Slides
Page 1
Sarah, living with DM1 Building the World’s Leading Neuromuscular Disease Company COMPANY OVERVIEW | JUNE 2025
Page 2
Forward-Looking Statements & Disclaimer 2 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 therapeutic potential of DYNE-101 DYNE-251, DYNE-302 and DYNE-401, the anticipated timelines for reporting additional data from the ACHIEVE and DELIVER clinical trials, enrolling registrational cohorts and initiating additional clinical trials, expectations regarding the timing and outcome of interactions with global regulatory authorities and the availability of expedited approval pathways for DYNE-101 and DYNE-251, and expectations regarding the timing of submitting applications for U.S. Accelerated Approval, plans to provide future updates on pipeline programs, and the sufficiency of Dyne's cash resources for the period anticipated, 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 data from clinical trials will be predictive of the final results of the clinical trials or other trials; whether data from clinical trials will support submission for regulatory approvals; 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 as to the regulatory approval process for Dyne's product candidates; 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-K 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.
Page 3
Aiming to Deliver Functional Improvement for People Living with Neuromuscular Diseases 3 Two clinical programs in registrational cohorts for DM1 and DMD following positive proof-of-concept data NEAR-TERM VALUE DRIVERS STRONG FINANCIAL POSITION LATE-STAGE PIPELINE Key data readouts in 2025 & 2026 potentially enabling two submissions for U.S. Accelerated Approval in 2026 Cash position of $677.5 million (as of 3/31/25) with expected runway into Q4 2026; all assets fully owned Note: DM1 = myotonic dystrophy type 1; DMD = Duchenne muscular dystrophy; FSHD = facioscapulohumeral muscular dystrophy. F O R C E DIFFERENTIATED PLATFORM FORCETM platform enables targeted delivery to muscle and CNS; broader pipeline includes FSHD and Pompe
Page 4
Leveraging Our FORCE Platform for Targeted Delivery 4 LINKER Connects Fab and payload PAYLOAD Modularity enables rational selection of payload to target the genetic basis of disease (ASO, PMO, siRNA, enzyme) ANTIBODY Proprietary Fab against TfR1 to enable targeted delivery to muscle and CNS Skeletal and smooth muscle Cardiac muscle CNS Note: Figure depicts oligonucleotide payload; ASO = antisense oligonucleotide; PMO = phosphorodiamidate morpholino oligomer; siRNA = small interfering RNA; CNS = central nervous system.
Page 5
Exogenous dsRNA Dicer complex Nucleus Cytoplasm RISC Messenger RNA Cleavage siRNA acts in the cytoplasm Double-Stranded Antisense (siRNA) Cell Membrane siRNA Duplex Subcellular distribution of ASO and siRNA FORCE delivers ASO payload for nuclear targets, siRNA payload for cytoplasmic targets Cytoplasmic localization Nuclear localization siRNA ASO RNaseH1 Recognizes Duplex mRNA-Antisense Duplex Single-Stranded Antisense DNA mRNA DNA AAAAEXON 3 Splicing EXON 1 EXON 3mRNA AAAA EXON 2 ASO acts in the nucleus and cytoplasm Splice-modulating ASO RNase H1 Enzyme Cleaves mRNA EXON1Pre-mRNA Cell Membrane Nucleus Rationally Select Payload to Target Genetic Basis of Disease 5Adapted from Ohrt T., et al. Nucleic Acids Res 2006;34:1369.
