Q4 2025 Definium Therapeutics Inc Earnings Call

February 26, 2026

Gitanjali Jain: Good afternoon, and welcome to the Definium Therapeutics Full Year 2025 Financial Results and Business Update Webcast. Currently, our participants are in listen-only mode. The webcast is live on the Investor and Media section of the Definium website at definiumtx.com, and a replay will be available after the webcast. I would now like to introduce Gitanjali Jain, Head of Investor Relations of Definium. Please go ahead.

Speaker #1: And a replay will be available after the webcast. I would now like to introduce Gita Jain, Head of Investor Relations of Definium. Please go ahead.

Speaker #2: Thank you, Operator, and good afternoon, everyone. Thank you for joining us today for a discussion of Definium's full-year 2025 financial results and business updates.

Gitanjali Jain: Thank you, operator, and good afternoon, everyone. Thank you for joining us today for a discussion of Definium's full year 2025 financial results and business updates. Leading the call today will be Rob Barrow, our Chief Executive Officer, who is joined by Dr. Dan Karlin, our Chief Medical Officer, Randy Roberts, our Chief Financial Officer, and Matt Wiley, our Chief Commercial Officer. An audio recording and webcast replay for today's conference call will also be available online, as detailed in the press release announcement for this call. During today's call, we will be making certain forward-looking statements, including, without limitation, statements about the potential safety, efficacy, and regulatory and clinical progress of our product candidates, our anticipated cash runway, and our future expectations, plans, partnerships, and prospects.

Speaker #2: Leading the call today will be Rob Barrow, our Chief Executive Officer, who is joined by Dr. Dan Carlin, our Chief Medical Officer, Brandi Roberts, our Chief Financial Officer, and Matt Wiley, our Chief Commercial Officer.

Speaker #2: An audio recording and webcast replay for today's conference call will also be available online as detailed in the press release announcement call. During today's call, we will be making certain forward-looking statements, including without limitation statements about the potential safety, efficacy, and regulatory and clinical progress of our product candidates, our anticipated cash runway, and our future expectations, plans, partnerships, and prospects.

Speaker #2: 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 and applicable Canadian securities regulators, including our annual report on Form 10-K filed today.

Gitanjali Jain: 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 and applicable Canadian securities regulators, including our annual report on Form 10-K filed today. Forward-looking statements are based on the assumptions, opinions, and estimates of management at the date the statements are made, including the non-occurrence of the risks and uncertainties that are described in the filings made with the SEC and the applicable Canadian securities regulators or other significant events occurring outside of Definium's normal course of business. You are cautioned not to place undue reliance on these forward-looking statements, which are made as of today, 26 February 2026.

Speaker #2: 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 and the applicable Canadian securities regulators, or other significant events occurring outside of Definium's normal course of business.

Speaker #2: Your caution not to place undue reliance on these forward-looking statements which are made as of today, February 26, 2026. Definium disclaims any obligation to update such statements, even if management's views change, except as required by law, with that, let me turn the call over to Rob.

Gitanjali Jain: Definium disclaims any obligation to update such statements, even if management's views change, except as required by law. With that, let me turn the call over to Rob.

Speaker #3: Thank you, Gita, and thank you, everyone, for joining our call today. We're incredibly excited to share today's updates as we rapidly approach our anticipated pivotal readouts for Lysergide tartrate, or DT120/ODT, and generalized anxiety disorder and major depressive disorder in the months ahead.

Rob Barrow: Thank you, Geeta, thank you, everyone, for joining our call today. We're incredibly excited to share today's updates as we rapidly approach our anticipated pivotal readouts for lysergide D-tartrate or DT120 ODT in generalized anxiety disorder and major depressive disorder in the months ahead. The momentum is palpable both across our development programs and in the world of psychiatry as we prepare for the adoption of psychedelics as potentially transformative new treatment options. We continue to believe in the potential of DT120 ODT as a best-in-class product candidate, and over the past year, our team has yet again set the standards for scientific rigor, efficiency, and thoughtfulness in execution. As I reflect on 2025, I could not be prouder of our team and the progress we have made.

Speaker #3: The momentum is palpable, both across our development programs and in the world of psychiatry, as we prepare for the adoption of psychedelics as potentially transformative new treatment options.

Speaker #3: We continue to believe in the potential of DT120/ODT as a best-in-class product candidate, and over the past year, our team has yet again set the standards for scientific rigor, efficiency, and thoughtfulness in execution.

Speaker #3: As I reflect on 2025, I could not be prouder of our team and the progress we have made. Over the course of the last year, we rapidly progressed our late-stage pipeline, significantly strengthened our balance sheet, and continued to expand our world-class leadership team and board of directors to drive our next phase of growth.

Rob Barrow: Over the course of the last year, we rapidly progressed our late-stage pipeline, significantly strengthened our balance sheet, and continued to expand our world-class leadership team and board of directors to drive our next phase of growth. Through ongoing engagement with the FDA under the Breakthrough Therapy Designation program, we reached alignment on many key aspects of our development and submission strategy, positioning us to maximize the speed and efficiency of our NDA submission for DT120 ODT, subject to positive trial readouts later this year. Our commercial strategy and organizational readiness have mirrored these R&D successes with the addition of key commercial leadership led by Matt Wiley, who joined as our Chief Commercial Officer in March 2025. We've seen strong engagement across the spectrum, positioning us to deliver on our aim to yet again define the standard of excellence in the adoption of psychedelics.

Speaker #3: Through ongoing engagement with the FDA under the Breakthrough Therapy Designation Program, we reached alignment on many key aspects of our development and submission strategy, positioning us to maximize the speed and efficiency of our NDA submission for DT120/ODT, subject to positive trial readouts later this year.

Speaker #3: Our commercial strategy and organizational readiness have mirrored these R&D successes, with the addition of key commercial leadership led by Matt Wiley, who joined as our Chief Commercial Officer in March 2025.

Speaker #3: We've seen strong engagement across the spectrum, positioning us to deliver on our aim to yet again define the standard of excellence in the adoption of psychedelics.

Speaker #3: We began 2026 with the launch of Definium Therapeutics, a refreshed brand that reflects the evolution of our company and our leadership in psychiatry. Our differentiated strategy, grounded in disciplined execution, scientific rigor, and an ambitious view of the impact we can drive, positions us to develop scalable, accessible treatments and drive long-term value for our shareholders.

Rob Barrow: We began 2026 with the launch of Definium Therapeutics, a refreshed brand that reflects the evolution of our company and our leadership in psychiatry. Our differentiated strategy, grounded in disciplined execution, scientific rigor, and an ambitious view of the impact we can drive, positions us to develop scalable, accessible treatments and drive long-term value for our shareholders. With three phase 3 readouts expected in 2026, the first of which is just months away, we expect the year ahead to be a pivotal one, both for Definium and psychiatry at large.... Our goal is clear, to address the urgent need for a new class of drugs that can offer meaningful relief to the millions of people who are living with GAD and MDD, disorders that have long been underserved by treatments with high burden, moderate efficacy, and often poor tolerability.

Speaker #3: With three Phase III readouts expected in 2026, the first of which is just months away, we expect the year ahead to be a pivotal one, both for Definium and psychiatry at large.

Speaker #3: Our goal is clear: to address the urgent need for a new class of drugs that can offer meaningful relief to the millions of people who are living with GAD and MDD, disorders that have long been underserved by treatments with high burden, moderate efficacy, and often poor tolerability.

Speaker #3: Building on our strong dose-optimization Phase IIb study, which was published in JAMA last September, our clinical program for DT120/ODT consists of four pivotal Phase III studies: two in GAD, the VOYAGE and PANORAMA studies, and two in MDD, the EMERGE and ASCEND studies.

Rob Barrow: Building on our strong dose optimization Phase 2b study, which was published in JAMA last September, our clinical program for DT120 ODT consists of 4 pivotal Phase 3 studies. 2 in GAD, the Voyage and Panorama studies, and 2 in MDD, the Emerge and Ascend studies. I'm pleased to share today that Emerge, our first pivotal study in MDD, is fully enrolled and we anticipate delivering top-line data in late Q2. While Emerge is the last of our 3 ongoing pivotal studies to be initiated, we could not be more excited to share this readout first across our Phase 3 programs. This sequencing both provides the opportunity to establish evidence in a second major market indication and enables us to engage with FDA with ample time to explore potential opportunities for accelerating our regulatory submission strategy for the MDD and GAD indications.

Speaker #3: I'm pleased to share today that Emerge, our first pivotal study in MDD, is fully enrolled and we anticipate delivering top-line data in late Q2.

Speaker #3: And while Emerge is the last of our three ongoing pivotal studies to be initiated, we could not be more excited to share this readout first across our Phase III programs.

Speaker #3: This sequencing both provides the opportunity to establish evidence in a second major market indication and enables us to engage with FDA with ample time to explore potential opportunities for accelerating our regulatory submission strategy for the MDD and GAD indications.

Speaker #3: We've also made significant progress in launching Ascend, our second pivotal study in MDD. Our first sites in Ascend have been activated, and we anticipate first participant dosing by early Q2.

Rob Barrow: We've also made significant progress in launching ASCEND, our second pivotal study in MDD. Our first sites in ASCEND have been activated, and we anticipate first participant dosing by early Q2. On to our GAD program. We continue to see strong enrollment across Voyage and Panorama. Enrollment in Voyage is approximately 80% complete, and based on the enrollment rate and current queue of patients, we expect to conclude enrollment in the coming weeks, with top-line data expected in early Q3. I'm also happy to share that with the pre-planned blinded sample size re-estimation is complete with no required increase in sample size. Dan will be sharing further details on the sample size re-estimation in a few moments. Enrollment in Panorama, our second Phase 3 study in GAD, is rapidly progressing, and we remain on track to deliver top-line data in the second half of 2026.

Speaker #3: Onto our GAD program, we continue to see strong enrollment across Voyage and Panorama. Enrollment in Voyage is approximately 80% complete and based on the enrollment rate and current Q of patients, we expect to conclude enrollment in the coming weeks with top-line data expected in early Q3.

Speaker #3: I'm also happy to share that with the pre-planned blinded sample size reestimation is complete with no required increase in sample size. Dan will be sharing further details on the sample size reestimation in a few moments.

Speaker #3: Enrollment in Panorama, our second Phase III study in GAD, is rapidly progressing and we remain on track to deliver top-line data in the second half of 2026.

Speaker #3: We plan to provide a further enrollment update and to disclose the outcome of the Panorama blinded sample size re-estimation at our investor and analyst day in April.

Rob Barrow: We plan to provide a further enrollment update and to disclose the outcome of the Panorama blinded Sample Size Re-Estimation at our Investor and Analyst Day in April. Our team remains focused on delivering high-quality data across our Phase 3 studies, targeting two of the largest and most impactful indications in psychiatry. We continue to believe in the best-in-class potential of DT120 ODT and are dedicated to the scientific rigor and disciplined execution that has defined our organization and successes to date. With that, I'll turn the call over to Dan to share additional details on our clinical programs.

Speaker #3: Our team remains focused on delivering high-quality data across our Phase III studies targeting two of the largest and most impactful indications in psychiatry. We continue to believe in the best-in-class potential of DT120/ODT and are dedicated to the scientific rigor and disciplined execution that has defined our organization and successes to date.

Speaker #3: With that, I'll turn the call over to Dan to share additional details on our clinical programs.

Speaker #4: Thanks, Rob. We've remained highly encouraged by the enrollment trends we are seeing across our Phase III GAD and MDD studies. We've been spending a lot of time with our sites and investigators and there is a high degree of excitement and engagement as we get closer to delivering top-line data.

Dan Karlin: Thanks, Rob. We remain highly encouraged by the enrollment trends we are seeing across our Phase 3 GAD and MDD studies. We've been spending a lot of time with our sites and investigators, and there is a high degree of excitement and engagement as we get closer to delivering top-line data. As Rob mentioned, we are especially excited to deliver Emerge as our first pivotal readout in late Q2. While our Phase 2 Montgomery-Åsberg Depression Rating Scale, or MADRS, results in GAD have given us great clinical confidence through the design and execution of Emerge, we have not previously had the opportunity to establish the efficacy of DT120 in a dedicated MDD population with patients in a major depressive episode.

Dan R. Karlin: Thanks, Rob. We remain highly encouraged by the enrollment trends we are seeing across our Phase 3 GAD and MDD studies. We've been spending a lot of time with our sites and investigators, and there is a high degree of excitement and engagement as we get closer to delivering top-line data. As Rob mentioned, we are especially excited to deliver Emerge as our first pivotal readout in late Q2. While our Phase 2 Montgomery-Åsberg Depression Rating Scale, or MADRS, results in GAD have given us great clinical confidence through the design and execution of Emerge, we have not previously had the opportunity to establish the efficacy of DT120 in a dedicated MDD population with patients in a major depressive episode.

Speaker #4: As Rob mentioned, we are especially excited to deliver Emerge as our first pivotal readout in late Q2. While our Phase II Montgomery-Asperger Depression Rating Scale, or MADRES, results in GAD, have given us great clinical confidence through the design and execution of Emerge, we have not previously had the opportunity to establish the efficacy of DT120 in a dedicated MDD population with patients in a major depressive episode.

Speaker #4: While GAD and MDD are substantially overlapping disorders, MDD is defined as an episodic illness with periods of euthymia, or normal mood, interrupted by major depressive episodes, which are characterized by dysthymia, or depressed mood, that must persist for at least two weeks and may last many months.

Dan Karlin: While GAD and MDD are substantially overlapping disorders, MDD is defined as an episodic illness with periods of dysthymia or normal mood, interrupted by major depressive episodes, which are characterized by dysthymia or depressed mood that must persist for at least 2 weeks and may last many months. GAD describes and is defined by a more continuous state of heightened anxiety. In our GAD program, starting with phase 2B, we demonstrated DT120's remarkable ability to improve this continuous background condition, while our MDD program is intended to demonstrate the same effect on the course of major depressive episodes. Taken together, these data suggest that, if approved, DT120 may represent a data-driven, evidence-based clinical choice for providers and patients with the potential to improve patient outcomes, whether the patient is currently in a major depressive episode or not.

Dan R. Karlin: While GAD and MDD are substantially overlapping disorders, MDD is defined as an episodic illness with periods of dysthymia or normal mood, interrupted by major depressive episodes, which are characterized by dysthymia or depressed mood that must persist for at least 2 weeks and may last many months. GAD describes and is defined by a more continuous state of heightened anxiety. In our GAD program, starting with phase 2B, we demonstrated DT120's remarkable ability to improve this continuous background condition, while our MDD program is intended to demonstrate the same effect on the course of major depressive episodes. Taken together, these data suggest that, if approved, DT120 may represent a data-driven, evidence-based clinical choice for providers and patients with the potential to improve patient outcomes, whether the patient is currently in a major depressive episode or not.

