Slide 1: Company Presentation
Company Presentation April 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: Driven by our proprietary Enhanced Delivery Oligonucleotide (EDO) platform
Driven by our proprietary Enhanced Delivery Oligonucleotide (EDO) platform, PepGen is creating a pipeline of disease-modifying therapeutics with the potential to safely and effectively target the underlying cause of serious genetic neuromuscular and neurological diseases
Slide 4: PepGen's Pipeline Enabled by EDO Technology
PepGen’s Pipeline Enabled by EDO Technology INVESTIGATIONAL CLINICAL INDICATIONS PRECLINICAL PHASE 1 PHASE 2 PIVOTAL CANDIDATES PROGRAMS PGN-EDO51 DMD – Exon 51 PGN-EDODM1 DM1 – DMPK PGN-EDO53 DMD – Exon 53 • DMD Exon 45, Exon 44 • Neurological diseases Research • Additional neuromuscular diseases N
Slide 5: The Challenge of Oligonucleotides
The Challenge of Oligonucleotides Naked Oligonucleotide (PMO) Naked oligonucleotides do not efficiently penetrate muscle cells and nucleus Red = oligo In vitro staining image is shown with 10µM concentration of PMO23 (naked oligonucleotide). C2C12 mouse cells were differentiated for 4 days into myot
Slide 6: PepGen's EDO Platform Has Been Designed and Developed to Solve this Decades Long Problem
PepGen’s EDO Platform Has Been Designed and Developed to Solve this Decades Long Problem PepGen’s EDO: Up to 25X Higher Nuclear Uptake of Oligonucleotide EDO platform results in nuclear delivery of oligonucleotide therapeutics Red = oligo In vitro staining image is shown with 10µM conc. of EDO23. C2
Slide 7: EDO Technology Has Been Shown to Increase Cellular Uptake and Endosomal Escape up to 24-Fold
EDO Technology Has Been Shown to Increases Cellular Uptake and Endosomal Escape up to 24-Fold PMO Delivery TOTAL CELLULAR UPTAKE ENDOSOMAL ESCAPE in Cells HeLa cells HOURS: 0 24 PMO or PPMO dose PMO EDO Tissue analysis (no peptide) (peptide with hydrophobic core) Cells were treated with 0.1 to 20 μM
Slide 8: PGN-EDODM1 for DM1
PGN-EDODM1 for DM1
Slide 9: 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 • US and EU over 110,000 gene patients • Onset of symptoms variable- • No approved therapies that childhood to adulthood address underlying cause
Slide 10: PGN-EDODM1 Blocking Approach Targets the 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 11: PGN-EDODM1 Reduced Pathogenic Nuclear Foci, Liberated MBNL1 and Corrected Mis-Splicing
PGN-EDODM1 Reduced Pathogenic Nuclear Foci, Liberated MBNL1 and Corrected Mis-Splicing in Patient Cells with Long CUG Repeats Foci Reduction MBNL1 Liberation Mis-Splicing Correction Not Treated Not Treated Across multiple transcripts 69% correction 54% reduction in PGN-EDODM1 Treated PGN-EDODM1 Trea
Slide 12: Multiple Doses of PGN-EDODM1 Led to Greater Improvement in Splicing Correction and Myotonia
Multiple Doses of PGN-EDODM1 Led to Greater Improvement in Splicing Correction and Myotonia vs Single Dose in Preclinical Studies Tissue Concentration Mis-Splicing Correction Correction of Myotonia Skeletal muscle Across multiple transcripts Pinch test 30 mg/kg - quad tissue conc HSALR 1 vs. 4 doses
