LATE-BREAKING AND COVID-19 ORAL COMMUNICATION SESSION ABSTRACTS

ABSTRACT

FLT180a is an investigational gene therapy medicinal product candidate intended for treating HB patients. It includes a novel synthetic capsid, AAVS3, with a higher liver transduction efficiency than wild type AAV, and a codon optimised F9 gene with a gain of function mutation. To assess the safety and efficacy of a single systemic adminis-tration of FLT180a in adult patients with HB. Phase 1/2, multi- centre, ongoing, open- label and long- term follow- up study assessing FLT180a dose levels in an escalating/descending adaptive design, to identify a dose that consistently normalises FIX activity (50- 150%). Participants have severe or moderately severe HB and are negative for neutralis-ing AAVS3 antibodies. Pre- emptive immunosuppression is given to mitigate vector related transaminitis and associated reduction in FIX expression. Ten patients with severe HB have been treated across 4 dose levels, with week 3 FIX activity levels ranging between 24 and 168%. The first two patients, receiving the 4.5e11vg/Kg dose, have stable, therapeutic, FIX activity levels through week 104. No patient has had a bleeding episode requiring FIX concentrates. The most common drug related serious adverse event was transient transaminitis (in four patients) requiring supplemental immunosup-pression. FIX activity levels above 150% have been observed, which were individually assessed for risk of thrombosis, and one patient is being treated with DOACs. Refinement of the immunosuppression regimen for the latest three patients (9.75e11 vg/kg dose) prevented transaminitis during the critical phase (4- 16 weeks). FLT180a achieves clinically meaningful, dura-ble FIX activity levels in patients with HB, associated with in-dependence from FIX replacement therapy and zero treated bleeds. Transient transaminitis was largely averted by prophy-lactic immunosuppression. A dose between 7.5 to 9.75e11vg/Kg can potentially create sustained, normal FIX activity levels in patients with severe HB.