Dyne Therapeutics, Inc. · NASDAQ:DYN
Dyne Therapeutics — Corporate Update (May 2024)
47 slides from Dyne Therapeutics's corporate update, May 20, 2024
Slide 1: Achieving the Promise of FORCE to Deliver for Patients
Exhibit 99.2 Achieving the Promise of FORCE to Deliver for Patients F O R C E ACHIEVE & DELIVER CLINICAL UPDATE | MAY 20, 2024
Slide 2: Forward-Looking Statements & Disclaimer
Forward-Looking Statements & Disclaimer This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding Dyne’s strategy, future operations
Slide 3: Program
Program Opening remarks John Cox, President & CEO DYNE-101 ACHIEVE Trial in DM1 Data DYNE-251 DELIVER Trial in DMD Data Wildon Farwell, M.D., MPH, Chief Medical Officer Q&A Closing Remarks John Cox, President & CEO 3
Slide 4: Our Mission
OUR MISSION Life-transforming therapies for patients with serious muscle diseases 4
Slide 5: Dyne FORCE Platform: Modern Oligo Therapeutics for Muscle Diseases
Dyne FORCE Platform: Modern Oligo Therapeutics for Muscle Diseases ANTIBODY Proprietary Fab targets TfR1 to enable muscle delivery PAYLOAD Modularity enables rational selection of payload to target the genetic basis of disease ASO siRNA LINKER Nuclear Cytoplasmic localization localization Clinically
Slide 6: Compelling Clinical Profiles for DYNE-101 and DYNE-251
Compelling Clinical Profiles for DYNE-101 and DYNE-251 Reinforce Opportunity to Transform the Treatment of DM1 and DMD Potential first-in-class DM1 therapy Potential best-in-class DMD exon skipping franchise with differentiated efficacy and safety profile with differentiated efficacy and safety prof
Slide 7: Program
Program Opening remarks John Cox, President & CEO DYNE-101 ACHIEVE Trial in DM1 Data DYNE-251 DELIVER Trial in DMD Data Wildon Farwell, M.D., MPH, Chief Medical Officer Q&A Closing Remarks John Cox, President & CEO 7
Slide 8: Developing Transformative Therapies for People Living with DM1
Developing Transformative Therapies for People Living with DM1 Clinical Presentation Population Overview • Mutation in the DMPK gene • Myotonia • >40,000 (US) • Onset at any point, depending • Muscle weakness • >74,000 (Europe) on DM1 phenotype • Cardiac arrhythmia • Life expectancy of 45 - 60 years
Slide 9: DM1 Community Urgently Needs Treatment Options
DM1 Community Urgently Needs Treatment Options “In a nutshell, it's a huge, complex disease. It not only affects every muscle in your body, but also your brain, cognition, your stamina, your endurance. And also, I think myotonic dystrophy is not just a physical disability, it also involves mental he
Slide 10: Phase 1/2 Clinical Trial to Evaluate DYNE-101 in Patients with DM1
Phase 1/2 Clinical Trial to Evaluate DYNE-101 in Patients with DM1 Population Primary Endpoints Additional Endpoints Stages of ACHIEVE • Adult patients living with • Safety and tolerability • Pharmacokinetics • Multiple Ascending Dose DM1 (MAD): 24 weeks • Change from baseline of: • Ages 18 to 49 ye
Slide 11: ACHIEVE Trial Design
ACHIEVE Trial Design Global, Randomized, Placebo-Controlled Stage Evaluating Once Monthly or Less Frequent Administration of DYNE-101 in Adult Patients Living with DM1 MAD Study Details Registrational Cohort Dose: TBD (Up to 10.2 mg/kg, Q4W or Q8W) • IV administration of DYNE- 101 or placebo every 4
Slide 12: Dosing Schedules for Treatment Arms
Dosing Schedules for Treatment Arms 1 Biopsy Placebo DYNE-101 Q4W Arm Recovery Arm Q8W Arm Baseline Week 4 Week 8 Week 12 Week 16 Week 20 Week 24 1. Needle biopsies taken from alternating TA muscles prior to dosing at baseline, Day 85, and Day 169. 12 Note: Represents dosing during 24-week multiple
