Low Seroprevalence Of Neutralizing Antibodies To Adeno-associated Virus Serotype 9 (AAV9) In Preparation For Mypeak-1, The First-in-Human Study Of TN-201, An Investigational AAV9-mediated Gene Therapy For Individuals With MYBPC3-associated...

Tenaya Therapeutics is developing TN-201, the first AAV9-mediated gene therapy for the leading cause of genetic HCM, MYBPC3 -associated hypertrophic cardiomyopathy (MYBPC3 + HCM). Patients with high levels of preexisting neutralizing antibodies (NAbs) to AAVs may fail to achieve desired transgene expression and/or be at risk of an inflammatory response. There have been no studies assessing AAV9 seroprevalence in MYBPC3 + HCM patients. Tenaya initiated the first observational seroprevalence study of MYBPC3+ HCM patients at US HCM clinics, enrolling participants 18-65 years of age with HCM and with one or more MYBPC3 mutation. Demographics, medical histories, symptom burden, and a single blood draw were collected. NAb titers were assessed via assay. Participants with preexisting NAb titers <1:40 were classified as seronegative to AAV9. Total antibody (TAb) titer to AAV9 was also assessed to compare with NAb titers. By March 2024, 104 participants had enrolled in this study. Median age was 48 years (IQR: 35-56 years) and 65% were male. The majority of participants (57%) had nonobstructive HCM, which included patients post-myectomy. Available data indicate that 78% (69/88) of participants with MYBPC3 + HCM were AAV9 seronegative. Preexisting AAV9 TAb titer strongly correlated with AAV9 NAb. AAV9 serostatus did not vary by gender, age, race, geography, clinical state, or medical history. Results suggest that MYBPC3 + HCM patients in the US have low levels of pre-existing AAV9 NAbs and that most would meet current NAb eligibility for clinical studies of TN-201 gene therapy. Tenaya is enrolling patients in MyPEAK-1, a Phase 1b/2a trial evaluating the safety, tolerability, and exploratory efficacy measures of TN-201 in MYBPC3 + HCM. [ABSTRACT FROM AUTHOR]