Definium Therapeutics, Inc. · NASDAQ:DFTX
Definium Therapeutics — Mind Medicine (MindMed) — Investor Presentation (March 2024)
44 slides from Definium Therapeutics's investor presentation, Mar 7, 2024
Slide 1: MM120 for GAD Investor Presentation March 2024
Exhibit 99.2 MM120 for GAD Investor Presentation March 2024
Slide 2: Disclaimer
Disclaimer This presentation (the “Presentation”) has been prepared by Mind Medicine (MindMed) Inc. (“MindMed”, the “Company”, “we”, “our” or “us) solely for informational purposes. None of MindMed, its affiliates or any of their respective employees, directors, officers, contractors, advisors, memb
Slide 3: Introductory Remarks
Introductory Remarks Robert Barrow Chief Executive Officer
Slide 4: We Aim To Be A Global Leader In Brain Health
We Aim To Be A Global Leader In Brain Health Pipeline Management Diversified pipeline of clinical Expertise in drug programs targeting development and significant unmet medical needs commercialization Research Expected Runway Leveraging decades of preclinical and Expected cash runway through key cli
Slide 5: MindMed Research & Development Pipeline
MindMed Research & Development Pipeline Product Candidate Indication Preclinical Phase 1 Phase 2 Phase 3 Registration Psychiatry Programs Generalized Anxiety MM120 1 Disorder (GAD) (Lysergide D-tartrate) Additional Psychiatric 2 Indication MM402 Autism Spectrum 1 Disorder (ASD) (R(-)-MDMA) Early Res
Slide 6: MM-120 Has the Potential to Address a Large Unmet Need in GAD
MM-120 Has the 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 , Potential Best-in-Class yet there are limited treatment options Therapy with Novel MOA • Symptoms may be debilitating and trea
Slide 7: Key Highlights of MM-120 Updates
Key Highlights of MM-120 Updates 1 Positive 12-Week Durability in Phase 2b Trial of GAD • Primary and secondary endpoints met with statistical significance • 7.7-point improvement over placebo (d=0.81; p=0.003) • 48% clinical remission rate at Week 12 2 Enhanced Product Profile with MM-120 ODTs • Di
Slide 8: Results for MM120 in GAD Delivered on Target Product Profile
Results for MM120 in GAD Delivered on Target Product Profile after 1,2 Single Dose with Significant Improvement in All Endpoints Fast Acting 1.8-point reduction in CGI-S within 24 hours (p<0.0001) 21.9-point improvement in HAM-A at Week 12 (p=0.003) Durable Activity represents further improvement fr
Slide 9: 12-Week Durability Observed with Effect Size Over Double the Standard of Care
12-Week Durability Observed with Effect Size Over Double the 1,3 Standard of Care Key Highlights of Phase 2b Comparative Effect Sizes in GAD 12 Week Results • Maximum observed effect size 2 MM120 100 µg 0.81 of 0.81 is more than double 2,3 the standard of care 4 Benzodiazapines 0.38 • Rapid and dura
Slide 10: PK Bridging Study Demonstrates Enhanced Product Profile for MM120 ODTs
PK Bridging Study Demonstrates Enhanced Product Profile for MM120 ODTs 1 Comparative PK Profile 2.5 MM120 Capsule Differentiated Performance of MM120 ODTs MM120 ODT 2 2 50% faster onset of action 1.5 3 17% improved bioavailability 1 4 0.5 23% increase in AUC at target conc. AUC 0 5 0 2 4 6 8 10 12 1
Slide 11: MM120 for GAD: Summary of Full Topline Results from Phase 2b Trial
MM120 LSD-D-tartrate for Generalized Anxiety Disorder (GAD) Summary of Full Topline Results from Phase 2b Trial Daniel R Karlin, MD, MA Chief Medical Officer
Slide 12: Positive 12-Week Topline Results from Phase 2b Study in GAD
