Slide 1: CONNECT1-EDO51 5 mg/kg Clinical Data
Exhibit 99.2 CONNECT1-EDO51 5 mg/kg Clinical Data July 30, 2024
Slide 2: Disclaimers
Disclaimers 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,” “goal,” “inte
Slide 3: Agenda
Agenda James McArthur, PhD President and Chief Executive Officer Platform, Key Takeaways, and Closing Remarks Michelle Mellion, MD Chief Medical Officer DMD Landscape and CONNECT1 Clinical Trial Design Hugh McMillan, MD, MSc 1 Pediatric Neurologist, CHEO and CONNECT1 Lead Investigator CONNECT1 5mg/k
Slide 4: Platform and Key Takeaways
Platform and Key Takeaways James McArthur, PhD President and Chief Executive Officer
Slide 5: PepGen's EDO platform and pipeline of disease-modifying 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 disorders.
Slide 6: The Challenge of Oligonucleotides
The Challenge of Oligonucleotides Naked Oligonucleotide (PMO) Naked oligonucleotides do not efficiently penetrate the muscle cells and the nucleus Red = oligo Note: 1. In vitro staining image is shown with 10µM conc. of PMO23 (naked oligonucleotide); 2. C2C12 mouse cells were differentiated for 4 da
Slide 7: PepGen's EDO Platform Designed 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 Note: 1. In vitro staining image is shown with 10µM conc. of
Slide 8: CONNECT1 Key Takeaways
CONNECT1 Key Takeaways • PGN-EDO51 was well tolerated at 5 mg/kg, currently dosing at 10 mg/kg • All patients demonstrated increased exon skipping and dystrophin production and have continued into the long-term extension study • PGN-EDO51 generated the highest levels of mean exon 51 skipping (2.15%)
Slide 9: Dystrophin Production Expected to Increase with Higher Dose and Longer Treatment
Based on These Results, Dystrophin Production Expected to Increase with Higher Dystrophin Transcript PGN-EDO51 generated the highest levels of mean exon 51 skipping seen to date versus all other exon 51 1 skipping therapies at even 2-fold higher doses With higher doses and a longer treatment period
Slide 10: DMD Overview and CONNECT1 Trial Design
DMD Overview and CONNECT1 Trial Design Michelle Mellion, MD Chief Medical Officer
Slide 11: More Effective Therapies are Urgently Needed to Treat DMD
More Effective Therapies are Urgently Needed to Treat DMD Living with Duchenne puts you in front of your own mortality. You’re kind of given a list of things that become impossible. Not that they necessarily do, but that’s the way it seems.” - Mallory, living with DMD 11
Slide 12: PepGen: Developing Potentially Transformative DMD Therapies
PepGen: Developing Potentially Transformative DMD Therapies Potential Addressable US and EU Patient Populations Unmet Need • Current treatments • US and EU ~40,000 patients produce negligible Exon 51 • ~21% patients amenable to: 5,200 amount of dystrophin or Exon 53 severely truncated – PGN-EDO51: P
Slide 13: Healthy Volunteer Study Results Led to CONNECT1
Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Healthy Volunteer Study Results Led to CONNECT1: Highest Levels of 1 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 adu
Slide 14: CONNECT1: Designed to Establish Proof-of-Concept and Inform CONNECT2
CONNECT1: Designed to Establish Proof-of-Concept and Inform CONNECT2-EDO51 Clinical Trial Study Design and Population Endpoints • Open label clinical trial in Canada • Safety and tolerability • DMD patients (n=10) with exon 51 skippable • Dystrophin mutation • Muscle tissue concentration of PGN-EDO5
Slide 15: CONNECT1 Trial Design
CONNECT1 Trial Design Open Label Study in Patients with DMD Amenable to Exon 51 Skipping Therapy Wk 13 Baseline DSMB N=4 TBD mg/kg Wk 13 Baseline DSMB Dosing N=3 10 mg/kg Baseline Wk 13 DSMB Initial data N=3 5 mg/kg readout All 3 patients in LTE PGN-EDO51 dose 15 Screening Biopsy Biopsy Biopsy Biops
Slide 16: PGN-EDO51 Development Path to Support Registration
PGN-EDO51 Development Path to Support Registration Ongoing Fast path to proof-of- concept: Exon skipping and Phase 2: Open-label dystrophin expression at 13 MAD trial in patients weeks Open in Canada Open Potential to support Phase 2: Randomized, 1 accelerated approval : double-blind, placebo- Exon
Slide 17: CONNECT1 5 mg/kg Clinical Data