Slide 13: ACHIEVE Baseline Participant Characteristics: By Cohort
ACHIEVE Baseline Participant Characteristics: By Cohort 1.8 mg/kg Q4W 3.4 mg/kg Q4W 5.4 mg/kg Q8W Mean(SD) or n(%) 1 1 2 (N=16) (N=16) (N=8) Age (years) 34.6 (10.4) 34.3 (7.6) 39.6 (7.0) Female n(%) 7 (43.8%) 3 (18.8%) 5 (62.5%) 2 BMI (kg/m ) 22.4 (5.3) 23.8 (3.8) 21.7 (2.7) CASI 0.62 (0.26) 0.67 (0
Slide 14: DYNE-101 Safety Profile Is Favorable to Date
PRO Safety Muscle Delivery Splicing Function DYNE-101 Safety Profile Is Favorable to Date 1 Summary of Treatment Emergent Adverse Events (TEAEs) Most TEAEs Were Mild or Moderate in Intensity • 4 serious TEAEs unrelated to study drug 3 Participants with ≥1 TEAE – n (%)▪ Atrioventricular block first d
Slide 15: DYNE-101 Designed to Address the Foundational Spliceopathy of DM1
DYNE-101 Designed to Address the Foundational Spliceopathy of DM1 to Enable Comprehensive Functional Improvement Early Indicator of Broad Robust Delivery Validated Biomarker Functional Improvement Functional Improvement Muscle Strength: Quantitative Muscle Testing Functional Assessments: 10-Meter Wa
Slide 16: Composite Alternative Splicing Index (CASI) as Biomarker
PRO Safety Muscle Delivery Splicing Function DMCRN NHS Enabled Establishment of Composite Alternative Splicing Index (CASI) as Biomarker Correlating with Clinical Function in DM1 CASI: Composite Alternative PSI = Percent Spliced In ASI: Alternative Splicing Index Splicing Index Compute the mean of n
Slide 17: Dose-Dependent Delivery and Consistent Splicing Correction at 3 Months
PRO Safety Muscle Delivery Splicing Function Monthly Dosing of DYNE-101 Demonstrated Dose-Dependent Delivery and Consistent Splicing Correction at 3 Months DYNE-101 Q4W DYNE-101 Q8W Months Biopsies nd 2 biopsy 1 month post most recent DYNE-101 dose ASO Muscle Concentration CASI-22 80 10 10% 0 60 63.
Slide 18: Recovery Data Supports Less Frequent Dosing Regimen
PRO Safety Muscle Delivery Splicing Function Recovery Data Supports Less Frequent Dosing Regimen CASI-22 Q4W Active Arm CASI-22 at 3 Months 15 DYNE-101 Months 10% Biopsies 5 nd 2 biopsy 1 month post most recent DYNE-101 dose -5 Q4W Recovery Arm -15 Placebo -19% 3% DYNE-101 -22% Months -25 Biopsies n
Slide 19: DYNE-101 Designed to Address the Foundational Spliceopathy of DM1
DYNE-101 Designed to Address the Foundational Spliceopathy of DM1 to Enable Comprehensive Functional Improvement Early Indicator of Broad Robust Delivery Validated Biomarker Functional Improvement Functional Improvement Muscle Strength: Quantitative Muscle Testing Functional Assessments: 10-Meter Wa
Slide 20: Continued Improvement in Functional Myotonia at 6 and 12 Months
PRO Safety Muscle Delivery Splicing Function Continued Improvement in Functional Myotonia at 6 and 12 Months 1.8 mg/kg Q4W myotonia benefit increased from 3.1 seconds at 3 Months to 4.4 seconds at 12 Months vHOT Middle Finger Change from Baseline 2.5 +0.7 sec., +9% change from baseline 0.0 -2.5 -3.1
Slide 21: Continued Improvement in Functional Myotonia at 6 and 12 Months
PRO Safety Muscle Delivery Splicing Function Continued Improvement in Functional Myotonia at 6 and 12 Months 1.8 mg/kg Q4W myotonia benefit increased from 3.1 seconds at 3 Months to 4.4 seconds at 12 Months vHOT Middle Finger Change from Baseline 2.5 +0.7 sec., +9% change from baseline 0.0 -3.1 sec.
