Pepgen Inc. · NASDAQ:PEPG
Pepgen — IDMC 2026 Late-Breaker
19 slides from Pepgen's conference presentation, May 2026
Slide 1: Analysis of Individual Patient Mis-Splicing Data from PGN-EDODM1 in DM1
Analysis of Individual Patient Mis-Splicing Data from PGN-EDODM1, an Investigational Therapy for Myotonic Dystrophy Type 1 (DM1) James McArthur, PhD, President and CEO, PepGen May 2026 J. Hamel, T. Wheeler, J. Brisson, H. Lochmuller, J. Sampson, N.A. Goyal, H. Phan, N. Johnson, J. Statland, J.B. Lil
Slide 2: Disclosures
Disclosures • Dr. McArthur is an employee of and is paid by PepGen • Dr. McArthur has PepGen stock and stock options • Dr. McArthur is an inventor on patents or patent applications licensed to PepGen 2
Slide 3: 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 4: PepGen is committed to transforming the lives of people with DM1
PepGen is committed to transforming the lives of people and families living with myotonic dystrophy type 1 (DM1). 4
Slide 5: PepGen's EDO Platform Designed to Solve the Oligonucleotide Delivery Challenge
PepGen’s EDO Platform Has Been Designed and Developed to Solve the Delivery Challenge of Oligonucleotides PGN-EDODM1 Delivery to DM1 Patient Myotubes EDO platform results in nuclear delivery of oligonucleotide therapeutics Red = oligo Immortalized myoblasts from a DM1 patient with 2600 CTG repeats w
Slide 6: PGN-EDODM1 Blocking Approach Targets Pathogenic CUGexp Repeats DMPK RNA
PGN-EDODM1 Blocking Approach Targets the Pathogenic CUGexp Repeats DMPK RNA PGN-EDODM1 binds selectively to the pathogenic DM1 is caused by pathogenic DMPK transcripts DMPK transcript Trapped Liberated MBNL1 is MBNL1 inactive and restores correct results in splicing mis-splicing • DM1 is caused by p
Slide 7: FREEDOM: Phase 1 PGN-EDODM1 Single-Ascending Dose Study Design
FREEDOM SAD FREEDOM: Phase 1 PGN-EDODM1 Single-Ascending Dose Study Design Single Dose PGN-EDODM1 or Placebo (randomized 3:1) Baseline DSMB D28 Wk 16 15 mg/kg Biopsy Biopsy Biopsy FREEDOM Phase 1 n=8 or PBO Study Overview Multinational, randomized, double-blind, placebo-controlled Baseline DSMB D28
Slide 8: PGN-EDODM1 Produced Dose-Dependent Best-in-Class Splicing Correction Following Single Dose
FREEDOM SAD PGN-EDODM1 Produced Dose-Dependent Best-in-Class Splicing Correction Following Single Dose Splicing Index Changes: 22-Gene Panel* at D28 % Mean change from baseline Improvement 3.3% 87.5% of participants -12.3% across all doses showed improved splicing -29.1% -53.7% Placebo1 5 mg/kg 10 m
Slide 9: PGN-EDODM1 Was Generally Well Tolerated, with TEAEs Primarily Mild to Moderate
FREEDOM SAD PGN-EDODM1 Was Generally Well Tolerated, with TEAEs Primarily Mild to Moderate Across Dose Cohorts • Most frequent TEAEs: nausea, nasopharyngitis, Placebo Cohort 1 Cohort 2 Cohort 3 Total and headache (n=6) 5 mg/kg 10 mg/kg 15 mg/kg (n=24) N (events) (n=6) (n=6) (n=6) • No electrolyte-re
Slide 10: ~11% of Untreated DM1 Patients Demonstrate >20% Splicing Improvement
Natural History ~11% of Untreated DM1 Patients Demonstrate >20% Splicing Improvement over a 2 to 3 Month Time Period Natural History Data in Untreated DM1 Patients* ~15% OF UNTREATED PATIENTS ~74% OF UNTREATED PATIENTS ~11% OF UNTREATED PATIENTS >20% ±20% >20% Worse Splicing Midrange Correction Spli
