Dyne Therapeutics, Inc. · NASDAQ:DYN
Dyne Therapeutics — RNA Leaders US 2026
19 slides from Dyne Therapeutics's conference presentation, Sep 25, 2026
Slide 1: DYNE-302 Leads to Functional Improvement and Resolves Muscle Transcriptomic Changes in Mouse Models of FSHD
DYNE-302 Leads to Functional Improvement and Resolves Muscle Transcriptomic Changes in Mouse Models of FSHD Thomas A. Natoli, PhD RNA Leaders US Sept 25, 2026
Slide 2: Forward-Looking Statements & Disclaimer
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
Slide 3: Dyne FORCE Platform: Modern Oligo Therapeutics for Muscle Diseases
Dyne FORCE Platform: Modern Oligo Therapeutics for Muscle Diseases ANTIBODY Proprietary Fab targets TfR1 to enable muscle delivery PAYLOAD Modularity enables rational selection of payload to target the genetic basis of disease ASO siRNA LINKER Val-cit cleavable linker, enables Nuclear Cytoplasmic pr
Slide 4: FORCE Platform Harnesses Cell Biology to Modify Disease
FORCE Platform Harnesses Cell Biology to Modify Disease FORCE • Harnesses natural mechanism of TfR1 receptor- Cytoplasm mediated delivery to transport therapeutics across TfR1 the cell membrane • Achieves endosomal escape without any membrane-destabilizing agents • Distinctive pharmacokinetic profil
Slide 5: FORCE Platform Designed to Deliver Significant Advantages
FORCE Platform Designed to Deliver Significant Advantages Targeted Delivery Targets Genetic Basis of Disease Leverages TfR1 expression Rationally select payloads on skeletal, cardiac, and smooth muscle to match target biology as well as blood-brain-barrier Provide Redosable administration Enhanced T
Slide 6: DYNE-302 Targets the Genetic Basis of FSHD
DYNE-302 Targets the Genetic Basis of FSHD HEALTHY Chromosome 4 FSHD 11-120 Repeats <10 Repeats DUX4 D4T Muscle Aberrant DUX4 transcription cell death D4Z4 REPEATS D4Z4 REPEATS DYNE-302: a FORCE-siRNA conjugate designed to address the genetic basis of disease by targeting pathogenic DUX4 expression
Slide 7: The hTfR1/iFLExD Mouse Model Recapitulates Multiple Aspects of Human FSHD
The hTfR1/iFLExD Mouse Model Recapitulates Multiple Aspects of Human FSHD Cell Cell Death DUX4 Regeneration Death Sporadic Slowly progressing DUX4 Years myopathy and activation functional decline FSHD Cell Cell Death DUX4 Regeneration Death Chronic, sporadic Slowly progressing DUX4 Weeks myopathy wi
Slide 8: Single Dose of DYNE-302 Achieves Robust, Durable, and Dose-Dependent D4T KD in Skeletal Muscle
Single Dose of DYNE-302 Achieves Robust, Durable, and Dose- Dependent D4T KD in Skeletal Muscle of hTfR1/iFLExD FSHD Mice DYNE-302 demonstrates potential for infrequent dosing Notes: Uninduced hTfR1/iFLExD mice dosed with vehicle or DYNE-302 on day 0, analyzed at indicated weeks. Data are means ± SD
Slide 9: Study to Establish Impact of DYNE-302 Preventative Treatment in the Induced hTfR1/iFLExD Mice
Study to Establish Impact of DYNE-302 Preventative Treatment in the Induced hTfR1/iFLExD Mice TMX Treadmill Induction Acclimation Training Treadmill Testing Study days: -14 -11 -7 -4 0 1 3 7 10 14 Vehicle Normal Control 1 mg/kg DYNE-302 2 mg/kg hTfR1/iFLExD 6 mg/kg IV Dose TMX, PO Study end Notes: I
Slide 10: Preventative Treatment with DYNE-302 Leads to Functional Improvement in hTfR1/iFLExD Mice
Preventative Treatment with DYNE-302 Leads to Functional Improvement in hTfR1/iFLExD Mice Notes: Mice dosed with vehicle or DYNE-302 on Day -14. Data are means ± SEM; n = 5 - 6. *p < 0.05; ***p = 0.0001, ****p < 0.001 compared to vehicle induced hTfR1/iFLExD mice, one-way ANOVA. 10 DYNE-302 is inves
