DYN
Building the World's
Leading Muscle
Disease Company
COMPANY OVERVIEW | NOVEMBER 2024
Sarah, living with DM1
OUR MISSION Life-transforming therapies
for patients with serious muscle diseases
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Dyne FORCE Platform: Modern Oligo Therapeutics for Muscle Diseases
ANTIBODY
Proprietary Fab targets TfR1 to enable muscle delivery
LINKER
Clinically validated, enables precise conjugation of multiple payloads to a single Fab
Adapted from Ohrt T., et al. Nucleic Acids Res 2006;34:1369.
PAYLOAD
Modularity enables rational selection of payload to target the genetic basis of disease
ASO siRNA
Nuclear Cytoplasmic
localization localization
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FORCE Platform Harnesses Cell Biology to Modify Disease
FORCE
TfR1
Cytoplasm
Endosome
Nucleus
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Rationally Select Payload to Target Genetic Basis of Disease
ASO acts in the
Subcellular distribution of ASO and siRNA
nucleus and cytoplasm
siRNA acts in the cytoplasm
Cell Membrane
mRNA-Antisense Duplex
mRNA
RNaseH1
Recognizes Duplex
RNase H1 Enzyme
Cleaves mRNA
DNA
Splice-modulating ASO
Nucleus
DNA
Pre-mRNA EXON1 EXON 2 EXON 3 AAAA
Splicing
mRNA EXON 1 EXON 3 AAAA
Single-Stranded Antisense
ASOsiRNA
NuclearCytoplasmic
localizationlocalization
FORCE delivers ASO payload for nuclear targets, siRNA payload for cytoplasmic targets
Exogenous dsRNA
Cell Membrane
Dicer complex
siRNA Duplex
RISC
Nucleus
Messenger
RNA Cleavage
Cytoplasm
Double-Stranded Antisense (siRNA)
Adapted from Ohrt T., et al. Nucleic Acids Res 2006;34:1369.
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FORCE Platform Designed to Deliver Significant Advantages
Stop or Reverse
Disease
Progression
Targeted Muscle Delivery
Leverages TfR1 expression
on skeletal, cardiac and smooth muscle
Redosable Administration
Potential for individualized patient
titration and longer-term efficacy
Extended Durability
Potential for prolonged disease-modifying effects, enabling less frequent dosing
Targets Genetic Basis of Disease
Rationally select payloads to match target biology
Enhanced Tolerability
Targeted delivery limits systemic drug exposure
Reduced Development and Manufacturing Costs
A single Fab and linker utilized across all programs
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Advancing Robust Portfolio Focused on Muscle Diseases
DISEASE
TARGET
DISCOVERY
PRECLINICAL
PHASE 1/2
ESTIMATED PATIENTS
Myotonic Dystrophy
DMPK
DYNE-101
Type 1 (DM1)
Exon 51
DYNE-251
Exon 53
Duchenne Muscular
Exon 45
Dystrophy (DMD)
Exon 44
Other Exons
Facioscapulohumeral
Muscular Dystrophy
DUX4
DYNE-302
(FSHD)
Pipeline Expansion Opportunities
Rare Skeletal
CNS
Cardiac
Metabolic
US: >40,000
Europe: >74,000
US: ~12,000-15,000
Europe: ~25,000
US: ~16,000-38,000
Europe: ~35,000
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Achieving the Promise of FORCE to Deliver for Patients
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 profile
Pursuing Expedited Approvals, including Accelerated Approval in the U.S., for Both Programs
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1. DYNE-101 data as August 20, 2024. 2. NSAA: North Star Ambulatory Assessment; SV95C: Stride Velocity 95th Centile. 3. DYNE-251 data as of August 21, 2024.
Developing Transformative Therapies for People Living with DM1
Overview
Clinical Presentation
Population
•
Myotonia
•
>40,000
(US)
•
Muscle weakness
•
>74,000
(Europe)
OUR APPROACH
Disease-Modifying Nuclear DMPK Knockdown
Targeting toxic gain of function DMPK RNA to potentially stop or reverse disease progression
NO
approved therapies
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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
DM1
• Change from baseline of:
• Ages 18 to 49 years
- Splicing
- DMPK RNA expression
- Multiple assessments of
muscle strength and
function
- Patient-reported
outcomes, including
DM1-ACTIVc and MDHI
Additional endpoints include select secondary and exploratory endpoints. DM1-ACTIVc: Myotonic Dystrophy type 1 Activity and participation scale. MDHI: Myotonic Dystrophy Health Index.
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Disclaimer
Dyne Therapeutics Inc. published this content on November 19, 2024, and is solely responsible for the information contained herein. Distributed by Public, unedited and unaltered, on November 19, 2024 at 04:00:07.177.