Positive 12-Week Topline Results from Phase 2b Study in GAD: Strong 1 Durability of Effect after Single Dose of MM120 2 • Met the primary and all secondary endpoints with statistical significance • MCP-Mod analysis results support dose-response relationship for MM120 in GAD 3,4 • Large observed effe
Slide 13: Phase 2b Trial Utilized Standard GAD Design and Endpoints
Phase 2b Trial of MM120 Utilized Standard GAD Design and Endpoints 1 and was Aligned with FDA Draft Guidance for Drug Class • Standard GAD study design with endpoints that have supported registration for approved drugs • Randomized, double-blind, placebo-controlled, 12-week trial o Single administra
Slide 14: Phase 2b Trial Schematic
1 Phase 2b Trial Schematic 198 participants total (actual) Study MMED008 | MM120 for GAD Week -5 to -1 1 4 8 12 2 A Phase 2b Dose Optimization Study of a Single Dose of MM120 in Dose Follow-Up Screening Generalized Anxiety Disorder MM120 200 µg KEY ENTRY CRITERIA MM120 100 µg • Men and Women • Ages
Slide 15: Phase 2b Treatment Paradigm: Standalone Drug Effects
Phase 2b Treatment Paradigm: Standalone Drug Effects with No 1 Psychotherapeutic Intervention • Dosing session monitors (DSMs) in the room provide no psychotherapeutic intervention 2 • Delivery protocol consistent with 2023 FDA Draft Guidance • No changes planned to drug delivery between Phase 2 and
Slide 16: Participant Disposition Aligned with Historical Expectations
1 Participant Disposition Aligned with Historical Expectations - Included in FAS population: 100% 200 µg - Completed 12 weeks (n=30) (n=40) - Discontinued early (n=10) 79% 12-week completion rate 2 in high dose groups despite need for follow-up - Included in FAS population: 100% 100 µg - Completed 1
Slide 17: Participant Demographics and Baseline Characteristics
Participant Demographics and Baseline Characteristics Generally 1 Balanced Across Groups MM120 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% 40.0% 70.0% 66.7% Race (% white) 84.6% 80.6% 9
Slide 18: Statistically and Clinically Significant Reductions in HAM-A Score
Week 12 Week 8 Week 4 Week 2 Week 1 Baseline Statistically and Clinically Significant Reductions in HAM-A Score 1,2 Continued at Week 12 HAM-A Change from Baseline 2 0 Change from Baseline • Week 4: -21.3 points • Week 12: -21.9 points -5 2 Improvement over Placebo -10 • Week 4: -7.6 pts, p=0.0004 •
Slide 19: Continued Response and Remission through Week 12
Continued Response and Remission through Week 12 with 65% 1 Clinical Responder Rate and 48% Clinical Remission Rate 2 2 HAM-A Response Rate at Week 12 HAM-A Remission Rate at Week 12 50 48 70 65 45 63 60 56 40 33 50 44 30 28 40 21 31 20 30 20 10 10 0 0 Placebo 25 µg 50 µg 100 µg 200 µg Placebo 25 µg
Slide 20: MCP-Mod Analysis Supports Dose Response Relationship
Primary & Key Secondary Analysis (MCP-Mod) Support Dose Response 1 Relationship for MM120 in GAD 2 Key Takeaways from MCP-Mod Analysis • Statistically significant dose response relationship with multiple model fits • Supports dose selection of 100 µg for subsequent studies in GAD • Pre-specified mod
Slide 21: Rapid and Sustained Improvements in CGI-S
Rapid and Sustained Improvements in Clinical Global Impressions – 1 Severity (CGI-S) Starting on Day 2 and Continuing through Week 12 2 CGI-S Improvement in 100 µg Group CGI-S Scores at Week 12 6 – Severely Ill • Statistically and clinically significant improvement by Day 2 5 – Markedly Ill and main
Slide 22: Significant Reductions in Comorbid Depression (MADRS)