Slide 22: Continued Improvement in Functional Myotonia at 6 and 12 Months
PRO Safety Muscle Delivery Splicing Function Continued Improvement in Functional Myotonia at 6 and 12 Months 1.8 mg/kg Q4W myotonia benefit increased from 3.1 seconds at 3 Months to 4.4 seconds at 12 Months vHOT Middle Finger Change from Baseline 2.5 +0.7 sec., +9% change from baseline 0.0 -2.0 sec.
Slide 23: DYNE-101 Designed to Address the Foundational Spliceopathy of DM1
DYNE-101 Designed to Address the Foundational Spliceopathy of DM1 to Enable Comprehensive Functional Improvement Early Indicator of Broad Robust Delivery Validated Biomarker Functional Improvement Functional Improvement Muscle Strength: Quantitative Muscle Testing Functional Assessments: 10-Meter Wa
Slide 24: Improvement in Muscle Strength Measured by QMT
PRO Safety Muscle Delivery Splicing Function DYNE-101 Demonstrated Improvement in Muscle Strength Measured by Quantitative Muscle Testing (QMT) QMT Total Score 5.0 2.5 0.0 -2.5 -5.0 -7.5 OLE Baseline Day 85 Day 169 Day 337 Visit: 3.4 mg/kg Q4W (n = 6) 5.4 mg/kg Q8W (n = 6) Placebo (n = 12) 1.8 mg/kg
Slide 25: Early and Sustained Potential Benefit Across Timed Function Tests
PRO Safety Muscle Delivery Splicing Function DYNE-101 Demonstrated Early and Sustained Potential Benefit Across Multiple Timed Function Tests 10-Meter Walk/Run Test 5 Times Sit to Stand 2.5 0.4 2.0 1.5 0.2 1.0 0.0 0.5 -0.2 0.0 -0.5 -0.4 -1.0 -0.6 -1.5 -0.8 -2.0 Baseline Day 85 Day 169 OLE Day 337 Ba
Slide 26: Improvement in Activities of Daily Living Measured by DM1-ACTIV
PRO Safety Muscle Delivery Splicing Function DYNE-101 Showed Improvement from Baseline in Activities of Daily Living c Measured by DM1-ACTIV Patient Reported Outcome c DM1-ACTIV 5.0 2.5 0.0 -2.5 -5.0 -7.5 OLE Baseline Day 169 Day 337 Visit: 3.4 mg/kg Q4W (n = 6) Placebo (n = 8) 1.8 mg/kg Q4W (n = 6)
Slide 27: Clinical Benefit Based on Well-Validated PRO: MDHI Subscales
PRO Safety Muscle Delivery Splicing Function DYNE-101 Demonstrated Clinical Benefit Based on Well-Validated PRO Showed Benefit in 17 out of 17 MDHI Subscales Upper Extremity Function Improved MDHI Total Score 15.0 20.0 10.0 0.0 -10.0 10.0 -20.0 Baseline Day 169 OLE Day 337 5.0 Gastrointestinal Issue
Slide 28: ACHIEVE Data Demonstrated DYNE-101 Best-in-Class Potential
ACHIEVE Data Demonstrated DYNE-101 Best-in-Class Potential Dose-dependent muscle delivery and compelling splicing ✓ correction consistent across patients Meaningful improvement in multiple clinical endpoints, including myotonia, muscle strength, timed functional ✓ assessments, and patient reported o
Slide 29: Building a Global DMD Franchise of Transformative Therapies
Building a Global DMD Franchise of Transformative Therapies Clinical Presentation Population Overview • Mutation in the DMD gene that • Muscle weakness • ~12,000 - 15,000 (US) encodes for dystrophin • Progressive loss of function • ~ 25,000 (Europe) • Onset in first few years of life • Loss of ambul
Slide 30: DMD Community Has Urgent Need for Improved Treatment Options
