvements in all of the secondary endpoints at all time points analyzed as part of the top-line analysis, which included HAM-A, CGIS, and Madras results through Week 4. AMIN 120 was well-tolerated in the trial with mostly transient, mild to moderate adverse events that predominantly occurred at the dose. In the context of currently available therapies for GAD, these results represent a major step forward in the field, which has suffered from practically no innovation in the last 20 years.

78% of participants achieved a 50% or greater reduction in PMA score.

Additionally, we observed clinically and statistically significant improvement in all of the secondary endpoints at all time points analyzed as part of the topline analysis, which included him a CGI S. Madras results through week four.

And then 120th was well tolerated in the trial with mostly transient mild to moderate adverse events that predominantly occurred on the dosing day.

In the context of currently available therapies for JD. These results represent a major step forward in the field that have suffered from practically no innovation in the last 20 years.

Cohen's D standardized effect sizes $0 88 in the 100 microgram dose group is more than double the effect size of the current standard of care for JV, which are estimated to have effect sizes below 0.4 on average.

We believe this result can be attributed to the Standalone effective and then 120 treatment as the study was conducted in the absence of any other therapeutic intervention.

These results also bill on over 20 legacy studies of Liza, Giner, LSD or anxiety depression, and other neurotic disorders, including our collaborators investigator initiated trial in anxiety.

Rob Barrow: The Cohen's d standardized effect size of 0.88 in the 100 microgram dose group is more than double the effect size of the current standard of care for GAD, which is estimated to have effect sizes below 0.4 on average. We believe this result can wholly be attributed to the stand-alone effect of MN-120 treatment as the study was conducted in the absence of any other therapeutic intervention.

Clifford statistically significant results in mid 2022.

We believe that the amendment 20 phase <unk> data clearly supports dose selection for our subsequent research and it supports advancement into pivotal phase III clinical trials for <unk>.

With the results of this trial, we achieved all of our goals of Phase II development, and then 120.

In particular, we have rigorously characterize a dose response relationship and then 120 <unk> achieved statistically significant and clinically meaningful results supporting its clinical activity and demonstrated the standalone impacted and then more in 'twenty to deliver rapid and durable clinical benefits validated and regulatory accepted.

Rob Barrow: These results also build on over 20 legacy studies of lysorgye or LSD in anxiety, depression, and other neurotic disorders, including an investigator-initiated trial and anxiety that delivered statistically significant results in mid 2022. We believe that the MN120 Phase IIb data clearly supports dose selection for our subsequent research, and it supports advancement into physical Phase III clinical trials for GAD. With the results of this trial, we achieved all of our goals of Phase II development for MM120. In particular, we have rigorously characterized the dose-response relationship of MM120 and GAD, achieved statistically significant and clinically meaningful results supporting its clinical activity, and demonstrated the stand-alone impact of MN-120 to deliver rapid and durable clinical benefits on validated and regulatory accepted.

With this exciting progress we are entering a phase of many anticipated key development milestones for the quarters ahead.

As I mentioned earlier at our upcoming Investor event on March 7th we will be sharing top line 12 week data from our phase <unk> study at the new 120, <unk>, along with PK bridging data Brian tend to go to market formulation, which we believe will serve to further differentiate our product candidate and demonstrated compelling clinical potential.

We anticipate having an end of phase two meeting with FDA in the first half of 2024 to align on the scope of our phase III development program in 2000 and <unk> as.

And to initiate our phase III clinical program in the second half of the year.

We also plan to present full data from our phase <unk> trial of <unk> at a scientific meeting in 2024 and are excited to share that breakfast findings from this rich dataset.

Additionally, based on the promising data we have observed and then 120 in indications beyond <unk> depression, we are actively evaluating additional clinical indications and believe the overall development program for and then 120 may represent the best in class treatment for <unk> and beyond.

Rob Barrow: With this exciting progress, we are entering a phase of many anticipated key development milestones in the quarters ahead. As I mentioned earlier, at our upcoming investor event on March 7th, we will be sharing top-line 12-week data from our Phase 2B study of MN120 and GAD, along with PK bridging data for our intended go-to-market formulation, which we believe will serve to further differentiate our product candidate and demonstrate its compelling clinical potential. We anticipate having an end-of-Phase II meeting with FDA in the first half of 2024 to align the scope of our Phase III development program for MN120 and GAD and to initiate our Phase III clinical program in the second half of the year. We also plan to present full data from our Phase IIb trial of MN120 and GAD at a scientific meeting in 2024, and are excited to share the breadth of findings from this rich dataset.

Our second lead program is <unk>, which is the arent answered Merit MDMA.

We believe and then 402 holds promise for its potential pro social effects and favorable tolerability profile versus racemic MDMA Rds enantiomer.

The focus and then for our <unk> program is to develop a regularly administered product that treats the core symptoms of autism spectrum disorder, where ASD and particular social communication difficulties.

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

MDMA often referred to as in pathogen synthetic molecule known to enhance feelings of connectedness and compassion.

And engineered MDMA in particular is believed to boost their turn another neurotransmitter levels in the brain leading to increase their stability and interpersonal emotional connection.

Rob Barrow: Additionally, based on the promising data we have observed for MM120 and indications beyond GAD, such as depression, we are actively evaluating additional clinical indications and believe the overall development of the program for MM120 may represent the best-in-class treatment for GAD and beyond. Our second lead program is MM402, which is the RN instrument of MDMA. We believe MMM402 holds promise for its potential pro-social effects and favorable tolerability profile versus racemic MDMA or the SNM. The focus of our MM402 program is to develop a regularly administered product that treats the core symptoms of Autism Spectrum Disorder, or ASD, and particular social communication difficulties. Remarkably, despite the significant and increasing prevalence of ASD, there are currently no approved therapies specifically targeted at its core symptoms. MDMA, often referred to as an empathogen, is a synthetic molecule known to enhance feelings of connectedness and compassion.

Preclinical studies of <unk>, including does we reported earlier in 2023 has shown an acute pro social and pathogenic effects, while it's reduced dopaminergic activity suggests it might exhibit fewer stimulate neurotoxic hypothermic and abuse related effects compared to racemic MDMA pretty afternoon here.

With robust preclinical evidence supporting our approach we've initiated our first clinical trial of <unk> for Iot.

Single ascending dose trial in adult healthy volunteers in the fourth quarter of 2023.

This phase one trial is intended to characterize tolerability pharmacokinetics and pharmacodynamics of <unk> and will enable further clinical studies to characterize the effects of repeated daily doses and in <unk>.

Good too.

Exploration of early signs of efficacy in the ASD population.

