Definium Therapeutics, Inc. · NASDAQ:DFTX
Definium Therapeutics — Mind Medicine (MindMed) — Technical Presentation (December 2023)
43 slides from Definium Therapeutics's technical presentation, Dec 14, 2023
Slide 1: MM-120 for Generalized Anxiety Disorder Phase 2b Topline Data
Exhibit 99.2 MM-120 for Generalized Anxiety Disorder (GAD) Phase 2b Topline Data December 2023
Slide 2: Disclaimer
Disclaimer This presentation (the “Presentation”) has been prepared by Mind Medicine (MindMed) Inc. (“MindMed” or the “Company”) solely for informational purposes. Any trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be c
Slide 3: Today's Agenda
Today’s Agenda Speaker Topic Introduction Schond Greenway - Chief Financial Officer Summary of Phase 2b GAD Trial Results Rob Barrow - Chief Executive Officer Phase 2b GAD Trial Results Analysis Dan Karlin, MD - Chief Medical Officer MM-120 Development Plan Rob Barrow - Chief Executive Officer Summa
Slide 4: Summary of Phase 2b GAD Trial Results
MM-120 Summary of Phase 2b LSD D-tartrate GAD Trial Results for Generalized Anxiety Disorder (GAD) December 2023 4 Topline Data from Study MMED008
Slide 5: Potential to Address a Large Unmet Need in GAD
MM-120 | Potential to Address a Large Unmet Need in GAD Opportunity in Generalized Anxiety Disorder (GAD) 1 • GAD is the 2nd most common mental disorder among adults , yet Potential Best-in-Class there are limited treatment options Therapy with Novel MOA • Symptoms may be debilitating and treatment
Slide 6: Summary of Topline Phase 2b Results
1 Summary of Topline Phase 2b Results • Met the primary endpoint with statistical significance; MCP-Mod analysis results support dose-response relationship for MM-120 in GAD 2,3 • Large observed effect size of d=0.88 at 100 µg dose level is more than double the standard of care • Statistically and c
Slide 7: Large Observed Effect Size is Over Double the Standard of Care
1 Large Observed Effect Size is Over Double the Standard of Care 1 Reported Effect Size in Generalized Anxiety Disorder Key Highlights of Phase 2b Results 2 ▶ Maximum observed effect size of MM-120 100 µg 0.88 0.88 is more than double the 2,3 2 standard of care MM-120 200 µg 0.64 ▶ Rapid and durable
Slide 8: Phase 2b GAD Trial Key Design Elements
MM-120 Phase 2b GAD Trial LSD D-tartrate Key Design Elements for Generalized Anxiety Disorder (GAD) December 2023 8 Topline Data from Study MMED008
Slide 9: Phase 2b Trial Design Overview
1 Phase 2b Trial Design Overview • Standard GAD study design with endpoints that have supported registration for approved drugs • Randomized, double-blind, placebo-controlled, 12-week trial o Single administration of MM-120 or placebo o No psychotherapeutic intervention o Trial design closely aligne
Slide 10: Phase 2b Trial Design Overview
1 Phase 2b Trial Design Overview PSYCHIATRY | MM-120 (LSD D-tartrate) | Indication: GAD | PHASE 2b Study MMED008 | MM-120 for GAD 198 participants total (actual) A Phase 2b Dose Optimization Study of a -5 to -1 1 2 4 8 12 Week Single Dose of MM-120 in Generalized Anxiety Disorder Screening Dose Foll
Slide 11: Details of Phase 2b Treatment Delivery Protocol
1 Details of Phase 2b Treatment Delivery Protocol • Designed to demonstrate drug-only effect with no psychotherapeutic intervention 2 • Delivery protocol consistent with 2023 FDA Draft Guidance • No planned changes to delivery protocol from Phase 2 to Phase 3 Pre-treatment During treatment Post-trea
Slide 12: Phase 2b GAD Trial Results Analysis
MM-120 Phase 2b GAD Trial LSD D-tartrate Results Analysis for Generalized Anxiety Disorder (GAD) December 2023 12 Topline Data from Study MMED008
Slide 13: Phase 2b GAD Participant Disposition
1 Phase 2b GAD Participant Disposition - Included in FAS population: 100% 200 µg - Completed 4 weeks (n=39) (n=40) - Discontinued at any time (n=8) 97.5% 4-week completion rate - Included in FAS population: 100% 2 100 µg in high dose groups despite need for follow- - Completed 4 weeks (n=39) (n=40)
Slide 14: Demographics and Baseline Characteristics
1 Demographics and Baseline Characteristics Participant demographics and baseline characteristics generally balanced across groups MM-120 Placebo Demographic (n=194) 25 µg 50 µg 100 µg 200 µg (n=39) (n=36) (n=40) (n=40) (n=39) Mean age (years) 38.0 45.3 42.7 42.1 38.7 Sex, female (%) 51.3% 55.6% 40.