Page 6
FORCE Enabled Oligonucleotide Delivery to Muscle and CNS 6 Notes for PMO: Results after repeat IV dose of naked ASO or DYNE-251 in male cynomolgus monkeys, 2 x 30 mg/kg on day 0 and day 7, analyzed day 28; n = 4 – 5. Notes for ASO: Results after a single IV dose of naked ASO or FORCE in male cynomolgus monkeys, 1 x 10 mg/kg on day 0, analyzed day 3; n = 2. FORCE conjugate consists of lead Fab and surrogate DMPK-targeting payload. The FORCE platform and DYNE-251 are investigational or otherwise in development and have not been approved as safe or effective by the FDA or any other regulatory authority. 0 5 10 15 20 25 30 35 Ratio of DYNE-251/Naked ASO 0 10 20 30 40 50 60 Ratio of DYNE-251/Naked ASO 0 10 20 30 40 50 60 70 Ratio of FORCE/Naked ASO Cortex CerebellumDeep Brain 0 10 20 30 40 50 Ratio of FORCE/Naked ASO 0 5 10 15 20 25 Ratio of FORCE/Naked ASO Diaphragm Heart Naked PMO FORCE Naked ASO FORCE
Page 7
Targets Genetic Basis of Disease Rationally select payloads to match target biology Enhanced Tolerability Targeted delivery limits systemic drug exposure and use of Fab minimizes disruption to TfR1 receptor Reduced Development and Manufacturing Costs A single Fab utilized across all programs Targeted Delivery Leverages TfR1 expression on skeletal, cardiac, and smooth muscle as well as blood-brain-barrier Extended Durability Potential for prolonged disease-modifying effects, enabling less frequent dosing Redosable administration Durable efficacy and treatment optionality Provide Functional Improvement FORCE Platform Designed to Deliver Significant Advantages 7
Page 8
Advancing Robust Portfolio Focused on Neuromuscular Diseases 8 PIPELINE EXPANSION OPPORTUNITIES Rare skeletal, CNS, Cardiac, Metabolic DISEASE TARGET PRECLINICAL PHASE 1/2 ESTIMATED PATIENTS Myotonic dystrophy type 1 (DM1) DMPK US: >40,000 Europe: >74,000 Duchenne muscular dystrophy (DMD) Exon 51 US: ~12,000-15,000 Europe: ~25,000 Exon 53 Exon 45 Exon 44 Other Exons Facioscapulohumeral muscular dystrophy (FSHD) DUX4 US: ~16,000-38,000 Europe: ~35,000 Pompe disease GAA US: ~3,800 Europe: ~7,000 DYNE-101 DYNE-251 DYNE-302 DYNE-401
Page 9
Restore normal RNA splicing to achieve functional improvement for those living with DM1 Functional Improvement via Splicing Correction in Nucleus OUR APPROACH • Mutation in the DMPK gene leads to mis-splicing of multiple genes • Onset at any point, depending on DM1 phenotype • Life expectancy of 45 - 60 years Overview • >40,000 (US) • >74,000 (Europe) Population • Muscle weakness & myotonia • CNS manifestations including fatigue, cognition, and sleep • Gastrointestinal issues • Cardiac arrhythmia • Pulmonary abnormalities Clinical Presentation NO approved therapies DM1 is a Devastating Neuromuscular Splicing Disorder 9Note: DM1 = myotonic dystrophy type 1; CNS = central nervous system.
Page 10
DYNE-101 Addressing the Central Pathobiology of DM1 to Enable Broad Functional Improvement1 10 Muscle Strength: Quantitative Muscle Testing Functional Assessments: 10-Meter Walk / Run; 5 Times Sit to Stand Patient Reported Outcomes: Myotonic Dystrophy Health Index (MDHI) Robust and widespread delivery DMPK degradation in the nucleus MBNL release and splicing correction MBNL trapped: Splicing defect CUG expansion MBNL released: Splicing corrected Differentiated MOADYNE-101 Myotonia: Video Hand Opening Time (vHOT) DMPK Early clinical effect DYNE-101 1. Image depicts the intended DYNE-101 mechanism of action (MOA); DM1 = myotonic dystrophy type 1. Broad functional improvement
Page 11
ACHIEVE Study to Support Accelerated Approval of DYNE-101 in DM1 11 ✓ Selection of registrational dose (6.8 mg/kg Q8W) based on multiple ascending dose (MAD) data Late 2026 Potential submission for U.S. Accelerated Approval based on data from Registrational Expansion Cohort ✓ Proof-of-concept that DYNE-101 can reverse disease progression across multiple functional endpoints Note: ACHIEVE is a Phase 1/2 global placebo-controlled clinical trial evaluating multiple doses of DYNE-101 in adult patients with myotonic dystrophy. 1. Data as of April 23, 2025 ✓ Data support vHOT improvement as early indicator of clinical benefit with DYNE-101 ✓ Favorable safety profile1 Phase 3 study planned to support full approval of DYNE-101 globally
Page 12
DYNE-101 at 6.8 mg/kg Q8W Improved Foundational Pathobiology of DM1 at 3 Months Note: One baseline sample in 6.8 mg/kg treatment groups not included within splicing assay as the sample did not meet QC criteria. 3 months = 85 days. CASI-22 = composite alternative splicing index. 12 n = 5 DMPK % Mean Change from Baseline DMPK n = 14 -7% -33% -40 -30 -20 -10 0 10 Placebo DYNE-101 11% -25% -30 -20 -10 0 10 Placebo DYNE-101 CASI-22 % Mean Change from Baseline n = 5n = 14 Splicing correction
Page 13
Robust and Sustained vHOT Improvement at 6 and 12 Months 13 vHOT Middle Finger -5 -4 -3 -2 -1 0 1 2 Middle Finger (sec)1 Change from Baseline (Mean +/- SEM) BL 3 months 6 months 12 months Placebo (N = 14) 6.8 mg/kg Q8W (N = 6) +0.4 sec. +5% Δ from BL -3.0 sec. -39% Δ from BL -2.9 sec. -38% Δ from BL Baseline (sec), 7.5 (0.8) 7.8 (1.5) mean (SEM) Improvement 1. vHOT Middle Finger (sec) is the average of all myotonia trials for an individual participant in ACHIEVE; vHOT = video hand opening time; SEM = standard error of the mean; BL = baseline. 3 months = 85 days; 6 months = 169 days; 12 months = 337 days.
