DFTX 8-K
Definium Therapeutics, Inc. (DFTX)
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
Item 8.01 Other Events.
On April 22, 2026, Definium Therapeutics, Inc. (the “Company”) issued a press release (the “Press Release”) announcing clinical and commercial updates presented at the Company's Investor and Analyst Day. A copy of the Press Release is attached as Exhibit 99.1 hereto, and is incorporated by reference herein.
On April 22, 2026, the Company posted the presentation from its Investor and Analyst Day (the “Presentation”) to its website. A copy of the Presentation is filed herewith as Exhibit 99.2 and is incorporated by reference in this Item 8.01.
Item 9.01 Financial Statements and Exhibits.
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99.1 |
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99.2 |
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104 |
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Cover Page Interactive Data File (embedded within the Inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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DEFINIUM THERAPEUTICS, INC. |
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April 22, 2026 |
By: |
/s/ Robert Barrow |
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Name: Robert Barrow |
Exhibit 99.1
04.22.26
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Definium Therapeutics Highlights DT120 ODT (Lysergide Tartrate) Clinical Advancements and Commercial Strategy at Investor and Analyst Day
MDD: Emerge topline data readout on track for late 2Q 2026; Ascend sites activated with first patient dosing anticipated in 2Q 2026
GAD: Voyage enrollment complete with 214 patients with topline data readout on track for early 3Q 2026; Panorama sample size re-estimation complete and target sample size updated to 200; screening closed with topline readout now expected in late 3Q 2026
PTSD: DT120 ODT program expanded into PTSD with Phase 3 Haven study expected to initiate in 2027
NEW YORK -- Definium Therapeutics, Inc. (Nasdaq: DFTX) (“Definium” or the “Company”), a late-stage clinical biopharmaceutical company developing a new generation of therapeutics intended to address the underlying causes of psychiatric and neurological disorders, today highlighted the advancement of its DT120 ODT (lysergide tartrate) clinical program and commercial strategy in major depressive disorder (MDD) and generalized anxiety disorder (GAD), with three anticipated topline readouts in the next six months serving as important near-term catalysts. The Company also announced an expansion of the DT120 ODT program with the planned initiation of the Phase 3 Haven study in posttraumatic stress disorder (PTSD).
“We are building Definium to be a leader in psychiatry, focused on delivering a differentiated, scalable franchise for patients with depression, anxiety, and trauma, anchored by DT120 ODT, which we believe could be a best-in-class therapy,” said Rob Barrow, Chief Executive Officer of Definium Therapeutics. “With three pivotal readouts expected over the next six months, we are rapidly establishing comprehensive clinical evidence for DT120 ODT. Together, these trial outcomes will inform our regulatory approach, including an expeditious path to a potential NDA submission. We continue to execute with focus and urgency to deliver transformative treatments for patients and sustained value for shareholders.”
The Company is preparing for its next phase of growth with the same rigor and discipline that have underpinned the clinical development of DT120 ODT, which represents a potential multi-billion-dollar commercial opportunity supported by a differentiated therapeutic profile and broad applicability across care settings. Definium is advancing a focused, patient-centric commercial strategy, including a scalable delivery model designed to support efficient adoption and long-term utilization. In parallel, the Company is proactively positioning for access and reimbursement with plans to leverage established and emerging practice patterns and existing administrative pathways to enable timely market uptake.
Clinical Advancements
DT120 ODT (lysergide tartrate) for MDD
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DT120 ODT (lysergide tartrate) for GAD
DT120 ODT (lysergide tartrate) for PTSD
Today’s Investor and Analyst Day featured Definium’s executive leadership team alongside distinguished expert clinicians, who discussed the evolving treatment landscape in psychiatry, persistent unmet need, and emerging opportunities to improve outcomes for patients, as well as the Company’s clinical progress and commercial strategy. Presentation materials from today’s event are available
here.
About DT120 (lysergide tartrate) Orally Disintegrating Tablet (ODT)
DT120 ODT is an ergoline derivative belonging to the group of classic serotonergic psychedelics, which acts as a partial agonist at serotonin-2A (5-HT2A) receptors. DT120 ODT is Definium’s proprietary and pharmaceutically optimized formulation of LSD. DT120 ODT is an advanced formulation incorporating Catalent’s Zydis® ODT fast-dissolve technology, designed to deliver several unique advantages, including faster absorption and onset of transient cognitive, perceptual, and affective changes, improved bioavailability, and a lower incidence of gastrointestinal side effects. Definium is developing DT120 ODT, the tartrate salt form of lysergide, for generalized anxiety disorder (GAD), major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and is exploring its potential applications in other serious brain health disorders. Definium maintains a strong foundation to protect and extend the long-term value of the DT120 ODT franchise through a multi-layered intellectual property strategy spanning composition, formulation, and methods-of-use patents.
About Lysergide (LSD)
Lysergide (LSD) is one of the most extensively studied psychopharmaceuticals in history, with over 1,000 published reports.1 First synthesized in 1938 by Swiss chemist Albert Hofmann in his search for active principles from ergot fungus, its profound psychological effects were discovered in 1943, which transformed psychiatric research.1 LSD, a definitional classic psychedelic, temporarily alters perception, cognition, and emotion, is physiologically safe, non-addictive, and isn’t associated with withdrawal.1 While its precise mechanism of action in the treatment of psychiatric illness is unknown, its acute perceptual, cognitive, and affective effects are mediated by agonism of the serotonin 5-hydroxytryptamine 2A (5-HT2A) receptor, and mechanistic hypotheses suggest that it causes sustained increases in neuroplasticity in a variety of brain regions.2,3
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About Definium Therapeutics
The mission of Definium Therapeutics is to forge a new era of psychiatry by applying scientific rigor to psychedelics, with the goal of developing accessible treatments that unlock healing at scale. Guided by a recognition that patients deserve more than better, Definium is relentlessly advancing a new generation of therapeutics intended to address underlying causes of psychiatric and neurological disorders. By turning evidence into impact, Definium aims to change the trajectory of today’s mental health care crisis and enable a healthier future. Headquartered in New York, Definium Therapeutics trades on Nasdaq under the symbol DFTX.
