Slide 1: FREEDOM-DM1 5 and 10 mg/kg Clinical Data Update
February 24, 2025 FREEDOM-DM1 5 and 10 mg/kg Clinical Data Update
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: Agenda
Agenda Paul Streck, MD, MBA Head of R&D FREEDOM Clinical Trial Design, Clinical Data, and Q&A James McArthur, PhD President and Chief Executive Officer Key Takeaways, DM1 Overview, EDO Platform, Closing Remarks, and Q&A Michelle Mellion, MD Chief Medical Officer Q&A
Slide 4: PGN-EDODM1 Initial Data FREEDOM-DM1 Study: Myotonic Dystrophy Type 1 Overview and EDO Platform
PGN-EDODM1 Initial Data FREEDOM-DM1 Study: Myotonic Dystrophy Type I Overview and EDO Platform James McArthur, PhD President and Chief Executive Officer
Slide 5: PGN-EDODM1 Has Demonstrated Robust Dose-Dependent Splicing Correction Following Single Dose
PGN-EDODM1 Has Demonstrated Robust Dose-Dependent Splicing Correction Following Single Dose in First Two Cohorts As of data cut-off date Dec 3, 2024 Favorable emerging safety profile in patients with myotonic dystrophy type 1 (DM1)1 Robust splicing correction at Day 28 Dose-dependent increases in dr
Slide 6: Myotonic Dystrophy Type 1 Overview and Unmet Medical Need
Myotonic Dystrophy Type 1 Overview and Unmet Medical Need Sources: Neuroepidemiology (2022) 56 (3): 163–173., Neurology 2021 Feb 16;96(7):e1045-e1053 CUG: cytosine-uracil-guanine; DMPK: dystrophia myotonica protein kinase Overview Market Opportunity CUG expansion in the DMPK gene Onset of symptoms v
Slide 7: Mis-Splicing is the Underlying Cause of DM1
DM1 Patient Unaffected Individual Mis-Splicing is the Underlying Cause of DM1 Lopez-Martinez, et al., An Overview of Alternative Splicing Defects Implicated in Myotonic Dystrophy Type 1, Genes, September 2020 Sznajder & Swanson, Short Tandem Repeat Expansions and RNA-Mediated Pathogenesis in Myoton
Slide 8: 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 cytosine-uracil-guanine (CUG) repeat sequences form hairpin lo
Slide 9: PGN-EDODM1 Blocking Approach Targets Only the Pathogenic DMPK RNA
PGN-EDODM1 Blocking Approach Targets Only the Pathogenic DMPK RNA PGN-EDODM1 is engineered to bind selectively to the pathogenic CUG repeat expansion present in DMPK transcript This reduces the ability of these CUG repeats to form hairpin loops and sequester RNA splicing proteins, including MBNL1, i
Slide 10: EDO Platform Enhances Nuclear Delivery and Uptake of Oligonucleotides
Immortalized myoblasts from a healthy individual or a DM1 patient with 2600 CTG repeats were cultured then differentiated for 4 days into myotubes and then treated with fluorescently tagged PGN-PMODM1 (PMO) or PGN-EDODM1 (PPMO) at concentrations detailed above. Cells were visualized by confocal micr
Slide 11: FREEDOM-DM1 Trial Design and Clinical Data
FREEDOM-DM1 Trial Design and Clinical Data Paul Streck, MD, MBA Head of R&D
Slide 12: FREEDOM: Phase 1 PGN-EDODM1 Single-Ascending Dose Study Design
FREEDOM: Phase 1 PGN-EDODM1 Single-Ascending Dose Study Design 1.15 mg/kg cohort added to expand pharmacokinetic and pharmacodynamic understanding DSMB: data safety monitoring board; IV: intravenous; PBO: placebo; SAD: single-ascending dose; PK: pharmacokinetics PGN-EDODM1 dose FREEDOM Study Overvie
Slide 13: FREEDOM: Demographics and Baseline Characteristics in First Two Cohorts
