Dyne Therapeutics : Company Overview November 2024

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.