Page 14
Strength Continues to Improve from Month 6 to Month 12 14 Quantitative Muscle Testing (QMT) Total Score QMT Total (%p) Change from Baseline (Mean +/- SEM) BL 3 months 6 months 12 months Placebo (N = 14) 6.8 mg/kg Q8W (N = 6) -2.0 %p -3.9% Δ from BL 10.3 %p 20.1% Δ from BL 5.2 %p 10.1% Δ from BL 0 5 10 15 -5 Baseline score, 51.5 (3.8) 51.3 (4.2) mean (SEM) Improvement SEM = standard error of the mean; BL = baseline; %p = percent predicted; 3 months = 85 days; 6 months = 169 days; 12 months = 337 days.
Page 15
Robust Benefit Across Multiple Timed Function Tests Sustained at 6 and 12 Months 15 5 Times Sit to Stand Test -3 -2 -1 0 1 2 5x Sit to Stand (sec) Change from Baseline (Mean +/- SEM) BL 3 months 6 months 12 months Placebo (N = 14) 6.8 mg/kg Q8W (N = 6) +0.5 sec. +5.2% Δ from BL -1.5 sec. -14.5% Δ from BL -1.2 sec. -12.4% Δ from BL Baseline (sec), 9.2 (0.5) 10.0 (1.4) mean (SEM) Improvement SEM = standard error of the mean; BL = baseline; 3 months = 85 days; 6 months = 169 days; 12 months = 337 days. -0.75 -0.50 -0.25 0.00 0.25 10-meter Run/Walk Test (sec) Change from Baseline (Mean +/- SEM) BL 3 months 6 months 12 months Placebo (N = 14) 6.8 mg/kg Q8W (N = 6) +0.1 sec. +4.3% Δ from BL -0.4 sec. -9.0% Δ from BL -0.3 sec. -7.2% Δ from BL Baseline (sec), 3.3 (0.1) 3.9 (0.6) mean (SEM) 10-Meter Walk/Run Test
Page 16
16 Myotonic Dystrophy Health Index (MDHI) Total Score -15 -10 -5 0 5 MDHI Total Score Change from Baseline (Mean +/- SEM) BL 6 months 12 months Placebo (N = 14) 6.8 mg/kg Q8W (N = 6) +1.9 sec. +10% Δ from BL -12.3 -46.5% Δ from BL -11.7 -44% Δ from BL Baseline, 18.7 (3.8) 26.5 (5.6) mean (SEM) Improvement Deep Improvement in Patient Reported Outcome Sustained at 6 and 12 Months SEM = standard error of the mean; BL = baseline; 3 months = 85 days; 6 months = 169 days; 12 months = 337 days.
