PepGen(US:PEPG)2025-11-13 22:00Summary 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.