Slide 13: 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 Biopsy 20 mg/kg n=8 or PBO FREEDOM Study Overview Dosing Baseline DSMB D28 Wk 16 Multinational, randomized, Biopsy Biopsy 15 mg/kg Biopsy double-bli
Slide 14: FREEDOM: Demographics and Baseline Characteristics in First Two Cohorts
FREEDOM: Demographics and Baseline Characteristics in First Two Cohorts Mean (SD) or n (%) Placebo 5 mg/kg 10 mg/kg (n=4) (n=6) (n=6) Age (years) 39.0 (10.9) 36.3 (9.0) 34.7 (8.2) Female, n (%) 3 (75%) 3 (50%) 3 (50%) BMI (kg/m2) 20.0 (3.3) 22.8 (5.0) 22.8 (5.7) Splicing Index 72.3 (16.3) 73.7
Slide 15: Favorable Emerging Safety Profile of PGN-EDODM1
Favorable Emerging Safety Profile of PGN-EDODM11 5 mg/kg 10 mg/kg Summary of Treatment Emergent (n=8)2 (n=8)2 PGN-EDODM1 was Generally Well-Tolerated Adverse Events (TEAEs) n(%) n(%) • Treatment-related TEAE reported in >1 participant was nausea Any related TEAE 1 (13) 3 (38) • SAE related to study
Slide 16: PGN-EDODM1 Demonstrated Normal Mean Serum Creatinine Levels
PGN-EDODM1 Demonstrated Normal Mean Serum Creatinine Levels Serum Creatinine Serum Creatinine 1.6 Serum Creatinine (mg/dL) ULN(M) 1.4 1.2 ULN(F) 1.0 All participants in Mean 0.8 both cohorts 0.6 remained below ULN 0.4 0.2 0.0 BL 12H 2 3 7 14 28 Days Post Single Dose 1 * 1 PGN-EDODM1 5 mg/kg (n=8) PG
Slide 17: PGN-EDODM1 Robust and Dose-Dependent Increase in Muscle Tissue Concentration
PGN-EDODM1 Observed to Have Robust and Dose-Dependent Increase in Muscle Tissue Concentration Following Single Dose Muscle Tissue Concentration at D28 44.1 13.7 (n=5)1 * 1. One participant’s biopsy was not collected at Day 28 due to pseudoaneurysm in connection with biopsy procedure SEM: standard er
Slide 18: 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 7.5 5 / 6 splicing 3 / 4 splicing Each participant with Improvement correction correction splicing correction in 10 mg/kg cohort showed >17% correction -12.3 -29.1 1. Provenz
Slide 19: Functional Outcomes Data After Single Dose
Functional Outcomes Data After Single Dose 10-Meter Walk Run Test (10MWRT) at D28 Myotonia (vHOT) at D28 Improvement Improvement -0.35 vHOT: video hand opening time 19
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 Dose-dependent Favorable Dose-dependent increases in emerging safety increase in drug evaluable patients2 profile1 in patients tissue in mean splicing with myotonic concentration correction dystrophy type 1 observed in f
Slide 21: FREEDOM2 Phase 2 MAD Study Underway
FREEDOM2 Phase 2 MAD Study Underway 4 Doses of PGN-EDODM1 or Placebo (randomized 3:1) DSMB Safety FU 20 mg/kg Biopsy Biopsy FREEDOM2 Study Overview n=8 or PBO Multinational, randomized, double- blind, placebo-controlled, MAD study open in UK and Canada DSMB Safety FU 10 mg/kg Biopsy Biopsy n=8 IV ad
Slide 22: PGN-EDO51 for DMD
PGN-EDO51 for DMD
Slide 23: Duchenne Muscular Dystrophy (DMD) Overview and Unmet Medical Need
Duchenne Muscular Dystrophy (DMD) Overview and Unmet Medical Need Overview Market opportunity • Caused by mutations in • US and EU ~40,000 patients dystrophin gene resulting in progressive muscle damage • ~13% of patients amenable to exon 51 skipping approach • Onset of symptoms in early childhood •
Slide 24: Healthy Volunteer Study Results Led to CONNECT1: Robust Exon 51 Skipping
