Dyne Therapeutics, Inc. · NASDAQ:DYN
Dyne Therapeutics — Corporate Update (January 2025)
43 slides from Dyne Therapeutics's corporate update, Jan 10, 2025
Slide 1: Clinical Update
Exhibit 99.2 Clinical Update JANUARY 10, 2025
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 New Data from DYNE-101 ACHIEVE Trial in DM1 Update on DYNE-251 DELIVER Trial in DMD Doug Kerr, M.D., Ph.D., Chief Medical Officer Closing Remarks John Cox, President & CEO 3
Slide 4: Aiming to Deliver Transformative Therapies for Neuromuscular Diseases
Aiming to Deliver Transformative Therapies for Neuromuscular Diseases Two clinical programs moving to registrational expansion LATE-STAGE cohorts for DM1 and DMD following positive proof-of- PIPELINE concept data NEAR-TERM Key data readouts in 2025 & 2026 potentially enabling two VALUE submissions f
Slide 5: DM1 Clinical Data Show Broad Functional Impact and Support Potential for Accelerated Approval
Myotonic Dystrophy Type 1 (DM1) Clinical Data Show Broad Functional Impact and Support Potential for Accelerated Approval Initiating Registrational Expansion Cohort in ACHIEVE trial to support potential 1 1H2026 submission for U.S. Accelerated Approval Potential best-in-class profile with meaningful
Slide 6: Advancing Next-Generation Exon 51-Skipping Therapeutic for DMD
Advancing Next-Generation Exon 51-Skipping Therapeutic for Duchenne Muscular Dystrophy (DMD) Ongoing Registrational Expansion Cohort in DYNE-251 DELIVER trial to support potential submission for U.S. Accelerated Approval early 2026, using dystrophin as 1 surrogate endpoint based on recent FDA feedba
Slide 7: Program
Program Opening Remarks John Cox, President & CEO New Data from DYNE-101 ACHIEVE Trial in DM1 Update on DYNE-251 DELIVER Trial in DMD Doug Kerr, M.D., Ph.D., Chief Medical Officer Closing Remarks John Cox, President & CEO 7
Slide 8: Developing Transformative Therapeutics for People Living with DM1
Developing Transformative Therapeutics 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 ye
Slide 9: DYNE-101 Addressing the Central Pathobiology of DM1
DYNE-101 Addressing the Central Pathobiology of DM1 to Enable 1 Broad Functional Improvement Robust and Correction of myotonia and broad DMPK degradation in MBNL release and widespread functional improvement the nucleus splicing correction delivery CUG expansion MBNL trapped: Splicing defect Muscle
Slide 10: DM1 is a Heterogeneous Disease with Widespread Muscle and CNS Manifestations
DM1 is a Heterogeneous Disease with Widespread Muscle and CNS Manifestations 1–4 1–4 CNS Ocular • Fatigue • Cataracts • Excessive daytime sleepiness • Ptosis • Difficulty concentrating 1–4 • Behavioral/personality changes Cardiac • Conduction disturbances 1–4 Skeletal muscle (respiratory) • Arrythmi
Slide 11: DYNE-101 Leverages FORCE Platform for Targeted Delivery
DYNE-101 Leverages FORCE Platform for Targeted Delivery ANTIBODY Proprietary Fab against TfR1 to enable targeted delivery Skeletal and smooth muscle Cardiac muscle LINKER Enables precise conjugation of payloads to Fab PAYLOAD CNS ASO localizes to nucleus, targeting mutant DMPK 11
Slide 12: Multiple Ascending Dose Portion of ACHIEVE is Complete
Multiple Ascending Dose (MAD) Portion of ACHIEVE is Complete Population Primary Endpoints Endpoints Stages of ACHIEVE • Adult patients living with • Safety and tolerability • Pharmacokinetics • Multiple Ascending Dose ü DM1 (MAD): 24 weeks • Change from baseline of: • Ages 18 to 49 years • Open-Labe
