Slide 1: August 2026 Company Presentation
August 2026 Company Presentation
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: Leveraging EDO Platform to Drive Meaningful Impact for Patients
Leveraging EDO Platform to Drive Meaningful Impact for Patients PGN-EDODM1: Myotonic Dystrophy Type 1 Best-in-class potential; selectively targets only pathogenic DMPK RNA Favorable emerging safety profile and FREEDOM2 5 mg/kg results supportive of the ongoing dosing in 10 mg/kg MAD cohort FREEDOM2
Slide 4: PGN-EDODM1 Delivery to DM1 Patient Myotubes
PGN-EDODM1 Delivery to DM1 Patient Myotubes Red = oligo PepGen’s EDO Platform Has Been Designed and Developed to Solve the Delivery Challenge of Oligonucleotides Immortalized myoblasts from a DM1 patient with 2600 CTG repeats were cultured then differentiated for 4 days into myotubes and then treate
Slide 5: EDO Technology Can Improve Endosomal Escape and Increase Nuclear Uptake up to 98-Fold
55x 98x 73x PMO Delivery in DM1 Cells EDO Technology Can Improve Endosomal Escape and Has Been Shown to Increase Nuclear Uptake up to 98-Fold NUCLEAR UPTAKE Immortalized myoblasts from a healthy individual or a DM1 patient with 2600 CTG repeats were cultured then differentiated for 4 days into myotu
Slide 6: PGN-EDODM1: A Differentiated Drug with Best-in-Class Potential
1. FREEDOM 15 mg/kg data readout when compared with prior published data. Differentiated Delivery Technology Receptor-independent EDO peptide delivery Designed to escape the endosome – unlike TfnR targeting 1 Differentiated Target Selectively targets pathogenic RNA (CUG repeat in DMPK) Demonstrated
Slide 7: PGN-EDODM1 – Myotonic Dystrophy Type 1 (DM1)
PGN-EDODM1 – Myotonic Dystrophy Type 1 (DM1)
Slide 8: 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 Jubal, retired professor living with DM1 Caused by CTG expansion in the DMPK g
Slide 9: DM1's Broad, Multisystemic Symptoms Underscore the Need for a Disease-Modifying Therapy
Cardiovascular: cardiac conduction issues Reproductive: low testosterone, gynecological problems CNS: fatigue, daytime sleepiness, difficulty concentrating, hypersomnia, learning difficulties Muscle: myotonia, weakness, wasting, myalgia, facial myopathy, balance issues Respiratory: sleep apnea, lung
Slide 10: PGN-EDODM1 Blocking Approach Targets the Pathogenic CUGexp Repeats DMPK RNA
PGN-EDODM1 Blocking Approach Targets the Pathogenic CUGexp Repeats DMPK RNA Wojciechowska, et al., Quantitative Methods to Monitor RNA Biomarkers in Myotonic Dystrophy, Nature, April 12, 2018 DM1 is caused by pathogenic DMPK transcripts PGN-EDODM1 binds selectively to the pathogenic DMPK transcript
Slide 11: PGN-EDODM1 Reduced Pathogenic Nuclear Foci, Liberated MBNL1 and Corrected Mis-Splicing
MBNL1 Liberation Foci Reduction PGN-EDODM1 Reduced Pathogenic Nuclear Foci, Liberated MBNL1 and Corrected Mis-Splicing in Patient Cells with Long CUG Repeats Immortalized myoblasts from healthy individual or DM1 patient with 2600 CTG repeats were cultured then differentiated for 4 days into myotubes
Slide 12: Multiple Doses Led to Greater Improvement in Splicing Correction and Myotonia vs Single Dose
Multiple Doses of PGN-EDODM1 Led to Greater Improvement in Splicing Correction and Myotonia vs Single Dose in Preclinical Studies Protocol: HSALR mice received 1 or 4 doses of PGN-EDODM1, with 4-week intervals between doses. Skeletal muscle tissues were collected 4 weeks post-final dose. Skeletal mu
Slide 13: PGN-EDODM1 – FREEDOM SAD Trial in DM1
PGN-EDODM1 – FREEDOM SAD Trial in DM1
Slide 14: FREEDOM: Phase 2 PGN-EDODM1 Single-Ascending Dose Study Design
FREEDOM: Phase 1 PGN-EDODM1 Single-Ascending Dose Study Design DSMB: data safety monitoring board; IV: intravenous; PBO: placebo; SAD: single-ascending dose; PK: pharmacokinetics PGN-EDODM1 dose Multinational, randomized, double-blind, placebo-controlled SAD study in patients Single IV administratio
Slide 15: PGN-EDODM1 Produced Dose-Dependent Best-in-Class Splicing Correction Following Single Dose
PGN-EDODM1 Produced Dose-Dependent Best-in-Class Splicing Correction Following Single Dose Splicing Index Changes: 22-Gene Panel* at D28 Improvement -53.7% -29.1% 3.3% -12.3% 87.5% of participants across all doses showed improved splicing % Mean change from baseline Placebo1 (n=5) 5 mg/kg (n=6) 10 m
Slide 16: Natural History Data in Untreated DM1 Patients
