Dyne Therapeutics : ACHIEVE & DELIVER Clinical Update Presentation

Achieving the Promise of

F O R C E

to Deliver for Patients

F O R C E

ACHIEVE & DELIVER CLINICAL UPDATE | MAY 20, 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 additional data from the ACHIEVE and DELIVER clinical trials and initiating registrational cohorts, expectations regarding the timing and outcome of interactions with global regulatory authorities and the availability of accelerated approval pathways for DYNE-101 and DYNE-251, and plans to provide future updates on pipeline programs, 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 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; uncertainties as to the FDA's and other regulatory authorities' interpretation of the data from Dyne's clinical trials and acceptance of Dyne's clinical programs and the regulatory approval process; whether Dyne's cash resources will be sufficient to fund its 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

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

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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

PAYLOAD

Modularity enables rational selection of payload to target the genetic basis of disease

ASO siRNA

Nuclear Cytoplasmic

localization localization

Adapted from Ohrt T., et al. Nucleic Acids Res 2006;34:1369.

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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 with differentiated efficacy and safety profile

• Dose-dependentmuscle delivery and compelling splicing correction consistent across patients

Potential best-in-class DMD exon skipping franchise with differentiated efficacy and safety profile

• Dose-dependentincrease in muscle delivery and dystrophin expression

• Meaningful improvement in multiple clinical endpoints, including myotonia, muscle strength, timed functional assessments and patient reported outcomes
• Early indication of durable effect beyond monthly dosing supports exploration of Q8W dosing
• Deepening of response with longer time on therapy
• Favorable safety profile to date1; 6.8 mg/kg Q8W cohort fully enrolled

• At 10.0 mg/kg Q4W dose, DYNE-251 showed compelling profile at 6 months
• • 3.2% unadjusted and 7.6% muscle content adjusted dystrophin
  • Trends in improvement in functional outcomes, including NSAA and SV95C3
• Favorable safety profile to date2; 40 mg/kg Q8W cohort fully enrolled

Based on Recent Regulatory Interactions, Pursuing Expedited Approvals for Both Programs with

Update on Registrational Pathway Expected by Year-End 2024

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1. DYNE-101 data as of May 8, 2024. 2. DYNE-251 data as of April 30, 2024. 3. NSAA: North Star Ambulatory Assessment; SV95C: Stride Velocity 95th Centile.

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

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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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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 health."

Sarah, living with DM1

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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

• Multiple Ascending Dose (MAD): 24 weeks
• Open-LabelExtension (OLE): 24 weeks
• Long-TermExtension (LTE): 96 weeks

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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