Dyne Therapeutics, Inc. · NASDAQ:DYN
Dyne Therapeutics — FSHD IRC 2021
11 slides from Dyne Therapeutics's conference presentation, Jun 25, 2021
Slide 1: FORCE Platform Enables Muscle-Targeted Delivery of ASO & Silencing of DUX4 Activity in an FSHD Cell Line
FORCETM PLATFORM ENABLES MUSCLE-TARGETED DELIVERY OF ASO & SILENCING OF DUX4 ACTIVITY IN AN FSHD CELL LINE NELSON HSIA FSHD IRC | JUNE 25, 2021 Howard, living with FSHD
Slide 2: Forward-Looking Statements
Forward-Looking Statements 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 Therapeutics, Inc.’s (the “Company”) strat
Slide 3: Dyne FORCE Platform: Modern Oligo Therapeutics for Muscle Diseases
Dyne FORCETM 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 Nuclear Cytoplasmic Clinically validated, enables loca
Slide 4: FORCE Platform Achieved Enhanced Distribution and WT DMPK KD Across NHP Muscles
FORCETM Platform Achieved Enhanced Distribution and WT DMPK KD Across NHP Skeletal, Cardiac and Smooth Muscles Gastrocnemius Soleus Deep Flexor Bicep Ileum (Near Cecum) 62% KD 39% KD 62% KD 51% KD 70% KD Heart-left Ventricle Diaphragm Masseter Quadricep Jejunum (Duodenum Ends) 36% KD 49% KD 41% KD 5
Slide 5: FORCE Platform Designed to Deliver Significant Advantages
FORCE Platform Designed to Deliver Significant Advantages Targeted Muscle Delivery Targets Genetic Basis of Disease Leverages TfR1 expression Rationally select payloads on skeletal, cardiac and smooth muscle to match target biology Stop or Reverse Redosable Administration Enhanced Tolerability Disea
Slide 6: FORCE Targets the Genetic Basis of FSHD
FORCE Targets the Genetic Basis of FSHD 4p15.33 4q21.21 4q31.21 4p15.1 4q13.1 4q22.1 4q28.1 4q32.1 4q34.1 4q35.2 4q24 4q31.23 4p15.31 4q21.23 4q28.3 4q32.3 4q34.3 4p16.2 4q13.3 4q22.3 4q26 4p13 HEALTHY FSHD Chromosome 4 11-120 Repeats <10 Repeats DUX4 Muscle Aberrant DUX4 transcription cell death D4
Slide 7: Activation of DUX4 Transcriptome in FSHD Patient Myotubes
Activation of DUX4 Transcriptome in FSHD Patient Myotubes • Immortalized FSHD patient cells selected as our in vitro model system • DUX4 transcriptome expression 125 occurs only after differentiation to (% of Expression at Day 7, Mean ± SD) MBD3L2 TRIM43 mRNA Expression 100 ZSCAN4 myotubes 75 • No s
Slide 8: FORCE-FM10 Shows Superior Suppression of DUX4 Transcriptome Relative to Naked FM10 PMO
FORCE-FM10 Shows Superior Suppression of DUX4 Transcriptome Relative to Naked FM10 PMO in FSHD Patient Myotubes 150 • FM10 is a PMO targeting DUX4 mRNA 125 for degradation (% of Vehicle Control, Mean ± SD) mRNA Expression 100 • FSHD patient cells were treated with either 8 nM of naked FM10 PMO or 75
Slide 9: FORCE-FM10 is Highly Potent in FSHD Patient Myotubes
FORCE-FM10 is Highly Potent in FSHD Patient Myotubes IC50 is in the Low Nanomolar Range 1.25 MBD3L2 Transcript Expression vs Vehicle TRIM43 ZSCAN4 1.00 0.75 DUX4 Transcriptome Marker IC50 MBD3L2 0.2 nM 0.50 TRIM43 0.05 nM ZSCAN4 0.2 nM 0.25 0.00 -12 -11 -10 -9 -8 -7 -6 -5 Log [FM10] (M) 9
Slide 10: Summary
Summary FORCE platform enables targeted muscle delivery of therapeutic oligonucleotides FORCE-FM10 achieves superior suppression of DUX4 transcriptome relative to naked PMO in FSHD patient cells Enhanced muscle distribution based on data in multiple NHP studies FSHD is one of three INDs planned betw
Slide 11: Acknowledgements
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