Concurrently we have collaborated with our colleagues at University Hospital Basel to conduct a comparative phase one pharmacokinetic and Pharmacodynamic study R. S. Racemic MDMA, which has been completed with data anticipated in the first half of this year.

Rob Barrow: The RN Antimer of MDMA in particular is believed to boost serotonin and other neurotransmitter levels in the brain, leading to increased sociability and interpersonal emotional connection. Preclinical studies of RMDMA, including those we reported earlier in 2023, have shown acute prosocial and pathogenic effects, while its reduced dopaminergic activity suggests it might exhibit fewer stimulant, neurotoxic, hyperthermic, and abuse-related effects compared to racemic MDMA or the S&A. With robust preclinical evidence supporting our approach, we initiated our first clinical trial of MM402, a single ascending-dose trial in adult healthy volunteers, in the fourth quarter of 2023. This phase one trial is intended to characterize the tolerability, pharmacokinetics, and pharmacodynamics of MM402 and will enable further clinical studies to characterize the effects of repeated daily doses of MM402 and the exploration of early signs of efficacy in the ASD population.

This study enrolled healthy volunteers and is designed to evaluate the tolerability pharmacokinetics and acute subjective physiological endocrine effects of the three molecules.

We believe the results from this trial will expand and expedite our understanding of <unk> pharmacological profile as we progress into later stage clinical development.

With that I will turn the call over to Sean Greenway to go over our financial results John.

Thanks, Rob and thank you all for joining us today.

We will now turn to our financial results for the year ended December 31 2023.

As of December 31, 2023, the company had cash and cash equivalents totaling $99 7 million.

Compared to $142 1 million.

As of December 31, 2022.

We believe that our available cash and cash equivalents as well as our committed credit facility are expected to fund operations into 2026, if certain milestones are achieved unlock additional capital.

For the year ended December 31, 2023, net cash used in operating activities was $64 4 million compared to $51 million for the year ended December 31 2022.

Rob Barrow: Currently, we have collaborated with our colleagues at University Hospital Basel to conduct a comparative phase one pharmacokinetic and pharmacodynamic study of R, S, and racemic MDMA, which has been completed, with data anticipated in the first half of this year. This study enrolled healthy volunteers and was designed to evaluate the tolerability of pharmacokinetics and Acute Subjective, Physiological, and Endocrine Effects of the Three

Research and development expenses were $52 1 million for the year ended December 31 2023.

<unk> to $36 2 million for the same period in 2022, representing an increase of $15 9 million.

Sean Greenway: We believe that the results from this trial will expand and expedite our understanding of MN402's pharmacological profile as we progress into later stage clinical development. With that, I will turn the call over to Sean Greenway to go over our financial results. John.

The increase was primarily due to increases of $16 1 million in expenses related to clinical research and product development for the <unk> phase two b trial.

And $2 $6 million and internal personnel costs as a result of increase in research and development capacities.

Sean Greenway: Thanks, Rob, and thank you all for joining us today. We will now turn to our financial results for the year ended December 31st, 2023. As of December 31st, 2023, the company had cash and cash equivalents totaling $99.7 million compared to $142.1 million as of December 31st, 2022.

Which were offset by a decrease of <unk> $7 million in expenses related to our <unk> two program a decrease of <unk> $8 million in expenses related to various external research and development operations and a decrease of $1 2 million in expenses related to preclinical activities.

General and administrative expenses were $41 $7 million for the year ended December 31 2023.

Sean Greenway: We believe that our available cash and cash equivalents, as well as our committed credit facility, are expected to fund operations into 2026. If certain milestones are achieved, unlock additional capital. For the year ended December 31st, 2023, net cash used in operating activities was $64.4 million, compared to $50.1 million for the year ended December 31st, 2020.

Compared to $30 2 million for the same period in 2022, representing an increase of $11 5 million.

The increase was primarily attributable to a professional services fees and expenses related to the proxy contest in connection with our 2023 annual general meeting of shareholders and additional cost to support the growth of our business.

The company's net loss for the year ended December 31 2023.

Sean Greenway: Research and development expenses were $52.1 million for the year ended December 31, 2023, compared to $36.2 million for the same period in 2022, representing an increase of $15.9 million. The increase was primarily due to increases of $16.1 million in expenses related to clinical research and product development for the MM120 GAD Phase IIb trial and $2.6 million in internal personnel costs as a result of an increase in research and development capacity, which were offset by decreases of $0.7 million in expenses related to our M402 program, a decrease of $0.8 million in expenses related to various external research and development collaborations, and a decrease of $1.2 million General and administrative expenses were $41.7 million for the year ended December 31, 2023, compared to $30.2 million for the same period in 2022, representing an increase of $11.5 million. The increase was primarily attributable to professional services fees and expenses related to the proxy contest in connection with our 2023 Annual General Meeting of Shareholders and additional costs to support the growth of our business. The company's net loss for the year ended December 31st, 2023, was $95.7 million compared to $56.8 million for the same period in 2012.

It was $95 7 million compared to $56 8 million for the same period in 2022.

I will now turn the call back to Rob who will provide some closing comments.

Thank you Sean.

This is a very exciting time for us at <unk>.

We believe that the initial data on <unk> hundred 20, and J D that we shared in December validates our scientific understanding of an inland twenty's mechanism of action and shows the potential for an emerging best in class product profile compared to today's standard of care.

We look forward to sharing the 12 week data from our phase <unk> study of an inventory and <unk> at our upcoming Investor event on March seven.

We're excited to be on the cusp of moving forward into phase III with this program, which we currently expect in the second half of the year following upcoming consultations with the FDA.

As we come to a close I want to extend my sincere appreciation and gratitude the critical work and unmatched execution, which has brought mindset 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 are investors and many other individuals who have been supportive, including especially our patients and their families.

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

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

Thank you to ask a question. Please press star one wanting your telephone and wait for your name to be announced.

To withdraw your question. Please press star one again, please standby will compile the Q&A roster.

Yeah.

Our first question comes from the line of Brian Abrahams with RBC capital markets. Your line is now open.

Hi, there good morning, Thanks for taking my questions and congrats on the continued progress.

Rob Barrow: I will now turn the call back to Rob, who will provide some closing comments. Thank you, Sean. This is a very exciting time for us at MindMed. We believe that the initial data on MM120 and GAD that we shared in December validates our scientific understanding of MM120's mechanism of action and shows the potential for an emerging, best-in-class product profile compared to today's standard of care. We look forward to sharing the 12-week data from our Phase 2B study of MIM-120 and GAD at our upcoming investor event on March 7. We're excited to be on the cusp of moving forward into Phase 3 with MIM-120, which we currently expect in the second half of the year following upcoming consultations with the FDA. As we come to a close, I want to extend my sincere appreciation and gratitude for the critical work and unmatched execution that has brought MindMed ever closer to realizing its mission.