Forward-Looking Statements
Certain statements in this news release related to the Company constitute "forward-looking information" within the meaning of applicable securities laws and are prospective in nature. Forward-looking information is not based on historical facts, but rather on current expectations and projections about future events and are therefore subject to risks and uncertainties which could cause actual results to differ materially from the future results expressed or implied by the forward-looking statements. These statements generally can be identified by the use of forward-looking words such as "will", "may", "should", "could", "intend", "estimate", "plan", "anticipate", "expect", "believe", "potential" or "continue", or the negative thereof or similar variations. Forward-looking information in this news release includes, but is not limited to, statements regarding the Company’s anticipated topline readout for the Phase 3 Voyage study of DT120 ODT in GAD in early 3Q 2026; the Company’s anticipated topline readout for the Phase 3 Panorama study for DT120 ODT in GAD in late 3Q 2026; the Company’s anticipated topline readout for the Phase 3 Emerge study for DT120 ODT in MDD in late 2Q 2026; the Company’s plans to dose the first patient in the Phase 3 Ascend study of DT120 ODT in MDD in 2Q 2026; the Company’s expectations regarding the enrollment for each of the Panorama and Ascend studies; the Company’s expectation to initiate the Haven study of DT120 ODT in PTSD in 2027; the Company’s expectations regarding enrollment and trial design for the Haven study; the Company’s beliefs regarding potential benefits of its product candidates; the Company's belief that DT120 ODT could be a best-in-class therapy; the Company's regulatory plans, including the timing of any potential NDA submissions; the Company's belief in DT120 ODT’s differentiated therapeutic profile and broad applicability across care settings; the potential market opportunity for DT120 ODT; the Company’s commercial strategy; and patient access to and reimbursement of DT120 ODT. There are numerous risks and uncertainties that could cause actual results and the Company's plans and objectives to differ materially from those expressed in the forward-looking information, including history of negative cash flows; limited operating history; incurrence of future losses; availability of additional capital; compliance with laws and regulations; legislative and regulatory developments, including decisions by the Drug Enforcement Administration and states to reschedule any of our product candidates, if approved, containing Schedule I controlled substances, before they may be legally marketed in the U.S.; difficulty associated with research and development; risks associated with clinical studies or studies; heightened regulatory scrutiny; early stage product development; clinical study risks; regulatory approval processes; novelty of the psychedelic inspired medicines industry; ability to maintain effective patent rights and other intellectual property protection; as well as those risk factors discussed or referred to herein and the risks, uncertainties and other factors described in the Company's Annual Report on Form 10-K for the fiscal year ended December 31, 2025 under headings such as "Special Note Regarding Forward-Looking Statements," and "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" and other filings and furnishings made by the Company with the securities regulatory authorities in all provinces and territories of Canada, which are available under the Company's profile on SEDAR+ at www.sedarplus.ca, and with the U.S. Securities and Exchange Commission on EDGAR at www.sec.gov. Except as required by law, the Company undertakes no duty or obligation to update any forward-looking statements contained in this release as a result of new information, future events, changes in expectations or otherwise.
For more information, visit https://definiumtx.com/ and follow Definium Therapeutics on Instagram, LinkedIn, and X.
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Investors:
Gitanjali Jain
VP, Head of Investor Relations [email protected]
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Investor & Analyst Day April 22, 2026
This presentation (the “Presentation”) has been prepared by Definium Therapeutics, Inc. (“Definium”, the “Company”, “we”, “our” or “us") solely for informational purposes. This Presentation does not constitute an offering of, or a solicitation of an offer to purchase, securities of Definium and under no circumstances is it to be construed as a prospectus or advertisement or public offering of securities. Any trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of the products or services of Definium. Any amounts are in USD unless otherwise noted. Definium’s securities have not been approved or disapproved by the U.S. Securities and Exchange Commission (the "SEC") or by any state, provincial or other securities regulatory authority, nor has the SEC or any state, provincial or other securities regulatory authority passed on the accuracy or adequacy of this Presentation. Any representation to the contrary is a criminal offense. Cautionary Note Regarding Forward-Looking Statements This Presentation contains, and our officers and representatives may from time to time make, “forward-looking statements” within the meaning of applicable securities laws and are prospective in nature. Forward-looking statements are not based on historical facts, but rather on current expectations and projections about future events and are therefore subject to risks and uncertainties which could cause actual results to differ materially from the future results expressed or implied by the forward-looking statements. These statements generally can be identified by the use of forward-looking words such as “will”, “may", “should”, “could”, “intend”, “estimate”, “plan”, “anticipate”, “expect”, “believe”, “potential”, “continue”, “budget”, “scheduled”, “forecasts”, “intends”, “anticipates”, “projects” or the negative thereof or similar variations. Forward-looking statements in this Presentation include, but are not limited to, statements regarding the anticipated design, timing, progress and results of our investigational programs for DT120 oral disintegrating tablet (“ODT”), a proprietary, pharmaceutically optimized form of lysergide tartrate (including the anticipated topline readouts for the Voyage, Panorama, Emerge and Ascend studies); our ability to identify new indications for our lead product candidates beyond our current primary focuses; the success and timing of our development activities; the success and timing of our planned clinical trials; our ability to meet the milestones set forth herein; the likelihood of success of any clinical trials or of obtaining U.S. Food and Drug Administration (“FDA”) or other regulatory approvals on an accelerated timeline or at all and the labeling under any approval we may obtain; our beliefs regarding potential benefits of our product candidates, including expectations related to safety, efficacy and durability; opinions of potential providers, patients and payors regarding our product candidates, if approved and commercialized; statements regarding potential coverage, reimbursement and coding for DT120 ODT, if approved and commercialized; our ability to maximize operational efficiencies through our trial designs; strategies to address drug class methodological considerations; our cash runway funding operations into 2028 based on our current operating plan and anticipated milestones; our pre-launch strategy; the potential commercial opportunity for DT120 ODT, if approved, including total addressable market; the potential delivery model for DT120 ODT, if approved; the potential for the markets that we are anticipating to access; protection of our intellectual property; and the potential for psychedelics as a class of treatment options for psychiatric and neurological disorders. There are numerous risks and uncertainties that could cause actual results, plans and objectives to differ materially from those expressed in forward-looking statements, including history of negative cash flows, limited operating history, incurrence of future