DMD Community Has Urgent Need for Improved Treatment Options “A potentially transformative treatment for me would be halting the progression of DMD and that would change everything for me and so many other people with it. And because right now the progression of it, yeah, it's very tough. Great peop
Slide 31: Phase 1/2 Clinical Trial to Evaluate DYNE-251 in Patients with DMD
Phase 1/2 Clinical Trial to Evaluate DYNE-251 in Patients with DMD Additional Endpoints Population Primary Endpoints Stages of DELIVER • Male patients with DMD • Safety and tolerability • Pharmacokinetics • Multiple Ascending Dose with mutations amenable (MAD): 24 weeks • Change from baseline in • C
Slide 32: DELIVER Trial Design
DELIVER Trial Design Global, Randomized, Placebo-Controlled Stage Evaluating Administration of DYNE-251 in Ambulant and Non-Ambulant Male DMD Patients with Mutations Amenable to Exon 51 Skipping Therapy Registrational Cohort MAD Study Details Dose: TBD (Up to 40 mg/kg, Q4W or Q8W) Fully • IV adminis
Slide 33: DELIVER Baseline Participant Characteristics: By Cohort
DELIVER Baseline Participant Characteristics: By Cohort mean (SD) or n(%) 0.7 mg/kg 1.4 mg/kg 2.8 mg/kg 5 mg/kg 10 mg/kg (N=6) (N=6) (N=6) (N=6) (N=8) Age (years) 10.8 (2.2) 7.8 (3.3) 10.7 (2.9) 8.3 (2.8) 6.6 (2.2) 2 BMI (kg/m ) 19.5 (3.4) 18.6 (2.3) 22.6 (6.3) 20.9 (1.6) 18.3 (3.2) Age of Symptom O
Slide 34: DYNE-251 Safety Profile Is Favorable to Date
Safety Muscle Delivery Exon 51 Skipping Dystrophin by WB Function DYNE-251 Safety Profile Is Favorable to Date Most TEAEs Were Mild or Moderate in Intensity 1 Summary of Treatment Emergent Adverse Events (TEAEs) • The 2 serious TEAEs are unrelated to study drug ▪ Dehydration due to gastroenteritis (
Slide 35: DYNE-251 Drove Dose Dependent Delivery of PMO to Muscle
Safety Muscle Delivery Exon 51 Skipping Dystrophin by WB Function DYNE-251 Drove Dose Dependent Delivery of PMO to Muscle PMO Muscle Concentration 2,500 2,156 2,000 1,500 1,000 657 500 0 Baseline 6 Months Baseline 6 Months Baseline 6 Months n=5 n=6 n=4 n=4 n=4 n=5 Placebo DYNE-251 5 mg/kg Q4W DYNE-2
Slide 36: DYNE-251 Demonstrated Dose-Dependent Exon Skipping
Safety Muscle Delivery Exon 51 Skipping Dystrophin by WB Function DYNE-251 Demonstrated Dose-Dependent Exon Skipping Exon 51 Skipping 3 2 1.96 1 0.90 0.09 0.04 0.10 0.07 0 Baseline 6 Months Baseline 6 Months Baseline 6 Months n=6 n=6 n=4 n=4 n=5 n=6 Placebo DYNE-251 5 mg/kg Q4W DYNE-251 10 mg/kg Q4W
Slide 37: DYNE-251 Showed >10 Fold Higher Dystrophin at 6 Months than Eteplirsen
Safety Muscle Delivery Exon 51 Skipping Dystrophin by WB Function DYNE-251 Showed >10 Fold Higher Dystrophin at 6 Months than Eteplirsen 1 Study with 12 Fold Lower PMO Dose Administered 4 Times Less Frequently 5 Unadjusted Dystrophin 2.97 4 3 3.22 2 0.06 1 0.88 0.25 0.60 0.47 0.30 0.46 0.24 0 Baseli
Slide 38: DYNE-251 Achieved 7.6% Muscle Content Adjusted Dystrophin at 6 Months