So looking forward to seeing the data and just a couple of weeks a couple of questions in that regard I guess I'm curious.

Is there an internal bar that you guys are aiming for with regards to the 12 week durability data or sort of a minimum minimum appropriate durability.

For for regulators.

Or for what Youre thinking would be the most viable commercial opportunity. There are you seeing anything different with regards to dropout rates between weeks four and 12 and then maybe just lastly on the ODT formulation I'm just curious what your expectations are for what the PK profile would need to show to maximize the chance of replicable.

<unk> in a phase III study thanks.

Terrific. Thanks, so much Brian.

Taking each of those in terms of expectations as we were heading into.

The announcement of our week four.

Primary data in December and we talked a lot about the backdrop of <unk> and the effect sizes. We are seeing there and each of those drugs has a different dynamic.

Operator: I would like to thank our highly talented and deeply committed team, our research collaborators and clinical investigator teams, our investors, and the many other individuals who have been supportive, including especially our patients and their families. We are working tirelessly to deliver on the therapeutic potential of our pipeline and to transform the treatment landscape for the many individuals living with brain health disorders. With that, I'd like to thank you all again for joining us today, and I'm happy to take any questions. Thank you. To ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again.

And it has been to of course be use acutely and has been approved on endpoints such as a four week end point.

Whereas ssris typically because they take longer to separate from Sue will take longer to take action I have looked at longer term endpoints.

That same sort of effect size standard I think it's something that we have incentives general expectation if we can exceed.

In effect size of 0.4 that would represent an improvement over the standard of care and of course, if we can do that after a single dose.

For up to three months that would be particularly exciting for us, but certainly what we saw at week four was a response, where we had half of the patients in remission at that point and we saw really a on average how many scores that were relatively stable and flat we didn't lose any activity between.

Operator: Please stand by while we compile the Q&A roster. Our first question comes from the line of Brian Abrahams with RBC Capital Markets. Your line is now open. Hi there.

One response to the weak for response.

Certainly in <unk>.

Optimistic scenario, we'd continue that kind of response out through 12 weeks and certainly from some of the historical data we have.

Brian Abrahams: Good morning. Thanks for taking my questions and congrats on the continued progress. So I'm looking forward to seeing the data in just a couple of weeks. I have a couple of questions in that regard. I guess I'm curious, is there an internal bar that you guys are aiming for with regard to the 12-week durability data or sort of a minimum appropriate durability for regulators or for what you're thinking would be the most viable commercial opportunity there? Are you seeing anything different with regard to dropout rates between weeks 4 and 12?

Seen from.

Studies of <unk>.

And anxiety and depression, we've seen in many instances.

Six to 12 months or even longer of activity. So we certainly are excited about the durability and think it will give us great insight in terms of.

How long does the effects can last many patients.

In terms of the dropout rate ore reserve any any comments there until we get to a final final presentation of the data next week on March seven.

Look forward to sharing that we're talking through certainly the dynamics of the population that study and then with respect to the ODT formulation.

Rob Barrow: And then maybe just lastly on the ODT formulation, I'm just curious what your expectations are for what the PK profile would need to show to maximize the chance of replicability in a phase 3 study. Thanks. Terrific, yeah. Thanks so much, Brian.

One of the things as we embarked on the development of that.

Formulation.

Okay.

We had improved product performance from a stability standpoint, LTM, particularly unstable molecule and one that by developing the ODT formulation, we have been able to stabilize and get shelf stable.

Rob Barrow: So taking each of those, in terms of expectations, as we were heading into the announcement of our week four primary data in December, and we talked a lot about the backdrop of SRIs and benzodiazepines and the effect size we are seeing there. And each of those drugs has a different dynamic, where benzodiazepines can, of course, be used acutely and have been approved on endpoints, such as a four-week endpoint, whereas SRIs, typically, because they take longer to separate from the CBO, take longer to take action, have looked at longer-term effects.

That we think is critical for commercial viability.

In terms of its PK and PD performance again.

Sharing all the data, but as I said in the past and one of the things, we're really hoping to see is faster absorption.

In that study, we can get the drug and faster and get above therapeutic concentrations.

Look at the general kind of concentrations that need to be achieved.

Induce the perceptual effects that.

Apparently other mechanism of action and drive this sort of psychological changes, resulting and dialytic effects.

We can increase the time.

The AUC above that concentration and get to that concentration faster than of course, the time a patient is spending.

Rob Barrow: But that same sort of effect size standard, I think is something that we would set as a general expectation. If we could exceed an effect size of 0.4, that would represent an improvement over the standard of care. And of course, if we can do that after a single dose for up to three months, that would be particularly exciting for us. But certainly, what we saw at Week 4 was a response from... We had half of the patients in remission at that point, and we saw, really, on average, Ham A scores that were relatively stable and flat. We didn't lose any activity, the week one response, the week four response. And so, in an optimistic scenario, we could continue that kind of response out through 12 weeks. And certainly from some of the historical data we've seen from studies of LSD and anxiety and depression, we've seen, in many instances, six to 12 months or even longer of activity. So we certainly are excited about the durability and think it will give us great insight. How long those effects can last in a patient

Any dosing session would effectively become more efficient in our view.

This additional.

Promise for the character of the Phase III, we don't see any substantial risk in terms of not having a bioequivalence product to take forward or a reasonably equivalent product that would support.

For us as we go into the Phase III program, but again, we will be excited to share all of the findings in that study at the end of next week.

Great. Thanks, so much Rob.

Thanks, Brian.

Thank you.

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

Yeah, Hey, good morning, Rob and team. Thanks for taking my question and congrats on the progress looking forward to March 7th appreciate the disclosure of that had a couple of questions with regard to phase III trial design.

I know, it's pending an update or meeting with agency, but when you think about the sizing of that trial and then think about the sample of your phase two b.

Rob Barrow: In terms of the dropout rate, we reserve any comments there until we get to a final presentation of the data next week on March 7th, so look forward to sharing that and talking through, certainly, the dynamics of the population and the study. And then with respect to the ODT formulation, one of the things as we embarked on the development of that, formulation. We certainly have improved product performance from a stability standpoint. LSD is a particularly unstable molecule and one that, by developing the ODP formulation, we've been able to stabilize and get self-stable in a way that we believe is critical for commercial viability.

Jim role, how could those things change in phase III, and then ill come back with another.

Other question. Thanks.

Yes, thanks, so much Charles so in terms of phase III trial design.