losses, availability of additional capital, compliance with laws and regulations, difficulty associated with research and development, risks associated with clinical trials or studies, heightened regulatory scrutiny, early stage product development, clinical trial risks, risks related to regulatory review and approval, including the possibility of delays, requests for additional data or analyses, restrictions or limitations on use, approval with labeling that is more limited than expected, or failure to obtain approval in the United States or other jurisdictions, novelty of the psychedelic inspired medicines industry, our ability to maintain effective patent rights and other intellectual property protection for our product candidates, our expectations regarding the size of the eligible patient populations for our lead product candidates, if approved and commercialized; our ability to identify third-party treatment sites to conduct our trials and our ability to identify and train appropriate qualified healthcare practitioners to administer our treatments; the pricing, coverage and reimbursement of our lead product candidates, if approved and commercialized; the rate and degree of market acceptance and clinical utility of our lead product candidates, in particular, and controlled substances, in general; as well as those risk factors described in the Company's Annual Report on Form 10-K for the fiscal year ended December 31, 2025 under headings such as “Special Note Regarding Forward-Looking Statements,” and “Risk Factors” and “Management's Discussion and Analysis of Financial Condition and Results of Operations” and other filings and furnishings made by the Company with the securities regulatory authorities in all provinces and territories of Canada, which are available under the Company's profile on SEDAR+ at www.sedarplus.ca, and with the SEC on EDGAR at www.sec.gov. Any forward-looking statement made by Definium in this Presentation is based only on information currently available to the Company and speaks only as of the date on which it is made. Except as required by law, the Company undertakes no duty or obligation to update any forward-looking statements contained in this Presentation as a result of new information, future events, changes in expectations or otherwise. Cautionary Note Regarding Regulatory Matters The United States federal government regulates drugs through the Controlled Substances Act. DT120 ODT is a proprietary, pharmaceutically optimized form of lysergide D-tartrate and DT402, or R(-)-MDMA, is our proprietary form of the R-enantiomer of MDMA (3,4-methylenedioxymethamphetamine). Lysergide and MDMA are Schedule I substances under the Controlled Substances Act. While the Company is focused on programs using psychedelic or hallucinogenic compounds and non-hallucinogenic derivatives of these compounds, including in DT120 ODT, DT402 and its other product candidates, the Company does not have any direct or indirect involvement with the illegal selling, production or distribution of any substances in the jurisdictions in which it operates. The Company is a neuro-pharmaceutical drug development company and does not deal with psychedelic or hallucinogenic substances except within laboratory and clinical trial settings conducted within approved regulatory frameworks. The Company's products will not be commercialized prior to applicable regulatory approval, which will only be granted if clinical evidence of safety and efficacy for the intended uses is successfully developed. Market and Industry Data This Presentation includes market and industry data that has been obtained from third-party sources, including industry publications. Definium believes that the industry data is accurate and that the estimates and assumptions are reasonable, but there is no assurance as to the accuracy or completeness of this data. Third-party sources generally state that the information contained therein has been obtained from sources believed to be reliable, but there is no assurance as to the accuracy or completeness of included information. Although the data is believed to be reliable, Definium has not independently verified any of the data from third-party sources referred to in this Presentation or ascertained the underlying economic assumptions relied upon by such sources. References in this Presentation to research reports or to articles and publications should not be construed as depicting the complete findings of the entire referenced report or article. Definium does not make any representation as to the accuracy of such information. Investor & Analyst Day | April 2026 Disclaimer
Investor & Analyst Day | April 2026 Topic Speaker(s) Timing Welcome & Introduction Definium Vision The Year Ahead Rob Barrow 5 min DT120 Program Overview Phase 2b Results Overview of Anxiety & Depression Phase 3 Program & Readout Expectations Rob Barrow & Dr. Dan Karlin 35 mins A Patient’s Perspective on the DT120 Experience Video 5 mins Panel Discussion – Clinical Readiness & Real-World Implementation Unmet Need in GAD & MDD Current Treatment Paradigm Panel Q&A Dr. Dan Karlin Dr. Brittany Albright Andrew Penn Shannon Sarkar 25 mins Commercial Strategy Matt Wiley 20 mins Building Long-Term Shareholder Value IP Strategy Financial Strength 2026 Anticipated Catalysts Brandi Roberts 5 mins Q&A All 25 min Lunch & On-Site Dosing Room 90 mins Today’s Agenda QR Code for Q&A Session
Investor & Analyst Day | April 2026 Investor & Analyst Day Speakers Rob Barrow Chief Executive Officer Dan Karlin, MD Chief Medical Officer Matt Wiley Chief Commercial Officer Brandi Roberts, CPA Chief Financial Officer Andrew Penn, MS, PMHNP Brittany Albright, MD, MPH, DABOM Shannon Sarkar, PhD, LPC, NCC
Investor & Analyst Day | April 2026 Target Product Profile to Address Significant Unmet Need Single dose regimen is being studied in pivotal clinical trials with primary and secondary outcome measures through 12 weeks after administration. Phase 3 studies include 40 week extension phase to characterize durability of response beyond 12 weeks in participants up until the time of discontinuation or the administration of open-label DT120. Required monitoring period for all participants in pivotal studies is 8 hours and requires that participants clear the End of Session Checklist. Ringeisen, H., et al. (2023). Mental and Substance Use Disorders Prevalence Study (MDPS): Findings Report, Zhou, Y,. Et al. (2017). Nature. Comorbid generalized anxiety disorder and its association with quality of life in patients with major depressive disorder. RTI International and current U.S. Census data and internal company estimates. 1 Dose1 Weeks of Durability1 Hours in the Clinic2 US Adults with GAD & MDD3 5-8 12+ 50M
Investor & Analyst Day | April 2026 Understanding the Patient Journey AE: adverse events; MDE: major depressive episode; PCP: primary care physician; Rx: prescription; SGA: second generation antipsychotic; SRI: serotonin reuptake inhibitors (including selective serotonin and selective serotonin and norepinephrine reuptake inhibitors); Tx: treatment Symptoms First Present Impact on life, work, relationships Impairment takes hold Discuss with PCP Prescribed SRI Hope Rx will provide relief Acutely exacerbated anxiety 4-week evaluation Dose adjustment 8-week evaluation 2-week evaluation Dose adjustment Little Evidence of Efficacy Sexual effects noted PCP switches SRI Anxiety exacerbated 12-week evaluation Dose adjustment 16-week evaluation 10-week evaluation Dose adjustment Some positive effects noted Noticeable weight gain Suppressed feelings Side effects “not worth it” Discontinue 2nd SRI Disappointment and worry Onset of depressive symptoms Referral to psychiatry Atypical antidepressant started Dose adjustment and augmentation with SGA 30-week evaluation 24-week evaluation Dose adjustment Partial response of depression Adjustment of SGA Additional Augmentation & Rx Cycles Psychiatry appt available Onset of new AEs
Investor & Analyst Day | April 2026 Receptor & Cellular Clinical Efficacy Neurocircuitry Psychological Bringing the field back to its origins in pursuit of best-in-class profile
Investor & Analyst Day | April 2026 Right Team, Right Experience Right Strategy Precise Science Boundless Impact Moving Psychiatry Forward – at a Scale Reflecting the Unmet Need