Week 12 Week 8 Week 4 Week 2 Week 1 Baseline Statistically and Clinically Significant Reductions in Comorbid Depression 1,2 (MADRS) at All Timepoints through Week 12 3 MADRS Change from Baseline 0 2,3 Change from Baseline • Week 4: -18.1 points • Week 12: -18.7 points -5 2,3 Improvement over Placebo
Slide 23: MM120 Well-tolerated with Mostly Transient, Mild-to-Moderate Adverse Events
MM120 was Well-tolerated with Mostly Transient, Mild-to-Moderate 1 Adverse Events Consistent with Drug Class Expectations • Virtually all AEs (99%) were mild-to-moderate in severity Favorable • Minimal (2.5%) TEAEs led to study withdrawal tolerability profile 2 • No drug-related serious adverse even
Slide 24: Most Common TEAEs in High-Dose Groups
Most Common (≥10%) TEAEs in High-Dose Groups Demonstrate 1,2 Favorable Tolerability Profile MM120 Preferred Term Placebo (n=39) 25 µg 50 µg 100 µg 200 µg (n=39) (n=40) (n=40) (n=40) Subjects (%) with AE DD AFT DD AFT DD AFT DD AFT DD AFT Illusion 12 (31) 1 (2.6) 18 (45) 1 (2.5) 24 (60) 1 (2.5) 30 (7
Slide 25: MM120 ODT PK Bridging Study
MM120 LSD-D-tartrate for Generalized Anxiety Disorder (GAD) MM120 ODT PK Bridging Study Daniel R Karlin, MD, MA Chief Medical Officer
Slide 26: PK Bridging Study Demonstrates Enhanced Product Profile for MM120 ODTs
PK Bridging Study Demonstrates Enhanced Product Profile for MM120 ODTs 1 Comparative PK Profile 2.5 MM120 Capsule Differentiated Performance of MM120 ODTs MM120 ODT 2 2 50% faster onset of action 1.5 3 17% improved bioavailability 1 4 0.5 23% increase in AUC at target conc. AUC 0 5 0 2 4 6 8 10 12 1
Slide 27: MM120 ODT PK Bridging Study Schematic
1 MM120 ODT PK Bridging Study Schematic Study MM120-101 | ODT-PK Bridging 29 participants total (actual) A Phase 1, Open-label Study to Compare the Pharmacokinetics of Day -21 to -1 1 2-13 14 15-29 Two Formulations of MM120 in Washout Dose 2 Follow-up Screening Dose 1 Healthy Volunteers MM120 MM120
Slide 28: Comparative PK of MM120 ODT vs Capsule
Comparative PK of MM120 ODT vs Capsule Demonstrates Favorable 1 Profile of MM120 ODTs 2.5 MM120 Capsule MM120 ODT MM120 MM120 1 2 PK Parameter Capsule ODT 1.5 T (hr) 2.25 2.0 max C (ng/mL) 2.63 2.68 max 1 AUC (ng*hr/mL) 15.7 18.7 0-∞ 0.5 AUC (ng*hr/mL) 9.7 12.0 >1ng/mL 0 0 2 4 6 8 10 12 14 16 18 20
Slide 29: MM120 ODT Demonstrates Faster Absorption
MM120 ODT Demonstrates Faster Absorption and Shorter Time to Reach Target Concentrations 1.2 MM120 Capsule 1 MM120 ODT Differentiated PK Profile of MM120 ODTs 1 2 50% faster onset of action 0.8 0.6 3 17% improved bioavailability 0.4 4 0.2 23% increased AUC above target conc. AUC 0 0 10 20 30 Time (m
Slide 30: MM120 ODT Demonstrates Improved Bioavailability
1 MM120 ODT Demonstrates Improved Bioavailability 1 Differentiated PK Profile of MM120 ODTs C max 2 50% faster onset of action GMR: 1.02 3 17% improved bioavailability AUC 0-∞ 4 GMR: 1.17 23% increased AUC above target conc. AUC 80% 100% 125% GMR Relative to Capsule 1. Company analysis of pharmacoki
Slide 31: MM120 ODT Achieves Increased AUC Above Target Concentration
MM120 ODT Achieves Increased AUC Above Target Concentration MM120 is Rapidly Absorbed 2.4 MM120 Capsule 1 Differentiated PK Profile of MM120 ODTs MM120 ODT 2.2 2 50% faster onset of action 2 1.8 3 17% improved bioavailability 1.6 1.4 4 23% increased AUC above target conc. AUC 1.2 1 0 2 4 6 8 Time (h
Slide 32: Summary Comments for MM120 Development Plan
Summary Comments for MM120 Development Plan Robert Barrow Chief Executive Officer
Slide 33: Multiple Studies Support Phase Development of MM120