Speaker #4: GAD describes and is defined by a more continuous state of heightened anxiety. In our GAD program, starting with Phase II-B, we demonstrated DT120's remarkable ability to improve this continuous background condition while our MDD program is intended to demonstrate the same effect on the course of major depressive episodes.

Speaker #4: Taken together, these data suggest that if approved, DT120 may represent a data-driven evidence-based clinical choice for providers and patients with the potential to improve patient outcomes whether the patient is currently in a major depressive episode or not.

Speaker #4: Each of our four pivotal studies across GAD and MDD is comprised of two parts: Part A,

Dan Karlin: Each of our 4 pivotal studies across GAD and MDD is comprised of 2 parts. Part A, a 12-week randomized, double-blind, placebo-controlled, parallel group period assessing the safety and efficacy of a single dose of DT120 ODT versus placebo. Part B, a 40-week extension period with opportunities for open label treatment. The primary endpoint in our MDD studies is the change from baseline and MADRS score at week 6 between DT120 ODT 100 micrograms and placebo. The MDD trials were designed with 80% power to detect a 5-point improvement over placebo on this endpoint. The primary endpoint in our GAD studies is the change from baseline in the Hamilton Anxiety Rating Scale, or HAM-A, at week 12 between DT120 ODT 100 micrograms and placebo. The GAD trials were designed to have 90% power to detect a 5-point improvement over placebo on this endpoint.

Dan R. Karlin: Each of our 4 pivotal studies across GAD and MDD is comprised of 2 parts. Part A, a 12-week randomized, double-blind, placebo-controlled, parallel group period assessing the safety and efficacy of a single dose of DT120 ODT versus placebo. Part B, a 40-week extension period with opportunities for open label treatment. The primary endpoint in our MDD studies is the change from baseline and MADRS score at week 6 between DT120 ODT 100 micrograms and placebo. The MDD trials were designed with 80% power to detect a 5-point improvement over placebo on this endpoint. The primary endpoint in our GAD studies is the change from baseline in the Hamilton Anxiety Rating Scale, or HAM-A, at week 12 between DT120 ODT 100 micrograms and placebo. The GAD trials were designed to have 90% power to detect a 5-point improvement over placebo on this endpoint.

Speaker #1: A 12 week randomized , double blind , placebo controlled , parallel group period assessing the safety and efficacy of a single dose of PTX one .

Speaker #1: 28 versus placebo and part B of 40 week extension period with opportunities for open label treatment . The primary endpoint in our MDD studies is the change from baseline in Madrs score at week six between PTX 120 of 100 micrograms and placebo .

Speaker #1: The MDD trials were designed with 80% power to detect a five point improvement over placebo . On this endpoint . The primary endpoint in our Gad studies is the change from baseline in the Hamilton Anxiety Scale , or Ham-a .

Speaker #1: At week 12 . Between d 120 of 100 micrograms and placebo , the Gad trials were designed to have 90% power to detect a five point improvement over placebo .

Speaker #1: On this endpoint Our phase three studies are modeled after our successful phase two study , in which we observed placebo adjusted improvements of 7.7 points on the Ham-a and 6.4 points on the Madras at week 12 .

Dan Karlin: Our Phase 3 studies are modeled after our successful Phase 2b study, in which we observed placebo-adjusted improvements of 7.7 points on the HAM-A and 6.4 points on the MADRS at week 12. In the context of other approved pharmacotherapies, which have typically shown a placebo-adjusted effect of less than 4 points on these endpoints, we believe DT120 has the potential to be not only a best-in-class product among psychedelics, but among anxiolytics and antidepressants broadly. While placebo-adjusted changes are critically important for establishing efficacy, the absolute magnitude of improvement may be a more representative measure of the real-world patient experience. This is where DT120 even further stood out, having demonstrated a 21.9 point absolute reduction in HAM-A scores at week 12, corresponding with a 48% clinical remission rate and a 65% response rate.

Dan R. Karlin: Our Phase 3 studies are modeled after our successful Phase 2b study, in which we observed placebo-adjusted improvements of 7.7 points on the HAM-A and 6.4 points on the MADRS at week 12. In the context of other approved pharmacotherapies, which have typically shown a placebo-adjusted effect of less than 4 points on these endpoints, we believe DT120 has the potential to be not only a best-in-class product among psychedelics, but among anxiolytics and antidepressants broadly. While placebo-adjusted changes are critically important for establishing efficacy, the absolute magnitude of improvement may be a more representative measure of the real-world patient experience. This is where DT120 even further stood out, having demonstrated a 21.9 point absolute reduction in HAM-A scores at week 12, corresponding with a 48% clinical remission rate and a 65% response rate.

Speaker #1: In the context of other approved pharmacotherapies , which have typically shown a placebo adjusted effect of less than four points on these endpoints .

Speaker #1: We believe D-120 has the potential to be not only a best-in-class product among psychedelics, but also among anxiolytics and antidepressants.

Speaker #1: Broadly , and while placebo adjusted changes are critically important for establishing efficacy , the absolute magnitude of improvement may be a more representative measure of the real world patient experience .

Speaker #1: This is where D 120 even further stood out . Having demonstrated a 21 .9. absolute reduction in Ham-d scores at week 12 , corresponding with a 48% clinical remission rate and a 65% response rate In addressing comorbid depressive symptoms .

Dan Karlin: In addressing comorbid depressive symptoms, we saw an 18.7 point absolute reduction in MADRS scores at week 12. I'll now recap progress with our MDD studies. Enrollment is complete, and we expect to deliver top-line data from Emerge in late Q2. Based on the progress in Emerge, we are moving forward with the execution of our second pivotal MDD study, Ascend. In Ascend, we are targeting enrollment of approximately 175 participants, randomized 2 to 1 to 2, to receive DT120 ODT 100 micrograms, 50 micrograms, or placebo. Our first sites in Ascend have been activated, and we expect to begin dosing by early Q2. We expect Ascend to continue to benefit from operational efficiencies that enabled the rapid enrollment of Emerge, including the ability to fast-track select sites that participated in Emerge and those that are actively enrolling in our GAD program.

Dan R. Karlin: In addressing comorbid depressive symptoms, we saw an 18.7 point absolute reduction in MADRS scores at week 12. I'll now recap progress with our MDD studies. Enrollment is complete, and we expect to deliver top-line data from Emerge in late Q2. Based on the progress in Emerge, we are moving forward with the execution of our second pivotal MDD study, Ascend. In Ascend, we are targeting enrollment of approximately 175 participants, randomized 2 to 1 to 2, to receive DT120 ODT 100 micrograms, 50 micrograms, or placebo. Our first sites in Ascend have been activated, and we expect to begin dosing by early Q2. We expect Ascend to continue to benefit from operational efficiencies that enabled the rapid enrollment of Emerge, including the ability to fast-track select sites that participated in Emerge and those that are actively enrolling in our GAD program.

Speaker #1: We saw an 18.7% absolute reduction in Madras scores at week 12 . I'll now recap progress with our MDD studies Enrollment is complete and we expect to deliver top line data from emerge in late Q2 Based on the progress in emerge .

Speaker #1: We are moving forward with the execution of our second pivotal MDD study . Ascend and Ascend . We are targeting enrollment of approximately 175 participants , randomized two to 1 to 2 to receive D 128 100 micrograms , 50 micrograms , or placebo Our first sites in ascend have been activated , and we expect to begin dosing by early Q2 We expect to ascend to continue to benefit from operational efficiencies that enable the rapid enrollment of emerge , including the ability to fast track , select sites that participated in Emerge and those that are actively enrolling in our Gad program Regarding our Gad program , we are in the final stages of enrollment in voyage with completion anticipated in the coming weeks In voyage , we are targeting enrollment of approximately 200 participants , randomized one to 1 to 1 2100 micrograms or placebo , while in panorama , we are targeting enrollment of 250 participants , randomized two to 1 to 2 .

Dan Karlin: Regarding our GAD program, we are in the final stages of enrollment in Voyage, with completion anticipated in the coming weeks. In Voyage, we are targeting enrollment of approximately 200 participants, randomized 1 to 1 to DT120 ODT 100mcg or placebo, while in Panorama, we are targeting enrollment of 250 participants, randomized 2 to 1 to 2 to DT120 ODT 100mcg, 50mcg, or placebo. Each GAD study includes a sample size re-estimation that allows for adjustment of the target enrollment based on a blinded evaluation of nuisance parameters. As Rob mentioned previously, we completed the sample size re-estimation for Voyage and determined that no increase in the trial's sample size is required. In the initial study power calculation, we assumed a standard deviation of 10 points and a non-evaluable rate of 15% at week 12.

Dan R. Karlin: Regarding our GAD program, we are in the final stages of enrollment in Voyage, with completion anticipated in the coming weeks. In Voyage, we are targeting enrollment of approximately 200 participants, randomized 1 to 1 to DT120 ODT 100mcg or placebo, while in Panorama, we are targeting enrollment of 250 participants, randomized 2 to 1 to 2 to DT120 ODT 100mcg, 50mcg, or placebo. Each GAD study includes a sample size re-estimation that allows for adjustment of the target enrollment based on a blinded evaluation of nuisance parameters. As Rob mentioned previously, we completed the sample size re-estimation for Voyage and determined that no increase in the trial's sample size is required. In the initial study power calculation, we assumed a standard deviation of 10 points and a non-evaluable rate of 15% at week 12.

Speaker #1: To one , 20 ot 100 micrograms , 50 micrograms , or placebo each . Gad study includes a sample size Re-estimation that allows for adjustment of the target enrollment based on a blinded evaluation of nuisance parameters as mentioned previously , we completed the sample size estimation for voyage and determined that no increase in the trial's sample size is required in the initial study , power calculation , we assumed a standard deviation of ten points and a non-evaluable rate of 15% .

Speaker #1: At week 12, among the first 100 participants who completed week 12, we saw a model-based standard deviation of 6.7 points on the HAM-A and a non-evaluable rate of 10%.

Dan Karlin: Among the first 100 participants who completed week 12, we saw a model-based standard deviation of 6.7 points on the HAM-A and a non-evaluable rate of 10%. These observations suggest that the study's ability to detect a statistically significant drug effect substantially exceeds the planned power. In fact, if these nuisance parameters were to remain unchanged in the final analysis, this would imply that the study has over 99% power to detect a five-point difference on the HAM-A and that the minimum difference required to achieve statistical significance would be less than two points. Beyond DT120, we are excited to have initiated our phase two study of DT402 in autism spectrum disorder, or ASD, in late 2025. DT402, the R-enantiomer of MDMA, has shown promising prosocial effects with a potentially favorable tolerability profile.

Dan R. Karlin: Among the first 100 participants who completed week 12, we saw a model-based standard deviation of 6.7 points on the HAM-A and a non-evaluable rate of 10%. These observations suggest that the study's ability to detect a statistically significant drug effect substantially exceeds the planned power. In fact, if these nuisance parameters were to remain unchanged in the final analysis, this would imply that the study has over 99% power to detect a five-point difference on the HAM-A and that the minimum difference required to achieve statistical significance would be less than two points. Beyond DT120, we are excited to have initiated our phase two study of DT402 in autism spectrum disorder, or ASD, in late 2025. DT402, the R-enantiomer of MDMA, has shown promising prosocial effects with a potentially favorable tolerability profile.

Speaker #1: These observations suggest that the study's ability to detect a statistically significant drug effect substantially exceeds the planned power . In fact , if these nuisance parameters were to remain unchanged in the final analysis , this would imply that the study has over 99% power to detect a five point difference on the Ham-a , and that the minimum difference required to achieve statistical significance would be less than two points beyond TW 120 .

Speaker #1: We are excited to have initiated our phase two study of DP 402 in autism Spectrum Disorder , or ASD , in late 2025 .

Speaker #1: DP 402 , the R enantiomer of MDMA , has shown promising prosocial effects with a potentially favorable tolerability profile . We're developing DPP 402 to target the core symptoms of ASD , specifically addressing social communication that is central to the experience of the disorder .

Dan Karlin: We're developing DT402 to target the core symptoms of ASD, specifically addressing social communication that is central to the experience of the disorder. We believe this program represents another significant treatment opportunity, given the high unmet need, the increasing prevalence of ASD, and no FDA-approved therapies that specifically address these core symptoms. Having completed a Phase 1 single ascending dose study that characterized the tolerability, pharmacokinetics, and pharmacodynamics of DT402 in healthy adult volunteers, we dosed the first participant in our Phase 2a study, and initial data is expected later this year. This study is a single-dose, open label design assessing early signals of efficacy in up to 20 adult participants with ASD. The objectives and endpoints of the study are designed to characterize the pharmacodynamics and clinical effects of DT402 across multiple functional domains.

Dan R. Karlin: We're developing DT402 to target the core symptoms of ASD, specifically addressing social communication that is central to the experience of the disorder. We believe this program represents another significant treatment opportunity, given the high unmet need, the increasing prevalence of ASD, and no FDA-approved therapies that specifically address these core symptoms. Having completed a Phase 1 single ascending dose study that characterized the tolerability, pharmacokinetics, and pharmacodynamics of DT402 in healthy adult volunteers, we dosed the first participant in our Phase 2a study, and initial data is expected later this year. This study is a single-dose, open label design assessing early signals of efficacy in up to 20 adult participants with ASD. The objectives and endpoints of the study are designed to characterize the pharmacodynamics and clinical effects of DT402 across multiple functional domains.

Speaker #1: We believe this program represents another significant treatment opportunity given the high unmet need . The increasing prevalence of ASD and no FDA approved therapies that specifically address these core symptoms Having completed a phase one single ascending dose study that characterized the tolerability , pharmacokinetics , and pharmacodynamics of DP 402 , in healthy adult volunteers , we dosed the first participant in our phase two study an initial data is expected later this year This study is a single dose open label design assessing early signals of efficacy in up to 20 adult participants with ASD The objectives and endpoints of the study are designed to characterize the pharmacodynamics and clinical effects of DPP 402 across multiple functional domains across our late stage pipeline , we are making strong progress and rapidly approaching multiple pivotal readouts for our Rd 120 ODT program .

Dan Karlin: Across our late-stage pipeline, we are making strong progress and rapidly approaching multiple pivotal readouts for our DT120 ODT program. We believe the remarkable profile of DT120 has the potential to be best in class among GAD and MDD pharmacotherapies, and we are confident in our strategy and execution to drive the broadest possible impact for the millions of patients in need. Now I'll turn it over to Matt for commercial comments on DT120.

