Freeline Initiates Dosing of Second Cohort in B-LIEVE Dose Confirmation Trial of FLT180a in Hemophilia B
Initial cohort one data suggest predictable and sustained Factor IX normalization, supporting additional dosing at the same low dose with the same optimized, prophylactic immune management regimen
Cohort one effficacy and safety data to be presented at ISTH Congress in July
Start-up activities for pivotal Phase 3 trial on track to begin H1 2023
LONDON, June 14, 2022 (GLOBE NEWSWIRE) -- Freeline Therapeutics Holdings plc (Nasdaq: FRLN) today announced that it has begun dosing the second cohort in its Phase 1/2 B-LIEVE dose confirmation trial of FLT180a in people with hemophilia B. Based on the strength of the data from cohort one and consistent with the advice of an Independent Data Monitoring Committee, patients in cohort two will receive the same low dose (7.7e11 vg/kg) of FLT180a and optimized prophylactic immune management regimen that were used in the first cohort. Dosing of the first cohort was completed in April and initial data from that cohort will be presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress being held July 9-13, 2022 in London, UK.
“The ultimate promise of gene therapy is a functional cure,” said Pamela Foulds, MD, Chief Medical Officer of Freeline. “The initial data from the first B-LIEVE cohort enhance our confidence that a low, one-time dose of FLT180a with a short, prophylactic immune management regimen has the potential to provide a functional cure to people with hemophilia B by delivering predictable and sustained FIX normalization together with a good safety profile. The data also provide confidence in the dosing for our pivotal Phase 3 trial, which we anticipate beginning in 2023 as planned.”
“Our goal is to provide transformative and durable one-time treatments to people with severe chronic diseases. We are working with urgency to advance our therapeutic candidates and are focused on finding the most effective way of bringing them to patients,” said Michael Parini, Chief Executive Officer of Freeline. “FLT180a is on track to deliver proof of concept that our gene therapies have the potential to achieve our goal. We continue to believe that executing in the clinic together with financial discipline and operational excellence will demonstrate Freeline’s value for patients, potential partners and investors alike.”
Freeline plans to report updated B-LIEVE data in the second half of 2022 and the first half of 2023, and initiate Phase 3 start-up activities in the first half of 2023. In parallel, the long-term follow-up of the B-AMAZE dose-finding trial continues to support the company’s belief in the potential of FLT180a to provide a functional cure to people with hemophilia B. In market research, physicians ranked predictable and durable Factor IX level normalization as the preferred attributes of an AAV-based gene therapy so that eligible patients can be free of bleeds.
About the B-LIEVE Dose Confirmation Trial
B-LIEVE is a Phase 1/2 dose confirmation trial of FLT180a manufactured at commercial scale using a short course of prophylactic immune management with the goal of normalizing FIX levels in patients with severe and moderately severe hemophilia B. The starting dose of 7.7e11 vg/kg was selected based on the results of the Phase 1/2 B-AMAZE dose-finding trial and multiple modeling approaches. Freeline expects the B-LIEVE trial to finalize a dose for the pivotal Phase 3 trial intended to consistently enable predictable and sustained Factor IX (FIX) expression in the normal range for people with hemophilia B.
About FLT180a for People with Hemophilia B
Freeline’s FLT180a candidate uses a potent, rationally designed AAVS3 capsid containing an expression cassette encoding a gain of function Padua variant of human Factor IX (FIX). FLT180a has been 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 in patients with moderate and severe hemophilia B. 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 to finalize a dose for a Phase 3 pivotal trial is in progress.
About Hemophilia B
Hemophilia B is a rare, debilitating, hereditary bleeding disorder caused by a defect in the coagulation Factor IX (FIX) gene. Hemophilia B is linked to the X chromosome and mainly affects boys and men; however, women who carry an affected copy of the coagulation factor gene may also experience symptoms. Hemophilia B is classified as mild, moderate or severe, depending on the level of FIX in the blood, and is diagnosed through blood tests. The 2020 Annual Global Survey by the World Federation of Hemophilia estimates that there are approximately 15,000 patients with hemophilia B in the United States, Europe and Japan. A meta-analysis using national registries in Australia, Canada, France, Italy, New Zealand and the UK estimated a prevalence in males of 3.8 in 100,000 or approximately 1 in 30,000.1
About Freeline Therapeutics
Freeline is a clinical-stage biotechnology company developing transformative adeno-associated virus (AAV) vector-mediated systemic gene therapies. The company is dedicated to improving patient lives through innovative, one-time treatments that provide functional cures for inherited systemic debilitating diseases. Freeline uses its proprietary, rationally designed AAV vector, along with novel promoters and transgenes, to deliver a functional copy of a therapeutic gene into human liver cells, thereby expressing a persistent functional level of the missing or dysfunctional protein into the patient’s bloodstream. The company’s integrated gene therapy platform includes in-house capabilities in research, clinical development and commercialization. The company has clinical programs in hemophilia B, Fabry disease, and Gaucher disease Type 1. Freeline is headquartered in the UK and has operations in Germany and the U.S.
This press release contains statements that constitute “forward looking statements” as that term is defined in the United States Private Securities Litigation Reform Act of 1995, including statements that express the opinions, expectations, beliefs, plans, objectives, assumptions or projections of Freeline Therapeutics Holdings plc (the “Company”) regarding future events or future results, in contrast with statements that reflect historical facts. Examples include, among other topics, statements regarding the timing, progress and results of the Company’s Phase 1/2 B-LIEVE dose confirmation clinical trial of FLT180a and data readouts from that trial, whether a dose of 7.7e11 vg/kg will be successful in preserving FIX activity levels in the normal range, and the timing of the Company’s planned pivotal Phase 3 clinical trial of FLT180a or the dose level to be used in such trial. 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Arne Naeveke, PhD
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1 Iorio A et al. Annals of Internal Medicine 2019;171(8):540-7