Investor & Analyst Day | April 2026 Phase 3 Program Built to Support a Broad Label Studies employ an adaptive design with interim blinded sample size re-estimation (“SSRE”) based on nuisance parameters (e.g. patient retention rate, variability of primary outcome measure) which allows for an adjustment of the sample size of up to 50% to maintain statistical power. Planned sample size indicated prior to any adjustments in accordance with the sample size re-estimation. Clinical study designs subject to change based on ongoing regulatory discussion and review, including of Phase 3 clinical trial protocols. DB: double blind; HAM-A: Hamilton Anxiety Rating Scale; MADRS: Montgomery-Åsberg Depression Rating Scale; ODT: orally disintegrating tablet; OL: open-label; RCT: randomized controlled trial Generalized Anxiety Disorder (GAD) Major Depressive Disorder (MDD) Planned n=2001 1:1 randomization DT120 ODT vs. Placebo Part A: 12-week DB, RCT Part B: 40-week Extension with OL Treatment Planned n=2501 2:1:2 randomization DT120 ODT vs. Placebo including 50 µg control Part A: 12-week DB, RCT Part B: 40-week Extension with OL Treatment Planned n=140 1:1 randomization DT120 ODT vs. Placebo Part A: 12-week DB, RCT Part B: 40-week Extension with OL Treatment Planned n=1752 2:1:2 randomization DT120 ODT vs. Placebo including 50 µg control Part A: 12-week DB, RCT Part B: 40-week Extension with OL Treatment Planned n=2002 1:1 randomization DT120 ODT vs. Placebo Part A: 12-week DB, RCT Part B: 40-week Extension with OL Treatment Posttraumatic Stress Disorder (PTSD)
Investor & Analyst Day | April 2026 SSREs Complete and Support Confidence in Decisive Phase 3 Outcomes Variable Planned SSRE3 Planned SSRE3 Enrollment 200 <200 250 <200 Standard deviation 10.0 Raw: 7.8 MMRM: 6.2 10.0 Raw: X.X MMRM: X.X Non-evaluable rate4 15% 10% 15% XX% Power for 5-point placebo-adjusted change from baseline (primary endpoint) 90% >99% 90% ##% Minimum required clinical difference 3.0 1.9 3.0 #.# Phase 2b Study MMED0081,2 Internal study documents. Robison, Reid et al. “Single Treatment With MM120 (Lysergide) in Generalized Anxiety Disorder: A Randomized Clinical Trial.” JAMA vol. 334,15 (2025): 1358-1372. doi:10.1001/jama.2025.13481 Non-evaluable rate based on data not available within visit analysis window as defined in study statistical analysis plan. SSREs conducted 12 weeks after enrollment of 50% of target sample size. Raw standard deviation based on observed cases at timepoint of interest. MMRM SD derived from model-based residual standard error. Power calculation based on the assumption that SSRE-observed nuisance parameters and revised target enrollment are maintained in final population and analysis. Minimum detectable difference refers to the placebo-adjusted difference above which a p-value less than 0.05 could be expected in the final analysis and are based on the SSRE-observed nuisance parameters assuming such parameters are maintained in final population and analysis; based on current enrollment at time of analysis. Δ: placebo-adjusted difference on primary endpoint; MMRM: Mixed Models or Repeated Measures; SD: standard deviation; SSRE: sample size re-estimation Enrollment Target Standard Deviation Non-evaluable rate3 Power for Δ=5 points3 Minimum detectable difference4 Observed Planned SSRE Outcome Planned SSRE Outcome 9.7 25% 200 10.0 15% 90% 3.0 200 Observed: 7.8 MMRM: 6.2 10% >99% 1.8 250 10.0 15% 90% 3.0 200 Observed: 7.6 MMRM: 7.4 6% 99% 2.4
Investor & Analyst Day | April 2026 Three Highly Powered Pivotal Readouts Anticipated in the Next 6 Months Generalized Anxiety Disorder (GAD) Major Depressive Disorder (MDD) Complete n=214 Early 3Q 2026 No required increase No required increase Target updated to n=200 Late 3Q 2026 Screening Closed Target n=200 >99% 99% Complete n=149 Late 2Q 2026 80% Enrollment Topline1 Power2 SSRE Outcome3 Anticipated timing of topline data Power to detect a 5-point placebo-adjusted change on the HAM-A scale; based on the SSRE conducted for each study. SSREs conducted 12 weeks after enrollment of 50% of target sample size. Power calculation and sample size requirements based on the assumption that SSRE-observed MMRM-derived nuisance parameters and are maintained in final population and analysis. HAM-A: Hamilton Anxiety Scale; n=sample size; SSRE: sample size re-estimation
DT120 Phase 2b Results in GAD
Investor & Analyst Day | April 2026 Key Phase 2b Efficacy and Safety Findings Support Best-In-Class Potential of DT1201,3 Standardized effect size more than double the standard of care1,2,3 Comparative Effect Sizes in GAD Rapid and durable response after single administration3 Rapid Response & Remission Durable Standalone Drug Effect Limited Adverse Event (AE) Burden 1.8-point reduction in CGI-S within 24 hours (p<0.0001) 21.9-point improvement on the HAM-A at Week 12 (p=0.003) 48% of participants in remission at Week 125 Favorable tolerability with most AEs on dosing day Observed drug effect without accompanying psychotherapy 0 0.2 0.4 0.6 0.8 Cohen’s d s4 DT120 100 µg2 0.81 0.38 0.36 0.17 Study MMED008 internal study documents and calculations. Comparisons to standard of care/other drug classes based on historical comparison not head-to-head comparison trial. HAM-A scores based on ANCOVA LS Mean. in Study MMED008. Effect size based on post hoc calculation using LS Mean change between group and pooled standard deviation of week 12 HAM-A scores between groups. Based on 100 µg dose group. RB Hidalgo, J Psychopharmacol. 2007 Nov;21(8):864-72. p-values not calculated for remission rates between groups. CGI-S: Clinical Global Impression – Severity scale; GAD: generalized anxiety disorder; HAM-A: Hamilton Anxiety scale; SRI: serotonin reuptake inhibitor
Dose Response in Phase 2b Provides Confidence in Dose Optimization & Robustness of Response Statistically significant dose response in Phase 2b Model supports 100 µg as optimal dose Results not explainable by “functional unblinding” supporting robustness of drug effect R Robison, JAMA. 2025 Sep 4; e2513481. doi:10.1001/jama.2025.13481. Model-Based Dose-Response Curve1 Key Findings Investor & Analyst Day | April 2026 Impacts
Primary Outcome: HAM-A Change from Baseline Source: Study MMED008 internal study documents and calculations. Full analysis set population. Based on 100 µg dose group. Based on observed MADRS score at each timepoint. Primary endpoint of the study was change in Hamilton Anxiety Scale (HAM-A) at week 4 using the MCP-Mod statistical analysis. Based on the pre-specified candidate dose response curves, the MCP-Mod model-estimated difference between 100 µg and placebo was 5.0 points versus the observed difference of 7.6 points at week 4. μg: microgram; HAM-A: Hamilton Anxiety Rating Scale; MADRS: Montgomery-Åsberg Depression Rating Scale NOTE: Significance achieved despite study not being powered for these pairwise comparisons. DT120 Showed Statistically & Clinically Significant Improvements on Anxiety and Depression Symptoms1,2 *p<0.05; **p≤0.01; ***p≤0.001 Baseline Week 1 Week 2 Week 44 Week 12 *** *** *** ** MADRS Change from Baseline ** ** * ** Change from Baseline2 Week 12: -21.9 points Improvement over Placebo2 Week 12: -7.7 pts, p=0.003 Change from Baseline2,3 Week 12: -18.7 points Improvement over Placebo2,3 Week 12: -6.4 points, p<0.01 Baseline Week 1 Week 2 Week 4 Week 12 Placebo 100 µg Investor & Analyst Day | April 2026
Remission (≤7) Symptoms are absent, insignificant, or clearly due to causes other than anxiety Mild (8-15) Symptoms are infrequent, with no impairment and no more than mild distress Moderate (16-23) Symptoms are more frequent, with moderate distress or limited interference with usual activities Very Severe Symptoms are incapacitating Severe (≥24) Symptoms are severe and persistent or result in severe distress or marked impairment in functioning DT120 Demonstrated Profound Changes in GAD Severity1 Source: Study MMED008 internal study documents and calculations. Full analysis set population. Response is a 50% or greater improvement on HAM-A score; Remission is a HAM-A score of ≤7; p-values not calculated. μg: microgram; HAM-A: Hamilton Anxiety Rating Scale HAM-A Response & Remission at Week 122 Median HAM-A Through Week 12 HAM-A Severity & Clinical Symptoms Baseline Week 1 Week 2 Week 4 Week 12 Week 8 Investor & Analyst Day | April 2026