Sizing of course, theres going to be multiple factors that play into the Finalization of the study sizing and what goes on population we enrolled in that study.

From a statistical standpoint of course, if we were to replicate and use the effects. We've seen now at four weeks to the size of the study into a power analysis.

<unk> indicated a very.

Small study.

Smaller size and we conducted in phase III now we want to make sure that the study we conducted is large enough to support the overall program and be generalizable.

Rob Barrow: In terms of its PK and PD performance, again, we'll look forward to sharing all of the data. But, as I said in the past, and one of the things we're really hoping to see is faster absorption in that study, where we can get the drug in faster and get above therapeutic concentrations. So as we look at the general kind of concentrations that need to be achieved to achieve the perceptional effects that apparently are the mechanisms of action and drive the sort of psychological changes that result in analyze effects, if we can increase the time or the AUC above that concentration and get that concentration faster, then of course, the time a patient is spending in a dosing session would effectively become more efficient, in our view, and give us additional promise for the carry through to Aschoff, Brian Abrahams, Patrick Trucchio, Elemer Piros, Francois Brisebois, and Broadway Gold. That's next week.

Something that we can stand behind as a pivotal clinical trial, but we certainly don't anticipate that we're talking.

A substantial.

Increased if we ultimately are able to see the kind of effects. We saw at four weeks characteristic to week 12.

Okay and then my second question is for sure. The pivotal study I guess I'm wondering as you look at the phase II B can you speak to the role of therapy or lack thereof, or functional blinding the data that <unk> seen and how you will consider that for the design of the phase III.

Yes, great question.

Certainly an important topic that theres been a lot of discussion around.

Functional and blinding is something that is.

Point of focus but it has been.

Ignored how prevalent it is and thank you hatrick drug development and we have entire classes of drugs such as the cycles stimulants, which of course have clear perceptual effects, we have to provide out where there is a clear.

Charles Duncan: Great, thanks so much, Rob. Thank you. Our next question comes from the line of Charles Duncan with Cantor. Your line is now open. Yeah. Good morning, Rob and team.

Sexual effect associated in effect in the majority of patients in those studies.

We really don't think from a methodological standpoint, there's actually anything different that would warrant.

<unk> from a long well established gold standard.

Rob Barrow: Thanks for taking our question and congrats on the progress. I'm looking forward to March 7th. Appreciate the disclosure of that. I had a couple of questions with regard to the design of the Phase 3 trial. You know, I know it's pending an update or a meeting with the agency, but when you think about the sizing of that trial and then think about the sample of your Phase 2B as enrolled, how could those things change in Phase 3? And then I'll come back with another question.

The design and conduct of these clinical trials.

The lack of therapeutic intervention in addition to the drop in our phase II study it means that.

In our view, it's very closely aligned with FDA guidance from 2023, and it means we don't have to make any changes to conform with that guidance as we go into our phase III program.

In terms of trial delivery and functional blinding, we anticipate we will continue to dose dose of the drug in the absence of any sort of therapeutic intervention patients will continue to be under <unk>.

Rob Barrow: Thanks. Yeah, thanks so much, Charles. So in terms of phase three trial design.., and sizing. Of course, there's going to be multiple factors that play in, finalization of the study's sizing and the total population we enrolled in that study. From a statistical standpoint, of course, if we were to replicate and use the effects we've seen now at four weeks to design a study and do a power analysis, it implicates or indicate a very, Aschoff, Brian Abrahams, Patrick Trucchio, Elemer Piros, Francois Brisebois, Broadway be something that we can stand behind as a pivotal clinical trial, but we certainly don't anticipate that we're talking any substantial, increase if we ultimately are able to see the kind of effects we saw four weeks carrying through to week 12.

Safety monitoring as we did in phase II, but overall because of the degree of protocol will look.

Nearly if not entirely identical.

Our phase two b approach.

In terms of functional binding and selection of controls again.

Actually seen that as we look across studies is that what appears to drive.

No <unk> effect is more of a therapeutic involvement in the studies for for studies, where there has been a heavy.

Adjunct is psychotherapeutic component to the clinical studies, we've seen many instances reduce placebo response or even a nocebo response.

Our study we saw a robust placebo response for sure again.

Don't believe.

We believe our robust.

Not including any sort of therapeutic intervention and it actually functional winding its just simply a sort of mechanism connect.

Connecting.

Experts expect to see biases reinforced by that therapy.

<unk> potential impact on our clinical outcomes.

That's helpful. Last quick question and then I'll hop back in the queue is related to intellectual property I guess, so if we fast forward to.

Rob Barrow: Okay, and then my second question is for the pivotal study. I guess I'm wondering as you look at phase 2b, can you speak to the role of therapy or lack thereof or functional blinding in the data that you've seen and how you'll consider that for the design of the study. Yeah, it's a great question. It's certainly an important topic that there's been a lot of discussion around, you know, functional and blinding is something that has been a point of focus, but I think it's been ignored how prevalent it is in psychiatric drug development, and we have entire classes of drugs, such as psychostimulants, which, of course, have clear perceptual effects. Bravado, where there was a clear path.

No.

Future World.

Successful pivotal and eventual approval I guess, how are you thinking about protecting the franchise is it is it may namely based on.

It is.

Is it driven by the ODT or could there be other.

Call it in market factors, such as the Rems that really provide.

The best protection against possible.

Rob Barrow: Perceptual Effect, Dissociative Effect, and a majority of patients in those studies. So we really don't think from a methodological standpoint that there's actually any. Different that would warrant deviating from a long, well-established gold standard. Aschoff, Brian Abrahams, Patrick Trucchio, Elemer Piros, Francois Brisebois, Broadway. In our view, it's very closely aligned. 23, and it means that we don't have to make any changes to conform with that guidance as we go into our phase three program. So, in terms of trial delivery and function, and blinding, we anticipate we will continue to dose the drug in the absence of any sort of therapeutic intervention. Patients will continue to be under safety monitoring as we did in phase two, but overall, the delivery protocol.

Call it competition. Thanks.

Okay.

Yes. Thanks, so much guys. So as we can see above and have developed our market protection strategy.

And also property as effectively a tool in the toolbox to protect our market.

It's really important that intellectual property and that the overall market protection strategy is something that is differentiated that is protected ball on that.

Ideally.

Yes.

Orange book listed patents that can utilize both regulatory and legal mechanisms to protect that market.

LSD.

We are developing as I enter my 20 product.

Something that had never been approved before.

And so in our view.

At a minimum we're looking at five years of marketing exclusivity.

First.

And to your approval. Additionally, with Orange book patents that we believe will protect our product candidate, we think that would extend.

Any sort of generic applicants and then protect from from those four.

