Positive Initial Clinical Data from the B-LIEVE Dose-Confirmation Trial for FLT180a in Hemophilia B Presented at the International Society on Thrombosis and Haemostasis Congress

FLT180a generated protective FIX levels with no bleeding or need for FIX replacement

The treatment was well tolerated with a good safety profile

LONDON, UK I July 10, 2022 I Freeline Therapeutics Holdings plc (Nasdaq: FRLN) today announced the presentation of safety and initial efficacy data from the first cohort of the Phase 1/2 dose-confirmation B-LIEVE trial for FLT180a, the company’s AAVS3-based gene therapy candidate for people with hemophilia B, at the International Society on Thrombosis and Haemostasis (ISTH) Congress being held in London, July 9-13, 2022.

As of the data cut-off of May 23, 2022, a one-time FLT180a dose of 7.7e11 vg/kg generated a rapid increase of coagulation factor IX (FIX), reaching levels in the normal range (93, 92 and 80 IU/dL) for the three patients in cohort 1 through days 77, 56 and 36, respectively. Patients stopped FIX prophylaxis and did not require FIX replacement or experience bleeding following treatment with FLT180a.

The treatment and the prophylactic immune management regimen were well tolerated. No serious adverse events or infusion reactions were observed, and there has been no evidence of FIX inhibitors. All adverse events (AEs) were mild, and most were transient. AEs related to immune management were consistent with the known profiles of corticosteroids and tacrolimus.

Dosing of cohort two was completed in June, with early results showing a similar initial response to FLT180a. Based on the data from cohort one and consistent with the advice of the independent Data Monitoring Committee of the B-LIEVE trial, patients in cohort two received the same dose of FLT180a and prophylactic immune management regimen that were used in the first cohort.

As the data continue to evolve since the data cut-off for cohort one, two patients have experienced a decrease in FIX expression together with a mild and transient increase in liver enzymes. All patients continue to have expression levels above baseline, and no patient has experienced a bleed or required FIX supplementation.

“The initial data show that FLT180a provides rapid and consistent elevations in FIX to normal levels, which can prevent bleeding and the need for regular FIX replacement in people with hemophilia B,” said Pamela Foulds, MD, Chief Medical Officer of Freeline. “Emerging data suggest that while FIX expression was maintained at protective levels, a further refined immune management regimen may be required to avoid mild and transient transaminitis and to sustain FIX levels in the normal range. Potential adjustments in cohort two and forthcoming results from that cohort will help us interpret this further.”

“Our strategy is to advance gene therapy programs that have the potential to deliver best-in-class or first-in-class treatments,” said Michael Parini, Chief Executive Officer of Freeline. “While we continue to believe FLT180a has the potential to deliver a best-in-class gene therapy for people with hemophilia B, the availability of other treatment options and the need to prioritize our valuable resources dictate that we evaluate strategic options for FLT180a. These include, but are not limited to, seeking a partner that would enable the continuation of FLT180a through Phase 3 development.”

“With two other promising programs in Fabry disease and Gaucher disease in the clinic, each with the potential to be first-in-class gene therapy treatments for these debilitating diseases, we will continue to focus our attention and resources on those programs that offer the highest value for patients and Freeline’s shareholders,” said Parini.

The poster #PB0213 entitled “Results from B-LIEVE, a Phase 1/2 Dose-Confirmation Study of FLT180a AAV Gene Therapy in Patients with Hemophilia B” by Guy Young et al. will be presented from 6:30pm-7:30pm BST today and will be made available on the Investors section of Freeline’s website.

About the B-LIEVE Dose-Confirmation Trial

B-LIEVE is a Phase 1/2 dose confirmation trial of FLT180a 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 modeling. The goal of the B-LIEVE trial is to finalize a dose for a pivotal Phase 3 trial that enables predictable and sustained factor IX (FIX) expression at protective levels.

About FLT180a for People with Hemophilia B

Freeline’s FLT180a candidate uses a potent AAVS3 capsid rationally designed for effective targeting and transduction of liver cells and 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 with the goal of normalizing FIX activity in patients with moderately severe 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 gene encoding coagulation factor IX (FIX). 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 may 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.

References

1 Iorio A et al. Annals of Internal Medicine 2019;171(8):540-7

SOURCE: Freeline Therapeutics

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