Pepgen Inc. · NASDAQ:PEPG
Pepgen — OTS Annual Meeting 2025
17 slides from Pepgen's conference presentation, Oct 22, 2025
Slide 1: OTS Annual Meeting
OTS Annual Meeting October 22, 2025 James McArthur, PhD I am a full time employee of PepGen Inc
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,
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Slide 4: PepGen's EDOs are Empirically Derived to Improve Activity and Tolerability
PepGen’s EDOs are Empirically Derived to Improve Activity and Tolerability First Generation CPPs Next Generation EDOs a a (RXR); Penetratin-like Sequence c ene a Hydrophobic RXRRBRRXR YOQFLI RXRBRXRB Pip6a >) R-tich Hydrophobic Rerich =z —$—$_$_$_____— * <17 amino acids length + Variations in hydrop
Slide 5: PepGen's EDO Platform Has Been Designed and Developed to Solve this Decades Long Problem
Slide 6: EDO Technology can Improve Endosomal Escape and Increase Nuclear Uptake up to 98-Fold
EDO Technology can Improve Endosomal Escape and Has Been Shown to Increase Nuclear Uptake up to 98-Fold PMO Delivery in DM1 Cells CELLULAR UPTAKE NUCLEAR UPTAKE 73x %# $%# 22x &DE)D! &DE)G+ /0$-%('*0NC(2%*+N,"-. !%--/-('*/0C(1%*+0,"-. $" &-,+- &G+,-)E)D! !%" 98x $# 19x !" !%# !# 55x 20x #%" " 15x #
Slide 7: Jubal, retired-professor living with DM1
Jubal, retired-professor living with DI : ansion in the DMPK + U.S. and EU over 115,000 patients * Onse ‘oms variable- * No approved therap childhood to adulthood address underlying Myotonia the disease Muscle weakness — Cardiac arrythmias Loss of lung function Fatigue rage life expectancy is 50-60
Slide 8: 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 9: 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 10: 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 15 mg/kg Biopsy FREEDOM Phase 1 n=8 or PBO1 Study Overview Multinational, randomized, double-blind, placebo-controlled Baseline DSMB D28 Wk 16 SAD
Slide 11: Favorable Emerging Safety Profile of PGN-EDODM1
Favorable Emerging Safety Profile of PGN-EDODM1 5 mg/kg 10 mg/kg 15 mg/kg Summary of Treatment (n=8)* (n=8)*1 (n=8)* Emergent Adverse Events (TEAEs) n(%) n(%) n(%) Any related TEAE 1 (13) 3 (38) 4 (50) • Mild/Moderate 1 (13) 2 (25) 4 (50) • Severe 0 1 (13) 0 (0) Any Serious Adverse Event (SAE) 1 (13
Slide 12: PGN-EDODM1 Continues to Demonstrate Favorable Safety Profile
PGN-EDODM1 Continues to Demonstrate Favorable Safety Profile W;SSE7< PGN-EDODM1 Serum Creatinine in FREEDOM* #$-=>*?-$"@&D&D$ #$-=>*?-$"@&D&D$*A>BRCaE M KEY TAKEAWAYS: . • All kidney AEs were <$"D*c*8S transient and mild or H moderate .LM'N+ • No interventions required F for kidney AEs .LM'2+ • No p
Slide 13: PGN-EDODM1 Produced Mean 53.7% Splicing Correction Following Single 15 mg/kg Dose
PGN-EDODM1 Produced Mean 53.7% Splicing Correction Following Single 15 mg/kg Dose Splicing Index Changes: 22-Gene Panel* at D28 % Mean change from baseline Improvement 3.3% 100% of patients in -12.3% the 15 mg/kg cohort responded to treatment with -29.1% PGN-EDODM1 -53.7% Placebo1 5 mg/kg 10 mg/kg2
Slide 14: Robust, Greater Than Dose-Proportional Increase in Muscle Tissue Concentration
Robust, Greater Than Dose-Proportional Increase in Muscle Tissue Concentration Following Single Dose Muscle Tissue Concentration at *+,-./M."1234+ D28 )'' Mean TA Muscle 56-3+-T8,T96-.:-#A#; 160.6 !"#$" Concentration (ng/g) ('' Mean ± SE C'' 44.1 %%$! 13.7 !&$' ' !"#A%# 5 mg/kg C'"#A%# 10 mg/kg1 C!"
Slide 15: FREEDOM2 Phase 2 MAD Study Underway
FREEDOM2 Phase 2 MAD Study Underway 4 Doses of PGN-EDODM1 or Placebo (randomized 3:1) FREEDOM2 Study Overview DSMB *Exploring protocol TBD mg/kg* Safety Biopsy Biopsy FU amendment to dose n=8 or PBO Multinational, randomized, double- between 10-15 mg/kg blind, placebo-controlled, MAD study open in U
Slide 16: Leveraging EDO Platform to Drive Meaningful Impact for Patients
Leveraging EDO Platform to Drive Meaningful Impact for Patients PGN-EDODM1: Myotonic Dystrophy Type 1 OUR VISION • Best-in-class potential; selectively targets only pathogenic DMPK RNA develop therapies that address • Favorable emerging safety profile and highest splicing correction ever reported in
Slide 17: Thank You!
THANK YOU! Clinical study participants and their families Clinical site staff and investigators Community and clinical advisors Preclinical collaborators 17