Slide 11: hTfR1/iFLExD Mice Recapitulate Transcriptional Profiles of Immune Response and Muscle Damage
hTfR1/iFLExD Mice Recapitulate Transcriptional Profiles of Immune Response and Muscle Damage Seen in Human FSHD Muscle Human transcriptome Mouse ortholog transcriptome in skeletal muscle biopsies in quadriceps Healthy Normal Inflammation Damage Muscle Phenotype Normal 11 Notes: each column represent
Slide 12: DYNE-302 Normalizes Transcriptional Profiles of Inflammation and Muscle Damage in hTfR1/iFLExD Mice
DYNE-302 Normalizes Transcriptional Profiles of Inflammation and Muscle Damage in hTfR1/iFLExD Mice Human transcriptome Mouse ortholog transcriptome in skeletal muscle biopsies in quadriceps Healthy Normal Inflammation Damage Muscle Phenotype Normal Notes: each column represents one individual, each
Slide 13: Study to Establish Impact of DYNE-302 Interventional Treatment in the Induced hTfR1/iFLExD Mice
Study to Establish Impact of DYNE-302 Interventional Treatment in the Induced hTfR1/iFLExD Mice TMX Treadmill Induction Acclimation Training Treadmill Testing Study days: -14 -11 -7 -4 0 1 3 7 10 14 Normal Control Vehicle hTfR1/iFLExD DYNE-302 6 mg/kg IV Dose TMX, PO Study end Notes: IV = intravenou
Slide 14: DYNE-302 Interventional Treatment Leads to Functional Improvement in hTfR1/iFLExD Mice
DYNE-302 Interventional Treatment Leads to Functional Improvement in hTfR1/iFLExD Mice Notes: Mice tested for function on treadmill run test. Treatment with single DYNE-302 dose 6 mg/kg. Data shown are means ± SEM, n = 6 - 7 animals/group. 14 DYNE-302 is investigational or otherwise in development a
Slide 15: FSHD Disease Pathogenesis Is the Foundation of DYNE-302 Biomarker Selection Strategy
FSHD Disease Pathogenesis Is the Foundation of DYNE-302 Biomarker Selection Strategy Proximal PD Distal PD biomarkers Clinical endpoints biomarkers DUX4 Inflammation/ Fatty replacement Weakness/ DUX4 target genes activation fibrosis of muscle fatigue DUX4 Plasma/serum Lean muscle Functional tests tr
Slide 16: Unbiased Proteomics Identified DUX4-Regulated KHDC1L as a Circulating Biomarker Candidate in FSHD Plasma
Unbiased Proteomics Identified DUX4-Regulated KHDC1L as a Circulating Biomarker Candidate in FSHD Plasma Study Subjects Sample Collection Proteomic Profiling Plasma KHDC1L Discovered in-house 15k Healthy FSHD FSHD patients from ** ** Patient Registry 10k (N=10) RFU 5k Ref. Cohort (CI) 0 Healthy cont
Slide 17: KHDC1L Upregulation in FSHD Tissue and Plasma: Consistent Evidence from Gene to Transcript to Protein
KHDC1L Upregulation in FSHD Tissue and Plasma: Consistent Evidence from Gene to Transcript to Protein KHDC1L plasma protein DUX4 binding site in KHDC1L mRNA is increased DUX4 KD inhibits KHDC1L levels increased in FSHD KHDC1L promoter1 in FSHD muscle biopsies2 mRNA expression in vitro 15k Healthy FS
Slide 18: Conclusions
Conclusions • DYNE-302 achieves dose-dependent and durable D4T KD in a chronic mouse model of FSHD • DYNE-302 normalizes inflammatory and muscle damage transcriptome in an FSHD mouse model • DYNE-302 leads to functional improvement in an FSHD mouse model with pre- existing and severe disease • Circu
Slide 19: Acknowledgements
Acknowledgements Special thanks Dyne R&D Dr. Rabi Tawil, University of Rochester, Rochester, NY Dr. Peter Jones, University of Nevada, Reno, NV Dr. Vincent Mouly, Institut de Myologie, Paris, France 19