Freeline Therapeutics Holdings plc presented long-term follow-up data from its Phase 1/2 B-AMAZE dose-finding trial of FLT180a for the treatment of hemophilia B at the 63rdAmerican Society of Hematology (ASH) Annual Meeting and Exposition. The event is being held from December 11 – 14, 2021 at the Georgia World Congress Center. The company also announced the first trial site in the Phase 1/2 B-LIEVE dose-confirmation trial of FLT180a has been initiated, one quarter ahead of its latest guidance. The Company anticipates an interim data readout from the B-LIEVE trial in the middle of 2022. Key Findings: Results suggest that a dose of 7.7e11 vg/kg, coupled with a short course of prophylactic immune management, has the potential to achieve durable FIX activity in the normal range (50-150%). and thereby prevent spontaneous bleeds and normalize hemostasis in the event of traumatic bleeds. Median follow up of 27.2 months (range 19.1-42.4) post-dosing across 10 patients. Dose-dependent increase in FIX activity observed and FIX expression sustained in nine of 10 patients. Annualized exogenous FIX consumption and bleeding declined after gene therapy. Across the nine of 10 patients with sustained FIX expression after FLT180a treatment, only one reported traumatic bleed was treated with FIX replacement; it occurred in a patient who had an endogenous FIX level of 57% at the time. The data cutoff date was September 20, 2021. Safety: FLT180a was generally well tolerated with a favorable safety profile. No infusion or allergic reactions and no evidence of FIX inhibitors were reported. Transient transaminitis with or without an associated decline in FIX was the most common FLT180a-related adverse event (AE). B-LIEVE Trial Site Initiation: the company has begun to apply these findings to advance the B-LIEVE trial, a Phase 1/2 dose-confirmation trial of FLT180a manufactured at commercial scale and using a starting dose of 7.7e11 vg/kg and a short course of prophylactic immune management. The first trial site was initiated on December 6, 2021. The starting dose of FLT180a in B-LIEVE was selected based on the results of B-AMAZE and multiple modeling approaches. The company expects the B-LIEVE trial will finalize a dose for the planned Phase 3 pivotal trial that is intended to consistently enable FIX expression in the normal range for patients with hemophilia B. The company is currently evaluating the timing of its Phase 3 pivotal trial and filing of a Biologics License Application and will provide more concrete guidance next year. About FLT180a for Hemophilia B: The Freeline hemophilia B program, FLT180a, uses a potent, rationally designed capsid (AAVS3) containing an expression cassette encoding a gain of function Padua variant of human factor IX (FIX). FLT180a was studied in B-AMAZE, a Phase 1/2 dose-finding trial in patients with severe and moderately severe hemophilia B with the goal of normalizing FIX activity. Patients treated in B-AMAZE are being followed in a long-term follow-up study. A Phase 1/2 dose-confirmation trial of FLT180a called B-LIEVE has been initiated.