Summary of Solid Biosciences Conference Call Company Overview - **Company**: Solid Biosciences (SLDB) - **Focus**: Precision genetic medicine, primarily gene therapy - **Key Programs**: - Duchenne muscular dystrophy (DMD) - Friedreich's ataxia (FA) - Catecholaminergic polymorphic ventricular tachycardia (CPVT) - Upcoming program for dilated cardiomyopathy (TNNT2) in 2026 - **Employee Count**: Approximately 110 employees based in Boston [2][2] Core Points and Arguments Duchenne Muscular Dystrophy (DMD) Program - **Unique Properties**: - Unique capsid and construct with R16, R17 domain for enhanced blood flow and reduced inflammation [4][4] - Modified AAV9 capsid with RGD peptides targeting skeletal and cardiac muscle, showing 20-fold greater cardiomyocyte targeting compared to AAV9 [5][5] - **Dosing and Safety**: - 15 boys aged 5 to 10 have been dosed, with positive safety outcomes including transient nausea and vomiting [8][8] - Fast tapering of steroids post-dosing, with 93% able to taper from day 30 to day 60 [9][9] - **Expression Data**: - High levels of vector genome copies observed, with a focus on positive fiber counts for assessing efficacy [10][10] - Emphasis on muscle integrity and biomarkers like ALT, AST, and troponin to monitor cardiac function [12][13] Upcoming FDA Meeting - **Goals**: Present data and seek a path for accelerated approval, aiming for a registrational study by year-end [21][22] - **Proposed Parameters**: 30-40 patients for safety database, 10% mean expression, and directional clinical benefit compared to natural history [23][24] Friedreich's Ataxia (FA) Program - **Target Population**: Initially targeting patients aged 18 and above, with plans to include younger patients [54][54] - **Administration Method**: Dual-route administration (IV and direct injection into the cerebellum) [55][55] - **Timeline**: First patient dosing expected in Q4 2025, with results anticipated in the first half of 2026 [61][61] Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Program - **Disease Overview**: Characterized by calcium overload due to mutations in the ryanodine channel, leading to arrhythmias [68][68] - **Market Need**: Approximately 20,000 patients in the U.S. with no current drug treatment available [71][71] - **Study Start**: Clinical trials for CPVT expected to begin in Q4 2025 [75][75] Dilated Cardiomyopathy (TNNT2) Program - **Status**: Preclinical data is promising, with no current market drugs or trials available for this condition [76][76] Other Important Insights - **Community Feedback**: Physicians and families show strong belief in gene therapy, with many families eager to participate in trials [48][50] - **Combination Therapy Outlook**: Long-term vision includes potential combination therapies with existing treatments like Skyclarys [52][52] - **Regulatory Challenges**: Emphasis on the importance of a clean safety profile for successful reimbursement and market access [46][46] This summary encapsulates the key points discussed during the Solid Biosciences conference call, highlighting the company's focus on innovative gene therapies and the strategic plans for upcoming clinical trials and regulatory engagements.