Dan R. Karlin: Across our late-stage pipeline, we are making strong progress and rapidly approaching multiple pivotal readouts for our DT120 ODT program. We believe the remarkable profile of DT120 has the potential to be best in class among GAD and MDD pharmacotherapies, and we are confident in our strategy and execution to drive the broadest possible impact for the millions of patients in need. Now I'll turn it over to Matt for commercial comments on DT120.

Speaker #1: We believe the remarkable profile of D3 120 has the potential to be best in class among Gad and MDD . Pharmacotherapies , and we are confident in our strategy and execution to drive the broadest possible impact for the millions of patients in need Now , I'll turn it over to Matt for commercial comments on D 120 .

Speaker #2: Thanks , Dan . As an organization , we are deeply committed to and focused on impeccable commercial readiness for the potential launches in Gad and MDD .

Matt Wiley: Thanks, Dan. As an organization, we are deeply committed to and focused on impeccable commercial readiness for the potential launches in GAD and MDD. Over the past year, we've comprehensively mapped the provider landscape nationwide and, in close collaboration with our cross-functional internal teams, prioritized key states for launch. If approved, we are fully positioned to execute rapidly and with precision. Our vision for Definium commercialization is to deliver a genuinely high-touch, white-glove experience for our providers, one that extends the collaborative, partnership-oriented approach that has distinguished us throughout our clinical development and with our trial sites. This philosophy has been a key differentiator for us, and we intend to make it a foundational element of our commercial model. We fully appreciate that providers will have multifaceted needs beyond just product information. They will see clear guidance on REMS certification, regulatory requirements, operational integration, and reimbursement pathways.

Speaker #2: Over the past year , we've comprehensively mapped the provider landscape nationwide and in close collaboration with our cross-functional internal teams , prioritized key states for launch .

Speaker #2: If approved , we are fully positioned to execute rapidly and with precision Our vision for definitive commercialization is to deliver a genuinely high touch white glove experience for our providers .

Speaker #2: One that extends the collaborative , partnership oriented approach that distinguished us throughout our clinical development and with our trial sites . This philosophy has been a key differentiator for us , and we intend to make it a foundational element of our commercial model We fully appreciate that providers will have multifaceted needs beyond just product information .

Speaker #2: They will see clear guidance on REM certification , regulatory requirements , operational integration and reimbursement pathways Accordingly , we are building the robust infrastructure and cross-functional teams required to address these elements seamlessly and support providers from day one .

Matt Wiley: Accordingly, we are building the robust infrastructure and cross-functional teams required to address these elements seamlessly and support providers from day one. To strengthen our launch capabilities, we've assembled an exceptional commercial leadership team over the past year in marketing, market access, and operations. This leadership team comes with deep experience in navigating complex launches, including experience with REMS and scheduled drugs. Their proven track record gives us tremendous confidence as we prepare for launch. We look forward to sharing more detail on our commercialization strategy at our upcoming Analyst Day on 22 April. Stepping back, our message is simple: We are preparing to introduce something meaningfully different. Historically, when new classes of medicines have been introduced in psychiatry, they've generated significant value and delivered multibillion-dollar opportunities.

Speaker #2: To strengthen our launch capabilities , we've assembled an exceptional commercial leadership team over the past year . In marketing , market access and operations .

Speaker #2: This leadership team comes with deep experience in navigating complex launches , including experience with Rems and scheduled drugs . Their proven track record gives us tremendous confidence as we prepare for launch .

Speaker #2: We look forward to sharing more detail on our commercialization strategy at our upcoming Analyst Day on April 22nd , but stepping back , our message is simple .

Speaker #2: We are preparing to introduce something meaningfully different Historically , when new classes of medicines have been introduced in psychiatry , they have generated significant value and delivered multibillion dollar opportunities .

Speaker #2: We believe DT 120 has the potential not only to participate in that kind of opportunity , but to improve on what has come before .

Matt Wiley: We believe DT120 has the potential not only to participate in that kind of opportunity, but to improve on what has come before, most importantly, for patients who urgently need more than better. With that, I'll turn our call over to Brandi to discuss our full year 2025 results. Brandi?

Speaker #2: Most importantly , for patients who urgently need more than better With that , I'll turn over to Brandy to discuss our full year 2025 results .

Speaker #2: Brandy

Speaker #3: Thanks , Matt Research and development expenses were $117.7 million for the year ended December 31st , 2025 , compared to $65.3 million for the year ended December 31st , 2020 .

Brandi: Thanks, Matt. Research and development expenses were $117.7 million for the year ended 31 December 2025, compared to $65.3 million for the year ended 31 December 2024, representing an increase of $52.4 million. This increase was primarily driven by $44.7 million in higher DT120 program expenses, $9.3 million in internal personnel costs, reflecting expanded research and development capabilities, and $0.4 million in preclinical and other program expenses, partially offset by a $2 million reduction in DT402 program expenses. General and administrative expenses were $48.6 million for the year ended 31 December 2025, compared to $38.6 million for the year ended 31 December 2024, an increase of $10 million.

Brandi Roberts: Thanks, Matt. Research and development expenses were $117.7 million for the year ended 31 December 2025, compared to $65.3 million for the year ended 31 December 2024, representing an increase of $52.4 million. This increase was primarily driven by $44.7 million in higher DT120 program expenses, $9.3 million in internal personnel costs, reflecting expanded research and development capabilities, and $0.4 million in preclinical and other program expenses, partially offset by a $2 million reduction in DT402 program expenses. General and administrative expenses were $48.6 million for the year ended 31 December 2025, compared to $38.6 million for the year ended 31 December 2024, an increase of $10 million.

Speaker #3: For representing an increase of $52.4 million , this increase was primarily driven by $44.7 million in higher d20 program expenses , $9.3 million in internal personnel costs , reflecting expanded research and development capabilities , and $0.4 million in preclinical and other program expenses .

Speaker #3: Partially offset by a $2 million reduction in DBT 402 program expenses General and administrative expenses were $48.6 million for the year ended December 31st , 2025 , compared to $38.6 million for the year ended December 31st , 2020 .

Speaker #3: Four . An increase of $10 million . The increase was primarily attributable to $6 million in professional services and pre-commercialization activities . $3.6 million in personnel related expenses to support expanded operational activities .

Brandi: The increase was primarily attributable to $6 million in professional services and pre-commercialization activities, $3.6 million in personnel-related expenses to support expanded operational activities, $0.7 million in directors' deferred share unit expense, driven by our year-over-year stock price appreciation, and $0.5 million in other administrative expenses, partially offset by a $0.8 million reduction in legal and patent-related expenses. Overall, our R&D and G&A expenses for 2025 were in line with our internal expectations as we continued to make significant progress across the DT120 and DT402 programs. Net loss for the year ended 31 December 2025 was $183.8 million, compared to $108.7 million for the year ended 31 December 2024.

Brandi Roberts: The increase was primarily attributable to $6 million in professional services and pre-commercialization activities, $3.6 million in personnel-related expenses to support expanded operational activities, $0.7 million in directors' deferred share unit expense, driven by our year-over-year stock price appreciation, and $0.5 million in other administrative expenses, partially offset by a $0.8 million reduction in legal and patent-related expenses. Overall, our R&D and G&A expenses for 2025 were in line with our internal expectations as we continued to make significant progress across the DT120 and DT402 programs. Net loss for the year ended 31 December 2025 was $183.8 million, compared to $108.7 million for the year ended 31 December 2024.

Speaker #3: $0.7 million in directors deferred share unit expense driven by our year over year stock price appreciation and $0.5 million in other administrative expenses , partially offset by a $0.8 million reduction in legal and patent related expenses Overall , our R&D and G&A expenses for 2025 were in line with our internal expectations as we continued to make significant progress across the DT .

Speaker #3: 120 and DT 402 programs . Net loss for the year ended December 31st , 2025 was $183.8 million compared to $108.7 million for the year ended December 31st , 2020 .

Speaker #3: For . As a reminder , our net loss can be significantly impacted by changes in the fair value of our 2022 . USD financing warrants During 2025 , the change in fair value was $22.8 million , reflecting an increase in our stock price from $6.96 at December 31st , 2024 , to $13.39 at December 31st , 2025 .

Brandi: As a reminder, our net loss can be significantly impacted by changes in the fair value of our 2022 USD financing warrants. During 2025, the change in fair value was $22.8 million, reflecting an increase in our stock price from $6.96 at 31 December 2024, to $13.39 at 31 December 2025. We ended 2025 with cash equivalents, and investments of $411.6 million, compared to $273.7 million at year-end 2024. Based on our current operating plan and anticipated milestones, we believe our cash equivalents, and investments as of 31 December 2025, will be sufficient to fund operations into 2028.

Brandi Roberts: As a reminder, our net loss can be significantly impacted by changes in the fair value of our 2022 USD financing warrants. During 2025, the change in fair value was $22.8 million, reflecting an increase in our stock price from $6.96 at 31 December 2024, to $13.39 at 31 December 2025. We ended 2025 with cash equivalents, and investments of $411.6 million, compared to $273.7 million at year-end 2024. Based on our current operating plan and anticipated milestones, we believe our cash equivalents, and investments as of 31 December 2025, will be sufficient to fund operations into 2028.

Speaker #3: We ended 2025 with cash , cash equivalents and investments of $411.6 million , compared to $273.7 million at year end 2024 . Based on our current operating plan and anticipated milestones , we believe our cash , cash equivalents and investments as of December 31st , 2025 will be sufficient to fund operations into 2028 .

Speaker #3: We are pleased to enter 2026 with the financial flexibility to accelerate several key initiatives , including NDA preparation , market access , priority activities , market research and coal education .

Brandi: We are pleased to enter 2026 with the financial flexibility to accelerate several key initiatives, including NDA preparation, market access, priority activities, market research, and KOL education. These investments are intended to support our path to market, and if DT120 ODT is approved, enable a well-prepared and robust commercial launch. We are also encouraged by the continued evolution of our investor base, with strong engagement from existing shareholders and growing interest from new investors as we progress through 2025. As we look ahead to a very important year in 2026, our focus remains on disciplined execution, thoughtful capital allocation, and advancing our programs in a way that supports long-term value creation. I'll now turn the call back to Rob for our closing remarks.

Brandi Roberts: We are pleased to enter 2026 with the financial flexibility to accelerate several key initiatives, including NDA preparation, market access, priority activities, market research, and KOL education. These investments are intended to support our path to market, and if DT120 ODT is approved, enable a well-prepared and robust commercial launch. We are also encouraged by the continued evolution of our investor base, with strong engagement from existing shareholders and growing interest from new investors as we progress through 2025. As we look ahead to a very important year in 2026, our focus remains on disciplined execution, thoughtful capital allocation, and advancing our programs in a way that supports long-term value creation. I'll now turn the call back to Rob for our closing remarks.

Speaker #3: These investments are intended to support our path to market, and if D20 OT is approved, enable a well and robust commercial launch.

Speaker #3: We are also encouraged by the continued evolution of our investor base, with strong engagement from existing shareholders and growing interest from new investors.

Speaker #3: As we progress through 2025, and as we look ahead to a very important year in 2026, our focus remains on disciplined execution, thoughtful capital allocation, and advancing our programs in a way that supports long-term value creation. I'll now turn the call back to Rob for our closing remarks.

Speaker #4: Thank you . Brandy 2025 was a year of bold ambition and disciplined execution . In 2026 , definition is set to deliver some of Psychiatry's most important data , highlighting our progress and ambition to bring novel , scalable therapies to patients underserved by today's standard of care With the strong balance sheet and a late stage pipeline with multiple catalysts in the months ahead , we're excited to continue driving value for our shareholders in the millions of patients who deserve more than better Of course , none of this progress will be possible without our exceptional team , whose passion , commitment and unmatched execution continue to set the standard for our field Thank you again for joining our call today .

Matt Wiley: Thank you, Brandi. 2025 was a year of bold ambition and disciplined execution. In 2026, Definium is set to deliver some of psychiatry's most important data, highlighting our progress and ambition to bring novel, scalable therapies to patients underserved by today's standard of care. With a strong balance sheet and a late-stage pipeline with multiple catalysts in the months ahead, we're excited to continue driving value for our shareholders and the millions of patients who deserve more than better. Of course, none of this progress would be possible without our exceptional team, whose passion, commitment, and unmatched execution continue to set the standard for our field. Thank you again for joining our call today. We'll now open the line for questions.

Rob Barrow: Thank you, Brandi. 2025 was a year of bold ambition and disciplined execution. In 2026, Definium is set to deliver some of psychiatry's most important data, highlighting our progress and ambition to bring novel, scalable therapies to patients underserved by today's standard of care. With a strong balance sheet and a late-stage pipeline with multiple catalysts in the months ahead, we're excited to continue driving value for our shareholders and the millions of patients who deserve more than better. Of course, none of this progress would be possible without our exceptional team, whose passion, commitment, and unmatched execution continue to set the standard for our field. Thank you again for joining our call today. We'll now open the line for questions.

Speaker #4: We'll now open the line for questions

Speaker #5: Thank you . Ladies and gentlemen , to ask a question at this time , you will need to press star one one on your telephone and wait for your name to be announced .

Gitanjali Jain: Thank you. Ladies and gentlemen, to ask a question at this time, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, simply press star one one again. Please stand by while we compile the attendee roster. First question coming from the line of Andrew Tsai with Jefferies. Your line is now open.

Operator: Thank you. Ladies and gentlemen, to ask a question at this time, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, simply press star one one again. Please stand by while we compile the attendee roster. First question coming from the line of Andrew Tsai with Jefferies. Your line is now open.

Speaker #5: To withdraw your question , simply press star one one again . Please stand by while we compile roster Now first question coming from the line of Andrew with Jefferies .

Speaker #5: Your line is now open

Speaker #6: Hey good afternoon . Thanks for the updates . Thanks for taking my question For this interim that you did , it's very interesting for voyage .

Andrew Tsai: Hey, good afternoon. Thanks for the updates. Thanks for taking my question. For this interim that you did, it's very interesting for Voyage. I'm curious, in the hypothetical scenario where the DMC asked or recommended you to upsize the trial, what would have been effectively the placebo-adjusted delta for that to happen, give or take? Just to confirm, there were no other scenarios with this interim, such as stopping for fertility or even stopping for success? Thanks.

Speaker #6: I'm curious in the hypothetical where the DMC asked or recommended you to upsize the trial , what would have been effectively the placebo adjusted delta for that to happen , give or take .

Speaker #6: And just to confirm, there were no other scenarios with this interim, such as stopping for futility or even stopping for success.

Speaker #6: Thanks .