Slide 15: Primary Endpoint: Change in HAM-A Score through Week 4
1 Primary Endpoint | Change in HAM-A Score through Week 4 Statistically and clinically significant reductions in HAM-A score at all timepoints through week 4 in 100 and 200 µg dose groups HAM-A Change from Baseline 0 Change to Week 4 ▶ 100 µg: -21.3 points ▶ 200 µg: -19.3 points -5 Improvement over
Slide 16: Exploratory Endpoint: HAM-A Response and Remission at Week 4
1 Exploratory Endpoint | HAM-A Response and Remission at Week 4 Dose-dependent increases in response with 78% responders in 100 and 200 µg dose groups; 50% of participants achieved remission in 100 µg dose group 2 2 HAM-A Response Rate at Week 4 HAM-A Remission Rate at Week 4 60 90 50 78 78 80 50 70
Slide 17: Primary Analysis: MCP-Mod of HAM-A
1 Primary Analysis | Multiple Comparison Procedure – Modeling (MCP-Mod) of HAM-A Statistically significant dose-response relationship with identification of target therapeutic range 2 Key Takeaways from MCP-Mod Analysis ▶ Statistically significant dose response relationship with multiple model fits
Slide 18: Secondary Endpoint: Clinical Global Impressions – Severity
1 Secondary Endpoint | Clinical Global Impressions – Severity (CGI-S) Statistically significant reductions in Clinical Global Impressions of Severity (CGI-S) scale through Week 4 in 100 and 200 µg dose groups 2 CGI-S Improvement in 100 and 200 µg Groups CGI-S Scores 6 – Severely Ill ▶ Statistically
Slide 19: Secondary Endpoint: Change in Comorbid Depression Scores (MADRS)
1 Secondary Endpoint | Change from Baseline in Comorbid Depression Scores (MADRS) 2 Statistically and clinically significant reductions in MADRS score at all timepoints through week 4 in 100 and 200 µg dose groups 2 MADRS Change from Baseline 0 Change to Week 4 -2 ▶ 100 µg: -18.1 points -4 ▶ 200 µg:
Slide 20: Safety Overview
1 Safety Overview MM-120 was well-tolerated with mostly transient, mild-to-moderate adverse events consistent with drug class expectations • Virtually all AEs (>98%) were mild-to-moderate in severity Favorable tolerability 2 • Minimal (2.5%) TEAEs led to study withdrawal (none in high dose groups )
Slide 21: Most Common TEAEs On Dosing Day
1,2 Most Common TEAEs On Dosing Day (>10% in High Dose Groups) MM-120 was well-tolerated across all dose groups with mostly transient, mild-to-moderate adverse events MM-120 Placebo Preferred Term 25 µg 50 µg 100 µg 200 µg Subjects (%) with AE (n=39) (n=40) (n=40) (n=40) (n=39) Illusion 12 (30.8) 18
Slide 22: Most Common TEAEs
1,2 Most Common TEAEs (>10% in High Dose Groups) MM-120 was well-tolerated across all dose groups with mostly transient, mild-to-moderate adverse events MM-120 Placebo Preferred Term 25 µg 50 µg 100 µg 200 µg Subjects (%) with AE (n=39) (n=40) (n=40) (n=40) (n=39) Illusion 12 (30.8) 18 (45.0) 24 (60
Slide 23: MM-120 Development Plan
MM-120 MM-120 Development Plan LSD D-tartrate for Generalized Anxiety Disorder (GAD) December 2023 23 Topline Data from Study MMED008
Slide 24: Multiple Studies Support Phase 3 Development of MM-120
