B-AMAZE long-term follow up data demonstrate sustained FIX expression up to 3.5 years; potential for expression levels in the normal range with relatively low vector doses
B-LIEVE trial to confirm dose and immune management for planned PhaseÂ 3 pivotal trial launched one quarter ahead of latest guidance
LONDON, Dec. 13, 2021 (GLOBE NEWSWIRE) — Freeline Therapeutics Holdings plc (Nasdaq: FRLN) (the “Company” or “Freeline”), a clinical-stage biotechnology company developing transformative AAV-mediated gene therapies for patients suffering from inherited systemic debilitating diseases, today presents 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 63rd American Society of Hematology (ASH) Annual Meeting and Exposition. The event is being held from December 11 – 14, 2021 at the Georgia World Congress Center. Freeline 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.
“The data presented today at ASH demonstrate that FLT180a gene therapy has the potential to deliver a durable, functional cure for hemophilia B,” said Michael Parini, Chief Executive Officer of Freeline. “Patients in the first cohort experienced sustained expression of Factor IX out to 3.5 years following treatment with FLT180a. The data from our B-AMAZE study also informed our B-LIEVE dose-confirmation study, enabling us to identify a dose and prophylactic immune management regimen that we believe can get and keep hemophilia B patients in the normal range of Factor IX expression. These results provide an important proof-of-concept for the Freeline platform, demonstrating the proprietary, rationally designed AAVS3 capsid has the potential to normalize FIX activity in patients with relatively low dosing due to its high potency.”
Mr. Parini continued, “We continue to execute across our programs, initiating the B-LIEVE study, our Phase 1/2 dose confirmation trial, ahead of schedule. We are excited to get this trial started and completed to enable a PhaseÂ 3 pivotal study. Enrollment in the ECLIPSE run-in study for the B-LIEVE trial has proceeded more quickly than expected and, as a result, we believe we have identified a sufficient number of patients to fully enroll the B-LIEVE trial. We look forward to continued progress with FLT180a as we work toward improving the lives of patients with hemophilia B.”
ASH Presentation Highlights
- 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.
- 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
Freeline 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. Freeline 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 hemophiliaÂ B.
Freeline 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.
ASH Poster Presentation Details
|Title:||Factor IX Expression within the Normal Range Prevents Spontaneous Bleeds Requiring Treatment Following FLT180a Gene Therapy in Patients with Severe Hemophilia B: Long-term Follow-up Study of the B-AMAZE Program|
|Presenter:||Pratima Chowdary, MD, MRCP, FRCPath, Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital and University College London|
|Date & Time:||December 13, 2021, 6:00 pm – 8:00 pm ET|
|Session Name:||801. Gene Therapies: Poster III|
The poster presentation is available online on the Investors section of the Freeline website.
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, manufacturing and commercialization. The Company has clinical programs in hemophilia B and Fabry disease, as well as preclinical programs in Gaucher disease Type 1 and hemophilia A. Freeline is headquartered in the UK and has operations in Germany and the US.
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.
Hemophilia is a genetic bleeding disorder caused by a deficiency in clotting factor protein that impairs blood clot formation. In hemophilia B, there is a deficiency of the clotting factor IX (nine) protein. Hemophilia B is an X-linked disease that mainly affects boys and men; however, women who carry an affected copy of the clotting factor gene may also experience symptoms. Hemophilia B affects about one in every 30,000 males. Hemophilia is classified as mild, moderate or severe, depending on the level of clotting factor VIII or IX in the blood and is diagnosed through blood tests.
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 Company’s opinions, expectations, beliefs, plans, objectives, assumptions or projections regarding future events or future results, in contrast with statements that reflect historical facts. Examples include, among other topics, statements regarding the initiation, timing, progress and results of the Company’s clinical trials, including data readouts from the Phase 1/2 B-LIEVE dose-confirmation clinical trial of FLT180a, whether the Company has identified a sufficient number of patients to fully enroll the B-LIEVE trial; and whether a dose of 7.7e11 vg/kg will be successful in preserving FIX activity levels in the normal range. 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Such risks and uncertainties may cause the statements to be inaccurate and readers are cautioned not to place undue reliance on such statements. We cannot guarantee that any forward-looking statement will be realized. Should known or unknown risks or uncertainties materialize or should underlying assumptions prove inaccurate, actual results could vary materially from past results and those anticipated, estimated or projected. Investors are cautioned not to put undue reliance on forward-looking statements. A further list and description of risks, uncertainties and other matters can be found in the Company’s Annual Report on Form 20-F for the fiscal year ended December 31, 2020 and in subsequent reports on Form 6-K, in each case including in the sections thereof captioned “Cautionary Statement Regarding Forward-Looking Statements” and “Item 3.D. 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David S. Arrington
Vice President Investor Relations & Corporate Communications
+1 (646) 668 6947