Speaker #4: Yeah , thanks so much for the question , Andrew . So this is this is a blinded sample size estimation . So an important feature of that analysis is that we don't ever unblind the study .

Matt Wiley: Yeah, thanks so much for the question, Andrew. It was a blinded Sample Size Re-Estimation. An important feature of that analysis is that we don't-

Rob Barrow: Yeah, thanks so much for the question, Andrew. It was a blinded Sample Size Re-Estimation. An important feature of that analysis is that we don't-

Rob Barrow: Everyone blind the study. We don't do any inferential testing, and as a result, we don't actually learn anything about the performance of the two groups independently or in relation to one another. Effectively, you can think of it as looking at the right side, right of the plus or minus on the 95% confidence interval to assess the standard error and ensure that the assumptions are made at the beginning of the study, are reflected, or we don't lose power because we made the wrong assumptions. There was no implication. There's no learnings or inference that can be derived either from this analysis or for any other outcomes of the analysis.

Speaker #4: We don't do any inferential testing . And as a result , we don't actually learn anything about the performance of the two groups independently or in relation to one another .

Speaker #4: Effectively , you can think of it as looking at the right side Right of the plus or minus on a 95% confidence interval to assess the standard error and ensure that the assumptions are made at the beginning of the study .

Speaker #4: Are reflected , or we don't lose power because we made the wrong assumptions . And so there was there was no implication , there was no learnings or inference that can be derived either from this analysis or for any other outcome of the analysis .

Rob Barrow: We are certainly excited to see that we're good with the assumptions we made. If anything, as Dan mentioned during the call, have certainly adequate power at 99% or greater if the current variables hold, nuisance parameters hold. We're eager to get to study results and ultimately do that inferential test and look at the performance of 120 versus placebo.

Speaker #4: But we were certainly excited to see that we're good with the assumptions we made , and if anything , as Dan mentioned during the call , have certainly adequate power at 99% or greater .

Speaker #4: If the current variables hold, nuisance parameters hold, and we're eager to get the study results and ultimately do that inferential test and look at the performance of 120 versus placebo.

Speaker #6: Wow . Okay , thanks . And then really quickly , by the time you top line the voyage data now in early Q3 , would you consider piecemealing some of the part B open label extension data just to further showcase how durable a single dose of 120 could be ?

Andrew Tsai: Wow. Okay, thanks. Really quickly, by the time you top line the VOYAGE data now in early Q3, would you consider piecemealing some of the Part B open label extension data just to further showcase how durable a single dose of DT120 could be? Otherwise, when would you share the open label portion? Thanks.

Speaker #6: Otherwise , when would you share the open label portion ? Thanks

Speaker #4: Yeah , absolutely . I think one of the things we've been really focused on is , is , of course , the durability and the response patterns over the course of an entire year .

Rob Barrow: Yeah, absolutely. you know, I think one of the things we've been really focused on is, of course, the durability and the response patterns over the course of an entire year. Of course, all of the studies have been running for quite a while now. As we continue to accrue patients who have gone through certain milestones and either events of retreatment or have made it through a fixed interval of time, we'll have, of course, increasing data and increasing confidence in those data to be able to share some insights. We haven't firmed up a commitment to exactly when we would present Part B data.

Speaker #4: And of course , in all of the studies have been been running for for quite a while now . And so as we continue to accrue patients who have gone through certain milestones and either events of retreatment or have made it through a fixed interval of time , or have , of course , increasing data and increasing confidence in those data to be able to share some insights .

Speaker #4: So, we haven't firmed up a commitment exactly when we would present Part B data. We certainly don't want to get ahead of ourselves and be presenting data that we don't feel are representative, or that we're not confident in, at any time.

Rob Barrow: We certainly don't want to get ahead of ourselves, and we present data that we don't feel are representative or we're not confident in at any time. We'll certainly be taking a look at that as we accrue those data, be it at any of the readouts from the ongoing studies or another time, we'll have an opportunity to share as much insights as we possibly can about the performance in Part A and Part B.

Speaker #4: So we'll certainly be taking a look at that . And as we accrue those data , be it at any of the readouts from the ongoing studies , or at another time we'll have an opportunity to share as much insights as we possibly can about the performance in part A and part B .

Speaker #6: Great . Makes sense . Thanks again .

Andrew Tsai: Great. Makes sense. Thanks again.

Speaker #5: Thank you. Our next question comes from the line of Margaret Mann with Leerink. The line is now open.

Gitanjali Jain: Thank you. Our next question coming from the line of Marc Goodman with Leerink. Your line is now open.

Operator: Thank you. Our next question coming from the line of Marc Goodman with Leerink. Your line is now open.

Operator: Good afternoon. This is Basma on for Marc. Thank you for taking our question. Our first question is on the interim look. Again, have you conducted the interim look for Panorama as well, or not yet? Or are you planning to do it once you hit 80% enrollment, similar to Voyage? Also regarding the MDD, when are you gonna plan to do the interim look exactly for the Emerge trial? Our second question is for the GAD readouts. What are your expectations regarding the remission rate? What would you consider as a good and differentiated rate versus the standard of care? Thank you. That's it for us.

Speaker #7: Good afternoon . This is Basma on for Mark . Thank you for taking our question Our first question is on the interim . Look again , have you conducted the interim look for Panorama as well or are not yet .

Basma Radwan: Good afternoon. This is Basma on for Marc. Thank you for taking our question. Our first question is on the interim look. Again, have you conducted the interim look for Panorama as well, or not yet? Or are you planning to do it once you hit 80% enrollment, similar to Voyage? Also regarding the MDD, when are you gonna plan to do the interim look exactly for the Emerge trial? Our second question is for the GAD readouts. What are your expectations regarding the remission rate? What would you consider as a good and differentiated rate versus the standard of care? Thank you. That's it for us.

Speaker #7: And or are you planning to do it once you hit 80% enrollment ? Similar to Voyager ? And also regarding the MDD , what when the when are you going to plan to do the interim look ?

Speaker #7: Exactly . For the Emerge trial , our second question is for the Gad readouts . What are your expectations regarding the remission rate ?

Speaker #7: What would you consider ? What would you consider it as a good and differentiated rate versus a standard of care ? Thank you .

Speaker #7: That's it for us

Rob Barrow: Yes, thanks so much, Basma. In terms of the interim analysis for Voyage, we of course, announced that today. For Panorama, our second pivotal study in GAD, we'll be sharing additional details and enrollment updates at our Analyst Day in April. For the 2 MDD studies, of course, Emerge is now fully enrolled, and the data, the top-line data that we'd be sharing would be the completed final top-line analysis from that study. We're not conducting an interim look on either of the MDD studies as planning currently. In terms of GAD and the remission rate, I'll turn it over to Dan to maybe comment about our thinking around response patterns and ultimately what drives patient experience and value in these populations.

Speaker #4: Thanks so much . So in terms of the interim analysis for voyage , we of course announced that today For Panorama , our second pivotal study in Gad , we will be sharing additional details and enrollment updates at our Analyst Day in April .

Speaker #4: For the two MDD studies . Of course , Emerge is now fully enrolled and the data pipeline data that we'll be sharing would be the completed final pipeline analysis from that study .

Speaker #4: So we're not conducting an interim look on either of the MDD studies as planned . Currently , in terms of Gad and remission rate , I'll turn it over to Dan to maybe comment about our thinking around response patterns and ultimately what drives patient experience and value in these populations .

Speaker #1: Yeah , it's a great question about the remission rate , because we've obviously talked about that from our phase two . Be outcomes .

Dan Karlin: Yeah, it's a great question about the remission rate, because we've obviously talked about that from our Phase 2b outcomes. I think it's important to note that mostly what we know about pharmacotherapy induced remission rate come from MDD studies. In MDD, what we see an SRI, as you know, the first-line treatment that's most commonly used, attributable remission rate in the real world is something in the 10% to 30% range. Of course, it's difficult to necessarily interpret those data because MDD is necessarily a cyclical illness. That, you know, when a major depressive episode is resolved, whether with meds or without, then that is a period of remission from the symptoms.

Dan R. Karlin: Yeah, it's a great question about the remission rate, because we've obviously talked about that from our Phase 2b outcomes. I think it's important to note that mostly what we know about pharmacotherapy induced remission rate come from MDD studies. In MDD, what we see an SRI, as you know, the first-line treatment that's most commonly used, attributable remission rate in the real world is something in the 10% to 30% range. Of course, it's difficult to necessarily interpret those data because MDD is necessarily a cyclical illness. That, you know, when a major depressive episode is resolved, whether with meds or without, then that is a period of remission from the symptoms.

Speaker #1: I think it's important to note that mostly what we know about pharmacotherapy induced remission rates come from MDD . Studies . And an MDD .

Speaker #1: What we see in Sri , the first line treatment is most commonly used attributable remission rate in the real world , something in the 10 to 30% range .

Speaker #1: But of course it's difficult to to necessarily interpret those data because MDD is necessarily a cyclical illness . So that , you know , when a major depressive episode is resolved , whether with meds or without , then that is that is a period of remission from from those symptoms .

Dan Karlin: We made some design choices in phase three for both GAD and MDD, which was to target open label treatment, so the Part B treatments, to the threshold between mild and moderate illness on the scale, so these on the HAM-A and the MADRS. In this case, what we are really looking at is, given the availability of open label treatment in the Part Bs, are we able to treat people down into that mild or better range reliably with the redosing? While we're not a priori specifying what we would hope for from an absolute remission rate, what we're intending here to do is to get people out of moderate or worse illness and see how well we can keep them in mild or better.

Speaker #1: We made some design choices in phase three for both Gad and MDD , which was to target open label treatments . So the part B treatments to the threshold between mild and moderate illness on the scales that we used on the Ham-a and the Madras .

Dan R. Karlin: We made some design choices in phase three for both GAD and MDD, which was to target open label treatment, so the Part B treatments, to the threshold between mild and moderate illness on the scale, so these on the HAM-A and the MADRS. In this case, what we are really looking at is, given the availability of open label treatment in the Part Bs, are we able to treat people down into that mild or better range reliably with the redosing? While we're not a priori specifying what we would hope for from an absolute remission rate, what we're intending here to do is to get people out of moderate or worse illness and see how well we can keep them in mild or better.

Speaker #1: So in this case , what we are really looking at is given the availability of open label treatment in part B's , are we able to treat people down into that mild or better range reliably with with the dosing ?

Speaker #1: So so while we're not a priori specifying what we would hope for from a from an absolute remission rate , what we're intending here to do is to get people out of moderate or worse illness and see how well we can keep them in mild or better .

Speaker #7: Thank you

Operator: Thank you.

Basma Radwan: Thank you.

Speaker #5: Thank you . Our next question coming from the line of If you side with Evercore ISI , Ellen is now open

Gitanjali Jain: Thank you. Our next question coming from the line of Ebizai with Evercore ISI. Your line is now open.

Speaker #8: Hi . You have EV on for Gavin . Congratulations on all the progress made this year It's great to see that the SSR is now complete .

[Analyst] (Unknown): Hi, you have Evie on for Gavin. Congratulations on all the progress made this year. It's great to see that the SSRE is now complete. Any color you could provide on enrollment and how it is trending for the second GAD and MDD trial, seeing as Voyage data is now expected by early Q3? Our second question is, in addition to the SSRE and variability, can you speak to anything else giving you incremental confidence? Could be something like baseline characteristics or rollover retention, screen failures or anything like that. Thank you.

Evie Kao: Hi, you have Evie on for Gavin. Congratulations on all the progress made this year. It's great to see that the SSRE is now complete. Any color you could provide on enrollment and how it is trending for the second GAD and MDD trial, seeing as Voyage data is now expected by early Q3? Our second question is, in addition to the SSRE and variability, can you speak to anything else giving you incremental confidence? Could be something like baseline characteristics or rollover retention, screen failures or anything like that. Thank you.

Speaker #8: Any color you could provide on enrollment and how it is trending for the second Gad and MDD trials , seeing as voyage data is now expected by early three Q .

Speaker #8: And our second question is in addition to the SSR and variability , can you speak to anything else giving you incremental confidence could be something like baseline characteristics , early rollover retention , screen failures or anything like that .

Speaker #8: Thank you

Speaker #4: Yes . Thanks so much for the question . So in terms of enrollment updates , of course , with emerge , our first MDD study now fully enrolled and with data expected in late Q2 .

Rob Barrow: Yes, thanks so much for the question. In terms of enrollment updates, of course, with Emerge, our first MDD study now fully enrolled and with data expected in late Q2, we've just been overwhelmed by how fast we were able to enroll that study and how excited we think that represents the field and the researchers who are working on this study has been and are about the potential here. We certainly are, and our team has done an incredible job at executing on these studies. In terms of Voyage, we shared that approximately 80% enrollment, and we continue to see incredibly strong enrollment with our best months yet. We absolutely are seeing the continued growth and acceleration of enrollment across the program.

Speaker #4: We've just been overwhelmed by how fast we were able to enroll that study . And how excited we think that represents the field .

Speaker #4: And the researchers who are working on this study have been and are about the potential here . We certainly are . And our team has done an incredible job at executing these studies in terms of voyage .

Speaker #4: We we shared that approximately 80% enrollment and we continue to see incredibly strong enrollment with our best months yet . And we absolutely are seeing the continued growth and acceleration of enrollment across the program .

Speaker #4: So for our second study for Panorama , you know , again , we'll be sharing further updates at our Analyst Day in April .

Rob Barrow: For our second study for Panorama, you know, again, we'll be sharing further updates at our Analyst Day in April. We've been encouraged across the board and really happy with where we are in enrollment in that study. Ascend, we're also of course will be starting in the coming weeks. We're really excited to get studies activated, really faster than even we anticipated. The ability to get studies DEA activated and DEA approvals in place in a matter of just a few weeks has allowed us to really accelerate the start of that second study in MDD. Really across the board, we've been very encouraged by the enrollment trends and where that positions us for 3 potential readouts over the course of this year.

Speaker #4: But we've been encouraged across the board and really happy with where we are in enrollment in that study . Ascend . We're also , of course , will be starting in the coming weeks .

Speaker #4: We're really excited to get studies activated really faster than I think even even we anticipated . And the ability to get studies , DEA activated , activated , and DEA approvals in place in a matter of just a few weeks has allowed us to really accelerate the start of that second study in MDD .

Speaker #4: So really, across the board, what we've been very encouraged by are the enrollment trends and where that positions us for three pivotal readouts over the course of this year. In terms of incremental confidence, we won't be commenting on specific variables or what we're seeing in those variables.