Slide 13: DYNE-101 Addresses Central Pathobiology: Differentiated Pharmacology
DYNE-101 Addresses Central Pathobiology: Differentiated Pharmacology with Potential to Lead to Broad Functional Benefit Delivery and exposure DMPK knockdown Splicing correction Broad functional benefit Muscle delivery at 3 mo Target engagement at 3 mo Biomarker response at 3 mo Benefit at 6 mo 20 20
Slide 14: DYNE-101: Favorable Safety Profile with No Serious Related TEAEs
DYNE-101: Favorable Safety Profile with No Serious Related TEAEs 1 1 Summary of Treatment Emergent Adverse Events (TEAEs) Most TEAEs Were Mild or Moderate in Intensity • 6 serious TEAEs unrelated to study drug Participants with ≥1 TEAE – n (%) 2 § Atrioventricular block first degree (1) TEAE § Pneum
Slide 15: Broad Improvement at Planned Registrational Dose of 6.8 mg/kg Q8W
Broad Improvement Demonstrated at 6 Months with Planned Registrational Dose of 6.8 mg/kg Q8W CASI-22 correction Middle Finger vHOT (sec) at 3 months 20 4 3 2 1 0 -1 -2 -3 -4 -5 -6 -7 -8 10 QMT Total (%p) 0 -8 -6 -4 -2 0 2 4 6 8 10 12 14 16 -10 5 Times Sit to Stand (sec) -20 2 1 0 -1 -2 -3 -4 -30 10-
Slide 16: Registrational Expansion Cohort Timeline Enables Potential Submission in H1 2026
Registrational Expansion Cohort Timeline Enables Potential Submission for U.S. Accelerated Approval in H1 2026 Accelerated Approval Path Enables Potential Profile Speed to Filing with Functional Benefit Planned Primary Endpoint (3 months) • Change from baseline in CASI N ~ 32, 3:1 ACHIEVE 6.8 mg/kg
Slide 17: DYNE-101 Improved Foundational Pathobiology of DM1 at 3 Months
DYNE-101 at 6.8 mg/kg Q8W Improved Foundational Pathobiology of DM1 at 3 Months DMPK Splicing correction 10 10 11% 0 -7% 0 -10 -10 -20 -20 -30 -33% -25% -40 -30 Placebo DYNE-101 Placebo DYNE-101 n = 14 n = 5 n = 14 n = 5 17 Notes: One baseline sample in 6.8 mg/kg treatment groups not included within
Slide 18: Early and Robust Improvement in Functional Myotonia
Early and Robust Improvement in Functional Myotonia vHOT Middle Finger 2 +0.4 sec. 1 +5% Δ from BL 0 -1 -2 -3 -2.9 sec. -38% Δ from BL -4 -5 Visit: Baseline 3 months 6 months Cohort: Placebo (N = 14) DYNE-101 6.8 mg/kg Q8W (N = 6) Baseline (sec), mean (SEM): 7.5 (0.8) 7.8 (1.5) 18 Notes: 1. vHOT Mid
Slide 19: Improved Muscle Strength
mprovement Improved Muscle Strength at 6 Months Quantitative Muscle Testing (QMT) Total Score 12.5 10.0 7.5 5.2 %p 10.1% Δ from BL 5.0 2.5 0.0 -2.5 -2.0 %p -3.9% Δ from BL -5.0 Visit: Baseline 3 months 6 months Cohort: Placebo (N = 14) DYNE-101 6.8 mg/kg Q8W (N = 6) Baseline, mean (SEM): 51.5 (3.8)
Slide 20: Early and Robust Benefit Across Multiple Timed Function Tests
Early and Robust Benefit Across Multiple Timed Function Tests 10-Meter Walk/Run Test 5 Times Sit to Stand +0.1 sec. +0.5 sec. 0.2 +4.3% Δ from BL +5.2% Δ from BL 1 0.0 0 -0.3 sec. -0.2 -7.2% Δ from BL -1 -0.4 -1.2 sec. -12.4% Δ from BL -2 -0.6 -0.8 -3 3 months Baseline 3 months 6 months Baseline 6 m
Slide 21: Improvement in MDHI Total Indicates Encouraging Patient Reported Outcome Trends
Improvement in MDHI Total Indicates Encouraging Patient Reported Outcome Trends Myotonic Dystrophy Health Index (MDHI) Total 10.0 +1.88 5.0 +10% Δ from BL 0.0 -5.0 -10.0 -11.65 -44% Δ from BL -15.0 -20.0 Visit: Baseline 6 Months Cohort: Placebo (N = 14) DYNE-101 6.8 mg/kg Q8W (N = 6) Baseline score,
Slide 22: CNS-related MDHI Subscales Show Improvement at Registrational Dose