Natural History Data in Untreated DM1 Patients* +70% +50% >20% Worse Splicing Worsens (% Change from Baseline) ~15% of untreated patients > +70% OUTLIER occurs in <2.6% of cases in natural history +20% 0% −20% −50% −70% Splicing Improves (% Change from Baseline) ~74% of untreated patients ~11% of un
Slide 17: Higher Doses Associated with Increased Number of Patients Achieving >20% Splicing Improvement
1.Missing samples due to unavailability of biopsy tissue or sample outside of assay window 2.One subject at 10 mg/kg biopsy was not collected at day 28 due to pseudoaneurysm in connection with biopsy and one participant’s splicing index fell below the pre-specified assay range at baseline and at day
Slide 18: PGN-EDODM1 Demonstrated >20% Splicing Correction in a Majority of Patients at ≥10 mg/kg
PGN-EDODM1 Demonstrated >20% Splicing Correction in a Majority of DM1 Patients after a Single Dose ≥10 mg/kg Splicing Improves (% Change from Baseline) >20% Correction ±20% Splicing Midrange 74% of Untreated Patients +20% 0% −20% −50% −70% Worsening Improvement Placebo SAD: 20% Pts >20% +3.3% Mean S
Slide 19: Greater Than Dose-Proportional Increase in Muscle Tissue Concentration
1.Missing samples due to unavailability of biopsy tissue 2.One subject at 15mg/kg received 77% of the dose and was still included in the muscle tissue concentration analysis for the cohort * Robust, Greater Than Dose-Proportional Increase in Muscle Tissue Concentration Following Single Dose 5 mg/kg
Slide 20: PGN-EDODM1 Was Generally Well Tolerated, with TEAEs Primarily Mild to Moderate
PGN-EDODM1 Was Generally Well Tolerated, with TEAEs Primarily Mild to Moderate Across Dose Cohorts *As of database lock on December 23, 2025. Unblinded FREEDOM safety data TEAE: treatment-emergent adverse event, SAE: serious adverse event, DLT: Dose limiting toxicity, eGFR(cys): estimated glomerular
Slide 21: PGN-EDODM1 – FREEDOM2 MAD Trial in DM1
PGN-EDODM1 – FREEDOM2 MAD Trial in DM1
Slide 22: FREEDOM2: Phase 2 MAD Study Design
FREEDOM2: Phase 2 MAD Study Design DSMB: data safety monitoring board; FU: follow-up; IV: intravenous; MAD: multiple-ascending dose; PBO: placebo; PK: pharmacokinetics; vHOT: video hand opening test; OLE: open label extension; 10MWT: 10-meter walk run test *The U.S. FDA placed a partial clinical hol
Slide 23: Favorable Emerging Safety Profile of PGN-EDODM1 in FREEDOM2
Any TEAE 7 (87.5) Mild Moderate Severe 4 (50.0) 3 (37.5) 0 (0.0) Any SAE 0 Any related SAE 0 Any AESI or dose-limiting toxicities 0 Any TEAE leading to study withdrawal 0 Any TEAE leading to death 0 Favorable Emerging Safety Profile of PGN-EDODM1; No Increase in Toxicity with Multiple Doses at 5 mg/
Slide 24: FREEDOM2 5 mg/kg Splicing Correction
FREEDOM2 5 mg/kg Splicing Correction Data cutoff date: 04 March 2026 *One patient’s muscle tissue concentration reading was pending at cutoff date. Splicing Analysis -7.3 5 mg/kg Collective Splicing Data Excluding notable splicing outlier mean splicing correction of 22.9% (n=5) Improvement FREEDOM2
Slide 25: FREEDOM2 5 mg/kg Myotonia (vHOT) Trends
FREEDOM2 5 mg/kg Myotonia (vHOT): PGN-EDODM1 Shows Promising Middle Finger vHOT Trends at Lowest Dose Improvement CFB: Change from baseline; SE: Standard error Data cutoff date: 04 March 2026 +2.5s (52% CFB) -2.95s (23% CFB) vHOT Analysis FREEDOM2 MAD Excluding notable splicing outlier, the active g
Slide 26: FREEDOM2 MAD at 10 & 12.5 mg/kg Has Potential to Build Upon Single-Dose Splicing Correction
FREEDOM2 MAD at 10 & 12.5 mg/kg has Potential to Build Upon Robust Single-Dose Splicing Correction Splicing Improves (% Change from Baseline) >20% Correction ±20% Splicing Midrange 74% of Untreated Patients +20% 0% −20% −50% −70% Worsening Improvement Placebo MAD: -6.8% Mean Splicing N=2 Placebo SAD
Slide 27: Promising Safety, Splicing and vHOT Data in FREEDOM2 Lowest Dose
Promising Safety, Splicing and vHOT Data in FREEDOM2 Lowest Dose – Supports Ongoing 10 mg/kg MAD Cohort Data cutoff date: 04 March 2026 AE: Adverse event; SAE: Serious adverse event Company on track to report clinical data from 10 mg/kg multiple dose cohort in November PGN-EDODM1 was generally well-
Slide 28: Summary of PGN-EDODM1 and FREEDOM Program
Summary of PGN-EDODM1 and FREEDOM Program Completed enrollment in the 10 mg/kg MAD cohort of FREEDOM2, with 7 of 8 patients having completed dosing 16 patients have enrolled in the FREEDOM-OLE at 5 mg/kg, including 6 patients from FREEDOM2; OLE now dosing at 10 mg/kg November: FREEDOM2 10 mg/kg clin
Slide 29: Thank you
g Thank you