Multiple Studies Support Phase 3 Development of MM-120 1 • Achieved goals of Phase 2 development o Characterized dose-response to inform dose selection in GAD o Achieved large, statistically significant and clinically meaningful effect in GAD o Showed rapid and durable therapeutic benefits on valida
Slide 25: MM-120 Development Pathway
MM-120 Development Pathway • Key design elements expected to be consistent between Phase 2b and Phase 3 studies o Hamilton Anxiety Scale (HAM-A) at week 4 expected primary endpoint o Limited changes to key inclusion/exclusion criteria o No planned change in dosing session monitoring protocol • Two P
Slide 26: Next Steps and Anticipated Milestones for MM-120 Program
Next Steps and Anticipated Milestones for MM-120 Program Q4 2023 Q1 2024 Q3 2024 Q4 2024 Q2 2024 MM-120 GAD MM-120 GAD MM-120 GAD Phase 2b Phase 2b Full data presentation at scientific meeting 4-wk Topline 12-wk Topline MM-120 GAD Zydis ODT PK Bridging Data MM-120 GAD EOP2 meeting MM-120 GAD Phase 3
Slide 27: Q&A
Q&A December 2023 27 Topline Data from Study MMED008
Slide 28: Appendix – Phase 2b GAD Study
Appendix – Phase 2b GAD Study December 2023 28 Topline Data from Study MMED008
Slide 29: Phase 2b Trial Design Aligns with Subsequent FDA Draft Guidance
1 Phase 2b Trial Design Aligns with Subsequent FDA Draft Guidance FDA issued 2023 draft guidance on clinical trials with psychedelic drugs • Provides clarity on regulatory expectations and R&D considerations • Guidance will “help researchers design studies that will yield interpretable results 1 tha
Slide 30: Primary Endpoint: HAM-A Score over Time
1 Primary Endpoint | HAM-A Score over Time Statistically and clinically significant reductions in HAM-A score at all timepoints through week 4 in 100 and 200 µg dose groups MM-120 Placebo Timepoint 25 µg 50 µg 100 µg 200 µg 2 Mean (SD) HAM-A score (n=39) (n=36) (n=40) (n=40) (n=39) Baseline 30.2 (6.
Slide 31: Exploratory Endpoint: HAM-A Response Rates over Time
Exploratory Endpoint | HAM-A Response Rates over Time 75% or greater HAM-A Response Rate achieved in 100 µg dose group from Weeks 1-4 2 HAM-A Response Rate over Time 90 78 78 78 78 80 75 70 58 60 54 53 51 51 50 47 50 38 40 33 31 30 20 10 0 Week 1 Week 2 Week 4 Placebo 25 μg 50 μg 100 μg 200 μg p-val
Slide 32: Secondary Endpoint: CGI-S through Week 4
1 Secondary Endpoint | Clinical Global Impressions – Severity through Week 4 Statistically significant reductions in Clinical Global Impressions of Severity (CGI-S) scale at all timepoints through Week 4 in 100 and 200 µg dose groups 2 CGI-S Scores Over Time 6 – Severely Ill 5 – Markedly Ill 4 – Mod
Slide 33: Primary Endpoint: Change in HAM-A Score through Week 4
1 Primary Endpoint | Change in HAM-A Score through Week 4 Statistically and clinically significant reductions in HAM-A score at all timepoints through week 4 in 100 µg dose group 2 HAM-A Scores Over Time 50 45 40 35 30 25 20 15 10 5 0 Baseline Week 1 Week 2 Week 4 p-values not displayed 1. Source: S
Slide 34: Secondary Endpoint: Comorbid Depression Scores (MADRS) over Time
1 Secondary Endpoint| Comorbid Depression Scores (MADRS) over Time 2,3 Statistically and clinically significant reductions in MADRS score at all timepoints through week 4 in 100 and 200 µg dose groups MM-120 Placebo Timepoint 25 µg 50 µg 100 µg 200 µg 2 Mean (SD) MADRS score (n=39) (n=36) (n=40) (n=