CONNECT1 5 mg/kg Clinical Data Hugh McMillan, MD, MSc Pediatric Neurologist, Children’s Hospital of Eastern Ontario, and CONNECT1 Lead Investigator
Slide 18: Dystrophin Gene is One of the Largest Genes
Dystrophin Gene is One of the Largest Genes (~2.6 Mb, 79 exons) Full length dystrophin produced 18
Slide 19: Dystrophin Gene with Out of Frame Mutation
Dystrophin Gene with “Out of Frame” Mutation No functional dystrophin produced 19
Slide 20: Mutated Dystrophin Sequence Results in Mutated Transcript
Mutated Dystrophin Sequence Results in Mutated Transcript Exon 51 skipping therapies bind to exon 51 allowing its exclusion 20
Slide 21: Dystrophin Gene After Converting Deletion to In Frame
Dystrophin Gene After Converting Deletion to “In Frame” Restores partial-length dystrophin expression 21
Slide 22: DMD Disease Progression
DMD Disease Progression • Loss of muscle • Progressive • Death from • Symptom onset <6 yo • Loss of ambulation respiratory muscle cardiorespiratory weakness complications (late 20’s) –8 – 11 yo w/o • Cardiomyopathy: Risk corticosteroids increases with age –10 – 14 yo w/ corticosteroids Asher D et al
Slide 23: 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) 2 BMI (kg/m ) 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 pa
Slide 24: CONNECT1 5 mg/kg: PGN-EDO51 Was Well Tolerated
1 CONNECT1 5 mg/kg: PGN-EDO51 Was Well Tolerated n (%) • All treatment emergent adverse events (TEAEs) Any TEAEs, n (%) 3 (100) were mild and resolved Related to study drug 1 (33.3) • Related TEAE was mild (abdominal pain, flatulence) • No discontinuations, dose modifications or dose • Mild 1 (33.3)
Slide 25: PGN-EDO51 Showed >2.5-Fold Mean Exon Skipping
PGN-EDO51 Showed >2.5-Fold Mean Exon Skipping With Fewer Doses and 1 Shorter Treatment Duration Exon Skipping 4 doses 6 doses 2 3 3 mos 6 mos 3 2.15 2.15 2 0.80 0.90 1 0.10 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 muscle biopsy taken approximately 7 days after
Slide 26: PGN-EDO51 Produced 59% Greater Muscle Content Adjusted Dystrophin Increase
PGN-EDO51 Produced 59% Greater Muscle Content Adjusted Dystrophin 1 Increase With Fewer Doses and Shorter Treatment Duration Muscle Content Adjusted Dystrophin 4 doses 6 doses 3 2 3 mos 6 mos 3 0.70 0.44 1.49 1.63 2 1.19 0.79 1 0 BL 3 mos BL 6 mos 5 mg/kg; n=3 5 mg/kg; n=4 PGN-EDO51 DYNE-251 2. PGN-
Slide 27: PGN-EDO51 Produced Similar Total Dystrophin Increase
PGN-EDO51 Produced Similar Dystrophin Increase With Fewer Doses and 1 Shorter Treatment Duration Total (unadjusted) Dystrophin 6 doses 4 doses 3 2 6 mos 3 mos 1.5 0.26 0.28 0.88 1.0 0.61 0.60 0.34 0.5 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 muscle biopsy taken
Slide 28: CONNECT1 Initial 5 mg/kg Data Demonstrated Encouraging Results
CONNECT1 Initial 5 mg/kg Data Demonstrated Encouraging Results Given its tolerability profile to date and promising early dystrophin production, PGN-EDO51 has the potential to improve on current treatment options for DMD patients 28
Slide 29: Closing Remarks
Closing Remarks James McArthur, PhD President and Chief Executive Officer
Slide 30: PGN-EDO51 Has Potential to Be Considerably More Potent
CONNECT1 5 mg/kg Data Suggests PGN-EDO51 Has the Potential to Be 1 Considerably More Potent Mean Exon Skipping Relative to PMO Concentration Mean Mean muscle Doses exon muscle Mean PMO and skipping PMO age conc duration over conc (yrs) (µg/g) baseline (µg/g) 8 per dose ~5 fold ~6-7 fold 5.9 6 PGN-ED
Slide 31: CONNECT1 Key Takeaways
CONNECT1 Key Takeaways • PGN-EDO51 was well tolerated at 5 mg/kg, currently dosing at 10 mg/kg • 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 the highest levels of mean exon 51
Slide 32: 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 33: Key Milestones Ahead
Key Milestones Ahead • CONNECT1 10 mg/kg initial clinical data readout expected in early 2025 • CONNECT2 − Currently open in UK EDO51 − Engaging with EU regulators − Expect to open clinical trial in US by year-end • Update on FREEDOM-DM1 clinical trial expected in Q4 2024 EDODM1 • Initiate dosing of
Slide 34: Thank you!
Thank you! • We sincerely thank patients, families and clinical investigators! • We now look forward to answering your questions 34