Page 17
17 -16 -12 -8 -4 0 4 8 12 BL 6 months 12 months -16 -12 -8 -4 0 4 8 BL 6 months 12 months Cognitive Impairment Communication -50 -40 -30 -20 -10 0 10 BL 6 months 12 months -15 -10 -5 0 5 10 BL 6 months 12 months Emotional Issues Sleep -30 -20 -10 0 10 BL 6 months 12 months -20 -15 -10 -5 0 5 BL 6 months 12 months Pain Fatigue Improvement Subscale Change from Baseline (Mean +/- SEM) SEM = standard error of the mean; BL = baseline; Patient-reported outcomes (PRO) including Myotonic Dystrophy Health Index (MDHI) collected at baseline, 6 months (169 days) and 12 months (337 days). Sustained Improvement in CNS-related MDHI Subscales Over Time
Page 18
Data Support vHOT Improvement as an Early Indicator of Clinical Benefit with DYNE-101 vHOT Change from Baseline at 6 Months -6 -4 -2 0 2 Middle Finger (sec) Change from Baseline (Mean +/- SEM) Placebo DYNE-101 6.8 mg/kg Q8W -4-3-2-1012 5 Times Sit to Stand (sec) -8 -6 -4 -2 0 2 4 6 8 10 12 14 16 QMT Total (%p) -0.8-0.6-0.4-0.20.00.20.4 10-Meter Walk Run Test (sec) -20-15-10-50510 MDHI Total Score 18 Placebo Month 6 (N=14) 6.8 mg/kg Q8W Month 12 (N=6) Improvement With DYNE-101, all participants at highest 3 doses who improved in 6M vHOT improved in 12M strength, 5xSTS, and/or 10MWR Notes: Mixed model for repeated measures (MMRM): fixed effects: dose, visit, baseline, dose by visit interaction, baseline by visit interaction. Data: all dose groups except recovery group; excluding placebo data after 6 months; Data presented are least squares (LS) mean change from baseline ± SEM (standard error of the mean); 6 months = 169 days, 12 months = 337 days; vHOT = video hand opening time; QMT = quantitative muscle testing; 10MWR = 10-meter walk/run test; 5xSTS = 5 times sit to stand test; MDHI = Myotonic Dystrophy Health Index; %p = percent predicted. Favors DYNE-101
Page 19
19 TEAE Category Participants with ≥1 TEAE – n (%) 1.8 mg/kg Q4W+Rec. N=16 3.4 mg/kg Q4W+Rec. N=16 3.4 mg/kg Q8W N=8 5.4 mg/kg Q8W N=8 6.8 mg/kg Q8W N=8 Overall (N=56) Any TEAE 16 (100%) 16 (100%) 8 (100%) 8 (100%) 8 (100%) 56 (100%) Any related TEAE 9 (56%) 10 (63%) 3 (38%) 6 (75%) 6 (75%) 34 (61%) Any serious TEAE 4 (25%) 0 1 (13%) 0 0 5 (9%) Any serious related TEAE 0 0 0 0 0 0 Any TEAE leading to withdrawal from study 0 0 0 0 0 0 Any TEAE leading to death 0 0 0 0 0 0 Most TEAEs Were Mild or Moderate in Intensity1 • 6 serious TEAEs unrelated to study drug ▪ Atrioventricular block first degree (1)2 ▪ Pneumonia (2 events in same participant) ▪ Pulmonary embolism (1)3 ▪ Hyponatremia (1) ▪ Influenza (1) • Most common TEAEs (≥20% participant incidence)4 ▪ Nasopharyngitis (41%) ▪ Procedural pain (34%) ▪ Influenza (30%) ▪ Infusion-related reaction (29%) ▪ Headache (27%) ▪ Diarrhea (23%) Additional Safety Data • Liver enzyme elevations have been observed in a minority of participants ▪ No impact on liver function (bilirubin or coagulation) ▪ Interpretation is complicated by underlying disease and elevated baseline values up to ~2.5x greater than the upper limit of normal • No participants have demonstrated persistent related anemia or thrombocytopenia DYNE-101: Favorable Safety Profile with No Serious Related TEAEs Summary of Treatment Emergent Adverse Events (TEAEs)1 ~1000 Doses of Study Drug Administered to Date Representing 93 Patient-Years of Follow-Up1 1. Data as of April 23, 2025; 2. Transient worsening of atrioventricular (AV) block in a participant with ongoing medical history of first-degree AV block; 3. Attributed to risk factors for pulmonary embolism; 4. All cohorts combined; preferred terms are reported.