Safety Muscle Delivery Exon 51 Skipping Dystrophin by WB Function DYNE-251 Achieved 7.6% Muscle Content Adjusted Dystrophin at 6 Months DYNE-251 dosed 10 mg/kg Q4W, SRP-5051 (PPMO) dosed 30 mg/kg Q4W 10 6.94 Muscle Content Adjusted Dystrophin Muscle-content 8 Dystrophin (MHC normalized) adjusted = 1
Slide 39: Encouraging Trends Across Multiple Functional Endpoints
Safety Muscle Delivery Exon 51 Skipping Dystrophin by WB Function Encouraging Trends Across Multiple Functional Endpoints Baseline values inform interpretation of data; ongoing exploration of higher dose cohorts and longer time points th NSAA Total Score Stride Velocity 95 Centile 1.5 0.4 0.0 0.2 -1
Slide 40: Opportunity to Build a Global DMD Franchise
Opportunity to Build a Global DMD Franchise: Leading with DYNE-251, Payloads Identified for Exons 53, 45, 44 Exon 51 – 13% Exon 53 – 8% Approximately Exon 45 – 8% Exon 44 – 6% Exon 50 – 4% 80% of patients Exon 52 – 4% Exon 43 – 4% have genotypes amenable Exon 55 – 2% to exon skipping Exon 8 – 2% Oth
Slide 41: FORCE Positions Dyne With Potential Leading Role in Evolving DMD Landscape
FORCE Positions Dyne With Potential Leading Role in Evolving DMD Therapeutic Landscape FORCE • Muscle delivery is the challenge • Clinical data to date validates FORCE’s targeted delivery to muscle Targeted muscle delivery, Potency ✓ • Non-targeted delivery modalities face near full-length dystrophi
Slide 42: DELIVER Data Demonstrated Potential for DMD Exon Skipping Franchise
DELIVER Data Demonstrated Potential for DMD Exon Skipping Franchise with Differentiated Efficacy and Safety Profile At 10.0 mg/kg Q4W dose, DYNE-251 showed compelling ✓ 1 profile vs. eteplirsen standard-of-care reported at 6 months : • 3.2% unadjusted and 7.6% muscle content adjusted dystrophin expr
Slide 43: Program
Program Opening remarks John Cox, President & CEO DYNE-101 ACHIEVE Trial in DM1 Data DYNE-251 DELIVER Trial in DMD Data Wildon Farwell, M.D., MPH, Chief Medical Officer Q&A Closing Remarks John Cox, President & CEO 43
Slide 44: Driving Towards Potentially Transformative DM1 and DMD Therapies
Driving Towards Potentially Transformative DM1 and DMD Therapies Delivered on the Promise of FORCE: Enhanced Delivery of Therapeutics to Muscle Compelling Impact on Key Disease Biomarkers and Improvement in Multiple Functional Endpoints in Both DM1 and DMD Favorable Safety & Tolerability Profile Sup
Slide 45: Advancing Robust Portfolio Focused on Muscle Diseases
Advancing Robust Portfolio Focused on Muscle Diseases Pipeline Update by YE 2024 Including FSHD and Other Pipeline Programs DISEASE TARGET DISCOVERY PRECLINICAL PHASE 1/2 ESTIMATED PATIENTS Myotonic Dystrophy US: >40,000 DMPK DYNE-101 Type 1 (DM1) Europe: >74,000 DYNE-251 Exon 51 Exon 53 Duchenne Mu
Slide 46: Building the World's Leading Muscle Disease Company
Building the World’s Leading Muscle Disease Company Dynamo Culture Own Muscle Delivery & Win in DM1, DMD, FSHD Leverage FORCE 46
Slide 47: Achieving the Promise of FORCE to Deliver for Patients
Achieving the Promise of FORCE to Deliver for Patients F O R C E ACHIEVE & DELIVER CLINICAL UPDATE | MAY 20, 2024