FREEDOM: Demographics and Baseline Characteristics in First Two Cohorts *n=5 as one participant’s sample showed splicing index outside the pre-specified assay range at Baseline (no detectable mis-splicing) Splicing Index (SI) Mild = 0–0.4, SI Moderate = 0.41–0.75, and SI Severe = 0.76–1.0. Provenzan
Slide 14: Favorable Emerging Safety Profile of PGN-EDODM1
Favorable Emerging Safety Profile of PGN-EDODM11 As of December 3, 2024 Includes all participants (placebo and PGN-EDODM1 treated); cohorts remain blinded Data Safety Monitoring Board reviewed event and recommended continuation of study/dosing SAE: serious adverse event; AESI: adverse event of speci
Slide 15: PGN-EDODM1 Demonstrated Normal Mean Serum Creatinine Levels
PGN-EDODM1 Demonstrated Normal Mean Serum Creatinine Levels * Serum Creatinine 1. Includes all participants (placebo and PGN-EDODM1 treated); cohorts remain blinded BL: baseline; ULN: upper limit of normal; M: male; F: female All participants in both cohorts remained below ULN 1 1
Slide 16: Robust and Dose-Dependent Increase in Muscle Tissue Concentration Following Single Dose
PGN-EDODM1 Observed to Have Robust and Dose-Dependent Increase in Muscle Tissue Concentration Following Single Dose 1. One participant’s biopsy was not collected at Day 28 due to pseudoaneurysm in connection with biopsy procedure SEM: standard error of the mean; Placebo tissue concentration was belo
Slide 17: PGN-EDODM1 Produced Mean 29% Splicing Correction Following Single 10 mg/kg Dose
PGN-EDODM1 Produced Mean 29% Splicing Correction Following Single 10 mg/kg Dose Splicing Index Changes: 22-Gene Panel1 at D28 Improvement Provenzano et al., The Splice Index as a prognostic biomarker of strength and function in myotonic dystrophy type 1, J Clin. Invest. 2025 In 10 mg/kg cohort: One
Slide 18: Functional Outcome Data After Single Dose
Functional Outcome Data After Single Dose vHOT: video hand opening time 10-Meter Walk Run Test (10MWRT) at D28 Myotonia (vHOT) at D28 -0.35 Improvement Improvement
Slide 19: Closing Remarks
Closing Remarks James McArthur, PhD President and Chief Executive Officer
Slide 20: PGN-EDODM1 Selectively Targets Only Pathogenic DMPK to Correct RNA Mis-Splicing
PGN-EDODM1 Selectively Targets Only Pathogenic DMPK to Correct RNA Mis-Splicing As of data cut-off date Dec 3, 2024 Two participants in the 10 mg/kg cohort were excluded from the splicing correction assay. One participant’s biopsy was not collected at Day 28 and the other participant’s splicing inde
Slide 21: FREEDOM2 Phase 1 MAD Study Underway
FREEDOM2 Phase 2 MAD Study Underway DSMB: data safety monitoring board; FU: follow-up; IV: intravenous; MAD: multiple-ascending dose; PBO: placebo; PK: pharmacokinetics; vHOT: video hand opening test PGN-EDODM1 dose every 4 weeks FREEDOM2 Study Overview Multinational, randomized, double-blind, place
Slide 22: Key Anticipated Milestones Ahead
Key Anticipated Milestones Ahead Key Expected Data Readouts/ Milestones 2H 2025: FREEDOM 15 mg/kg clinical results Q1 2026: FREEDOM2 5 mg/kg clinical results Q3 2025: CONNECT1 10 mg/kg clinical results
Slide 23: Question and Answer Session
Question and Answer Session Paul Streck, MD, MBA Head of R&D James McArthur, PhD President and Chief Executive Officer Michelle Mellion, MD Chief Medical Officer
Slide 24: Thank you!
24 Community and clinical advisors Clinical study participants and their families Thank you! Clinical site staff and investigators Preclinical collaborators