Rob Barrow: Nearly it's not entirely identical to our Phase 2B approach. In terms of functional blinding and selection of controls, again, what we've actually seen as we look across studies is that what appears to drive the Nocebo effect is more of a therapeutic involvement in the studies for studies where there has been a heavy adjunctive psychotherapeutic involvement. In the conduct of those studies, we've seen, in many instances, a reduced placebo response or even a no-placebo response.

At least the 30 month stay on the back end of that now from an IP standpoint, and again, it's been very important for us to develop our IP in the context of a broader market protection strategy, where whereby we have the ODT formulation that we hope to show a differentiated product profile again as I mentioned before we've already are you actually seeing that in its physic.

Alright and stability performance.

That puts us in a position where.

It would be quite difficult to replicate if not impossible to replicate our product we are using Cadillac, which is the only provider of.

Charles Duncan: Aschoff, Brian Abrahams, Patrick Trucchio, Elemer Piros, Francois Brisebois, and Broadway, connecting the expectancy biases reinforced by that therapy to potentially impact our kind of life. It's helpful. Last quick question, then I'll hop back on the queues related to intellectual property. I guess if we fast forward to, you know, a future world of successful, pivotal, and eventual approval, how are you thinking about protecting the franchise? Is it mainly based on IP?

The only manufacturer of Odt's dissolved as rapidly as is <unk> and.

And by protecting that inventor great.

Three narrow path that someone would have to develop to try to replicate our product and we have a robust IP fortress or around that pathway. So we feel very very confident in the <unk>.

IP protection itself, but beyond that even as you mentioned a rems there's certainly.

Rob Barrow: Is it driven by the ODP? Or could there be other, you know, call it, market factors such as the REMS that really provide the best protection against possible, you know, call it, competition? Yeah, thanks so much, Charles. As we conceive of and have developed our market protection strategy, intellectual property is effectively a tool in the toolbox. It's really important that intellectual property and the overall market protection strategy is something that is differentiated, that is protectable, and, ideally, Orange Book Listed Patents that can utilize both regulatory and legal mechanisms.

Many incidences, where our rems and some of the delivery dynamics are an area, where we will see an enhanced market protection and differentiation of our product and company and that's something that we're we're also integrating and discharge planning and strategy for margin protection as we go forward.

Thanks, Rob for all the color.

Thank you.

Our next question comes from the line of Francois <unk> with Oppenheimer. Your line is now open.

Great. Thanks for taking the question and the updates here.

In terms of that I was wondering if we could touch on the commercial side I think what's helpful. Maybe if you could help remind us of what's going on with the <unk> on the provider side and just maybe the learnings.

Rob Barrow: The LSD, the API that we are developing, the MM120 product, is something that has never been approved before by the FDA. And so, in our view, at a minimum, we're looking at five years of marketing exclusivity as the first step. It's important for us to develop our IP in the context of a broader market protection strategy whereby we have the ODP formulation that we hope to show a differentiated product profile. Again, as I mentioned before, we've already actually seen that in its physical form, and the rest of us. Thank you. Thank you. That puts us in a position where... It would be quite difficult to replicate, if not impossible, to replicate our product.

Then that gives you confidence.

Your potential commercial opportunity.

Yes.

Yes, thanks, so much Frank.

So.

Anyone who has been following the neuro innovator in interventional psychiatry area has seen so I think that they.

Explosion of those clinics and now adoption and sales ops provider, which J&J is now guiding for between one and $5 billion of sales incredibly promising and exciting new treatments in this session based delivery paradigm or having such a.

Significant uptake.

Look at the dynamics for delivery for reimbursement for provision of care and the incentive structures at each level debt.

Rob Barrow: We are using Catalan, which is the only provider and manufacturer of ODTs that dissolve as rapidly as the Zytus ODTs do. And by protecting that, it then sort of creates a very narrow path that someone would have to take. Aschoff, Patrick Trucchio, Elemer Piros, Francois Brisebois, Broadway Gold, Thanks for having us, everyone. Thanks for having us. Thank you. Our next question comes from the line by Francois Brisebois with Oppenheimer.

That motivate providers to adopt and delivers provider and when we look at each of those levels, we believe that.

Our product actually stacks up favorably and in many of the interactions we have with payers with.

Sites with providers prescribers, we also think conclusion that the dynamics of delivering a drug one time for one day over the course.

Francois Brisebois: Your line is now open. Thanks for the questions and the updates here. Just in terms of the commercial side, I was wondering if we could touch on the commercial side. I think what's helpful is maybe if you could help remind us of what's going on with esketamine on the Spravato side and just maybe the learnings from them that it gives you confidence with your potential commercial opportunities. Yeah, thanks so much, Frank.

Several hours.

These favorable than having patients come back up to 56 times a year to comply with this for providing administration.

And that the overall time against we're able to show durable clinical effects out to three months or beyond.

The overall pie I'm, a patient would be spending in the clinic is actually significantly reduced compared to provider.

Rob Barrow: So anyone who's been following the NeuroInnovator and Interventional Psychiatry area has seen the explosion of both clinics and now adoption and sales of Spravata, which J&J is now guiding for between $1 and $5 billion in sales. It is incredibly promising and exciting that new treatments in this session-based delivery paradigm are having such a significant uptake. We look at the dynamics for delivery, for reimbursement, for provision of care, and the incentive structures at each level that motivate providers to adopt and deliver Spravato. And when we look at each of those levels, we believe our product stacks up favorably in many of the interactions we have with payers, sites with providers, and prescribers. We also come to the same conclusion, the dynamics of delivering a drug one time for one day over several hours is favorable than having patients come back up to 56 times a year to comply with the Supervisory Administration and that the overall time were able to show durable clinical effects out, three months or beyond. The overall time a patient would be spending in the clinic is actually significantly reduced compared to this robotic. From a reimbursement standpoint, there are also some advantages here where because of that reduced time in the clinic, things that are getting reimbursed like patient monitoring for spravata, which is reimbursed and can cost in excess of $15,000 a year as a medical benefit to payers, we would potentially have savings to offer for reimbursement to payers there.

From a reimbursement standpoint, as all systems advantages here, where because of that reduce time in the clinic things are getting reimbursed like patient monitoring force provider, which are reimbursed and can cost.

In excess of $15000 a year at a medical benefit to payers.

We would typically have savings.

Or to reimbursement to payers there.

They are clearly defined codes and mechanisms for both prescribing of interventional psychiatry drugs likes provider that would be applicable to our product for monitoring as I mentioned beforehand of course for reimbursement of the drug so.

Really I think while there is certainly is work to be done.