DT120 Phase 2b Results in Context
Investor & Analyst Day | April 2026 DT120 Delivers Clinical Activity that Stands Apart from Approved GAD Treatments1 1) The information presented in this slide is derived from multiple clinical trials, each conducted under distinct protocols and settings. As such, these data may not be directly comparable due to the lack of a head-to-head comparison. Differences in trial design, patient demographics, and other variables may account for variations in the observed outcomes. Study results for each drug are intended to be representative, however, multiple trials of the approved treatments have been conducted with varying results, including results that may have demonstrated a larger or smaller treatment effect than those presented. BuSpar and Xanax are approved for anxiety disorders which include GAD.; 2) R Robison, JAMA. 2025 Sep 4; e2513481. doi:10.1001/jama.2025.13481; 3) C Allgulander, Curr Med Res Opin. 2007;23(6):1245–1252; 4) JRT Davidson, Depress Anxiety. 2004;19(4):234–240; 5) K Rickels K, Am J Psychiatry 2003; 160:749-756. 2005;62(9):1022–1030; 6) AJ Gelenberg AJ, JAMA. 2000;283(23):3082–3088; 7) JJ Sramek JJ, Journal of Clinical Psychiatry. 1996;57(7):287–291; 8) K Rickels, Arch Gen Psychiatry. 2005;62(9):1022–1030. GAD: generalized anxiety disorder, Tx: treatment All trademarks are property of their respective owners. 2 3 4 5 6 7 8
Investor & Analyst Day | April 2026 DT120 Delivers Clinical Activity that Stands Apart from Latest Generation of Treatments for Depression Symptoms1 The information presented in this slide is derived from multiple clinical trials, each conducted under distinct protocols and settings. As such, these data may not be directly comparable due to the lack of a head-to-head comparison. Differences in trial design, patient demographics, and other variables may account for variations in the observed outcomes. Study results for each drug are intended to be representative, however, multiple trials of the approved treatments have been conducted with varying results, including results that may have demonstrated a larger or smaller treatment effect than those presented. Depression treatments include those indicated for MDD, TRD and BPD. Only includes results from Phase 3 studies for which MADRS data are available and which were studied as a monotherapy. Results for approved drugs as reported on US Prescribing Information. In instances with multiple studies, the most favorable US study results presented. Compass Pathways results based on Study COMP005 Adj: adjunctive; BPD: bipolar depression; GAD: generalized anxiety disorder; MDD: major depressive disorder; TRD: Treatment Resistant Depression;Tx: treatment All trademarks are property of their respective owners. 2
DT120 was Well-Tolerated with Adverse Events Mostly Limited to Dosing Day1 Study MMED008 internal study documents and calculations. Safety population. One serious adverse event (SAE) was observed in the 50 µg dose group: panic attack on study day 98 that was deemed not related to treatment. Suicidality assessment based on reported adverse events. Virtually all (99%) adverse events (AEs) were mild-to-moderate in severity Minimal (2.5%) treatment emergent AEs (TEAEs) led to study withdrawal AE profile consistent with historical studies and drug class Favorable tolerability profile No SAEs related to study drug No suicidal behavior or suicidality signal3 Only SAE was in 50 µg dose group and deemed unrelated2 No drug-related serious AEs (SAEs)2 No suicidal or self-injurious behavior No indication of increased suicidality or suicide-related risk ≤2 participants per arm reported suicidal ideation during the study Investor & Analyst Day | April 2026
Anxiety & Depression
Interplay Between GAD & MDD Highlights Opportunity for a Dual Intervention1 Severe Remission Mild Moderate GAD chronic background anxiety burden Anxiety Depression Between MDEs often characterized by residual anxiety MDD major depressive episodes with inter-episode euthymia Investor & Analyst Day | April 2026 1. Conceptual illustration of disease progression in comorbid GAD and MDD. GAD: generalized anxiety disorder; MDD: major depressive disorder; MDE: major depressive episode
Investor & Analyst Day | April 2026 Diagnostic Definitions With Intersecting Symptoms Source: Diagnostic and Statistical Manual of Mental Disorders, 5th edition Text Revision (DSM-V-TR) 1. Restlessness or feeling keyed up/on edge 2. Being easily fatigued 3. Difficulty concentrating or mind going blank 4. Irritability 5. Muscle tension 6. Sleep disturbance Major Depressive Disorder (MDD)1 Generalized Anxiety Disorder (GAD)1 Must have ≥3 of 6 symptoms: Frequency & Duration: More days than not for ≥6 months Psychological effects Physical effects 1. Depressed Mood 2. Markedly diminished interest or pleasure 3. Significant weight loss/gain or appetite change 4. Insomnia or hypersomnia 5. Fatigue or loss of energy 6. Feeling of worthlessness or excessive/inappropriate guilt Must have ≥5 symptoms: At least one must be #1 or #2 Frequency & Duration: ≥ 2 weeks 7. Diminished ability to think or concentrate; indecisiveness 8. Recurrent thoughts of death or suicidal ideation/behavior
Investor & Analyst Day | April 2026 Clinical Outcome Assessments in GAD and MDD Share Many Domains Montgomery-Åsberg Depression Rating Scale (MADRS)2 Range: 0-60 Hamilton Anxiety Scale (HAM-A)1 Range: 0-56 1. Apparent sadness 2. Reported sadness 3. Inner Tension 4. Reduced Sleep 5. Reduced Appetite 6. Concentration Difficulties 7. Lassitude 8. Inability to Feel (Anhedonia) 9. Pessimistic Thoughts 10. Suicidal Thoughts 1. Anxious mood – worry, fear 2. Tension – restlessness, inability to relax 3. Fears – of dark, strangers, being alone, etc. 4. Insomnia 5. Intellectual – concentration, memory 6. Depressed Mood 7. Somatic (muscular) – aches, twitching 8. Somatic (sensory) – tinnitus, blurred vision 9. Cardiovascular symptoms – palpitations, chest pain 10. Respiratory symptoms – shortness of breath 11. Gastrointestinal symptoms – nausea, cramps 12. Genitourinary symptoms – frequency, libido changes 13. Autonomic symptoms – dry mouth, sweating 14. Behavior during interview – fidgeting, restlessness Psychological effects Source: Hamilton M.The assessment of anxiety states by rating. Br J Med Psychol 1959; 32:50–55. Source: Montgomery, S. A., & Åsberg, M. (1979). A new depression scale designed to be sensitive to change. British Journal of Psychiatry, 134(4), 382–389. Physical effects
DT120 ODT Phase 3 Program
Investor & Analyst Day | April 2026 Phase 3 DT120 ODT Development Program Aiming for Broad Label Studies employ an adaptive design with interim blinded sample size re-estimation (“SSRE”) based on nuisance parameters (e.g. patient retention rate, variability of primary outcome measure) which allows for an adjustment of the sample size of up to 50% to maintain statistical power. Target sample size in accordance with the sample size re-estimation. Clinical study designs subject to change based on ongoing regulatory discussion and review, including of Phase 3 clinical trial protocols. DB: double blind; HAM-A: Hamilton Anxiety Rating Scale; MADRS: Montgomery-Åsberg Depression Rating Scale; ODT: orally disintegrating tablet; OL: open-label; RCT: randomized controlled trial Generalized Anxiety Disorder (GAD) Major Depressive Disorder (MDD) Final n=2141 1:1 randomization DT120 ODT vs. Placebo Part A: 12-week DB, RCT Part B: 40-week Extension with OL Treatment Target n=2001 2:1:2 randomization DT120 ODT vs. Placebo including 50 µg control Part A: 12-week DB, RCT Part B: 40-week Extension with OL Treatment Final n=149 1:1 randomization DT120 ODT vs. Placebo Part A: 12-week DB, RCT Part B: 40-week Extension with OL Treatment Planned n=1752 2:1:2 randomization DT120 ODT vs. Placebo including 50 µg control Part A: 12-week DB, RCT Part B: 40-week Extension with OL Treatment Planned n=2002 1:1 randomization DT120 ODT vs. Placebo Part A: 12-week DB, RCT Part B: 40-week Extension with OL Treatment Posttraumatic Stress Disorder (PTSD)