Page 20
Demonstrated Proof of Concept in MAD and LTE Comprehensive Development Program for DYNE-101 in DM1 20 Registrational Expansion Cohort to Support U.S. Accelerated Approval Planned Phase 3 Study ✓ Selected registrational dose of 6.8 mg/kg Q8W Data support vHOT improvement as early indicator of clinical benefit with DYNE-101 ✓ Potential best-in-class profile across myotonia, strength, timed function tests, and patient reported outcomes, including CNS-related ✓ Favorable safety profile1; no serious related TEAEs✓ • 60 participants (3:1); 6.8 mg/kg Q8W • Primary endpoint: Change from baseline in middle finger myotonia as measured by vHOT at 6 months, compared to placebo • Secondary endpoints include: CASI-22, QMT, 10MWR, 5xSTS, and MDHI at 6 months • Planning to initiate confirmatory Phase 3 clinical trial in Q1 2026 1. Safety data as of April 23, 2025; DM1 = myotonic dystrophy type 1; MAD = multiple ascending dose; LTE = long term extension; CASI-22 = composite alternative splicing index; vHOT = video hand opening time; 10MWR = 10-meter walk/run test; QMT = quantitative muscle testing; 5xSTS = 5 times sit to stand test; MDHI = myotonic dystrophy health index. • Enrollment completion planned for Q4 2025 • Ongoing engagement with global regulators to finalize trial design • Data planned for mid-2026 to support potential U.S. Accelerated Approval submission in late 2026
Page 21
Potential Best-in-class Targeted Exon Skipping Increase dystrophin expression and enable less frequent dosing to deliver functional improvement OUR APPROACH • Mutation in the DMD gene that encodes for dystrophin • Onset in first few years of life • Life expectancy ~30 years Overview • ~12,000 - 15,000 (US) • ~ 25,000 (Europe) Population • Muscle weakness • Progressive loss of function • Loss of ambulation • Respiratory/cardiac failure Clinical Presentation Current Approved Exon 51 Therapies Only Increased Dystrophin Production <1% Building a Global DMD Franchise of Transformative Therapies 21
Page 22
DELIVER Study to Support Accelerated Approval of DYNE-251 in DMD 22 ✓ Selection of registrational dose (20 mg/kg Q4W) based on multiple ascending dose (MAD) data Early 2026 Potential submission for U.S. Accelerated Approval based on data from fully enrolled Registrational Expansion Cohort ✓ Proof-of-concept that DYNE-251 can lead to unprecedented early and robust functional improvement Note: DELIVER is a Phase 1/2 global placebo-controlled clinical trial evaluating multiple doses of DYNE-251 in ambulant and non-ambulant males with Duchenne muscular dystrophy (DMD) who are ages 4 to 16 and have mutations amenable to exon 51 skipping. 1. Amongst patients amenable to exon 51 skipping. 2. Safety data as of February 7, 2025. ✓ Demonstrated unsurpassed dystrophin expression1, to serve as a surrogate endpoint ✓ Favorable safety profile2 Phase 3 study planned to support full approval of DYNE-251 globally
Page 23
DYNE-251 Achieved Robust Dystrophin Expression DYNE-251 Showed 3.7% Unadjusted and 8.7% Adjusted Dystrophin at 6 Months 23 Mean MHC Normalized Dystrophin (% Normal) + SEM1 0.52 0.48 0 2 4 6 8 10 12 Baseline 6 Months Placebo n = 8n = 8 n = 6n = 6 DYNE-251 20 mg/kg Q4W Unadjusted Dystrophin 0.57 3.72 Baseline 6 Months 3.15 Note: MHC = myosin heavy chain 1. DELIVER biopsy taken approximately 28 days after most recent dose; 6 months = Week 25 for DELIVER. 1.35 8.72 Baseline 6 Months n = 5n = 6 7.37 Mean MCA MHC Normalized Dystrophin (% Normal) + SEM1 1.84 1.58 0 2 4 6 8 10 12 Baseline 6 Months n = 8n = 7 Muscle Content Adjusted Dystrophin Muscle- content adjusted dystrophin1 Dystrophin (MHC normalized) % Muscle Content =
Page 24
Clear Improvement in Dystrophin Localization to Sarcolemma 24 Baseline DYNE-251 5 mg/kg Q4W at 6 Months Notes: DELIVER biopsy taken approximately 28 days after most recent dose. Scale bar is 100 µm. Dystrophin Laminin
Page 25
