Dyne Therapeutics : ACHIEVE and DELIVER Clinical Data Update Presentation

Achieving the Promise of

F O R C E

to Deliver for Patients

F O R C E

ACHIEVE & DELIVER CLINICAL DATA UPDATE | JANUARY 3, 2024

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, prospects and plans, objectives of management, the potential of the FORCE platform, the anticipated timelines for reporting data for the DYNE-101 and DYNE-251 trials, plans to optimize dose and dose regimen for DYNE-101 and DYNE-251, and the trial design of the DYNE-101 and DYNE-251 clinical trials, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "objective," "ongoing," "plan," "predict," "project," "potential," "should," or "would," or the negative of these terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Dyne may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including: uncertainties inherent in the identification and development of product candidates, including the initiation and completion of preclinical studies and clinical trials; uncertainties as to the availability and timing of results from preclinical studies and clinical trials; the timing of and Dyne's ability to initiate and enroll patients in clinical trials; whether results from preclinical studies and initial data from early clinical trials will be predictive of the final results of the clinical trials or future trials; whether Dyne's cash resources will be sufficient to fund the Company's foreseeable and unforeseeable operating expenses and capital expenditure requirements; as well as the risks and uncertainties identified in Dyne's filings with the Securities and Exchange Commission (SEC), including the Company's most recent Form 10-Q and in subsequent filings Dyne may make with the SEC. In addition, the forward-looking statements included in this presentation represent Dyne's views as of the date of this presentation. Dyne anticipates that subsequent events and developments will cause its views to change. However, while Dyne may elect to update these forward- looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Dyne's views as of any date subsequent to the date of this presentation.

This presentation also contains estimates, projections and other statistical data made by independent parties and by the Company relating to market size and growth and other data about the Company's industry and business. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. The Company has not independently verified the accuracy and completeness of the information obtained by third parties included in this presentation. In addition, projections, assumptions and estimates of the Company's future performance and the future performance of the markets in which the Company operates are necessarily subject to a high degree of uncertainty and risk.

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Program

Opening remarks

Joshua Brumm, President & CEO

DYNE-101 ACHIEVE Trial Data

Wildon Farwell, M.D., MPH, Chief Medical Officer

Perspectives on Myotonic Dystrophy Type 1 (DM1)

Valeria A. Sansone, M.D., Ph.D., Clinical and Scientific Director, Clinical Center

NeMO, Milan; Professor of Neurology, University of Milan and a Principal

Investigator for the ACHIEVE Trial

Q&A

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Program

DYNE-251 DELIVER Trial Data

Wildon Farwell, M.D., MPH, Chief Medical Officer

Perspectives on Duchenne Muscular Dystrophy (DMD)

Perry Shieh, M.D., Ph.D., Professor of Neurology and Pediatrics at the David

Geffen School of Medicine at UCLA and a Neurologist at the Ronald Reagan

UCLA Medical Center in Los Angeles and a Principal Investigator for the

DELIVER Trial

Q&A

Closing remarks

Joshua Brumm, President & CEO

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Program

Opening remarks

Joshua Brumm, President & CEO

DYNE-101 ACHIEVE Trial Data

Wildon Farwell, M.D., MPH, Chief Medical Officer

Perspectives on Myotonic Dystrophy Type 1 (DM1)

Valeria A. Sansone, M.D., Ph.D., Clinical and Scientific Director, Clinical Center

NeMO, Milan; Professor of Neurology, University of Milan and a Principal

Investigator for the ACHIEVE Trial

Q&A

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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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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
✓ Proof-of-concept achieved for DYNE-101	✓ Proof-of-concept achieved for DYNE-251

• Dose-dependentmuscle delivery, DMPK KD, and splicing correction consistent across patients
• Meaningful functional improvement in myotonia (vHOT) at lowest 1.8 mg/kg dose
• Favorable safety profile to date; 5.4 mg/kg Q8W cohort fully enrolled 2

• At initial 5.0 mg/kg Q4W dose, DYNE-251 showed compelling profile vs. eteplirsen standard-of-care reported at 6 months:1
• • >2.5x higher dystrophin expression with 24x lower PMO dose administered 4x less frequently vs. eteplirsen1
  • 2x higher increase in exon skipping vs. eteplirsen1
  • ~2x higher change from baseline PDPF vs. eteplirsen1
• Favorable safety profile to date; 20 mg/kg Q4W cohort fully enrolled 2

Clinical Proof-of-Concept Achieved in ACHIEVE & DELIVER in Early Cohorts

Driving Towards Potentially Transformative Therapies for DM1 & DMD Patients in Later Cohorts

PDPF: percent dystrophin-positive fibers.

1. No head-to-head trials have been conducted comparing DYNE-251 to eteplirsen. Eteplirsen data may not be directly comparable due to differences in trial protocols, dosing regimens8 and patient populations. Accordingly, these cross-trial comparisons may not be reliable. Eteplirsen data from J Neuromuscul Dis 2021; 8(6):989-1001; 2. Data as of December 6, 2023.

Program

Opening remarks

Joshua Brumm, President & CEO

DYNE-101 ACHIEVE Trial Data

Wildon Farwell, M.D., MPH, Chief Medical Officer

Perspectives on Myotonic Dystrophy Type 1 (DM1)

Valeria A. Sansone, M.D., Ph.D., Clinical and Scientific Director, Clinical Center

NeMO, Milan; Professor of Neurology, University of Milan and a Principal

Investigator for the ACHIEVE Trial

Q&A

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Developing Transformative Therapies for People Living with DM1

Overview

Clinical Presentation

Population

• Mutation in the DMPK gene
• Onset at any point, depending on DM1 phenotype
• Life expectancy of 45 - 60 years

•	Myotonia	•	>40,000	(US)
•	Muscle weakness	•	>74,000	(Europe)

• Cardiac arrhythmia
• Pulmonary abnormalities
• CNS manifestations

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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