Investor & Analyst Day | April 2026 Why We Believe DT120 ODT Is Well Positioned for Phase 3 Success Strong Phase 2b results with effects on anxiety and depression symptoms Phase 3 design enhancements support patient retention Existing and expanded key research site relationships Alignment with FDA Industry Guidance & ICH Guidelines Collaborative FDA dialogue informing Phase 3 design Continuous hands-on oversight of trial execution
Multiple Programs with Shared Development Strategy Source: Definium internal study documents. ClinRO: clinician reported outcome; ePRO: electronic patient reported outcome; MADRS: Montgomery-Åsberg Depression Rating Scale; MDD: Major Depressive Disorder; ODT: orally disintegrating tablet DT120 ODT 100 µg Placebo Part A 12 Week Randomized, Double-Blind Part B 40 Week Extension with Opportunity for Open-Label Treatment DT120 ODT 100 µg Placebo PHASE 3 STUDY1 Single Dose Primary Endpoint: MDD: MADRS at Week 6 GAD: HAM-A at Week 12 PTSD: CAPS-5 at Week 8 Up to four open-label doses of DT120 ODT 100 µg Single Dose Follow-up Observation ePRO: biweekly Central ClinRO: monthly or when ePRO>threshold Potential Treatment Eligible for open-label treatment when ClinRO>moderate DT120 ODT 50 µg control Investor & Analyst Day | April 2026
Investor & Analyst Day | April 2026 Eligibility Process in Phase 3 Supports Trial and Population Integrity Source: Definium internal study documents. CRO: contract research organization; MGH SAFER: Massachusetts General Hospital SAFER independent diagnostic interview 01 Site Diagnosis Comorbidities Severity Eligibility 02 Central Rater Severity 03 MGH SAFER Diagnosis Comorbidities Severity 04 CRO Medical Team Diagnosis Comorbidities Severity Eligibility 05 Sponsor Medical Team Diagnosis Comorbidities Severity Eligibility
DT120 ODT Treatment Paradigm: Standalone Drug Effects with No Psychotherapeutic Intervention1 Source: Study MMED008 internal study documents. DSM: dosing session monitor; EOSC: end of session checklist DT120 Patient Journey Pre-treatment activities consist of a comprehensive informed consent process Eligibility evaluation Continuous monitoring by DSMs Music, eye shades, reading, writing Concludes when EOSC criteria met Follow-up visits for assessment only Pre-treatment During treatment Post-treatment Not Part of Patient Journey No “preparation” therapy No “assisted therapy” No psychotherapy and no therapeutic intervention beyond study drug No “integration” therapy No ongoing therapeutic engagement as part of clinical trial activities 31 Dosing session monitor (DSM) in the room provides no psychotherapeutic intervention Delivery protocol consistent with 2023 FDA Draft Guidance2 No changes to session conduct between Phase 2 and Phase 3 Investor & Analyst Day | April 2026
Efficient single-visit model with full-session reimbursement streamlines administrative burden2 Investor & Analyst Day | April 2026 Clinical Dosing Paradigm with Potential Translatability to Efficient Real-World Delivery1,2 Dosing and monitoring paradigm based on Phase 3 clinical protocols. Required monitoring period for all participants in pivotal studies is 8 hours and requires that participants clear the End of Session Checklist. Existing coding systems could potentially be applied or be changed for DT120. Reimbursement and coding for DT120 have yet to be established. ODT: orally disintegrating tablet DT120 ODT disintegrates in seconds 15-30 minutes (time to onset) Effects move to resolution Hour 5: Dosing Session Monitor (DSM) evaluates patient hourly with an end-of-session checklist to determine when the patient can leave safely Hour 4-6 Ordinary perception, affect, and cognition return Normal activities resume the next day, including driving Hour 6-8 and post-session Transient perceptual, affective, and cognitive drug effects vary from person to person Effects at maximum intensity Hours 4-6: effects start to resolve Hour 2-4
Investor & Analyst Day | April 2026 Evolution of Patient Monitoring based on Clinical Evidence & Anticipating Real-World Setting 12-hour monitoring requirement based on inclusion of 200 µg dose of DT120 in Phase 2b The required monitoring period in pivotal studies of DT120 is 8 hours and requires that participants clear the End of Session Checklist. EOSC: End of Session Checklist Phase 2 Study Pivotal-Stage Studies Expansive Research-oriented Checklist Patient-reported physical status Patient-reported mental status Assessed mental status (7 criteria) Sensory & Psychomotor status (5 criteria) DSM-5 Criteria for Hallucinogen Intoxication (9 criteria) Practice-oriented End of Session Checklist EOSC intended to inform & reflect requirements under potential REMS program Refined based on discussions with the FDA 8 Item Scale 23 Total Criteria 5-8 Hour Monitoring via EOSC2 to Inform Real-World Conditions of Safe Use 8-12 Hour Research Monitoring to Inform Phase 3 Study Design1
Investor & Analyst Day | April 2026 Few Comments on Methodology & Research with Psychedelic Treatments Functional Unblinding Comparator Controls Population
Accelerating DT120 ODT on a Disciplined Path to NDA Submission 1. Study MMED008 internal study documents and calculations. Comparisons to standard of care/other drug classes based on historical comparison not head-to-head comparison trial. NDA: new drug application; ODT: orally disintegrating tablet FDA Breakthrough Therapy Designation Phase 2b demonstrated substantial improvement over current therapies1 Phase 3 program in alignment with FDA guidance Phase 3 study designs mirror positive Phase 2b study Investor & Analyst Day | April 2026 Ready for Expeditious Path to Submission upon Phase 3 completion Studies designed to demonstrate standalone drug effect
DT120 ODT Phase 3 Data Expectations
Preview of Emerge Topline Readout Investor & Analyst Day | April 2026 Drug response : Placebo-adjusted change: Disposition, Demographics & Baseline characteristics Adverse events & suicidality (C-SSRS) Duration of session Time to inefficacy (i.e., return of moderate+ symptoms) Maintenance of MADRS improvement Retreatment patterns Primary outcome: MADRS at Week 6 Select secondary outcomes through Week 12 Trial & Design Efficacy Safety Dosing Session Dynamics Preliminary Outcomes from Extension Phase C-SSRS: Columbia-Suicide Severity Rating Scale; MADRS: Montgomery-Åsberg Depression Rating Scale
Investor & Analyst Day | April 2026 Putting the Numbers in Perspective1 GAD Placebo adjusted changes in HAM-A MDD Placebo adjusted changes in MADRS The information presented in this slide on comparative treatments is derived from multiple clinical trials, each conducted under distinct protocols and settings. As such, these data may not be directly comparable due to the lack of a head-to-head comparison. Differences in trial design, patient demographics, and other variables may account for variations in the observed outcomes. Study results for each drug are intended to be representative, however, multiple trials of the approved treatments. Based on Phase 3 clinical trial protocols and SSRE results. Data on file. Median placebo-adjusted change of comparative treatments for GAD (see slide 19) Median placebo-adjusted change of comparative treatments for depression symptoms (see slide 20) R Robison, JAMA. 2025 Sep 4; e2513481. doi:10.1001/jama.2025.13481 MADRS change from Baseline to week 12 was a secondary endpoint in Study MMED008. -3.6 SRIs -3.8 Benzodiazepines -1.7 Buspirone 5.0 3.23 7.7 6.46 3.94 3.0 4.0 1.8 – 2.4 Minimum Detectable Difference2 Latest Generation of Comparative Treatments Phase 3 Powering Assumption2 Phase 2b Results in GAD5 We believe a 4.0+ point placebo-adjusted difference, along with safety and durability, could represent a best-in-class profile 1 2 3 4 5 6 7 8 Improvement
A Patient’s Perspective on the DT120 Experience
Panel Discussion
Investor & Analyst Day Speakers Investor & Analyst Day | April 2026 Dan Karlin, MD Chief Medical Officer Andrew Penn, MS, PMHNP Brittany Albright, MD, MPH, DABOM Shannon Sarkar, PhD, LPC, NCC Chief Medical Officer Definium Psychiatrist, Addiction Psychiatry Sweetgrass Psychiatry Medical University of South Carolina Psychiatric-Mental Health Nurse Practitioner Salma Health UCSF Licensed Professional Counselor Here We Go Therapy Missouri Baptist University External speakers have been compensated by Definium for their participation in today’s discussion.