Stride Velocity 95th Centile (SV95C) is Qualified as a Digital Primary Endpoint by EMA in Studies in Boys with DMD ≥4 Years Old1 EMA, European Medicines Agency; DMD, Duchenne muscular dystrophy; MCID, minimal clinically important difference; 6MWT, 6-minute walk test; NSAA, North Star Ambulatory Assessment; 4SC, 4-stair climb. 1. EMA. Opinion on SV95C. July 2023. Accessed February 11, 2025. https://www.ema.europa.eu/en/documents/scientific-guideline/qualification-opinion-stride-velocity-95th-centile-primary-endpoint-studies- ambulatory-duchenne-muscular-dystrophy-studies_en.pdf; 2. Servais L, et al. Nat Med. 2023;29(10):2391–2; 3. Servais L, et al. Sci Rep. 2024;14(1):29681; 4. McDonald CM, et al. Muscle Nerve. 2013;48(3):357–68; 5. EMA. Opinion on SV95C. April 2019. Accessed February 11, 2025. https://www.ema.europa.eu/en/documents/scientific-guideline/qualification-opinion-stride-velocity-95th-centile- secondary-endpoint-duchenne-muscular-dystrophy-measured-valid-and-suitable-wearable-device_en.pdf. A digital objective endpoint of ambulatory performance in patients’ normal daily environment 1,2 SV95C Each stride identified1 Each stride quantified: stride speed, stride length1 Distribution of stride speed computed1 Stride speed n 95th percentile • Correlated with traditional hospital-based clinical outcomes (6MWT, NSAA, 4SC)1,2 • Demonstrated sensitivity to detect change over time in natural history, steroid-treated patients, and in clinical trials1 ▪ SV95C has greater sensitivity vs other function tests, i.e. can detect change earlier1,3 • Proposed SV95C MCID = 0.1 m/s (36 m in 6 min) corresponds to 6MWT MCID = 30 m1,4,5 • Continuously collects data over a period of time; minimally impacted by social, familial, or environmental factors1,5 25
Page 26
Early and Sustained Improvements in SV95C at 20 mg/kg DYNE-251 Functional improvement observed vs baseline through 18 months; proposed MCID achieved by 6 months 3 months = 85 days; 6 months = 169 days; 12 months = 337 days; 18 months = 505 days. LTE, long-term extension; m, meter; M, month; MCID, minimal clinically important difference; OLE, open-label extension; Q4W, every 4 weeks; sec, seconds; SEM, standard error of mean; SV95C, stride velocity 95th centile. 1. EMA. Opinion on SV95C. July 2023. Accessed February 11, 2025. https://www.ema.europa.eu/en/documents/scientific-guideline/qualification-opinion-stride-velocity-95th-centile-primary-endpoint-studies- ambulatory-duchenne-muscular-dystrophy-studies_en.pdf; 2. Servais L, et al. Sci Rep. 2024;14(1):29681; 3. EMA. Opinion on SV95C. April 2019. Accessed February 11, 2025. https://www.ema.europa.eu/en/documents/scientific-guideline/qualification-opinion-stride-velocity-95th-centile-secondary-endpoint-duchenne-muscular-dystrophy-measured-valid-and-suitable-wearable-device_en.pdf. 26
Page 27
Long-term Functional Improvement vs Baseline Observed Across Multiple Endpoints through 18 Months 3 months = 85 days; 6 months = 169 days; 12 months = 337 days; 18 months = 505 days. BL = baseline; LTE = long-term extension; m = meter; M = month; NSAA = North Star Ambulatory Assessment; OLE = open-label extension; Q4W = every 4 weeks; sec = seconds; SEM = standard error of mean. 27
Page 28
DYNE-251 Safety Profile Is Favorable 1. Data as of February 7, 2025, all participants, placebo-controlled period, open-label period, long-term extension period; 2. Events have same day of onset in a single participant with a non-serious related TEAE of anemia in the context of fever, hemolysis, diarrhea, and positive blood in stool; together these events are c onsistent with hemolytic uremic syndrome with a possible infectious etiology; 3. Participant has a history of hemolytic anemia of unidentified etiology; presented with fever and tonsilitis; symptoms resolved without therapeutic intervention; 4. All cohorts combined; preferred terms are reported; 5. All infusion-related reactions have been mild or moderate in intensity; dosing has continued in all participants; 6. Data as of February 21, 2025. Q4W, every 4 weeks; Q8W, every 8 weeks. TEAE category Participants with ≥1 TEAE – n (%) 0.7 mg/kg Q4W N=6 1.4 mg/kg Q4W