Rob Barrow: In terms of experimental confidence, we won't be commenting on specific variables or what we're seeing in those variables. We're extraordinarily confident in the profile of 120. As Dan mentioned during his prepared remarks, with the observed parameters that we saw in the interim analysis for Voyage, that would imply a quite high, over 99% power to detect a 5-point difference and less than 2 points required in terms of the separation between the groups in order to achieve a statistically positive result if those nuisance variables are the same at the end of the study as they were at the interim analysis. That gives us quite a bit of confidence if, you know, if the study only has to show a couple points difference to get a statistically positive outcome.

Speaker #4: So we're we're extraordinarily confident in the profile of of 120 . And as Dan Mission during his prepared remarks with the observed parameters that we saw in the interim analysis for voyage , that would imply a quite high over 99% power to detect a five point difference in less than two points required in terms of the separation between the groups in order to achieve a statistically positive result .

Speaker #4: If those nuisance variables are the same at the end of the study as they were at the interim analysis , so that gives us quite a bit of confidence .

Speaker #4: If you know , if a study only has to show a couple points difference to get a statistically positive outcome , of course we would hope to see better than that .

Rob Barrow: Of course, we would hope to see better than that. We think that a four-point difference between the arms is something we'd really like to see that would really stand out as the best drug we've seen, the best results we've seen in GAD to date. We're certainly excited to deliver those data. All that we're seeing across all the studies gives us continued confidence in the program and positioning us really well for these readouts later in the year.

Speaker #4: We think that a four point difference between the arms is something we'd really like to see . That would really stand out as the best drug we've seen , the best results we've seen in Gad to date .

Speaker #4: And so we're certainly excited to deliver those data. But all that we're seeing across all the studies gives us continued confidence in the program and positions us really well for these readouts later in the year.

Speaker #8: Thank you .

[Analyst] (Unknown): Thank you.

Evie Kao: Thank you.

Speaker #5: Thank you . Our next question comes from the line of Brian Abrahams with RBC Capital Markets . Your line is now open .

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

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

Speaker #9: Hey, good afternoon, guys. Thanks for taking my questions. Congrats on all the progress, and looking forward to very exciting data.

Brian Abrahams: Hey, good afternoon, guys. Thanks for taking my questions. Congrats on all the progress and looking forward to a very exciting data-rich year. Two for me. I guess first, you've had some slight changes in the enrollment timelines versus prior expectations, in both directions. I guess I'm curious the impact that has on your views of the addressable populations of patients with these respective conditions who may be interested in a psychedelic. Just with the interim passing and obviously the low variability in dropouts, it sounds like a very narrow delta could still be statistically significant in Voyage. Can you maybe elaborate a little bit more on your latest views on clinically meaningful delta?

Speaker #9: Rich year two for me . I guess first , you've had some slight changes in the enrollment timelines versus prior expectations in both directions , and I guess I'm curious the impact that has on your views of the addressable populations of patients with these respective conditions who may be interested in a psychedelic and then just with the interim passing and obviously the low variability and dropouts , it sounds like a very narrow delta could still be statistically significant in voyage .

Speaker #9: So can you maybe elaborate a little bit more on your latest views on clinically meaningful delta , and really , how would hitting stat sig with a smaller delta potentially impact your plans in Panorama , as well as how you'd see the drug positions commercially ?

Brian Abrahams: Really, how would hitting stat sig with a smaller delta potentially impact your plans in Panorama as well as how you'd see the drug positioned commercially? Thanks.

Speaker #9: Thanks

Speaker #4: Yeah , thanks so much , Brian . And both great questions . I'll turn over to Dan to talk about the first one and just Dan , you can reflect on how we think about these populations .

Rob Barrow: Yeah, thanks so much, Brian. Both great questions. I'll turn over to Dan to talk about the first one. Just, Dan, maybe you can reflect on, you know, how we think about these populations and also how these patients of course show up in trials and show up for clinical attention.

Speaker #4: And also how these patients of course , show up in trials and show up for clinical attention .

Speaker #1: Yeah , it's an excellent question and good observation . And while the timeline changes don't necessarily change how we think about patient population , certainly what we know is that in the current environment of psychiatry and with the drugs that are currently available , MDD has been a target of both drug development and clinical focus for for really the last 30 years or so .

Dan Karlin: Yeah. It's an excellent question and good observation. While the timeline changes don't necessarily change how we think about the patient population, certainly what we know is that in the current environment of psychiatry and with the drugs that are currently available, MDD has been a target of both drug development and clinical focus for really the last 30 years or so, and left GAD a bit behind with no new drugs approved in GAD since 2007. The reality is that this is a massively overlapping patient population and that while GAD is a more continuous sort of background condition that people live with this experience day by day, in many cases for much of their life. And that both makes people not necessarily seek care.

Dan R. Karlin: Yeah. It's an excellent question and good observation. While the timeline changes don't necessarily change how we think about the patient population, certainly what we know is that in the current environment of psychiatry and with the drugs that are currently available, MDD has been a target of both drug development and clinical focus for really the last 30 years or so, and left GAD a bit behind with no new drugs approved in GAD since 2007. The reality is that this is a massively overlapping patient population and that while GAD is a more continuous sort of background condition that people live with this experience day by day, in many cases for much of their life. And that both makes people not necessarily seek care.

Speaker #1: And left Gad a bit behind with no new drugs approved in Gad since 2007 , the reality is that this is a massively overlapping patient population and that while Gad is a more continuous sort of background condition that people people live with , this experience day by day , in many cases for much of their life .

Speaker #1: And that both makes people not necessarily seek care . They're sort of used to being the way they are , even if it is quite disruptive to their lives .

Dan Karlin: They're sort of used to being the way they are, even if it is quite disruptive to their lives. It's not an acute change that people notice in their lives as they do when they enter a major depressive episode, which often drives people to seek care. We're really excited about the opportunity to potentially provide a drug here that regardless of what induces someone to go seek care, whether it's this ongoing state of anxiety or newly developed anxiety or entering a major depressive episode, which represents a real state change for them.

Dan R. Karlin: They're sort of used to being the way they are, even if it is quite disruptive to their lives. It's not an acute change that people notice in their lives as they do when they enter a major depressive episode, which often drives people to seek care. We're really excited about the opportunity to potentially provide a drug here that regardless of what induces someone to go seek care, whether it's this ongoing state of anxiety or newly developed anxiety or entering a major depressive episode, which represents a real state change for them.

Speaker #1: But it's not an acute change that people notice in their lives as they do when they enter a major depressive episode , which often drive people to seek care .

Speaker #1: So we're really excited about the opportunity to to potentially provide a drug here that regardless of what induces someone to go seek care , whether it's a ongoing state of anxiety or newly developed anxiety or or entering a major depressive episode , which which represents a real state change for them .

Dan Karlin: bout this is that regardless of the driver of the presentation, we intend to provide a body of evidence that demonstrates that DT120 would be a good choice for the patient. That gives us some temporal flexibility for people in the course of their lives and in the course of their illness

Dan R. Karlin: bout this is that regardless of the driver of the presentation, we intend to provide a body of evidence that demonstrates that DT120 would be a good choice for the patient. That gives us some temporal flexibility for people in the course of their lives and in the course of their illness

Speaker #1: The way we think about this is that regardless of the the driver of the presentation that we intend to provide a body of evidence that demonstrates that that d20 would be would be a good choice for for the patient , so that that gives us some some temporal flexibility for people in the course of their lives .

Speaker #1: And in the course of their illness

Speaker #4: Yeah . Thanks , Dan . In terms of your second question about clinical meaningfulness , it also is a great one . And , you know , I think really important contextually , both in terms of that , that difference and in terms of the overall magnitude of change .

Rob Barrow: Thanks, Dan. In terms of your second question about clinical meaningfulness, it also is a great one, and, you know, I think really important contextually, both in terms of the difference and in terms of the overall magnitude of change. I think there is certainly a lot of different approaches out there to these concepts. In our minds, Dan mentioned this a little bit in the prepared remarks, but in the real world, patients, of course, don't get placebo.

Speaker #4: I think there is certainly a lot of of different approaches out there to these , to these concepts in our minds . Dan mentioned this a little bit in the prepared remarks , but in the real world , patients , of course , don't get placebo .

Speaker #4: So we definitely want to demonstrate as large of a placebo adjusted response as we can . It observing an absolute magnitude of change that that stands out relative to the other options that are available , they're always limitations comparing across studies and such .

Rob Barrow: While we definitely want to demonstrate as large of a placebo-adjusted response as we can, observing an absolute magnitude of change that stands out relative to the other options that are available, you know, there are always limitations comparing across studies and such, but we think that's an important variable to focus on as well. When it comes down to that placebo adjusted change, again, when we're talking about drugs that we believe have the potential to be transformative, we think that should also be reflected in terms of the consistency with which, you know, patients are seeing the benefit and the magnitude of that benefit over a placebo.

Speaker #4: But we think that's an important variable to focus on as well . When it comes down to that placebo adjusted change . Again , when we're talking about drugs that we believe have the potential to be transformative , we think that should should also be reflected in terms of the consistency with which patients are seeing the benefit and the magnitude of that benefit over over a placebo .

Speaker #4: And so while yes , we you know , we're very encouraged when we have a low clinical bar relative to where we started and where we powered the study , we absolutely would like to see a change that stands out and continues to stand out .

Rob Barrow: While, yes, we, you know, we're very encouraged when we have a low clinical bar relative to where we started and where we powered the study, we absolutely would like to see a change that stands out and continues to stand out as we saw in phase 2. You know, in GAD, when we look at the landscape of currently approved therapies, not one of them consistently delivers, you know, at or above a 4-point delta over placebo in those studies. If we're seeing a magnitude of change that's, you know, as large or larger than those, and the placebo-adjusted change that's larger than 4 points, it's hard not to get incredibly excited about that in our minds.

Speaker #4: As we saw in phase two . And , you know , in Gad , when we look at the the landscape of currently approved therapies , not one of them consistently delivers , you know , at or above a four point delta over placebo in those studies .

Speaker #4: And so if we're seeing a magnitude of change that's , you know , as large or larger than those , and the placebo adjusted change that's larger than four points , it's hard not to to get incredibly excited about that in our minds .

Speaker #4: So , well , we don't set a sort of bright line on any of these kinds of concepts . We very much are looking for data that impress and data that get us .

Rob Barrow: While we don't set a sort of bright line on any of these kinds of concepts, we very much are looking for data that impress and data that get us, and we think payers and providers and everyone excited about the potential, because we certainly believe it's there and hope the data stands up to support that.

Speaker #4: And we think payers and providers and everyone excited about the potential , because we certainly believe it's there . And and hope the data stands up to to support that .

Speaker #9: Thank you .

Dan Karlin: Thank you.

Brian Abrahams: Thank you.

Speaker #5: Thank you . Our next question coming from the line of Francois Islam with Lifesci Capital . Your line is now open

Gitanjali Jain: Thank you. Our next question coming from the line of Francois Biswal with LifeSci Capital. Your line is now open.

Operator: Thank you. Our next question coming from the line of Francois Biswal with LifeSci Capital. Your line is now open.

Speaker #1: Hi . Thanks for taking the questions and a lot of a lot of interesting questions . A lot of interesting answers to . And I was just wondering , so you touched on the four point kind of bar that is not a hard bar or anything , but something that you've been mentioning on the Gad side .

Francois Biswal: Hi, thanks for taking the questions. A lot of interesting questions, a lot of interesting answers, too. I was just wondering, you touched on the four-point kind of bar that, you know, is not a hard bar or anything, but it's something that you've been mentioning on the GAD side. Can you just remind us now that MDD will be first, can you just kind of do the same exercise in terms of what you'd like to see and compare it to what's been seen for MDD? Maybe also remind everyone, what you had seen previously, on the MADRS side in the prior trial, and maybe caveats around, you know, what you had seen because the trial wasn't necessarily for that originally.

François Brisebois: Hi, thanks for taking the questions. A lot of interesting questions, a lot of interesting answers, too. I was just wondering, you touched on the four-point kind of bar that, you know, is not a hard bar or anything, but it's something that you've been mentioning on the GAD side. Can you just remind us now that MDD will be first, can you just kind of do the same exercise in terms of what you'd like to see and compare it to what's been seen for MDD? Maybe also remind everyone, what you had seen previously, on the MADRS side in the prior trial, and maybe caveats around, you know, what you had seen because the trial wasn't necessarily for that originally.

Speaker #1: Can you just remind us now that MDD will be first ? Can you just kind of do the same exercise in terms of what you'd like to see and compare it to what's been seen for MDD and maybe also remind everyone what you had seen previously on the Madras side in the prior trial .

Speaker #1: And maybe , maybe caveats around what you had seen , because the trial wasn't necessarily for that originally

Speaker #4: Yeah . Thanks so much for the question , Frank . I mean , again , when we look at at the landscape of of approved products and products that are in development , we continue to be encouraged qualitatively in the research we've done to date .

Rob Barrow: Yeah, thanks so much for the question, Frank. I mean, again, when we look at the landscape of approved products and products that are in development, we continue to be encouraged qualitatively in the research we've done to date. Dan mentioned that we saw it was in a GAD population with, you know, milder illness. I think we really focus a lot on the severity of both MDD and GAD because those severity are representative of impact on patients and drive a lot of the burden and the value. You know, as we think about the response, we think about severity and that overall magnitude of change.

Speaker #4: Dan mentioned it that we saw is , in a Gad population with with milder illness . I think we really focus a lot on the severity of both MDD and Gad , because those severity are representative of of impact on patients and drive a lot of of the burden and the value .

Speaker #4: And so , you know , as we think about the response , we think about severity . And that overall magnitude of change , and that's again where we saw really impressive results on both symptom sets on anxiety symptoms and on depression symptoms .

Rob Barrow: That's, again, where we saw really impressive results on both symptom sets, on anxiety symptoms and on depression symptoms. We saw a 6.4 point difference between DT120 and placebo in MADRS scores. That was starting from a lower point than what we would expect in a dedicated MDD population with patients in a major depressive episode. We'll certainly be painting that picture, I think, more comprehensively as we get to the analyst day in April. I think as we get closer and closer to the readouts, we want to set full context for those expectations and just for the realities of that landscape.

Speaker #4: So we saw a 6.4. difference between 120 and placebo in Madrs scores . And basically that was starting from from lower point than what we would expect in dedicated MDD population with patients in a major depressive episode .

Speaker #4: We'll certainly be painting that picture . I think , more comprehensively as we get to the Analyst Day in April and I think as we get closer and closer to the readouts , we want to set full context for for those expectations and just for the realities of that landscape .

Speaker #4: But when we look at roughly when we look at that today , again , seeing an effect , a placebo adjusted effect that is greater than four points seems quite important .