Healthy Volunteer Study Results Led to CONNECT1: Robust Exon 51 Skipping in Humans Following Single Dose of PGN-EDO51 Phase 1 Healthy Volunteer (HV) Trial Design Trial Results: Exon Skipping (Biceps) • Study population: Healthy adult males (N=32; 8 per cohort, 3:1 PGN-EDO51:placebo) 1.4% 2.0% • Dosi
Slide 25: CONNECT1: Designed to Establish Proof-of-Concept and Inform CONNECT2
CONNECT1: Designed to Establish Proof-of-Concept and Inform CONNECT2 Clinical Trial Design Open Label Study in Patients with DMD Amenable to Exon 51 Skipping Therapy Long-term extension study (LTE) CONNECT1 Study Overview Wk 16 DSMB Dosing* Biopsy Biopsy Open label, multiple ascending dose n=4 All p
Slide 26: CONNECT1 5 mg/kg: Baseline Characteristics of Participants
CONNECT1 5 mg/kg: Baseline Characteristics of Participants (n=3) Mean (SD) Age (years) 11.7 (1.5) BMI (kg/m2) 19.8 (2.7) Height (cm) 132.0 (9.9) Weight (kg) 34.4 (3.9) Age of DMD genetic diagnosis (years) 6.3 (1.5) Number of patients on daily corticosteroid dosing regimen 3 Number of ambulatory pati
Slide 27: Favorable Emerging Safety Profile of PGN-EDO51
Favorable Emerging Safety Profile of PGN-EDO511 5 mg/kg 10 mg/kg Summary of Treatment Emergent All Treatment-Related Adverse Events (n=3) (n=4) Adverse Events (TEAEs) Have Been Mild n(%) n(%) Any related TEAE 2 (67) 3 (75) • Treatment-related TEAEs reported in >1 participant were nausea, vomiting an
Slide 28: PGN-EDO51 Showed High Levels of Mean Exon Skipping
PGN-EDO51 Showed High Levels of Mean Exon Skipping1 Exon Skipping 4 doses 6 doses 6 doses 3 mos2 6 mos3 6 mos3 2. PGN-EDO51 muscle biopsy taken approximately 7 days after last dose 3. DYNE-251 muscle biopsy taken approximately 28 days after last dose 1. No head-to-head trials have been conducted com
Slide 29: PGN-EDO51 Produced Greater Muscle Content Adjusted Dystrophin Increase
PGN-EDO51 Produced Greater Muscle Content Adjusted Dystrophin Increase in Half the Treatment Duration and Fewer Doses1 Muscle Content Adjusted Dystrophin 4 doses 6 doses Content Adjusted Dystrophin (%) + SEM 3 mos2 6 mos3 Mean MHC Normalized Muscle 3 0.70 0.44 1.49 1.63 2 1.19 0.79 1 0 BL 3 mos BL 6
Slide 30: PGN-EDO51 Produced Similar Dystrophin Increase in Half the Treatment Duration
PGN-EDO51 Produced Similar Dystrophin Increase in Half the Treatment Duration1 Total (Unadjusted) Dystrophin 4 doses 6 doses 3 mos2 6 mos3 Mean MHC Normalized 1.5 Dystrophin (%) +SEM 0.26 0.28 0.88 1.0 0.61 0.60 0.5 0.34 0.0 BL 3 mos BL 6 mos 5 mg/kg; n=3 5 mg/kg; n=4 PGN-EDO51 DYNE-251 2. PGN-EDO51
Slide 31: CONNECT1 Key Preliminary Takeaways
CONNECT1 Key Preliminary Takeaways • Observed favorable emerging safety profile1 • All patients dosed at 5 mg/kg demonstrated increased exon skipping and dystrophin production and have continued into the long-term extension study • PGN-EDO51 generated encouraging levels of muscle adjusted dystrophin
Slide 32: Conclusions
Conclusions
Slide 33: Key Anticipated Milestones Ahead
Key Anticipated Milestones Ahead • 2H 2025: FREEDOM 15 mg/kg clinical results • Q1 2026: FREEDOM2 5 mg/kg clinical results Key Expected Data Readouts/ Milestones • Q3 2025: CONNECT1 10 mg/kg clinical results 33