Important for us to as we have talked about in R&D to really to continue to emphasize that there is a already existing infrastructure and delivery paradigm that is seeing overwhelming success and an uptake now and that really launching into a market, where we can out compete at those.

Locations and other dynamics.

The base case based on the profile of our drug so far development, we certainly believe that there's even more expansive opportunity for additional locations, where the drug could be administered because we don't have.

Yes.

Ultimately proven out in phase III studies, we don't see sort of geological risk that would require.

Any sort of physiological monitoring to date, so that gives us extraordinary opportunity and excitement around the potential to both our compete in the locations and pathways and channels Thats provided was being delivered today, but even beyond that to expand into other delivery locations.

And easier adoption in a broader set of kind.

Kind of locations.

Rob Barrow: There are clearly defined codes and mechanisms for both prescribing interventional psychiatric drugs like spravata that would be applicable to our product for monitoring, as I mentioned before, and, of course, for reimbursement of the drug. So, really, I think that while there certainly is work to be done. It's important for us to, as we have talked about in R&D, really continue to emphasize that there is an already existing infrastructure that is really in the delivery paradigm that is seeing overwhelming success and uptake now, and that really launching into a market where we can outcompete at those locations and on those dynamics is just the base case. Based on the profile of our drug so far in development, we certainly believe that there's an even more expansive opportunity for additional locations So that gives us, again, an extraordinary opportunity and excitement around the potential to both out-compete in the locations and pathways and channels that Votto is being delivered today, but even beyond that, to expand into other delivery locations and to facilitate easier adoption in a broader set of locations. That's super helpful, Rob.

That's super helpful. Thanks, and then so is it fair to assume that from discussions that from a tiered.

Perspective.

It seems like what they might care about is maybe remission.

Rapid onset durability, and if thats correct. If those are kind of the big three if theres anything I am missing. Please let me know but.

In that case of durability for weeks as great from the Companys perspective, its a little follow up on the previous question.

Is the 12 week kind of gravy here or.

It is extremely important when you are.

You have discussions with payers.

Certainly.

The durability.

You mentioned are really the key remission.

We haven't had many drugs in psychiatry.

Where a significant portion of patients.

It really enter remission in <unk>.

It quickly and stay there.

If we are ultimately able to show that as four weeks at 50% one and two patients are in clinical remission didn't have anxiety symptoms and wonder if you're able to show that out to 12 weeks of course, it means that for three months. After a single dose patients who came in with severe anxiety would not have anxiety.

Rob Barrow: And so, is it fair to assume that from, you know, discussions, from the payer perspective, it seems like what they might care about is maybe remission, rapid onset, and durability? And if that's correct, if those are kind of the big three, if there's anything I'm missing, please let me know.

That's extraordinary that's a game changer in terms of.

Patient care.

In terms of onset that's another one that is particularly important as we talk to Kols and RSA SAP for instance.

To have patients come into door and reliably know with them as we saw in the phase II study 24 hours there was a clinical response.

Rob Barrow: But on that case of durability, you know, four weeks is great. From the company's perspective, it's a little follow-up on the previous question. Is the 12 weeks kind of gravy here, or is this extremely important when you have discussions? I certainly think so. The durability, each of the components you mentioned is really the key to remission. We haven't had many drugs in psychiatry where a significant portion of patients really enter remission and enter it quickly and stay there. If we're ultimately able to show that at four weeks, we had 50%, one in two patients, clinical remission and no anxiety. If we're able to show that out to 12 weeks, of course, it means that for three months after a single dose, patients who came in with severe anxiety would not have anxiety. That's extraordinary!

The CGI apps, which is.

That's the only metric we have in the study to measure that rapid change.

But to have rapid.

And that also gives providers the ability to know very quickly whether a patient is having benefit or not it's important from a payer standpoint.

But I think critically important is also to understand because of that onset payers want to.

Capture value they want to they were happy to pay for in prior discussions the payers. They have said we will pay for it.

These kinds of drugs, if we can capture value and capturing value is a function of how clearly and how robustly patients respond to the drug and how durably. So all of that sort of convergence around if we see rapid onset with durable clinical benefit and a significant portion of our patients remaining in <unk>.

<unk>.

Rob Barrow: That's a game changer in terms of patient care. In terms of onset, that's another one that is particularly important as we talk to KOLs and our SAB, for instance, to have patients come in the door and reliably know within, as we saw in the phase two study, 24 hours, the clinical response on the CGIS. Aschoff, Brian Abrahams, Patrick Trucchio, Elemer Piros, Francois Brisebois, Broadway, But I think critically important is also to understand, because of that onset, payers want to, of course, capture value. They want to

We think both the provision of care and payer level, there is a clear path.

Success there.

You mentioned.

Expectations are after 12 weeks.

Certainly what the data we have seen so far which is three or four weeks.

Puts us in a position where we are.

Moving forward into a pivotal program. If we were to see continued response and durability out to 12 weeks.

That would just can continue.

Build on the case and the prospects for the program, but certainly what we've seen so far is enough to move forward and we're making plans accordingly.

Alright, Thank you very much congrats on the progress.

Thanks, Greg.

Thank you. Our next question comes from the line of Mark Carney with Canaccord Genuity. Your line is now open.

Rob Barrow: They were happy to pay for it, and prior to the payers, they had said, you know, we will pay for it. Aschoff, Brian Abrahams, Patrick Trucchio, Elemer Piros, Francois Brisebois, Broadway, If we see rapid onset with durable clinical benefit in a significant portion of our patients, remaining in remission, we think both at the provision of care and at the payroll level, there's a clear path to success there. You mentioned expectations are out to 12 weeks; certainly, what the data we have seen so far, which is through four weeks, puts us in a position where we are.

Good morning, Thanks for taking my questions I have a two parter and then 'twenty development and a financial one for Sean after that so the two part could be expect to also see 12 week data on the change in the Mayo score when you present, the durability data on March 7th and if you were to ultimately pursue an indication for depression with <unk> is that a breath.

And whether you would like to target major depressive disorder <unk> resistant depression.

Yes, thanks, so much.

Rob Barrow: Absolutely moving forward into a physical program if we were to see continued build on the case and the prospects for the program. But certainly, what we've seen so far is enough to move forward, and we're making plans accordingly. All right, thank you very much. Congratulations on the project. Thank you. Our next question comes from the line of Sumant Kulkarni with Canaccord Genuity.

In terms of data, we'll be presenting next week, we would expect in terms of outcome measures to prevent similar incentive commissions. We presented for week. Four so that would include handmade CGI S and address so it's exciting to shared data both.

<unk> response with anxiety symptoms of ASO with Comorbid depression symptoms.