Rob Barrow: When we look at roughly, when we look at that today, again, seeing an effect, a placebo-adjusted effect that is greater than 4 points seems quite important, and seeing a double-digit absolute magnitude of change also seems quite important in our minds. That's true, especially in the MDD population, where taking patients from severe depression symptoms to high, moderate, or low severe wouldn't represent a major change in our minds. As we think about this readout, we again want to see a large absolute magnitude of change and as large of a placebo-adjusted change as the drug can deliver.

Speaker #4: And seeing a double digit absolute magnitude of change also seems quite important in our minds . And that's true especially in the MDD population , where taking patients from severe depression symptoms to high , moderate or low severe wouldn't represent a major change in our mind .

Speaker #4: And so as we think about this readout , we again want to see a large absolute magnitude of change . And as large of a placebo adjusted change as a drug can , can deliver .

Speaker #1: Okay , maybe if I could sneak in just the last one there in terms of do some work on it , you hear a lot of comments around , well , from going from the phase two to phase three .

Dan Karlin: Okay. Maybe if I could sneak in just a last one there. In terms of, when you do some work on it, you hear a lot of comments around, well, from going from the phase 2 to phase 3, it's totally normal to get a smaller delta with placebo. Is that something that makes sense to people? Is there a reason behind that or, is that just kind of protecting yourself a little bit?

François Brisebois: Okay. Maybe if I could sneak in just a last one there. In terms of, when you do some work on it, you hear a lot of comments around, well, from going from the phase 2 to phase 3, it's totally normal to get a smaller delta with placebo. Is that something that makes sense to people? Is there a reason behind that or, is that just kind of protecting yourself a little bit?

Speaker #1: It's totally normal to get a smaller delta with placebo . Is that something that makes sense to people ? Is there a reason behind that or is that just kind of protecting yourself a little bit Yeah .

Rob Barrow: Yeah, no, I think the reality is that we certainly, in historical studies, in psychiatry, there are studies at times where that happens. I think where we see, and we've seen this in schizophrenia, we've seen this in a number of other occasions as well, where some of the best-performing drugs continue to not see that sort of compression as they progress in development. The design changes, operational changes, those sorts of things can have an impact, and that's why we've been so encouraged with our approach in Phase 3.

Speaker #4: No , I think the reality is that we certainly in historical studies in psychiatry , there are studies at times where that that happens .

Speaker #4: I think where we see and we've seen this in schizophrenia , we've seen this a number of other indications as well , where some of the best performing drugs continue to not see that sort of compression as they progress in development .

Speaker #4: So the design changes , operational changes , those sorts of things can have an impact . And that's why we've been so encouraged with our approach in phase three .

Speaker #4: And we designed our phase two program to be exactly executed and designed like a phase three study . Although we thought it critically important to establish a dose response and select the appropriate dose to take into the pivotal studies , which is why we did the phase two the way we did .

Rob Barrow: We designed our Phase 2 program to be exactly executed and designed like a Phase 3 study, although we thought it critically important to establish a dose response and select the appropriate dose to take into the pivotal studies, which is why we did the Phase 2 the way we did. That also means we made minuscule operational changes between the Phase 2 and Phase 3 studies. We're virtually doing the same thing over again. It's just with 2 or 3 arms instead of 5 arms, as we did in Phase 2. That again gives us a lot of confidence. Then a number of dynamics in the study designs that we think will drive better patient retention through the primary outcome of these studies.

Speaker #4: That also means we made minuscule operational changes between the phase two and phase three study . So we're actually doing the same thing over again .

Speaker #4: It's just with 2 or 3 arms instead of five arms , as we did in phase two . So that again gives us a lot of confidence .

Speaker #4: And then a number of dynamics in the study design that we think will drive better patient retention . And through the primary outcome in these studies , Dan mentioned that the non-evaluable rate that we saw in in the interim analysis in voyage was was 10% .

Rob Barrow: Dan mentioned that the non-evaluable rate that we saw in the interim analysis in Voyage was 10%. You compare that to over 25% in our phase 2 data, which we think is largely driven by the fact that we're seeing with the Part B, the 9-month extension period, patients have an ability to access open label 120 if they complete the full 12-week blinded control period. All of those dynamics give us a lot of confidence about the operationalization of these studies and gives a lot of confidence as we approach data.

Speaker #4: You compare that to over 25% in our phase two data , which we think is largely driven by the fact that we're seeing with the part B , the nine month extension period .

Speaker #4: Patients have ability to access open label 120 if they complete the full 12 week blinded , controlled period . And so all of those dynamics give us a lot of confidence about the the operationalization of these studies .

Speaker #4: And it gives a lot of confidence as we approach data

Dan Karlin: Great stuff. Thank you.

François Brisebois: Great stuff. Thank you.

Speaker #1: So thank you .

Speaker #5: Thank you . Our next question comes from the line of Pete Raffles with cancer Fitzgerald . Your line is now open

Gitanjali Jain: Thank you. Our next question coming from the line of Pete Stavropoulos with Cantor Fitzgerald. Your line is now open.

Operator: Thank you. Our next question coming from the line of Pete Stavropoulos with Cantor Fitzgerald. Your line is now open.

Speaker #10: Hi . Good afternoon . Nice to see the progress . And thank you for taking our questions First one , just curious to hear how you're thinking about a potential filing strategy .

Pete Stavropoulos: Hi. Good afternoon. nice to see the progress, and thank you for taking our questions. First one, you know, just curious to hear how you're thinking about a potential filing strategy if the two GAD phase 3s are positive, and if the first phase 3 MDD study emerges positive. You know, will you complete two MDD studies before filing an sNDA, or is there a reason to wait for the second study?

Speaker #10: If the two Gad phase threes are positive , and if the first phase three MDD study emerge is positive , you know , will you complete two MDD studies before filing an NDA ?

Speaker #10: Or is there a reason to wait for the second study ?

Speaker #4: Yeah . Thanks so much for the question , Pete . It'd be premature to comment specifically on filing strategy , given that we don't have have data in hand , but certainly we we think that the stronger the data , the more compelling an argument , a sponsor can make .

Rob Barrow: Yeah. Thanks so much for the question, Pete. It'd be premature to comment specifically on filing strategy given that we don't have data in hand. Certainly, we think that the stronger the data, the more compelling an argument a sponsor can make, and that's true across the board. So we'll be looking, you know, very closely at the data. If we're seeing an impressive result, both placebo-adjusted and absolute magnitude of change, something that gets us quite excited, we, you know, we'll very much be engaging in those conversations to explore the most efficient pathway forward for both the indications.

Speaker #4: And and that's true across the board . And so we'll be looking very closely at the data . And if we're seeing impressive result , both placebo adjusted and absolute magnitude of change , something that gets us quite excited .

Speaker #4: We will very much be engaging in those conversations to explore the most efficient pathway forward for for both the indications .

Speaker #10: Okay . And then just to touch on your earlier stage assets on 402 , if you can give us a little bit of color in terms of assessing clinical effect , which skills are key for you ?

Pete Stavropoulos: Okay. Just to touch on your earlier stage asset, DT402. You know, if you can give us a little bit of color in terms of assessing clinical effect, which scales are key for you? In your deck and in today's PR, it mentions functional biomarkers. Can you just elaborate on that?

Speaker #10: And in your deck and in the PR in today's PR , it mentions functional biomarkers . Can you just elaborate on that ?

Speaker #4: Yeah . Turn over to Dan to comment on .

Rob Barrow: Yeah. I'll turn that one over to Dan to comment on.

Speaker #1: Yeah . Happy to comment on that . And thanks for asking about about 402 . Obviously with all the excitement around 120 sometimes we don't get a chance to come on this .

Dan Karlin: Yeah. Happy to comment on that, and thanks for asking about DT402. Obviously, with all the excitement around DT120, sometimes we don't get a chance to comment on this as much as we'd like to because we're really excited about the program. We've gotten through a single ascending dose safety study, which gives us good data for dosing in a single dose paradigm, which is exactly what we've said we've done, which is to bring the drug forward in a single dose open-label paradigm. The question of measurement in ASD is always an interesting one. You're asking after the scales and the Vineland and other scales that have been used in attempts at approval before.

Dan R. Karlin: Yeah. Happy to comment on that, and thanks for asking about DT402. Obviously, with all the excitement around DT120, sometimes we don't get a chance to comment on this as much as we'd like to because we're really excited about the program. We've gotten through a single ascending dose safety study, which gives us good data for dosing in a single dose paradigm, which is exactly what we've said we've done, which is to bring the drug forward in a single dose open-label paradigm. The question of measurement in ASD is always an interesting one. You're asking after the scales and the Vineland and other scales that have been used in attempts at approval before.

Speaker #1: As much as we'd like to because we're really excited about the program . We've gotten through single ascending dose safety study , which gives us a good data for dosing in a in a single dose paradigm , which is which is exactly what we've said we've done , which is to bring the drug forward in a single dose , open label paradigm .

Speaker #1: And the the question of measurement in ASD is always an interesting one . You're asking after the scales and the Vineland and other scales that have been used in attempts at approval before , of course , with no approved drugs for the core symptoms of the disorder , the right measure at the right time remains a pretty open conversation , both in the field with experts who treat folks with ASD , with regulators who are eager to be able to approve drugs for this .

Dan Karlin: Of course, with no approved drugs for the core symptoms of the disorder, the right measure at the right time remains a pretty open conversation both in the field with experts who treat folks with ASD, with regulators who are eager to be able to approve drugs for this condition that really doesn't have treatments that target its core symptoms. What we're looking at in the current early signals efficacy study are measures that have high granularity. We want high sensitivity and high granularity measures so that we are able to repeatedly measure over the course of a dosing day to look at change that is consistent with the expected PK and PD of the drug.

Dan R. Karlin: Of course, with no approved drugs for the core symptoms of the disorder, the right measure at the right time remains a pretty open conversation both in the field with experts who treat folks with ASD, with regulators who are eager to be able to approve drugs for this condition that really doesn't have treatments that target its core symptoms. What we're looking at in the current early signals efficacy study are measures that have high granularity. We want high sensitivity and high granularity measures so that we are able to repeatedly measure over the course of a dosing day to look at change that is consistent with the expected PK and PD of the drug.

Speaker #1: This condition that really doesn't have treatments that target . It's its core symptoms . What we're looking at in the in the current early signal of efficacy study are measures that have high granularity .

Speaker #1: So we want high sensitivity and high granularity measures so that we are able to repeatedly measure over the course of a dosing day to look at change that is consistent with the expected PK and PD of the drug .

Speaker #1: And so we have brought we have about about exactly what measures we're using , but we are using components of established measures along with some novel ways of looking at social interaction , social communication and the other domains where we think that the drug would be will be effective .

Dan Karlin: We haven't talked about exactly what measures we're using, but we are using components of established measures along with some novel ways of looking at social interaction, social communication, and the other domains where we think that the drug will be effective. Considering measurement from the outset and very much thinking about measurement techniques that can track along with the drug through its phases of development and ultimately through to regulatory submission if and when we get there, and potentially even measures that could travel with the drug out into the world if it's approved.

Dan R. Karlin: We haven't talked about exactly what measures we're using, but we are using components of established measures along with some novel ways of looking at social interaction, social communication, and the other domains where we think that the drug will be effective. Considering measurement from the outset and very much thinking about measurement techniques that can track along with the drug through its phases of development and ultimately through to regulatory submission if and when we get there, and potentially even measures that could travel with the drug out into the world if it's approved.

Speaker #1: So considering measurement from the outset and very much thinking about measurement techniques that can track along with the drug through its phases of development and ultimately through to to regulatory submission for if and when we get there and potentially even measures that could could travel with the drug out into the into the world .

Speaker #1: If it's approved .

Speaker #10: Right. Thank you. And congrats once again.

[Analyst] (H.C. Wainwright & Co.): ... Thank you and congrats once again.

Pete Stavropoulos: ... Thank you and congrats once again.

Speaker #5: Thank you. Our next question comes from the line of Christopher Chen with Baird. Ellen, your line is now open.

Gitanjali Jain: Thank you. Our next question coming from the line of Christopher Chen with Baird. Your line is now open.

Operator: Thank you. Our next question coming from the line of Christopher Chen with Baird. Your line is now open.

Speaker #11: Good afternoon . Thanks for taking my question and congrats on on the progress . I had a question regarding MDD . So , you know , one of the things we hear about Spravato is that it's good at alleviating symptoms of TRD , but not so good at increasing overall productivity of daily life .

Christopher Chen: Good afternoon. Thanks for taking my question, and congrats on the progress. I had a question regarding MDD. You know, one of the things we hear about SPRAVATO is that it's good at alleviating symptoms of TRD, but not so good at increasing overall productivity of daily life, like just work, your productivity at work, one example. I know you're measuring a number of quality-of-life metrics in Emerge, but I'm particularly interested in the WPAI. If you don't mind just expanding on your expectations there, and can you provide any high-level color on what you're hearing about how these patients are doing beyond just MDD symptom alleviation? I have one more after that.

Speaker #11: Like just work productivity at work . One example . So I know you're measuring a number of quality of life metrics and emerge , but I'm particularly interested in the WPI .

Speaker #11: And so if you don't mind , just expanding on your expectations , there , and can you provide any high level color on what you're hearing about how these patients are doing beyond just MDD symptom alleviation ?

Speaker #11: And then I have one more after that .

Speaker #4: Yeah . Thanks , Chris . I'll turn it over to to Dan and talks about WPI . I guess I'd first say that with the dosing regimen , it's required to go into a clinic for multiple hours , multiple or at least one time a week for for long time .

Rob Barrow: Yeah, thanks, Chris. I'll turn it over to Dan to talk about WPAI. I guess I'd first say that with the dosing regimen that's required to go into a clinic for multiple hours, or at least one time a week for a long time, being at work is certainly going to be a thing that drives productivity. A treatment where you only have to come in frequently, which is if we're able to establish the same kind of durability as we've seen in trials so far, certainly something that we think would differentiate DT120 from anything that's out there in the world today, would be a pretty important impact, right? If going to the doctor's office once or twice a week is quite a burden.

Speaker #4: Being at work is certainly going to be a thing that drives productivity . So a treatment where you only have to come in infrequently , which is if we're able to establish the same kind of durability as we've seen in trials so far .

Speaker #4: Certainly something that we think would differentiate 120 from anything that's out there in the world today would would be a pretty important impact , right ?

Speaker #4: It's going to the doctor's office once or twice a week is quite a burden . And so even beyond the actual measurable productivity , the presence at work and being able to do that is going to be an important driver .

Rob Barrow: Even beyond the actual measurable productivity, the presence at work and being able to do that is going to be an important driver and certainly something that also shows up in patient satisfaction and overall utilization of the drug, we would think. I'll turn it to Dan to elaborate maybe on the WPAI.

