Summary of PepGen Conference Call Company Overview - **Company**: PepGen (NasdaqGS:PEPG) - **Focus**: Development of EDO platform technology for treating myotonic dystrophy type 1 (DM1) Key Points Clinical Study Updates - **FREEDOM-DM1 Clinical Study**: - Early data showed significant splicing improvements: - 5 mg/kg: 12% improvement - 10 mg/kg: 29% improvement - 15 mg/kg: over 50% improvement, a first in DM1 [2][3] - Upcoming data from multiple ascending dose (MAD) study expected in Q1 next year, with a focus on 5 mg/kg and 10 mg/kg doses [3][22] Efficacy and Mechanism - **EDO Technology**: - Engineered to enhance nuclear delivery of therapeutic agents, achieving nearly 100-fold higher delivery compared to traditional methods [5][6] - Targets pathogenic RNA specifically, reducing off-target effects [6] - **Expectations for Splicing Improvement**: - Anticipated that multiple doses will yield greater splicing improvements than single doses, with functional benefits expected to translate from splicing improvements [7][10] Patient Selection and Functional Measures - **Patient Selection for MAD**: - Adjustments made to baseline myotonia requirements to minimize variability in results [9] - **Functional Measures**: - Focus on hand strength and ankle dorsiflexion as key indicators of disease progression [10] - VHOT (Voluntary Hand Opening Test) is a primary endpoint, but the company is exploring other functional measures for potential registration [11][12] Safety Profile - **Safety Data**: - No treatment-emergent adverse events related to kidney observed at 5 and 10 mg/kg doses in DM1 patients [17] - Previous DMD program showed mild to moderate renal biomarker changes, but these were transient and reversible [15][21] - **Dosing Strategy**: - 10 mg/kg is expected to be safe and well-tolerated, with potential for further exploration of higher doses [18] Regulatory Considerations - **FDA Perspective**: - Emphasis on benefit-risk assessment, particularly regarding transient and reversible side effects [20] - The company aims to establish reliable and predictable efficacy endpoints for potential registration [11] Future Plans - **Geographic Expansion**: - Plans to expand clinical studies into multiple geographies to facilitate timely data collection [27] - **Upcoming Data Releases**: - Full data from the 5 mg/kg cohort expected in Q1 next year [25][26] Additional Insights - **Natural History of Disease**: - Limited understanding of how splicing levels correlate with functional outcomes, but improvements in splicing are anticipated to enhance functional benefits [10][12] - **Patient-Centric Focus**: - The company aims to address broader patient needs beyond VHOT, including improvements in mobility, digestion, and overall quality of life [13] This summary encapsulates the key discussions and insights from the PepGen conference call, highlighting the company's advancements in clinical studies, safety profiles, and future directions in the treatment of DM1.

Summary of PepGen Conference Call Company Overview - **Company**: PepGen - **Event**: Guggenheim's 2025 Healthcare Innovations Conference - **Key Presenters**: James McArthur (President and CEO), Paul Strak (EVP and Head of R&D) [1][2] Industry Focus - **Industry**: Neuromuscular diseases - **Technology**: EDO platform technology for delivering therapeutic oligonucleotides [3] Core Points and Arguments 1. **Clinical Study Results**: - Reported a 54% splicing improvement at the top dose of 15 mg/kg in the Freedom clinical study, significantly higher than the previous 22% improvement achieved with a different approach [3][4] - The study showed that the treatment was generally safe, with no serious adverse events reported [4] 2. **Future Expectations**: - Anticipates reporting results from a multiple ascending dose study in Q1 2024, aiming to build upon the 12% splicing improvement seen with a single dose [4][9] - Plans to report data from a second cohort at 10 mg/kg in the second half of 2024, expecting to improve upon the 29% splicing improvement previously reported [4] 3. **Market Potential**: - The DM1 patient population is significantly larger than that of SMA, with no approved therapies currently available for DM1 [5][18] 4. **Therapeutic Index**: - Observed a better-than-dose-dependent increase in muscle concentration and splicing, with mild transient changes in renal function noted [4][5] 5. **Preclinical Data**: - In a mouse model, a three-and-a-half-fold increase in oligo concentration in muscle was observed with multiple doses, leading to nearly complete splicing improvement [6] 6. **Safety Monitoring**: - Safety is monitored in real-time during trials, with a focus on ensuring no adverse effects from the treatment [7] 7. **Regulatory Pathways**: - The company is considering both accelerated approval pathways and a single large phase three study, depending on the outcomes of the ongoing studies [16] 8. **Differentiation from Competitors**: - Emphasizes the unique targeting approach of the EDO platform, which focuses on pathogenic RNA, potentially leading to better outcomes compared to existing therapies [13][18] 9. **Secondary Endpoints**: - Plans to monitor additional endpoints such as 10-meter walk/run and hand grip strength, with optimism for improvements in larger muscle groups [14] 10. **Future Indications**: - While currently focused on DM1, the company is exploring other neuromuscular indications like Charcot-Marie-Tooth for future development [20] Additional Important Points - **Delivery Method**: Currently focused on IV formulation, with no immediate plans to shift to subcutaneous delivery [19] - **Patient Enrollment**: Plans to enroll patients both in the U.S. and internationally for ongoing studies [22] - **Timeline for Data**: Expected data for the 5 mg/kg dose in Q1 2024 and for the 10 mg/kg dose in the second half of 2024 [21][22]