CNS-related MDHI Subscales Show Improvement at Registrational DYNE-101 Dose Sleep Cognitive impairment Fatigue 10 12 10 8 0 0 4 0 -10 -10 -4 -20 -8 -30 -12 -20 -16 -40 -30 -50 Emotional issues Pain Communication 8 10 10 4 5 5 0 0 0 -5 -4 -5 -10 -8 -10 -15 -12 -15 -20 -16 Baseline 6 Months Baseline 6
Slide 23: Benefit Strengthened when Adjusting for Baseline Imbalances
Benefit at 6 Months Strengthened when Adjusting for Baseline Imbalances CASI-22 correction at 3 months Middle Finger vHOT (sec) 20 QMT Total (%p) 10 0 5 Times Sit to Stand (sec) -10 -20 10-Meter Walk Run Test (sec) -30 MDHI Total Score -40 Favors DYNE-101 Placebo (N = 14) DYNE-101 6.8 mg/kg Q8W (N =
Slide 24: Additional Data: Robust DMPK KD, Splicing Correction, and vHOT
Additional Data: Robust DMPK KD, Splicing Correction, and vHOT Placebo 3.4 mg/kg Q4W 5.4 mg/kg Q8W 6.8 mg/kg Q8W DMPK 15 8% 1% 5 -5 -12% -16% -7% -15 -25 -33% -40% -42% -35 -48% -51% -45 -55 n = 14 n = 14 n = 5 n = 6 n = 6 n = 6 n = 6 n = 6 n = 5 n = 5 3 months 6 months 3 months 6 months 11 months 3
Slide 25: Additional Data: Benefit on 5x Sit to Stand with Baseline Adjustment
Additional Data: Early, Sustained and Deepening Benefit on 5x Sit to Stand with Baseline Adjustment 5 Times Sit to Stand 2.0 1.0 0.0 -1.0 -2.0 OLE -3.0 Baseline 3 months 6 months 12 months Visit: Placebo (N = 14) DYNE-101 3.4 mg/kg Q4W (N = 6) DYNE-101 5.4 mg/kg Q8W (N = 6) DYNE-101 6.8 mg/kg Q8W (N
Slide 26: DM1 Clinical Data Show Broad Functional Impact and Support Accelerated Approval
Myotonic Dystrophy Type 1 (DM1) Clinical Data Show Broad Functional Impact and Support Potential for Accelerated Approval Initiating Registrational Expansion Cohort: primary endpoint of splicing correction at 3 ü months, supported by functional endpoints and PROs; full enrollment expected mid-2025 6
Slide 27: Building a Global DMD Franchise of Transformative Therapeutics
Building a Global DMD Franchise of Transformative Therapeutics 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 am
Slide 28: Registrational Expansion Cohort of DELIVER Rapidly Enrolling
Registrational Expansion Cohort of DELIVER Rapidly Enrolling Additional Endpoints Population Primary Endpoints Stages of DELIVER • Male patients with DMD • Safety and tolerability • Pharmacokinetics • Multiple Ascending Dose ü with mutations amenable (MAD): 24 weeks • Change from baseline in • Chang
Slide 29: DYNE-251 Safety Profile Is Favorable
DYNE-251 Safety Profile Is Favorable 1 Summary of Treatment Emergent Adverse Events (TEAEs) 1 Most TEAEs Were Mild or Moderate in Intensity • 3 serious TEAEs potentially related to study drug in two participants 2 Participants with ≥1 TEAE – n (%) • Acute kidney injury (1); thrombocytopenia (1) 3 •
Slide 30: Previously Presented Data: DYNE-251 Achieved Robust Dystrophin Expression
Previously DYNE-251 Achieved Robust Dystrophin Expression Presented Data DYNE-251 Showed 3.7% Unadjusted and 8.7% Adjusted Dystrophin at 6 Months Unadjusted Dystrophin Muscle Content Adjusted Dystrophin 12 12 7.37 Muscle- 10 10 Dystrophin (MHC normalized) content = adjusted % Muscle Content 1 dystro
Slide 31: Unprecedented Clinically Meaningful Benefits Observed at Registrational Dose
mprovement mprovement Unprecedented Clinically Meaningful Benefits Observed at Previously Presented Data Registrational Dose North Star Ambulatory Assessment th Stride Velocity 95 Centile (SV95C) (NSAA) Total Score 0.3 3 2 0.2 1 0.1 0 0.0 -1 -0.1 -2 -0.2 -3 -4 -0.3 Baseline Day 85 Day 169 Baseline D
Slide 32: Registrational Expansion Cohort Timeline Enables Potential Submission in Early 2026
