Slide 1: FREEDOM-DM1 15 mg/kg Cohort Data Update
FREEDOM-DM1 15 mg/kg Cohort Data Update September 2025
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,
Slide 3: Myotonic Dystrophy Type 1 Overview and EDO Platform
Myotonic Dystrophy Type 1 Overview and EDO Platform
Slide 4: PGN-EDODM1 Produces Unprecedented Splicing Correction in DM1 Patients
DM1 Pathology Due to Spliceopathy: PGN-EDODM1 Produces Unprecedented Splicing Correction in DM1 Patients FREEDOM STUDY GOALS: Mis-Splicing is the Known Cause of DM1 Highest Splicing Correction Ever Reported in Patients PRIMARY: SAFETY • 53.7% mean splicing correction observed following single 15 q F
Slide 5: Myotonic Dystrophy Type 1 Overview and Unmet Medical Need
Myotonic Dystrophy Type 1 Overview and Unmet Medical Need Jubal, retired professor living with DM1 Overview Market Opportunity • CUG expansion in the DMPK • U.S. and EU over 115,000 gene patients • Onset of symptoms variable- • No approved therapies that childhood to adulthood address underlying cau
Slide 6: DM1 is Caused by Pathogenic CUG Repeats in DMPK RNA
DM1 is Caused by Pathogenic CUG Repeats in DMPK RNA DM1 is caused by pathogenic DMPK transcripts • Approximately 50% of DMPK transcripts are pathogenic while the remaining DMPK transcripts are normal1 • Pathogenic DMPK transcripts containing Trapped cytosine-uracil-guanine (CUG) repeat MBNL1 is sequ
Slide 7: PGN-EDODM1 Blocking Approach Targets Only the Pathogenic DMPK RNA
PGN-EDODM1 Blocking Approach Targets Only the Pathogenic DMPK RNA PGN-EDODM1 binds selectively to the pathogenic DMPK transcript • PGN-EDODM1 is engineered to bind selectively to the pathogenic CUG repeat expansion present in DMPK transcript Liberated MBNL1 • This reduces the ability of these restor
Slide 8: FREEDOM-DM1 Overview and Results
FREEDOM-DM1 Overview and Results
Slide 9: FREEDOM Phase 1 PGN-EDODM1 Single-Ascending Dose Study Design
FREEDOM: Phase 1 PGN-EDODM1 Single-Ascending Dose Study Design Single Dose PGN-EDODM1 or Placebo (randomized 3:1) Baseline DSMB D28 Wk 16* Biopsy Biopsy 15 mg/kg Biopsy FREEDOM Phase 1 n=8 or PBO1 Study Overview Multinational, randomized, double-blind, placebo-controlled Baseline DSMB D28 Wk 16 SAD
Slide 10: PGN-EDODM1 Produced Mean 53.7% Splicing Correction Following Single 15 mg/kg Dose
PGN-EDODM1 Produced Mean 53.7% Splicing Correction Following Single 15 mg/kg Dose Splicing Index Changes: 22-Gene Panel* at D28 % Mean change from baseline Improvement 3.3% 100% of patients in -12.3% the 15 mg/kg cohort responded to treatment with -29.1% PGN-EDODM1 -53.7% Placebo1 5 mg/kg 10 mg/kg2
Slide 11: Greater Than Dose-Proportional Increase in Muscle Tissue Concentration Following Single Dose
Robust, Greater Than Dose-Proportional Increase in Muscle Tissue Concentration Following Single Dose Muscle Tissue Concentration at D28 M12E"34"#5ST81 /-- 9:ET1E;<2;=:E"'EA%A+ M12E">"?@ .-- !"#quot; ,-- !' %%$! - !"#A%CA" ,-"#A%CA"1 ,!"#A%CA"* * 'E)*+ 'E)!+ 'E)!+ 1. One subject at 10 mg/kg did not ha
Slide 12: Favorable Emerging Safety Profile of PGN-EDODM1
Favorable Emerging Safety Profile of PGN-EDODM1 Cohorts Include Placebo & Active PGN-EDODM1 Generally Well-Tolerated at 15 mg/kg: * Summary of Treatment 5 mg/kg 10 mg/kg 15 mg/kg Emergent Adverse Events (n=8)* (n=8)*1 (n=8)* • All treatment related TEAEs were mild or moderate in severity (TEAEs) n(%
Slide 13: PGN-EDODM1 Continues to Demonstrate Favorable Safety Profile
PGN-EDODM1 Continues to Demonstrate Favorable Safety Profile W;SSE7< PGN-EDODM1 Serum Creatinine in FREEDOM* #$-=>*?-quot;@&D&D$ #$-=>*?-quot;@&D&D$*A>BRCaE M KEY TAKEAWAYS: . <quot;D*c*8S • All kidney AEs were transient H and mild or moderate .LM'N+ • No interventions required for kidney AEs F .LM'2+ • No p
Slide 14: Functional Outcomes After Single Dose
Functional Outcomes After Single Dose 10-Meter Walk Run Test (10MWRT) at D28 Myotonia (vHOT) at D28 Mean Middle Finger vHOT (sec) Mean CFB in 10MWRT (sec) Improvement Improvement Baseline Day 28 Baseline Day 28 vHOT: video hand opening time 14
Slide 15: Closing Remarks
Closing Remarks
Slide 16: PGN-EDODM1 Designed to Address the Underlying Cause of DM1
PGN-EDODM1 Designed to Address the Underlying Cause of DM1 Safety & Tolerability: Highest Ever Reported Mean Splicing Correction in DM1 • PGN-EDODM1 was • 100% of patients responded to PGN-EDODM1 in 15 mg/kg cohort generally well-tolerated across all doses • More than dose-proportionate increases in
Slide 17: FREEDOM2 Phase 2 MAD Study Underway
FREEDOM2 Phase 2 MAD Study Underway 4 Doses of PGN-EDODM1 or Placebo (randomized 3:1) FREEDOM2 Study Overview DSMB *Exploring protocol TBD mg/kg* Safety Biopsy Biopsy FU amendment to dose n=8 or PBO Multinational, randomized, double- between 10-15 mg/kg blind, placebo-controlled, MAD study open in U
Slide 18: FREEDOM Study Exceeded Splicing Correction Objectives, Positioning FREEDOM2 for Readouts in 2026
FREEDOM Study Exceeded Splicing Correction Objectives, Positioning FREEDOM2 for Important Readouts in 2026 FREEDOM STUDY GOALS: PHASE 2 FREEDOM2 (MAD) PRIMARY: SAFETY − Currently dosing 5 mg/kg cohort − 10 mg/kg cohort expected to begin dosing in Q1 2026 q Favorable emerging safety profile EXPLORATO