Speaker #4: And certainly something that also shows up in patient satisfaction . And overall utilization of the drug . We would think . But I'll turn it to Dan to elaborate , maybe on the WPI .

Speaker #1: Yeah . You know , the domains that I look at absenteeism , not not being able to make it into our presenteeism , being being impaired while at work and sort of tries to assess an overall percentage of , of impairment while at work .

Dan Karlin: Yeah, you know, the domains that the WPAI look at, absenteeism, not being able to make it into work, presenteeism, being impaired while at work, and tries to assess an overall percentage of impairment while at work. Of course, this isn't a primary outcome, and we're not looking to try to demonstrate efficacy overall based on a scale like this. I think as you observed, this is really important, right? That just having a lower reported set of symptoms or suppressed symptoms doesn't necessarily mean that someone is back, able to do the things that they need to do and want to do in their lives.

Dan R. Karlin: Yeah, you know, the domains that the WPAI look at, absenteeism, not being able to make it into work, presenteeism, being impaired while at work, and tries to assess an overall percentage of impairment while at work. Of course, this isn't a primary outcome, and we're not looking to try to demonstrate efficacy overall based on a scale like this. I think as you observed, this is really important, right? That just having a lower reported set of symptoms or suppressed symptoms doesn't necessarily mean that someone is back, able to do the things that they need to do and want to do in their lives.

Speaker #1: And of course , this isn't this isn't a primary outcome . And we're not looking to try to demonstrate efficacy overall based on a scale like this .

Speaker #1: But I think as you observe , this is really important , right ? That the just having a lower reported set of symptoms or suppressed symptoms doesn't necessarily mean that someone is back able to do the things that they need to do and want to do in their lives , and we very much are oriented toward the idea that just as we saw in phase two , that the experience of participants after treatment , because of course , unlike Salvador , where the treatment is , is a continuous , intermittent course , we anticipate having long periods of time between treatment , if such retreatment is even always necessary , and the way that folks describe their experience post-treatment and in the phase two , with less about , as you're pointing out , sort of symptom suppression and more about having an outlook that that was changed as it relates to the future .

Dan Karlin: We very much are oriented toward the idea that just as we saw in phase two, that the experience of participants after treatment, because of course, unlike SPRAVATO, where the treatment is a continuous intermittent course, we anticipate having long periods of time between treatment if such retreatment is even always necessary. The way that folks describe their experience post-treatment in the phase two was less about, as you're pointing out, sort of symptom suppression and more about having an outlook that was changed as it relates to the future in GAD. Obviously, as we hope to see in MDD, as it relates to sort of the anhedonic or inability to take pleasure in activities that would generally give the person pleasure.

Dan R. Karlin: We very much are oriented toward the idea that just as we saw in phase two, that the experience of participants after treatment, because of course, unlike SPRAVATO, where the treatment is a continuous intermittent course, we anticipate having long periods of time between treatment if such retreatment is even always necessary. The way that folks describe their experience post-treatment in the phase two was less about, as you're pointing out, sort of symptom suppression and more about having an outlook that was changed as it relates to the future in GAD. Obviously, as we hope to see in MDD, as it relates to sort of the anhedonic or inability to take pleasure in activities that would generally give the person pleasure.

Speaker #1: In Gad . And obviously , as we we hope to see in MDD as it relates to sort of the the Anhedonic or inability to take pleasure in activities that would generally give the person pleasure .

Speaker #1: So , so we measuring the WPI and other scales of , of function and participation in life for exactly that reason . Because we , we remain optimistic and hopeful that the sort of change that we see with HT .

Dan Karlin: We're measuring the WPAI and other scales of function and participation in life for exactly that reason, because we remain optimistic and hopeful that this sort of change that we see with DT120 represents a more whole person change toward a state of what could be called recovery.

Dan R. Karlin: We're measuring the WPAI and other scales of function and participation in life for exactly that reason, because we remain optimistic and hopeful that this sort of change that we see with DT120 represents a more whole person change toward a state of what could be called recovery.

Speaker #1: 20 represents a more whole person change toward a state of of what could be called recovery

Speaker #11: Great . That's very helpful . And then just a quick one . Are you collecting time to just patient time to discharge data in these trials ?

Christopher Chen: Great. That's very helpful. Just a quick one. Are you collecting time to patient time to discharge data in these trials? If so, are you seeing, you know, anything that may suggest any shifts from that 6 to 8-hour monitoring period?

Speaker #11: And if so , are you seeing you know , anything that may suggest any shifts from that 6 to 8 hour monitoring period

Rob Barrow: Yeah, it's a great question. We are absolutely collecting high granularity data. We think it's critically important to have data-driven arguments and a data-driven understanding of what's happening on a dosing day to ultimately characterize that to inform regulatory discussions. We start assessing, we have a structured set of assessments that we measure on an hourly basis, starting at hour five. We, of course, observe all patients regardless of the dose or whether they receive placebo through hour eight in the study. At the end of the day, we expect to have again, a high granularity assessment of the different domains and ultimately, the time to which patients are able to be discharged safely, we think, from a treatment session.

Speaker #4: it's a great question . And we are absolutely collecting high granularity data . We think it's critically important to have data driven arguments and data driven understanding of what's happening on a dosing day .

Speaker #4: And to ultimately characterize that to inform discussions . We start assessing . We have a structured set of assessments that we measure on an hourly basis , starting at hour five , and we , of course , observe all patients , regardless of the dose or whether they receive placebo through our eight .

Speaker #4: In the study . And at the end of the day , we expect to have , you know , again , a high grade granularity assessment of the different domains and ultimately the time to which patients are are able to be discharged safely .

Speaker #4: We think , from a treatment session . So we of course , given that we have a number of open label treatment sessions , we have some insights .

Rob Barrow: We of course, given that we have a number of open label treatment sessions, we have some insights there, which we can't share quite yet in great detail. We want to again, aggregate enough data to feel confident in sharing that before we do so. Certainly as we progress and as we get to a top-line readout, we think it's really important, given the nature of these drugs, to start characterizing that. Something we've been doing with a really thoughtful approach, beginning with our phase two study and certainly being refined and giving us increasing confidence as we've gotten through the conduct of our phase three program.

Speaker #4: There which we can't share quite yet in great detail . We want to aggregate enough data to feel confident in sharing that before we do so .

Speaker #4: But certainly as we progress and as we get to a top line readout , we think it's really important given the nature of these drugs , to start characterizing that something we've been doing with a really thoughtful approach , beginning with our phase two study .

Speaker #4: And certainly being refined and giving us increasing confidence as we've gotten through the conduct of phase three program

Speaker #11: Thank you .

Christopher Chen: Thank you.

Speaker #5: Thank you . Our next question coming from the line of Patrick Tsuchiya with H.C. when right is now open .

Gitanjali Jain: Thank you. Our next question coming from the line of Patrick Trucchio with H.C. Wainwright & Co. Your line is now open.

Operator: Thank you. Our next question coming from the line of Patrick Trucchio with H.C. Wainwright & Co. Your line is now open.

Speaker #12: Hi . This is Arabella on for Patrick . Thank you so much for taking the question . And congrats on all the progress .

[Analyst] (H.C. Wainwright & Co.): Hi, this is Arabella on for Patrick. Thank you so much for taking the question, and congrats on all the progress. We're looking forward to the upcoming readouts. Since Panorama also includes European sites, are there any meaningful differences in diagnostic practice, placebo behavior, or standard of care that could introduce additional variability?

Arabella Ng: Hi, this is Arabella on for Patrick. Thank you so much for taking the question, and congrats on all the progress. We're looking forward to the upcoming readouts. Since Panorama also includes European sites, are there any meaningful differences in diagnostic practice, placebo behavior, or standard of care that could introduce additional variability?

Speaker #12: We're looking forward to the upcoming readouts. Since Panorama also includes European sites, are there any meaningful differences in diagnostic practice, placebo behavior, or standard of care that could introduce additional variability?

Speaker #4: Yeah , I'll turn that one over to Dan .

Rob Barrow: Yeah, I'll turn that one over to Dan.

Speaker #1: It's an excellent question and a good observation . The panorama study does include European sites and while there are , as you note in the practice of psychiatry , regional variations , even within within the United States , different areas of the country have different different practice patterns .

Dan Karlin: It's an excellent question and a good observation. The Panorama study does include European sites. While there are, as you note, in the practice of psychiatry, regional variations, even within the United States, different areas of the country have different practice patterns. Though the diagnostic criteria remain the same, the way they're applied can be different from place to place. We work our way through that by being very highly specified in our protocols. Diagnostic criteria that we use are standard from, you know, from one country to the next and one site to the next, of course.

Dan R. Karlin: It's an excellent question and a good observation. The Panorama study does include European sites. While there are, as you note, in the practice of psychiatry, regional variations, even within the United States, different areas of the country have different practice patterns. Though the diagnostic criteria remain the same, the way they're applied can be different from place to place. We work our way through that by being very highly specified in our protocols. Diagnostic criteria that we use are standard from, you know, from one country to the next and one site to the next, of course.

Speaker #1: And so the diagnostic criteria remain the same. The way they're applied can be different from place to place. We work our way through that by being very highly specified in our protocols.

Speaker #1: So diagnostic criteria that we use are standard from from one country to the next . And one site to the next . Of course .

Speaker #1: And the way they're applied is standardized . And that , that standardization is supervised and monitored from beyond the site level that all of our participants have really a three part confirmatory set of of assessments , only one of which is based on the site assessment .

Dan Karlin: The way they're applied is standardized, and that standardization is supervised and monitored from beyond the site level, that all of our participants have really a three-part confirmatory set of assessments, only one of which is based on the site assessment. We have central diagnostic confirmation and central severity confirmation so that it takes that kind of site variability out. Another advantage to the patient population is because we take both in the case of GAD, which as you know, has the European sites and MDD, which hasn't. Because we aren't dedicating enrollment in our studies on some set of past treatments or having been failed by some set of past treatments, local treatment pattern variation is not gonna have an impact on who we bring into the trial.

Dan R. Karlin: The way they're applied is standardized, and that standardization is supervised and monitored from beyond the site level, that all of our participants have really a three-part confirmatory set of assessments, only one of which is based on the site assessment. We have central diagnostic confirmation and central severity confirmation so that it takes that kind of site variability out. Another advantage to the patient population is because we take both in the case of GAD, which as you know, has the European sites and MDD, which hasn't. Because we aren't dedicating enrollment in our studies on some set of past treatments or having been failed by some set of past treatments, local treatment pattern variation is not gonna have an impact on who we bring into the trial.

Speaker #1: We have , we have . Central diagnostic confirmation and central severity confirmation , so that it takes that that kind of site variability out another advantage to the patient population is because we take both in the case of Gad , which is , you know , it has the European sites and MDD , which hasn't because we aren't medicating enrollment in our studies on some set of past treatments or having been failed by some set of past treatments , local treatment pattern variation is not going to have an impact on on who we bring into the trial .

Speaker #1: So we are incredibly confident that across sites here in the States and and sites in Europe that we're getting the participants who we intend to to get into the study .

Dan Karlin: We are incredibly confident that across sites here in the States and sites in Europe that we're getting the participants who we intended to get into the study. Because we're testing as monotherapy, of course, we're getting participants independent of what might be local practice patterns for the treatment of these disorders.

Dan R. Karlin: We are incredibly confident that across sites here in the States and sites in Europe that we're getting the participants who we intended to get into the study. Because we're testing as monotherapy, of course, we're getting participants independent of what might be local practice patterns for the treatment of these disorders.

Speaker #1: And because we're testing as monotherapy , of course , we're getting participants independent of what might be local local practice patterns for for the treatment of these disorders

Speaker #12: Great . Thank you so much . And then really quickly , I know we already touched on it , but specifically for Gad .

[Analyst] (H.C. Wainwright & Co.): Great. Thank you so much. Really quickly, I know we already touched on it, specifically for GAD, I know it's still early, if both Voyage and Panorama are positive, would that allow you to file, or is there any additional long-term safety data or anything else that might gate submitting an NDA?

Arabella Ng: Great. Thank you so much. Really quickly, I know we already touched on it, specifically for GAD, I know it's still early, if both Voyage and Panorama are positive, would that allow you to file, or is there any additional long-term safety data or anything else that might gate submitting an NDA?

Speaker #12: And I know it's still early . If both Voyage and Panorama are positive , would that allow you to file or is there any additional long term safety data or anything else that might gate submitting an NDA

Rob Barrow: Of course, it's premature to talk finally about, you know, filing strategy and filing dynamics until at a final discussions with FDA at a pre-NDA meeting. Based on a really positive dialogue we've had with FDA throughout our pivotal programs, we feel highly encouraged that delivering Part A data, durability data out to 12 weeks is what we need for filing. As we get to top line data from these studies, we're already doing a ton of work to get ourselves ready to be in a position to file as quickly as possible and to again, try to set that standard for how efficient and how quickly we can go to race across the finish line.

Speaker #4: Of course , it's premature to talk . Finally about filing strategy and filing dynamics until , at a final discussion with FDA at NDA meeting .

Speaker #4: But based on on a really positive dialogue we've had with FDA throughout our pivotal programs , we feel highly encouraged that delivering part A data durability data out to 12 weeks is is what we need for for filing .

Speaker #4: And so as we get to topline data from these studies , we're already doing a ton of work to get ourselves ready to to be in a position to file as quickly as possible and to again try to set that standard for for how efficient and how quickly we can go to , to cross the finish line .

Speaker #12: Perfect . Thank you so much .

[Analyst] (H.C. Wainwright & Co.): Perfect. Thank you so much.

Arabella Ng: Perfect. Thank you so much.

Speaker #5: Thank you. Our next question is coming from the line of Amy Faria with Needham and Company. Ellen, you are now open.

Gitanjali Jain: Thank you. Our next question coming from the line of Ami Fadia with Needham & Company. Your line is now open.

Operator: Thank you. Our next question coming from the line of Ami Fadia with Needham & Company. Your line is now open.

Speaker #13: Hi . Good afternoon . Thanks for taking my question and congrats on all the progress . My question was on . I've got two .

Ami Fadia: Hi. Good afternoon. Thanks for taking my question and congrats on all the progress. My question was on, I've got two. Firstly, just on the MDD program. You indicated that the study is 80% powered to show a 5-point change, and in your GAD study on MADRS, you've seen a 6.4-point change. What I want to understand is from a commercial perspective, in order to be able to tap into a meaningful portion of the MDD market, not just, you know, the really, you know, the patients that are treatment-resistant, what type of a profile would you like to see?

