Pepgen Inc. · NASDAQ:PEPG
Pepgen — Investor Presentation (May 2025)
27 slides from Pepgen's investor presentation, May 28, 2025
Slide 1: May 2025 Company Presentation
May 2025 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: PepGen EDO platform and pipeline of neuromuscular therapeutics
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: The Challenge of Oligonucleotides
The Challenge of Oligonucleotides In vitro staining image is shown with 10µM concentration of PMO23 (naked oligonucleotide). C2C12 mouse cells were differentiated for 4 days into myotubes and treated with fluorescently tagged compounds for 24h. PMO: phosphorodiamidate morpholino oligonucleotide Nake
Slide 5: PepGen's EDO: Up to 25X Higher Nuclear Uptake of Oligonucleotide
PepGen’s EDO: Up to 25X Higher Nuclear Uptake of Oligonucleotide Red = oligo PepGen’s EDO Platform Has Been Designed and Developed to Solve this Decades Long Problem In vitro staining image is shown with 10µM conc. of EDO23. C2C12 mouse cells were differentiated for 4 days into myotubes and treated
Slide 6: EDO Technology Increases Cellular Uptake and Endosomal Escape up to 24-Fold
PMO or PPMO dose Tissue analysis HOURS: PMO Delivery in Cells HeLa cells 0 24 EDO Technology Has Been Shown to Increases Cellular Uptake and Endosomal Escape up to 24-Fold Cells were treated with 0.1 to 20 μM HiBiT-conjugate for 24 h. Following live cell measurement, 0.01% digitonin was added and ce
Slide 7: PGN-EDODM1 for DM1
PGN-EDODM1 for DM1
Slide 8: DM1: PGN-EDODM1 Latest Achieved Milestones
FREEDOM-DM1 (Phase 1) open in U.S., Canada and UK; initial data from 5 and 10 mg/kg cohorts Observed favorable emerging safety profile1 Mean splicing correction of 29% after single dose of 10 mg/kg at 28 days post-dosing2 Dose-dependent increases in drug tissue concentration and splicing, from 5 to
Slide 9: 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 10: PGN-EDODM1 Blocking Approach Targets 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 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 Splicing Correction and Myotonia Improvement Preclinically
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: 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 14: 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 15: 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 Summary of Treatment Emergent Adverse Events (TEAEs) 5 m
Slide 16: 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 17: 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 18: PGN-EDODM1 Produced Mean 29% Splicing Correction at 10 mg/kg
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 19: Functional Outcomes Data After Single Dose
Functional Outcomes 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 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 Through February 24, 2025 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 index values w
Slide 21: FREEDOM2 Phase 2 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: Recent Corporate Developments – PGN-EDO51 for DMD
Recent Corporate Developments – PGN-EDO51 for DMD
Slide 23: PGN-EDO51 Update: CONNECT1-EDO51 Did Not Achieve Target Dystrophin Levels
CONNECT1-EDO51 Phase 2 study results did not achieve target dystrophin levels Observed favorable emerging safety profile1 – all treatment-related adverse events were mild Mean maximal exon skipping of 4.26% (mean increase of 3.5%) after 4 doses of 10 mg/kg at 28 days post-dosing Mean maximal dystrop
Slide 24: PGN-EDODM1 Has a Distinct MOA and Greater Exposure
PGN-EDODM1 has a Distinct MOA and Demonstrates Robust Target Engagement and Greater Exposure PGN-EDODM1 (Myotonic Dystrophy Type 1) PGN-EDO51 (Duchenne Muscular Dystrophy) MOA Exposure Target Engagement Binding 1 preRNA can produce one skipped RNA Binding 1 hairpin loop may release multiple MBNL1 pr
Slide 25: PGN-EDODM1 Demonstrates Greater Systemic Exposure in Patients
Systemic Exposure in Humans1 PGN-EDODM1 Demonstrates Greater Systemic Exposure in Patients 0 50000 100000 150000 AUCinf (h*ng/ml) 200000 PGN-EDODM1 (FREEDOM) PGN-EDO51 (HNV SAD) PGN-EDO51 (CONNECT1) 10 mg/kg Participants were dosed with either 10 mg/kg of PGN-EDODM1 (FREEDOM n=6) or PGN-EDO51 (HNV S
Slide 26: Conclusions
Conclusions
Slide 27: Continued Execution Toward Key DM1 Readouts Through 2026
1. As of May 8, 2025 based on current operating plan Continued Execution Toward Key DM1 Readouts Through 2026 with Existing Cash Funding Operations for 12 Months1 Key Expected Data Readouts/ Milestones 2H 2025: FREEDOM 15 mg/kg clinical results Q1 2026: FREEDOM2 5 mg/kg clinical results DM1: PGN-EDO