First-in-human study of TN-201, an AAV9 gene replacement therapy in MYBPC3 -associated hypertrophic cardiomyopathy: initial safety, pharmacodynamic, and imaging results from MyPEAK-1

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  Figure 1. TN-201 mechanism of action and immunosuppression, efficacy of TN-201 in MYBPC3-associated HCM. (A) Visual depiction of TN-201, an AAV9-based MYBPC3 gene replacement therapy: investigational therapy utilizes AAV9 serotype—a capsid known for cardiomyocyte tropism—as well as the expression cassette contained therein. The cassette contains two key elements—a copy of the MYBPC3 gene and a cardiac-selective promoter to enhance expression in the target cell. Additionally, a schematic of the Phase 1b/2 trial (MyPEAK-1), depicting the dose cohorts, DSMB review process, and interim outcomes assessed in the trial. (B) Corticosteroid duration and mean daily dose: patients in Cohort 2 were consistently on corticosteroids for much shorter periods than Cohort 1, despite comparable mean daily doses of corticosteroids and the two-fold higher dose of TN-201. Biomarker and echocardiographic assessments may have occurred while patients were on immunosuppression; the effect of those agents on those assessments can be mapped for each patient using their respective immunosuppression duration and the values for their assessments displayed in other panels. (C) MyBP-C protein normalized to myosin was…