Matt Wiley, CCO DT120 ODT Commercial Strategy
Investor & Analyst Day | April 2026 The Building Blocks for DT120 Commercial Success Are in Place Our Time to Execute Providers are Primed for Adoption Positive Payor Indications Patients Want Better
Investor & Analyst Day | April 2026 The Near-Term Opportunity & Launch Source: Ringeisen, H., et al. (2023). Mental and Substance Use Disorders Prevalence Study (MDPS): Findings Report, Zhou, Y,. Et al. (2017). Nature. Comorbid generalized anxiety disorder and its association with quality of life in patients with major depressive disorder. RTI International and current U.S. Census data and internal company estimates. Veeva COMPASS Open Claims Analysis Data on File, 2017 – 2025. 50 million US Adults with GAD / MDD 26 million Diagnosed with GAD / MDD 13 million Rx Treated 4.2 million Failed by 2+ Rx Strong Patient Desire & Willingness Large & Expanding Treatment Network Payer Understanding & Intent Large & Growing Unmet Need We see a significant near-term commercial opportunity in a well-defined, high unmet-need population
Investor & Analyst Day | April 2026 Launch is Only the Starting Point for a Broader DT120 Market Opportunity 50 million US Adults with GAD / MDD 26 million Diagnosed with GAD / MDD 13 million Rx Treated 4.2 million Failed by 2+ Rx Increased screening & awareness Increased treatment of mental health disorders Removal of access barriers Source: Ringeisen, H., et al. (2023). Mental and Substance Use Disorders Prevalence Study (MDPS): Findings Report, Zhou, Y,. Et al. (2017). Nature. Comorbid generalized anxiety disorder and its association with quality of life in patients with major depressive disorder. RTI International and current U.S. Census data and internal company estimates. Veeva COMPASS Open Claims Analysis Data on File, 2017 – 2025. We are planning for an ambitious growth in the market to achieve our long-term mission
Investor & Analyst Day | April 2026 Psychiatry Continues to Evolve Toward Faster, More Targeted Intervention1-5 Institution-centered care Limited care in asylums. Early ECT, sedatives Pharmacology-based treatment Medication options in outpatient setting. TCAs, MAOIs, antipsychotics Transformative care Rapid-acting inpatient treatments with durable results. Esketamine, psychedelics, including DT120 Custodial System Outpatient Shift Episodic Care Precision Approach Pre-1950s 1950-1970 1980-Early 2000s 2005-2019 2020-Today Directly targets brain circuitry. VNS, TMS Chronic Disease Model Office-based psychiatry Medical treatments with psychotherapy. SRIs Interventional & digital emergence 1. Potash JB et al. Psychiatr Res Clin Pract. 2025;7(2):80-90; 2. Karrouri R et al. World J Clin Cases. 2021;9(31):9350-9367; 3. Williams NR et al. J Clin Psychiatry. 2014;75(8):895-7; 4. Backman I. The Rise of Interventional Psychiatry. Accessed: Apr 16 2026. https://medicine.yale.edu/news/yale-medicine-magazine/article/the-rise-of-interventional-psychiatry/; 5. Robison R et al. JAMA. 2025;334(15):1358-1372. ECT: electroconvulsive therapy; MAOIs: monoamine oxidase inhibitors; SRI: serotonin reuptake inhibitors (including selective serotonin and selective serotonin and norepinephrine reuptake inhibitors); TCAs: tricyclic antidepressants; TMS: transcranial magnetic stimulation; VNS: vagus nerve stimulation From medication to devices, psychiatry has continually embraced innovation to expand treatment options
Investor & Analyst Day | April 2026 Despite Limitations, New Classes in Psychiatry Have Represented Major Market Opportunities $6.3B1 $ 6.2B1 $3-3.5B2 $ 5.4B1 $ 7.4B1 $ 6.6B1 $ 8.8B1 $ 4.3B1 Peak annual sales estimates. Peak sales from Evaluate Pharma, includes 3% annual inflation adjustment for drugs with peak years prior to 2025. Calculations on file. Johnson&Johnson Earnings Guidance, April 2025. Axsome Therapeutics February 2026 corporate presentation. All trademarks are property of their respective owners. We believe psychedelics could be the next significant class of treatments in psychiatry $ 7.1B1 $1-3B3 SSRIs Glutamatergics Atypical Antipsychotics SNRIs
Investor & Analyst Day | April 2026 Limitations of Current SOC Leads to Medication Cycling and Patient Discouragement Sources: Clarivate analysis 2022 GAD Patient Journey, July 2022 (n=16 Clinicians n=24 Patients) Depression Patient Journey, November 2023 (n=16 Clinicians n=24 Patients) ECT: electroconvulsive therapy; PCP: primary care physician; SSRI: Selective Serotonin Reuptake Inhibitor; SNRI: serotonin and norepinephrine reuptake inhibitors; TMS: Transcranial Magnetic Stimulation Maintenance Hope Frustration GAD Struggling in silence MDD Persistent worry for years Ongoing treatment to sustain symptom control SSRI/SNRI ± adjunctive treatments (e.g., benzodiazepine) When GAD and MDD coexist, depression is often prioritized—leaving anxiety insufficiently addressed Symptoms Treatment Initiation First line SSRI/SNRI ± therapy Cycling Switching, augmentation, trial and error over months Diagnosis PCP or specialist confirms diagnosis and initiates plan Unresolved Symptoms Current treatments do not address root issue Comorbid Diagnoses Unresolved symptoms often lead to secondary diagnoses Desperation Lack of energy, no enjoyment in life, social withdrawal Treatment Resistance Session-Based Treatment SSRI/SNRI ± adjunctive treatments (e.g., atypical antipsychotics) Desperation ECT, TMS, Spravato® Struggling in silence Hope Frustration
Patients With MDD and/or GAD Are Coping— They Are Not Satisfied With the Efficacy of Their Medications Source: Definium market research, on file. Investor & Analyst Day | April 2026
Investor & Analyst Day | April 2026 Most Patients Quit Current Treatments within 6 Months Source: Veeva Compass Patient - Claims Analysis Covering 2017-2025 All trademarks are property of their respective owners. Physicians contend with patients leaving treatment due to side effects, inefficacy, and schedule constraints Discontinuation punctuates patient journey frustrations Payers pay for therapeutic interventions that are not sustained 50 Key Insights on Early Treatment Persistence Impacts Impacts Key Insights on Early Treatment Persistence Month
Growing Psychiatrist Awareness and Positive Sentiment Support DT120 Adoption Potential Psychiatrist Perception of DT120 1. GAD Demand Study 2024 Among Total HCP Respondents (n=273). Percentage based on top 3 box (scale 1-7) 2. DT120 Awareness and Perception Tracking: Wave 3, 2026. Total prescribers (n=135). HCP: healthcare professional; MOA: mechanism of action 58% HCPs surveyed have positive views of DT120 profile1 HCPs cite quick onset of action, symptom resolution, response and MOA as top attributes1 Awareness of DT120 has sharply increased from 27% to 64% in the last two waves of research (2024 to 2026)2 5 - 7 Positive 3 - 4 Neutral 1 - 2 Hesitant Investor & Analyst Day | April 2026 51 Psychiatrist Perception of Psychedelic Treatments2
Strong In-Practice Intent Among High-Priority HCPs 1. GAD Target Validation Market Research, 2025. High-priority HCPs represent deciles 7-10 of GAD prescribers. In the conduct of market research, DT120 was blinded as “Treatment X” to respondents. D B I would prescribe and administer this treatment in my practice I would refer out this treatment I would only discuss if a patient brought up this treatment DT1201 *No respondents selected would not consider I prescribe and administer this treatment in my practice Refer out for esketamine Refer out for evaluation (without specifying esketamine in referral) Esketamine1 Investor & Analyst Day | April 2026 52
Investor & Analyst Day | April 2026 DT120 Appeal in Treatment-Experienced Patients Source: Definium market research on file.