Registrational Expansion Cohort Timeline Enables Potential Submission for U.S. Accelerated Approval in Early 2026 Accelerated Approval Path Enables Potential Profile Speed to Filing Primary Endpoint (6 months) • Change from baseline in dystrophin protein N ~ 32, 3:1 DELIVER levels by Western Blot 20
Slide 33: Program
Program Opening Remarks John Cox, President & CEO New Data from DYNE-101 ACHIEVE Trial in DM1 Update on DYNE-251 DELIVER Trial in DMD Doug Kerr, M.D., Ph.D., Chief Medical Officer Closing Remarks John Cox, President & CEO 33
Slide 34: Robust Portfolio Focused on Neuromuscular Diseases
Robust Portfolio Focused on Neuromuscular Diseases with Opportunities to Expand by Leveraging FORCE Delivery DISEASE TARGET DISCOVERY PRECLINICAL PHASE 1/2 ESTIMATED PATIENTS Myotonic Dystrophy US: >40,000 DMPK Type 1 (DM1) Europe: >74,000 Exon 51 Exon 53 Duchenne Muscular US: ~12,000-15,000 Exon 45
Slide 35: Building Momentum Toward Potential Launches in 2027
Building Momentum Toward Potential Launches in 2027 2024 2025 2026 Registrational Expansion Cohort Fully enroll ü MAD Complete readout (H1 2026) DYNE-101 for Registrational Expansion Cohort DM1ü Registrational dose Submission for U.S. (mid-2025) selected Accelerated Approval (H1 2026) ü Registration
Slide 36: Q&A
‘THERAPEUTICS Q&A
Slide 37: Appendix: Additional Study Results
Appendix: Additional Study Results 37
Slide 38: ACHIEVE Baseline Participant Characteristics: By Treatment
ACHIEVE Baseline Participant Characteristics: By Treatment 1.8 mg/kg 3.4 mg/kg 5.4 mg/kg 6.8 mg/kg Placebo Mean (SD) Q4W Q4W Q8W Q8W (N=14) (N=6) (N=6) (N=6) (N=6) Age (years) 32.6 (9.6) 37.0 (10.5) 31.2( 4.4) 40.2 (6.5) 37.2 ( 9.7) 2 BMI (kg/m ) 24.4 (4.7) 21.6 (5.8) 21.1 (1.8) 21.4 ( 2.5) 23.4 ( 5
Slide 39: Early and Sustained Improvement in Functional Myotonia
Early and Sustained Improvement in Functional Myotonia vHOT Middle Finger 2.0 +0.4 sec. +5% Δ from BL 0.0 -2.0 sec. -30% Δ from BL -3.5 sec. -2.0 -53% Δ from BL -2.9 sec. -38% Δ from BL -4.0 -5.3 sec. -6.0 -5.7 sec. -44% Δ from BL -48% Δ from BL -8.0 OLE -10.0 Baseline 3 months 6 months 12 months Vi
Slide 40: Improvement in Muscle Strength
Improvement in Muscle Strength at 6 and 12 Months QMT Total Score 10.0 6.2 %p 2.1 %p 7.5 13.4% Δ from BL 4.6% Δ from BL 5.0 5.2 %p 10.1% Δ from BL 2.5 0.0 -2.5 -2.0 %p -5.0 -3.9% Δ from BL -7.5 OLE -10.0 Baseline 3 months 6 months 12 months Visit: Placebo (N = 14) DYNE-101 3.4 mg/kg Q4W (N = 6) DYNE
Slide 41: Early and Sustained Benefit Across Measures of Daily Function
Early and Sustained Benefit Across Measures of Daily Function 10-Meter Walk/Run Test 5 Times Sit to Stand 2.0 +0.1 sec. 0.2 +4.3% Δ from BL +0.5 sec. 1.0 +5.2% Δ from BL 0.0 0.0 -0.3 sec. -7.2% Δ from BL -1.2 sec. -1.0 -0.2 -12.4% Δ from BL -2.0 -1.5 sec. -0.4 -11.6% Δ from BL -3.0 -0.4 sec. -0.4 se
Slide 42: Encouraging Trends on MDHI Total PRO
Encouraging Trends on MDHI Total PRO MDHI Total Score 15.0 10.0 5.0 0.0 -5.0 -10.0 -15.0 OLE -20.0 Visit: Baseline 6 months 12 months Placebo (N = 14) 3.4 mg/kg Q4W (N = 6) 5.4 mg/kg Q8W (N = 6) 6.8 mg/kg Q8W (N = 6) Baseline score, mean (SEM): 18.7 (3.8) 30.2 (9.5) 14.8 (3.0) 26.5 (5.6) 42 Notes: P
Slide 43: CNS-related MDHI Subscales Show Improvement at Registrational DYNE-101 Dose
CNS-related MDHI Subscales Show Improvement at Registrational DYNE-101 Dose Sleep Cognitive impairment Fatigue 20 20 30 10 20 10 0 10 -10 0 0 -20 -10 -30 -10 -40 -20 -50 OLE -20 OLE OLE -30 Emotional issues Pain Communication 20 20 20 10 10 10 0 0 0 -10 -10 -10 OLE OLE OLE -20 -20 -20 Baseline 6 Mon