In terms of development and the ultimate indication reserve that is.

Sumant Kulkarni: Your line is now open. Morning, thanks for taking my questions. I have a two-parter on MM 120 development and a financial one for Sean after that. So the two-parter is, could we also expect to see 12-week data on the change in the MADERS score when you present your durability data on March 7th? And if you were to ultimately pursue an indication for depression with MM 120, is there a preference on whether you would like to target major depressive disorder or treatment-resistant depression? Yeah, thanks so much, Suman. In terms of data we'll be presenting next week, we would expect, in terms of outcome measures, to present a similar set of outcome measures we presented for week four. So that would include HAM-A, CGI-S, and MADRA.

The advance in planning and scoping potential.

Additional indication in psychiatry.

The appropriate time, what we'll get further clarity there I think it's important.

As we talked about reimbursement.

There are multiple dynamics here just because the drug is approved for major depressive disorder as we've seen some of the more recent.

Entrants the more recent ssris that have come to market that are labeled for major depressive disorder of course programs like stage and Biogen Serrano loan program, which was ultimately being developed and Mgd the.

The regulatory label certainly provide a broader set of patients that could be.

Digital on label for administration of the drug, but I think what we had anticipated that.

Payers are likely to expect.

To be treating patients, where there is value in that as well.

A function of severity and non response to prior treatment. So.

Okay reserves as a final determination or guidance on what that indication would be but I'm, certainly considering a broad scope and depress related indications.

Rob Barrow: So we're excited to share data both on response with anxiety symptoms but also with comorbid depression symptoms. However, in terms of development and the ultimate indication, we reserve that. Aschoff, Brian Abrahams, Patrick Trucchio, Elemer Piros, Francois Brisebois, and Broadway, as we talked about reimbursement. There are multiple dynamics here. Just because a drug is approved for a major depressive disorder, as we've seen some of the more recent, and Entrance, the more recent SRIs that have come to market that are labeled for major depressive disorder, of course, programs like SAGE and Biogen's Ranalone program, which was ultimately being developed for MDD.

Got it and then the financial question.

You comment on what your cash runway would be without the additional unlocking from milestones.

Okay.

Yes.

Yes.

Two quick questions for Mark I think that right now.

From our standpoint.

Our historical per Arne has typically been somewhere between $15 million plus or minus.

1%.

And so and.

Addition to that.

As it relates to the K two facility again those are milestones that are that are performance based milestones.

Such that we have the option and asked me as we continue to execute on our plan to be able to draw those items down. So they are in part part of the part of the overall funding strategy.

Got it thank you.

Rob Barrow: The regulatory label certainly provides a broader set of patients that could be all eligible for on-label pre-eigenenstration of the drug, but something we did anticipate is that payers are likely to expect to be treating patients where there's value. And that is both a function of severity and non-response to prior treatment. So again, reserve this kind of final determination or guidance on what that indication would be, but I'm certainly considering a broad scope and depression-related indication. Got it. And then on the financial question, could you comment on what your cash runway would be without the additional unlocking from milestones? Um, good question, Shamont. I think that, at least from our standpoint, our historical burn has typically been somewhere between $15 million plus or minus 20 percent.

Thank you.

Our next question comes from the line of LMR, Paris, with Rodman and Renshaw. Your line is now open.

Good morning, gentlemen, can you hear me.

Hi, Oliver.

Good morning.

So I'd just like to re circle back to and I think the question was asked my choice on the size of the phase III trial.

We clearly saw a massive signal to noise ratio into phase III trial at least up to week four.

But how do you balance.

Rob.

The fact that they are IC H guidelines out there and this drug could be potentially approved for millions of patients in terms of menu design.

Sean Greenway: And so, in addition to that, As it relates to the K-2 facility, again, those are milestones that are performance-based milestones such that we have the option, as we continue to execute on a plan, to be able to draw those items down. So they are, in part, part of the overall funding strategy.

Phase III set of phase III trials.

Okay.

Yes. Thanks, so much all right and then it's a great point and question, that's why too when we talked about.

The finalization of the Phase III program in protocol.

As there are many factors that come into play of course overall patient exposures I wanted to make sure that the results are externally valid and generalizable to that magnitude of a population.

Sean Greenway: Our next question comes from the line of Elemer Piros with Rodman and Rensselaer. Your line is now open. Good morning, gentlemen. Can you hear me?

We're really particularly encouraged by seeing recently Lycos therapeutics MDMA for post traumatic stress disorder NDA.

Elemer Piros: Weekend Highline. Um, so I'd just like to recircle back to you, and I think the question was asked by Charles on the size, face redraw, and be clearly seen. Math, signal-to-noise ratio.

<unk> by FDA in that development program was.

In the mid one hundreds of overall exposures granted there is a lot of historical.

Elemer Piros: Charlotte. Week 4. How do you balance, Rob, the fact that there are ICH guidelines out there? This drug could potentially be the phase three set of phase three. Yeah, thanks so much. It's a great point in question.

Suppose your data there at like with LSD right. There is a sort of thing.

One understanding of these molecules and a long history of research of these molecules in this drug class.

But I mean, as we can see about a phase III program again, we want to make sure that it is something that.

Rob Barrow: That's why, you know, when we talk about the finalization of the phase three program and protocol, there are many factors that come into play. Of course, overall patient exposures, we're gonna make sure that the results are externally valid and generalizable to that magnitude of a population. I mean, what we're really particularly encouraged by seeing recently Lycos Therapeutics MDMA for post-traumatic stress disorder, the NDA be accepted by FDA, and that development program was in the mid-hundreds of overall exposures. Granted, there's a lot of history.

Is generalizable that supports an overall development strategy that leads us to a marketing application.

But again kind of reserve the right reserve the final commentary on.

Exactly what size that will be.

Enter into phase two.

In your discussions with FDA in an upswing right and our final study.

Yes, and Rob you alluded to this earlier.

Less much less emphasis on the therapy component you are going to be talking to the FDA.

Rob Barrow: Aschoff, Brian Abrahams, Patrick Trucchio, Elemer Piros, Francois Brisebois, Broadway Gold, But as we conceive of a phase three program, again, we want to make sure that it is something that is generalizable that supports an overall development strategy that leads us to a marketing application, but you know again we're going to reserve the right to reserve the final commentary on exactly what size that will be as Yes, and Rob, you alluded to this earlier, plays less, much less. You're going to be talking to the FDA, possibly several, while they are evaluating the lichens. He is heavily dependent on therapy. How do you distinguish them?

Months.

While we are evaluating go iqos applications reduce heavily dependent on therapy.

How do you distinguish.

Two the FDA between two paradigms of the necessity of adjacent therapy versus.