Slide 11: Higher Doses Associated with More Patients Achieving >20% Splicing Improvement
FREEDOM SAD Higher PGN-EDODM1 Doses Associated with Increased Number of Patients Achieving >20% Splicing Improvement4 >20% 40 Splicing Worsening 20 (% change from baseline) ±20% 0 Splicing Midrange Splice Index -20 -40 Placebo1 >20% -60 5 mg/kg SAD Splicing Improvement 10 mg/kg SAD2 -80 -100 15 mg/k
Slide 12: PGN-EDODM1 Demonstrated >20% Splicing Correction in Majority of Patients at ≥10 mg/kg
FREEDOM SAD PGN-EDODM1 Demonstrated >20% Splicing Correction in a Majority of DM1 Patients after a Single Dose ≥10 mg/kg ±20% >20% Splicing Midrange Correction 74% of Untreated Patients Splicing Improves (% Change from Baseline) Worsening Improvement +20% 0% −20% −50% −70% Placebo SAD: 5 mg/kg SAD:
Slide 13: FREEDOM2: Phase 2 MAD Study Design
FREEDOM2 MAD FREEDOM2: Phase 2 MAD Study Design 4 Doses of PGN-EDODM1 or Placebo (randomized 3:1) DSMB FREEDOM2 Phase 2 12.5 mg/kg* Safety Biopsy Biopsy FU n=8 Study Overview or PBO Multinational, randomized, double- 7d post final dose blind, placebo-controlled, MAD study open in Canada, UK, NZ, Aus
Slide 14: Favorable Emerging Safety Profile; No Increase in Toxicity with Multiple Doses
FREEDOM2 MAD Favorable Emerging Safety Profile of PGN-EDODM1; No Increase in Toxicity with Multiple Doses at 5 mg/kg Summary of Treatment Emergent PGN-EDODM1 was Generally Well-Tolerated, 5 mg/kg (n=8) Adverse Events (TEAEs)1 n(%) with All AEs Mild or Moderate in Severity1 • All participants complet
Slide 15: FREEDOM2 5 mg/kg Splicing Correction
FREEDOM2 MAD FREEDOM2 5 mg/kg Splicing Correction 5 mg/kg Collective Splicing Data 5 mg/kg Individual Splicing Data Splicing FREEDOM2 5mg/kgAnalysis Mean splicing data FREEDOM2- 5mg/kg Individual Splicing data 20 100 Excluding (Mean % change from baseline ± SE) 80 70.8 notable splicing outlier % cha
Slide 16: Myotonia (vHOT): Promising Middle Finger vHOT Trends at Lowest Dose
FREEDOM2 MAD FREEDOM2 5 mg/kg Myotonia (vHOT): PGN-EDODM1 Shows Promising Middle Finger vHOT Trends at Lowest Dose vHOT Analysis 6 +2.5s Excluding notable splicing outlier, 4 (52% CFB) the active group did not return to 2 baseline (n=5) Improvement 0 Splicing outlier demonstrated -2 -2.95s 22 sec di
Slide 17: FREEDOM2 MAD at 10 & 12.5 mg/kg Potential to Build on Single-Dose Correction
FREEDOM SAD FREEDOM2 MAD at 10 & 12.5 mg/kg FREEDOM2 MAD has Potential to Build Upon Robust Single-Dose Splicing Correction ±20% >20% Splicing Midrange Correction 74% of Untreated Patients Splicing Improves (% Change from Baseline) Worsening Improvement +20% 0% −20% −50% −70% Placebo SAD 5 mg/kg SAD
Slide 18: Summary of PGN-EDODM1 and FREEDOM Trials
Summary of PGN-EDODM1 and FREEDOM Trials 1 Differentiated Delivery Technology PHASE 2 FREEDOM2 MAD & OLE 2 Differentiated Target Promising Safety, Splicing and vHOT Data in FREEDOM2 Lowest Dose – Supports Ongoing 10 mg/kg MAD Cohort FREEDOM STUDY: • Company has completed enrollment in the 10 mg/kg M
Slide 19: Thank you
Thank you Clinical trial participants and their families Clinical site staff and investigators Community and clinical advisors 19