One-time oral dosing DT120’s first-in-class anxiolytic MoA Rapid onset of efficacy + durability of effect Key Strengths of DT120 Value Proposition Align with Payer Preferences Source: Definium market research on file. Key Strengths Noted in Payer Engagements Investor & Analyst Day | April 2026 54
DT120 Reimbursement Outlook Is Anchored by Spravato® Precedent Source: Definium Market Research on File; Disclaimer: Definium finds it prudent to understand the economic ramifications of DT120 across multiple stakeholders. However, Definium has no intention of marketing the economic merits of its drug. Any discussions or analyses regarding the economic impact are solely for internal understanding and strategic planning purposes. This information should not be construed as promotional material or an endorsement of the drug’s economic benefits. Esketamine Rx Approvals (Total Rx - 2025) 86% 86% 89% Payer Insights on Pricing & Access Payers reference Spravato as the primary price analog Payers indicate expectation that FDA-approved psychedelic treatments will be covered Payers expect to manage use of DT120 with prior authorizations in line with other branded psychiatric products Investor & Analyst Day | April 2026 55
Predictive Analytics Help Focus Resources Where Adoption Potential Is Highest Priority GAD / MDD Prescribers Data-Driven Deployment Prioritizes the Highest-Value Prescriber Opportunities OR Investor & Analyst Day | April 2026
We Aspire to Provide the Best Support Patients Have Ever Experienced Standard components of patient and HCP support services that are being considered for DT120 launch. HCP Field Infrastructure Medical Support Access Support Site of Care Support Patient Field Sales HUB Model REMS Patient Support Affordability Support for Patients Case Management 1 2 3 4 5 6 Trade and Distribution Benefits Investigation and PA Support Investor & Analyst Day | April 2026 57
Modest Adoption in Target Population Supports Blockbuster Revenue Opportunity Investor & Analyst Day | April 2026 Source: Claims Analysis Data on File, 2026 Assuming median Spravato® surrogate pricing range; the price of DT120 has not been established. Range is based on Spravato surrogate low dose, low frequency ($28k) to high dose, high frequency ($70k) annually. Market Research, Data on file, 2026 All trademarks are property of their respective owners. 4.2 million patients have been failed by 2 or more treatments1 $2 billion revenue opportunity per 1% penetration2 Potential Revenue (billions) $2.8B $4.9B $7.0B At $28k annual price At $49k annual price At $70k annual price Potential Value ($B) for every 100,000 patients treated with DT1203
Brandi Roberts, CFO Building Long-Term Shareholder Value
Section 505 of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. § 355. Definium’s currently-pending applications related to DT120 ODT will, if granted, have 20-year expiration dates between 2042 and 2044, not accounting for any reductions or extensions term which may be applicable, such as terminal disclaimers, Patent Term Adjustment, or Patent Term Extension. ODT: oral dissolving tablet; PK: pharmacokinetics; PD: pharmacodynamics PK: pharmacokinetic; PD: pharmacodynamic; ODT: orally disintegrating tablet; Investor & Analyst Day | April 2026 +1y +2y +3y +4y +9y +5y +7y … 2043+ New Chemical Entity Exclusivity 30-Month Stay Potential Patent Protection Method of Use / Method of Treatment: Treatment of a Disorder Delivery: Delivery Method, PK / PD Drug Product: Method of Manufacture/Process API: Polymorph, Salt Form Supply chain availability Exclusive rights to key technology Lifecycle management with improved product performance Trade secrets & know-how Differentiated product performance Differentiated combination (drug and/or device products) Additional Potential Protections Regulatory Protection1 2 DT120 ODT Launch
Investor & Analyst Day | April 2026 What We Believe Large market opportunities Patients want better options Ability to make an impact at scale First new GAD drug approval since 2007 Why We’re Positioned for Success Compelling Phase 2b results Rigorous Phase 3 program Differentiated strategy & execution Experienced, credible team What to Watch Multiple anticipated 2026 topline Phase 3 data readouts: Emerge (late 2Q 2026) Voyage (early 3Q 2026) Panorama (late 3Q 2026) Ascend Phase 3 study execution Evolution of commercial organization DT120 Represents a Transformational Opportunity 1 2 3 Strong financial position with $411.6M in cash, cash equivalents and investments at December 31, 20251 Cash runway expected to extend into 2028 based on the Company’s current operating plan and anticipated milestones. GAD: generalized anxiety disorder; MDD: major depressive disorder; ODT: oral dissolving tablet
Value Creation Opportunity Shaped by Two Distinct Drivers1 Timing estimates subject to clinical progress and regulatory interactions. ASD: autism spectrum disorder; GAD: generalized anxiety disorder; TLR: topline data readout Clinical & Regulatory Execution 2026 2027 2028 Commercial Execution Value Creation Expanding Site of Care Engagement & Commercial Footprint Accelerating Scheduling & Reimbursement Optimizing Patient Care Model Emerge TLR Voyage TLR Initial DT402 Data in ASD Panorama TLR Potential Pipeline Expansion Ascend TLR Commercial Launch GAD & MDD Investor & Analyst Day | April 2026
Q&A Session Key Anticipated Readouts: Emerge (MDD) Topline Readout | late 2Q 2026 Voyage (GAD) Topline Readout | early 3Q 2026 Panorama (GAD) Topline Readout | late 3Q 2026 Ask a Question