Speaker #13: Firstly, just on the MDD program, you indicated the study is 80% powered to show a five-point change. And in your GAD study on MADRS, you've seen a 6.4.

Speaker #13: change . What I want to understand is from a commercial perspective , in order to be able to tap into a meaningful portion of the MDD market , not just the really , you know , or the patients that are treatment resistant .

Speaker #13: What type of profile would you like to see ? And then secondly , as you think about the regulatory landscape and how that's changing and the recent FDA stance on wanting to move towards a one trial You know , requirement , do you think you still need to study in each of the two indications , or would there be opportunity to , you know , explore fewer studies ?

Ami Fadia: Secondly, as you think about the regulatory landscape and how that's changing and the recent FDA stance on wanting to move towards a 1 trial, you know, requirement, do you think you still need 2 studies in each of the 2 indications? Would there be opportunity to, you know, explore fewer studies should maybe, you know, the studies this year turn out to be positive? Thank you.

Speaker #13: Should maybe , you know , the studies this year turn out to be positive . Thank you .

Speaker #4: Yeah , thanks very much . And take them in reverse order and ask Matt and or Dan to to comment on your first question in terms of regulatory stance , the statutory requirements for drug approvals have been in place for quite a while and we're incredibly encouraged to see some some of some of the dialogue around efficient pathways and regulatory understanding and flexibility .

Rob Barrow: Yeah. Thanks so much, Ami. Perhaps I'll take them in reverse order and ask Matt and or Dan to comment on your first question. In terms of regulatory stance, you know, the statutory requirements for drug approvals have been in place for quite a while. We're incredibly encouraged to see some of the dialogue around efficient pathways and regulatory understanding and flexibility, although we are gonna continue to hold ourselves to the highest standards of rigor. That all said, these are highly overlapping indications, we are seeing, of course, and measuring symptoms of anxiety and symptoms of depression across all four of the studies.

Speaker #4: Although we are going to continue to hold ourselves to the highest standards of rigor . That all said , these are highly overlapping indications and we are seeing , of course , and measuring symptoms of anxiety and symptoms of depression across all four of the studies .

Speaker #4: And so aggregating a large body of evidence , if we're seeing consistent results across multiple studies , across multiple domains , with a high degree of of both standalone and placebo adjusted change , and the better the data are , the stronger the arguments are going to be , whether it's one , two , or more studies for any program .

Rob Barrow: Aggregating a large body of evidence, if we're seeing consistent results across multiple studies, across multiple domains, with a high degree of both standalone and placebo-adjusted change, the better the data are, the stronger the arguments are gonna be, whether it's 1, 2 or more studies for any program. We'll certainly take all of that into consideration and depending on the strength and magnitude of responses that we're seeing across these studies, be in a position to chart a regulatory path forward there. To the first point, again, I think it's a little bit premature to talk overly precisely about segmentation, about exactly where this would land in, you know, in a commercial setting.

Speaker #4: And so we'll certainly take all of that into consideration. And depending on the strength and the magnitude of responses that we're seeing across these studies, we'll be in a position to charter a regulatory path forward.

Speaker #4: There. To the first point, again, I think it's a little bit premature to talk overly precisely about segmentation and about exactly where this would land.

Speaker #4: And in a commercial setting , I turn it over to Matt to maybe comment just how we think about think about that , and sort of expectations and hopes we would think about for both commercial adoption and for for reimbursement and such .

Rob Barrow: I'll turn it over to Matt to maybe comment, just how we think about that in the sort of expectations and hopes we would think about for both, for commercial adoption and for reimbursement and such?

Speaker #2: Yeah . Thanks , Rob , and thanks for the question . You know , as it pertains to the patient profile on MDD , first of all , we take a step back and look at both of these indications .

Matt Wiley: Yeah. Thanks, Rob, and thanks for the question. you know, as it pertains to the patient profile in MDD, first of all, we take a step back and look at both of these indications. These are highly prevalent indications. There are over 50 million patients in the United States for both indications. there's a still very significant unmet need. As we conduct market research with HCPs, we see that the unmet need is greater than 70% across both the indications. Even with the care that they have access to today, there's still something left significantly lacking in the treatment paradigms.

Speaker #2: These are highly prevalent . Indications are over 50 million patients in the United States for both indications . And there's a still very significant unmet need as we conduct market research with Hcp's , we see that the unmet need is is greater than 70% across both the indications .

Speaker #2: So even with the care that they have access to today , there's still something left significantly lacking in the treatment paradigms . So we know that payers do manage drugs and branded drugs that enter the market typically have a step or two .

Matt Wiley: you know, we know that payers do manage drugs and branded drugs that enter the market typically have a step or two. We believe that that can narrow the overall addressable market slightly. There are for both GAD and MDD, a significant number of patients that are going to benefit, if approved, from DT120.

Speaker #2: And so we believe that that can narrow the the overall addressable market slightly . But there are for both Gad and MDD , a significant number of patients that are going to if approved from D 120 .

Andrew Tsai: Got it. I appreciate the response. Thank you.

Ami Fadia: Got it. I appreciate the response. Thank you.

Speaker #13: I appreciate the response . Thank you .

Gitanjali Jain: Thank you. Our next question coming from the line of Sumant Kulkarni with Canaccord. Your line is now open.

Operator: Thank you. Our next question coming from the line of Sumant Kulkarni with Canaccord. Your line is now open.

Speaker #5: Thank you . Our next question coming from the line of Suman Kulkarni with Canaccord . Your line is now open

Speaker #14: Good afternoon . Thanks for taking our questions . As we eagerly await all the data expect announced this year . I have two questions , one on product development and the other on the commercial side .

Sumant Kulkarni: Good afternoon. Thanks for taking our questions as we eagerly await all the data expect to announce this year. I have two questions, one on product development and the other on the commercial side. First, conceptually, we think investors are perhaps somewhat unfairly holding psychedelic therapeutics to a higher bar on point separations on scales in clinical trials. Our view for some time now has been that where the bar really should be different, where the standard of care is on durability of effect. Is that a fair, real-world characterization from your perspective? I'm asking that because I don't think I heard an explicit call-out for durability in your earlier answer on clinical relevance of a statistic score on HAM-A or, and perhaps even more so on MADRS.

Speaker #14: First , conceptually , we think investors are perhaps somewhat unfairly holding psychedelic therapeutics to a higher bar on point separations on scales in clinical trials .

Speaker #14: But our view for some time now has been that where the bars really should be different versus standard of care is on durability of effect .

Speaker #14: Is that a fair , real world characterization from your perspective ? And I'm asking that because I don't think I heard an explicit call out for durability in your earlier answer on clinical relevance of a statistics score on Ham-a , or perhaps even more so on Madrs

Speaker #4: Yeah , thanks so much for the question , Simon . When we think about durability , there , both the the practical limitations of how long out in time you can look at single dose durability in a placebo controlled manner .

Rob Barrow: Yeah, no, thanks so much for the question, Samant. When we think about durability, there are both the practical limitations of how long out in time you can look at single-dose durability in a placebo-controlled manner. There are certainly insights that we can gain beyond that, in our conduct of the studies, we'll be looking at response patterns and the ultimate duration to events beyond just a 12-week period. You know, when we look at the landscape, 12 weeks is the outer bound of what most studies, particularly drugs that don't require a long time. For instance, SRIs can take many weeks to show any sort of activity. Of course, sponsoring those studies would wait well beyond that to try to drive that separation.

Speaker #4: There are certainly insights that we can gain beyond that . And in our conduct of the studies , we'll be looking at response patterns and the ultimate duration to events beyond just the 12 week period .

Speaker #4: But when we look at the landscape , 12 weeks is the outer bound of what most studies , particularly drugs that don't require a long time .

Speaker #4: For instance , SSRIs can take many weeks to to show any sort of activity . And so of course , sponsored those studies would wait well beyond that to try to drive that separation .

Speaker #4: But when we think about the and our dialogue With regulators to date and ability to show durability at 12 weeks past a single intervention is really at or close to the highest bar one could set for a drug .

Rob Barrow: When we think about the durability in our dialogue with regulators to date, an ability to show durability at 12 weeks past a single intervention is really at or close to the highest bar one could set for a drug. Part of the decision making in the design of our Phase 3 program was to have our primary end point be at that time, where we would be showing, if successful in these studies, really the longest durability of response that we could hope to or could hope to be established within a parallel group phase of the study. That stands out among all of the product candidates that we're seeing in late stage development, certainly in our field.

Speaker #4: And so, you know, part of the decision-making and the design of our Phase 3 program was to have our primary endpoint be at that time. We would be showing a successful outcome in these studies.

Speaker #4: Really the longest durability of response that we could could hope to or could hope to be established with in a parallel group phase of a study that stands out among all of the product candidates that we've seen in late stage development , certainly in our field .

Speaker #4: So we absolutely agree that durability is important and that durability , well beyond a few weeks after a single treatment or the last treatment of a drug , is really meaningful and why we've designed our studies the way we have .

Rob Barrow: We absolutely agree that durability is important and that durability well beyond a few weeks after a single treatment or the, you know, the last treatment or drug is really meaningful and why we've designed our studies the way we have.

Sumant Kulkarni: Got it. Yeah, that's really why I was asking, because you've shown a really good durability so far. On the commercial side, Matt, you mentioned a, quote, unquote, "high touch, white glove experience." What are your latest thoughts on pricing in MDD and GAD, at least relative to SPRAVATO for TRD, if that's still a good benchmark, what fraction of that high touch, white glove experience can be paid for by insurers?

Speaker #14: Yeah , that's really why I was asking , because you've shown a good durability so far , and on the commercial side , Matt , you mentioned a quote unquote high touch white glove experience .

Speaker #14: So what are your latest thoughts on pricing in MDD and Gad , at least relative to Spravato for TRD ? If that's still a good benchmark ?

Speaker #14: And what fraction of that high touch white glove experience can be paid for by insurers

Matt Wiley: Hmm.

Speaker #2: Yeah , that's great .

Rob Barrow: Yeah, thanks.

Matt Wiley: a great question.

Speaker #4: Thanks so much . Yeah , I'll just say briefly I think both Matt , I think the when we think of of pricing certainly premature to talk specifically about pricing .

Rob Barrow: Thanks so much, Sumant. Yeah, I'll just say briefly, you know, I think, I'll turn it over to Matt. I think the when we think of, you know, pricing, it's early premature to talk specifically about pricing, when we think about the dynamics, you know, we continue to believe and sort of build conviction in our belief that the failure of currently available therapies to address a patient's depression or anything else is not a good proxy to define a population. That what we see also in a lot of our HEOR or our work, is that severity is a huge driver of disease burden. Shouldn't be surprising.

Speaker #4: But when we think about the dynamics and we continue to to believe and sort of build conviction in our belief that the failure of currently available therapies to address a patient's depression or anything else is not a good proxy to define a population .

Speaker #4: And that what we see also in a lot of our or our work is that severity is a huge driver of disease . Burden .

Speaker #4: It shouldn't be surprising the fact that drugs that don't work particularly well in a population haven't worked in the population doesn't mean that those who were underserved by those therapies are worse off , necessarily .

Rob Barrow: The fact that drugs that don't work particularly well in a population, haven't worked in the population, doesn't mean that those who were underserved by those therapies are worse off necessarily. While we understand the dynamics of likely not being a first-line therapy for everyone, we do think that those distinctions and are somewhat artificial, and as a result, something that we both can look at within our subpopulations in our studies, but wouldn't sort of shy away from things like SPRAVATO as a comparator, given the sort of artificiality of that distinction. I'll turn it over to Matt to comment further on that.

Speaker #4: And and so while we understand the dynamics of likely not being a first line therapy for , for everyone , we do think that those distinctions and are somewhat artificial .

Speaker #4: And as a result , something that we both can look at within our subpopulations and our studies . But but wouldn't sort of shy away from things like Spravato as a comparator , given the sort of artificiality of that distinction .

Speaker #4: But I'll turn it over to Matt to comment further on that .

Speaker #2: Yeah . So Samantha , as we as we think about the the high touch or white glove type of orientation we have for this launch is really to remove any friction that a patient or provider could experience .

Matt Wiley: Yeah. Sumant, as we think about the high touch or white glove type of orientation we have for this launch, is really to remove any friction that a patient or provider could experience. That will involve a hub service model being really clear on the reimbursement pathway, how to bill and code, et cetera, ensuring that the patient out-of-pocket is not an obstacle. Basically removing any of the obstacles to get to therapy as quickly as possible. That's our ambition. That's what we're building towards, whether it's through field team and high touch field team exposure to either HCPs or otherwise in market access, and ensuring that we have a seamless hub model that really helps coordinate all of the different touch points to ensure that the patient experience is positive. Thank you.

Speaker #2: And so that will involve hub service model being really clear on the reimbursement pathway , how to bill and code , etc. , ensuring that the patient out of pocket is not an obstacle .

Speaker #2: Basically , removing any of the obstacles to get to therapy as quickly as possible . That's our ambition . That's what we're building towards .

Speaker #2: Whether it's through field team and high touch field team , exposure to either HCP or otherwise in market access and ensuring that we have a seamless hub model that that really helps coordinate all of the different touch points to , to ensure that the patient experience is positive

Speaker #15: Thank you

Speaker #5: Thank you. And that's all the time we have for the question and answer session. I will now turn the call back over to Mr. Robert Barrow for any closing remarks.

Gitanjali Jain: Thank you. That's all the time we have for our question and answer session. I will now turn the call back over to Mr. Rob Vera for any closing remarks.

Operator: Thank you. That's all the time we have for our question and answer session. I will now turn the call back over to Mr. Rob Vera for any closing remarks.

Speaker #4: I think everyone for joining us on the call today . We were incredibly excited to come to our top line readout for Emerge First and the months ahead .

Matt Wiley: I just thank everyone again for joining us on the call today. We're incredibly excited to come to our top line readout for Emerge first in the months ahead and with three total readouts across the course of the year. We think this is really a defining year for us and are incredibly excited to get to those data readouts. Thank you again for joining us today and hope you'll join us at our upcoming events in April and thereafter.

Rob Barrow: I just thank everyone again for joining us on the call today. We're incredibly excited to come to our top line readout for Emerge first in the months ahead and with three total readouts across the course of the year. We think this is really a defining year for us and are incredibly excited to get to those data readouts. Thank you again for joining us today and hope you'll join us at our upcoming events in April and thereafter.

Speaker #4: And with three pivotal readouts across the course of the year , we think this is really a defining year for us and our incredibly excited to get to those data readouts .

Speaker #4: So thank you again for joining us today . And and I hope you'll join us at our upcoming events in April . And thereafter

Gitanjali Jain: Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.

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