Multiple Studies Support Phase 3 Development of MM120 1 • Achieved goals of Phase 2 development o Characterized dose-response to inform dose selection in GAD o Large, statistically significant and clinically meaningful effect in GAD o Rapid and durable therapeutic benefits on validated endpoint o St
Slide 34: MM120 Development Pathway
MM120 Development Pathway 1 • Two Phase 3 pivotal clinical trials in planning o 12-week randomized, placebo-controlled primary efficacy study design o Open-label extension to establish retreatment parameters o Expect to initiate Phase 3 development in the second half of 2024 • Key design elements ex
Slide 35: Next Steps and Anticipated Milestones for MM120 and Pipeline Programs
Next Steps and Anticipated Milestones for MM120 and Pipeline Programs Q1 2024 Q2 2024 Q3 2024 Q4 2024 MM120 GAD MM120 GAD Phase 2b / 12-wk Topline Full data presentation at scientific meeting MM120 GAD Zydis ODT PK Bridging Data MM120 GAD MM120 GAD Phase 3 initiation End-of-Phase-2 meeting w/FDA MM1
Slide 36: Q&A
Q&A 37 Investor Presentation | March 2024
Slide 37: Appendix
<<) MindMed Appendix
Slide 38: 65% HAM-A Response Rate Achieved at Week 12
1,3 65% HAM-A Response Rate (HAM-A) Achieved at Week 12 2 HAM-A Response Rate Over Time 90 78 78 78 78 80 75 70 68 70 65 63 58 60 56 54 53 51 51 50 49 50 47 44 44 38 40 33 31 31 31 30 20 10 0 Week 1 Week 2 Week 4 Week 8 Week 12 p-values not calculated Placebo 25 µg 50 µg 100 µg 200 µg 1. Source: Stu
Slide 39: 48% HAM-A Remission Rate Achieved through Week 12
1,3 48% Remission Rate (HAM-A) Achieved through Week 12 2 HAM-A Remission Rate Over Time 60 50 50 48 45 45 45 43 40 38 35 33 33 33 33 33 33 33 31 30 28 28 26 25 21 21 21 20 18 15 10 0 Week 1 Week 2 Week 4 Week 8 Week 12 p-values not calculated Placebo 25 µg 50 µg 100 µg 200 µg 1. Source: Study MMED0
Slide 40: Significant Improvement in CGI-S Score by Day 2
Statistically Significant Improvement in Clinical Global Impressions – Severity 1,2 (CGI-S) Score Achieved by Day 2 and Sustained through Week 12 CGI-S Scores Over Time 6 – Severely Ill 5 – Markedly Ill 4 – Moderately Ill * **** 3 – Mildly Ill **** ** **** **** * * * *** **** ** 2 – Borderline Ill 1
Slide 41: 65% Response Rate for Comorbid Depression Symptoms (MADRS)
65% Response Rate for Comorbid Depression Symptoms (MADRS) Achieved 1,3 through Week 12 2 MADRS Response Rate Over Time 90 80 78 80 70 70 70 70 65 65 63 58 60 55 54 53 51 50 50 47 46 44 44 44 44 41 40 33 33 33 28 30 20 10 0 Week 1 Week 2 Week 4 Week 8 Week 12 p-values not calculated Placebo 25 µg 50
Slide 42: 60% Remission Rate from Comorbid Depression Symptoms (MADRS)
60% Remission Rate from Comorbid Depression Symptoms (MADRS) 1,3 Achieved through Week 12 2 MADRS Remission Rate Over Time 90 78 80 70 70 63 63 60 60 60 55 55 49 48 48 50 47 46 44 42 42 41 41 39 38 38 40 33 31 28 28 30 20 10 0 Week 1 Week 2 Week 4 Week 8 Week 12 p-values not calculated Placebo 25 µg
Slide 43: Most Common TEAEs Across All Groups
1 Most Common (≥10%) TEAEs Across All Groups MM120 was well tolerated across all dose groups with mostly transient, mild to moderate adverse events MM120 Placebo (n=39) Preferred Term 25 µg 50 µg 100 µg 200 µg (n=39) (n=40) (n=40) (n=40) Subjects (%) with AE DD AFT DD AFT DD AFT DD AFT DD AFT Illusi
Slide 44: Most Common TEAEs Across All Groups (cont)
1 Most Common (≥10%) TEAEs Across All Groups (cont) MM120 was well tolerated across all dose groups with mostly transient, mild to moderate adverse events MM120 Placebo (n=39) Preferred Term 25 µg 50 µg 100 µg 200 µg (n=39) (n=40) (n=40) (n=40) Subjects (%) with AE DD AFT DD AFT DD AFT DD AFT DD AFT
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