N=6 2.8 mg/kg Q4W N=6 5 mg/kg Q4W N=6 10 mg/kg Q4W N=8 20 mg/kg Q4W N=8 40 mg/kg Q8W N=8 40 mg/kg Q4W N=6 Overall N=54 Any TEAE 6 (100) 6 (100) 6 (100) 6 (100) 7 (87.5) 8 (100) 8 (100) 6 (100) 53 (98.1) Any related TEAE 3 (50.0) 3 (50.0) 2 (33.3) 6 (100) 2 (25.0) 4 (50.0) 2 (25.0) 3 (50.0) 25 (46.3) Any serious TEAE 0 0 1 (16.7) 0 0 1 (12.5) 2 (25.0) 3 (50.0) 7 (13.0) Any serious related TEAE 0 0 0 0 0 0 0 2 (33.3) 2 (3.7) Any TEAE leading to withdrawal from study 0 0 0 0 0 0 0 0 0 Any TEAE leading to death 0 0 0 0 0 0 0 0 0 Summary of treatment-emergent adverse events (TEAEs)1 970 doses of study drug administered to date over a period of 77.1patient-years of follow-up1 546 doses of study drug at 20 mg/kg dose level administered to date6 Potentially related serious TEAEs • Acute kidney injury; thrombocytopenia2 • Pancytopenia3 Most frequent TEAEs4 • Pyrexia (48%) • Headache and vomiting (each 37%) • Fall (35%) • Nasopharyngitis (33%) • Cough (26%) • Infusion-related reaction5 (24%) Additional safety data • Other than two participants with serious TEAEs in the 40 mg/kg Q4W cohort: ▪ No participants have demonstrated persistent related anemia or thrombocytopenia ▪ No participants have demonstrated kidney injury • No participants have demonstrated clinically meaningful changes in electrolytes, including magnesium 28
Page 29
FORCE Positions Dyne With Potential Leading Role in Evolving DMD Therapeutic Landscape 29 Potency Durability Dosing Tolerability Manufacturing FORCE Targeted muscle delivery, near full-length dystrophin Durable target engagement Re-dosable, infrequent Favorable safety profile1 Well-established, scalable ✓ ✓ ✓ ✓ ✓ • Muscle delivery is the challenge • Clinical data to date validates FORCE’s targeted delivery to muscle • Non-targeted delivery modalities face significant challenges, including an acceptable therapeutic index • SMA landscape strong analog to DMD with ZOLGENSMA (gene therapy) and SPINRAZA (oligo) playing an important role in evolving standard of care 1. DYNE-251 safety data as of February 7, 2025.
Page 30
Demonstrated Proof of Concept Comprehensive Development Program for DYNE-251 in DMD 30 Registrational Expansion Cohort to Support U.S. Accelerated Approval Planned Phase 3 Study ✓ Selected registrational dose of 20 mg/kg Q4W Demonstrated unsurpassed dystrophin expression1✓ Unprecedented clinically meaningful benefits✓ Favorable safety profile2; no serious related TEAEs at 20 mg/kg Q4W✓ • Potential submission for U.S. Accelerated Approval in early 2026 • 32 patients (3:1); 20 mg/kg Q4W • Primary endpoint: Change from baseline in dystrophin protein by Western blot at 6 months • Additional endpoints: exon 51 skipping levels, muscle tissue PDPF, NSAA, SV95C, time to rise 1. Amongst patients amenable to exon 51 skipping. 2. Safety data as of February 7, 2025. Note: PDPF = percent dystrophin positive fibers; NSAA = North Star Ambulatory Assessment; SV95C = stride velocity 95th centile. • Supports full approval globally Enrollment Complete
Page 31
Opportunity to Build a Global DMD Franchise: Leading with DYNE-251, Payloads Identified for Exons 53, 45, 44 May not be amenable to exon skipping – ~20% Exon 51 – 13% Exon 53 – 8% Exon 45 – 8% Exon 44 – 6% Exon 50 – 4% Other exon skips – ~30% Exon 52 – 4% Exon 43 – 4% Exon 55 – 2% Exon 8 – 2% Approximately 80% of patients have genotypes amenable to exon skipping 31
Page 32
Building Momentum Toward Two Potential Launches in 2027 32 DYNE-101 for DM1 DYNE-251 for Exon 51 DMD Q4 2025 Complete enrollment planned for Registrational Expansion Cohort Q1 2025 Completed enrollment of Registrational Expansion Cohort Mid-2026 Data planned for Registrational Expansion Cohort Late 2025 Data planned for Registrational Expansion Cohort Late 2026 Potential submission for U.S. Accelerated Approval Early 2026 Potential submission for U.S. Accelerated Approval 2027 Potential U.S. launch 2027 Potential U.S. launch 1st potential launch for Dyne DM1 = myotonic dystrophy type 1; DMD = Duchenne muscular dystrophy.