Focusing on the drug effect in your case.

Yeah.

A really important topic in terms of differentiating.

There's a lot of.

Discussion in Reagan you don't Foundation recently put on a panel.

It may have attended where there we had some discussions dialogue on the panel.

US with compass and with maps about these sorts of batteries.

So from a development standpoint, and approaching FDA really we limit any sort of engagement.

Rob Barrow: to the FDA to pair it up. Yeah, you know, it's a really important topic in terms of differentiating, you know, there's a lot of discussion and the Reagan Udall Foundation recently put on a panel that you may have attended where we had some discussions and dialogue on the panel with Aschoff, Brian Abrahams, Patrick Trucchio, Elemer Piros, Francois Brisebois, and Broadway, with formal We. Day One charted a very clear course that was to demonstrate the stand-alone drug effect of our product candidates and that there's certainly a discreet, well, Aschoff, Brian Abrahams, Patrick Trucchio, Elemer Piros, Francois Brisebois, Broadway, and their guidance from 2023 made quite clear the need to characterize the stand-alone effects of a drug. And that's exactly what we did, really uniquely for the first time in the field.

With formal meetings with FDA to the scope of our development program.

Since day, one chartered a very clear of course that is to demonstrate standalone drug effect of our product candidates and that there is a certainly a discrete well.

There's a loose definition that includes things like all mind altering substances, such as provider and ketamine and DMA, we're talking about really a distinct drug class with the search and heidrick psychedelics and within them on 'twenty in particular, and so our approach will be informed by our data and by our strategy.

And by our understanding and engagement previously with FDA about what the expectations are there has been a clear.

The guidance for 2023 made it quite clear the need to characterize the standalone effects of a drug and that's exactly what we've done really uniquely for the first time in the field have done so.

Rob Barrow: So we feel really confident in our approach and our ability. Port, DataGee, Esmeiner, Pivotal, Pivotal, Study. Thank you very much. Thank you. Our next question comes from the line of Patrick Trucchio with H.C. Wainwright. Your line is now open. Good morning, team. This is Luis Santos on behalf of Patrick.

So we feel.

Really confident in our approach and the ability.

To support that as we as we enter pivotal pivotal studies.

Thank you very much Rob.

Thanks for your time.

Thank you.

Our next question comes from the line of Patrick <unk> with H C. Wainwright. Your line is now open.

Good morning team. This is luis samples for Patrick.

Patrick Trucchio: Understanding that depression is different from anxiety, should we anticipate a phase three program design similar to comp 360 design in depression? And should we anticipate a true placebo being part of a program? And then there is a follow-up question. Yeah, in terms of control conditions, of course, it's like a topic we'll want to work around with FDA and the interface to meeting. We fundamentally believe that regardless of the mechanism of action of drugs and regardless of the qualitative, and others.

Extending that the question.

It is different from anxiety should we anticipate a phase III program designed similar to 360 design in depression and should.

Should we anticipate a true placebo being part of a program and then I have a follow up question.

Yes in terms of.

Control conditions and of course, it's likely a tactical one align around.

With FDA at our end of phase two meeting.

We fundamentally believe that regardless of the mechanism of action of drugs and regardless of the qualitative differences in the perceptual effects of this drug class versus say Psycho stimulants oriented associated anesthetics like kilometres provider out there.

Rob Barrow: And I'm going to talk about the perceptual effects of this drug class. And I'm going to talk about the perceptual effects of this drug class. Stimulants, or dissociative anesthetics like ketamine or sperbato, the gold standard in research, and Duck Placebo Controlled.

Old standard in research is to conduct a placebo controlled studies.

Using a non placebo control as a comparator in studies is something that causes the question interpret ability of those study results and really I think that the validity of.

Studies.

Rob Barrow: Using a non-placebo control as a comparator in studies is something that calls into question the interpretability of those study results and, really, I think, their validity. Aschoff, Brian Abrahams, Patrick Trucchio, Elemer Piros, Francois Brisebois, Broadway, In terms of the scope of the Phase III development program, as we've said previously, I think we anticipate doing two 12-week placebo-controlled studies as a target, but we're going to reserve final commentary around the study design and the dynamics there when we are in the Phase II meeting with FDA. We do anticipate continuing patients on into open-label extensions to characterize what happens upon re-treatment and just demonstrate even further durability outcomes, perhaps for a year. Thank you. And does the start of the Phase 3 program depend on the outcome of the bridging study? And if so, when do you expect that data to be reported?

Nature in general so our certainly our preference and our strong belief is that placebo controlled research is the right way to conduct research. It's why it's a gold standard and it's why it's indicated by.

In fact, IC agent effectively every international body that regulates and conducts research and medicine.

In terms of the scoping phase III development program.

We've said previously I think we anticipate doing that.

212 week placebo controlled studies.

As a target, but we're going to reserve final commentary around study design and the dynamics there.

When we have our end of phase II meeting with FDA, we do anticipate continuing patients are in the open label extension study to characterize what happens upon re treatment and just demonstrate even further.

Durability out perhaps a year longer.

Thank you.

Yeah.

The phase III program starts depend on the outcome from the bridging study and if so when do you expect that data to be reported.

Patrick Trucchio: Yeah, phase three program planning is underway. We anticipate starting that in the second half of this year. Our PK bridging data for our ODT product, which we'll be sharing next week at our March 7th investor event as well, so look forward to sharing that. Right now, we're continuing to focus on and plan to implement and use that product as we enter phase three.

Yes Phase III program is planning is underway, we anticipate starting that in the second half of this year.

Bridging PK bridging data for <unk> ODT product, we'll be sharing.

Next week at our March 7th Investor, Venezuela, So look forward to sharing that but right now we're continuing to focus and plan to implement use that product as we enter a phase III program.

Rob Barrow: Great, thank you so much. Thank you. I would now like to turn the call back over to Rob Barrow for a closing remark. Thank you, operator. Thank you everyone again for joining us here today. We hope you can all join us next week on March 7 for an investor event and look forward to sharing what resulted from that call. Thank you so much. This concludes today's conference call. Thank you for your participation. You may now disconnect.

Great. Thank you so much.

Thank you I would now like to turn the call back over to Rob Darrow for closing remarks.

Terrific. Thank you operator, and thanks, everyone again for joining us here today.

Hope you all join US next week on March 7th Investor event, and look forward to sharing.

Thanks, so much.

This concludes today's conference call. Thank you for your participation you may now disconnect.

Operator: This is a story about a man and a woman who met on the street and fell in love with each other. This is a story about a man and a woman who met on the street and fell in love with each other. This is a story about a man and a woman who met on the street and fell in love with each other.

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