Slide 35: Comorbid Depression Scores (MADRS) over Time in 100 µg Dose Group
1 Secondary Endpoint | Comorbid Depression Scores (MADRS) over Time in 100 µg Dose Group 2,3 Comorbid depressive symptoms in GAD improved through week 4 with 75% meeting remission and >75% responders 2 MADRS Scores Over Time 50 45 40 35 30 25 20 15 10 5 0 Baseline Week 1 Week 2 Week 4 p-values not d
Slide 36: Most Common TEAEs with ≥10% Incidence in Any Dose Group
1 Most Common TEAEs with ≥10% Incidence in Any Dose Group MM-120 Placebo Preferred Term Subjects (%) with AE 25 µg (n=39) 50 µg (n=40) 100 µg (n=40) 200 µg (n=40) (n=39) Illusion 12 (30.8) 18 (45.0) 24 (60.0) 30 (75.0) 3 (7.7) Hallucination, visual 6 (15.4) 9 (22.5) 9 (22.5) 6 (15.0) 1 (2.6) Euphori
Slide 37: Appendix – Intellectual Property
Appendix – Intellectual Property December 2023 37 Topline Data from Study MMED008
Slide 38: Multiple Layers of Intellectual Property and Barriers to Entry
1 MM-120 | Multiple Layers of Intellectual Property and Barriers to Entry 2 Regulatory Barriers New Chemical Entity Exclusivity 30-Month Stay +1y +2y +3y +4y +5y +7y +9y … 2043+ MM-120 Launch Patent Protection API: Polymorph, Salt Form Method of Use / Method of Treatment: Treatment of a Disorder Dru
Slide 39: Multipronged Market Protection Strategies
MM-120 | Multipronged Market Protection Strategies 1 • Highlights of Patent Protection Strategy o Methods of treating GAD o Stability and methods of manufacturing for API (salt form and polymorphs) o Improved product performance with faster absorption, less variability and potential shorter duration
Slide 40: Intellectual Property Portfolio Highlights
MM-120 | Intellectual Property Portfolio Highlights 1 1 1 2 Patent / Application Title / Overview Status Estimated Expiration Provisional TBD [Claims based on pharmacokinetic findings from ODT bridging study] 2043 Application Provisional TBD [Claims based on pharmacodynamic findings from ODT bridgin
Slide 41: Recent Addition to Intellectual Property Portfolio
MM-120 | Recent Addition to Intellectual Property Portfolio • Exclusive license agreement with Catalent for its patented Zydis® 1 fast-dissolve technology for use with MM-120 o Exclusive rights for the use of the Zydis® technology to develop all salt and polymorphic forms of lysergide in the U.S., U
Slide 42: Strong Innovative Intellectual Property Moat for Incumbency Position
MM-120 | Strong Innovative Intellectual Property Moat for Incumbency Position 505(b)(1) 505(b)(2) 505(j) ANDA / Generic Original “Standalone” NDA “Follow-on” NDA 1 Description• Contains full reports of investigations of safety • Contains full reports of investigations of safety and • Generally dupli
Slide 43: Benefits of a New Chemical Entity (NCE) First Filer
MM-120 | Benefits of A New Chemical Entity (NCE) First Filer 1 Expected Protection for MM-120 with NCE Filing Status Submission Package for NCE Initial Filer Legal/Regulatory Exclusivity • Lysergide has not been previously approved, enabling NCE status; key differentiator versus Full NDA package. Al
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