Page 33
DUX4 knockdown to achieve functional improvement Targeting toxic DUX4 mRNA expression to potentially stop or reverse disease progression and enable functional improvement OUR APPROACH • Aberrant expression of DUX4 • Onset in teen years or young adulthood • Normal life expectancy Overview • ~16,000 - 38,000 (US) • ~35,000 (Europe) Population • Progressive wasting and skeletal muscle loss • Significant physical limitations Clinical Presentation NO approved therapies FSHD Program 33
Page 34
DYNE-302 Targets the Genetic Basis of FSHD 34 Aberrant DUX4 transcription Chromosome 4 Muscle cell death DUX4 11-120 Repeats HEALTHY <10 Repeats FSHD D4Z4 REPEATS D4Z4 REPEATS DYNE-302: a FORCE-siRNA conjugate designed to address the genetic basis of disease by targeting toxic DUX4 expression D4T • Highly selective DUX4 siRNA payload with favorable in vitro off-target and in vitro tolerability profile • Extended duration of action intended to overcome sporadic DUX4 activation
Page 35
DYNE-302 Achieved Robust, Durable, and Dose-Dependent D4T KD in Skeletal Muscle of hTfR1/iFLExD FSHD Mice Notes: Uninduced hTfR1/iFLExD mice dosed with vehicle or DYNE-302 on day 0, analyzed at indicated weeks. Data are means ± SD; n = 4 - 12. D4T is an average of mouse Wfdc3, Sord, and Serpinb6c mRNA markers. KD = knockdown. DYNE-302 demonstrates potential for infrequent dosing, out to Q12W Vehicle DYNE-302 1 mg/kg DYNE-302 2 mg/kg DYNE-302 6 mg/kg 35 Quadriceps Gastrocnemius Tibialis anterior
Page 36
Single Dose of DYNE-302 Corrected Muscle Pathology in Quadriceps of hTfR1/iFLExD FSHD Mice at 12 Weeks Quantification of hypotrophic myofiber reduction Notes: Uninduced hTfR1/iFLExD mice dosed with vehicle or DYNE-302 on day 0, analyzed on week 12. Data are means + SD; n = 4 – 9. DYNE-302 is investigational or otherwise in development and has not been approved as safe or effective by the US FDA, EMA, or any other regulatory authority Vehicle Fiber splitting (hypotrophic myofibers) Laminin DYNE-302 6 mg/kg DYNE-302 reduces hypotrophic myofibers hTfR1/iFLExD 6 mg/kg 36
Page 37
DYNE-302 Normalized Transcriptional Profiles of Inflammation and Muscle Damage in hTfR1/iFLExD Mice 37 Healthy Normal Inflammation Muscle Damage Human transcriptome in skeletal muscle biopsies Mouse ortholog transcriptome in quadriceps Phenotype Normal Notes: each column represents one individual, each row represents an individual gene; human data from Wang et al., 2019.
Page 38
-10 -8 -6 -4 -2 0 2 4 6 8 10 12 14 0 50 100 150 200 Total distance (m) DYNE-302 Led to Functional Improvement in hTfR1/iFLExD FSHD Mice Note: Mice tested for function on forced treadmill run test. Treatment with single DYNE-302 dose 6 mg/kg. Data shown are mean ± SEM, n = 5-7 animals/group. Vehicle 6 mg/kg DYNE-302VehicleFSHD mice:Normal mice: Day DYNE-302 led to functional improvement in mice by preventing onset of severe disease -10 -8 -6 -4 -2 0 2 4 6 8 10 12 14 16 18 20 0 50 100 150 200 250 300 Total distance (m) DYNE-302 IV dose Severe disease induction DYNE-302 led to functional improvement in mice with pre-existing, severe disease Day 38 DYNE-302 IV dose Severe disease induction Improvement Improvement
Page 39
Aiming to Deliver Functional Improvement for People Living with Neuromuscular Diseases 39 Two clinical programs in registrational cohorts for DM1 and DMD following positive proof-of-concept data NEAR-TERM VALUE DRIVERS STRONG FINANCIAL POSITION LATE-STAGE PIPELINE Key data readouts in 2025 & 2026 potentially enabling two submissions for U.S. Accelerated Approval in 2026 Cash position of $677.5 million (as of 3/31/25) with expected runway into Q4 2026; all assets fully owned DM1 = myotonic dystrophy type 1; DMD = Duchenne muscular dystrophy; FSHD = facioscapulohumeral muscular dystrophy. F O R C E DIFFERENTIATED PLATFORM FORCETM platform enables targeted delivery to muscle and CNS; broader pipeline includes FSHD and Pompe
Page 40
Building the World’s Leading Neuromuscular Disease Company