New England Journal of Medicine Publishes Positive Long-Term Data on Freeline’s Gene Therapy Candidate FLT180a for People with Hemophilia B

Treatment with FLT180a led to durable expression of coagulation factor IX (FIX) and strong decreases in both bleeding rates and need for FIX replacement among patients

LONDON, July 21, 2022 (GLOBE NEWSWIRE) — Freeline Therapeutics Holdings plc (Nasdaq: FRLN) today announced that the New England Journal of Medicine (NEJM) published positive data that expand upon previously announced long-term follow-up data for up to 3.5 years from the Phase 1/2 dose-finding B-AMAZE trial of the company’s AAVS3 gene therapy candidate, FLT180a, for people with hemophilia B, a debilitating inherited bleeding disorder caused by a deficiency in coagulation factor IX (FIX).

“The B-AMAZE long-term data continue to support our confidence that a single dose of FLT180a could protect people with hemophilia B from bleeding and the need for lifelong FIX replacement through durable expression of FIX at protective levels,” said Pamela Foulds, MD, Chief Medical Officer of Freeline.

Key findings published today in the NEJM article “Phase 1-2 Trial of AAVS3 Gene Therapy in Patients with Hemophilia B” by Pratima Chowdary et al. include:

  • All patients had dose-dependent increases in FIX levels following treatment with FLT180a. Nine of 10 patients had sustained FIX activity at a median follow-up of 27.2 (19.1-42.4) months.
  • At the last follow up, five patients had FIX levels in the normal range (51-78%), three patients had levels ranging from 23% to 43%, and one high-dose patient (1.28e12 vg/kg) was at 260%.
  • The mean annualized bleeding rate across all patients decreased from 2.93 (0-7.33) events/year at baseline to 0.71 (0-1.7) events/year after treatment with FLT180a.
  • The mean annualized FIX consumption per patient decreased from 226,026 (83,263-423,333) IU/year at baseline to 9,723 (0-95,532) IU/year.
  • Treatment was generally well tolerated, with transient transaminitis being the most common FLT180a-related adverse event (AE). No patient discontinued infusion or withdrew from the study. No infusion reactions occurred, and no inhibitors to FIX were detected. AEs related to immune management were consistent with the known safety profiles of corticosteroids and tacrolimus.

In the B-AMAZE trial, patients had received one of four doses of FLT180a (3.84e11, 6.4e11, 8.32e11 or 1.28e12 vg/kg) together with a prophylactic immune management regimen. The cutoff date for the published follow-up data was September 20, 2021. The follow-up continues.

“In addition to the promise FLT180a holds for people with hemophilia B, these long-term data demonstrate the potential of our proprietary AAVS3 capsid to enable strong and durable gene expression at low vector doses to effectively treat debilitating inherited diseases with a good safety profile,” said Michael Parini, Chief Executive Officer of Freeline.

“Gene therapy is still a young field that pushes the boundaries of science for people with severe genetic diseases,” said Amit Nathwani, MD, PhD, Professor of Haematology at the University College London Cancer Institute, one of the study authors and co-founder and board member of Freeline. “The B-AMAZE long-term data add to the growing body of evidence that gene therapy has the potential to free patients from the challenges of having to adhere to lifelong therapy or could provide treatment where none exists today.”

About the B-AMAZE Dose-Finding Trial

B-AMAZE was a multicenter, open-label, single-dose Phase 1/2 trial of FLT180a in 10 adult men (≥18 years) with severe (FIX activity <1%) or moderately severe (FIX activity 1-2% with severe bleeding phenotype) hemophilia B. All patients tested negative for AAVS3 neutralizing antibodies prior to enrolling in the trial. The primary endpoints were safety, as assessed by adverse events, and efficacy, as assessed by FIX levels at Week 26. Secondary endpoints included changes in annualized bleeding rates and FIX concentrate consumption, development of FIX inhibitors, and clearance of viral genomes.

Four dose levels were assessed in an ascending/descending adaptive design: 3.84e11, 6.4e11, 8.32e11 and 1.28e12 vector genomes per kilogram (vg/kg). Prophylactic immune management consisted of prednisolone ± tacrolimus. Increases in liver transaminases were treated with prednisolone, tacrolimus, and IV methylprednisolone. Patients were followed for 26 weeks before enrolling in ongoing long-term follow up with the objective to assess safety and durability of FIX normalization for 15 years.

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) present on the X chromosome. Hemophilia B 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.

About University College London (UCL)

UCL is a diverse global community of world-class academics, students, industry links, external partners, and alumni. UCL’s powerful collective of individuals and institutions work together to explore new possibilities. Since 1826, UCL has championed independent thought by attracting and nurturing the world’s best minds. A community of more than 43,800 students from 150 countries and over 14,300 staff pursues academic excellence, breaks boundaries and makes a positive impact on real world problems. UCL is consistently ranked among the top 10 universities in the world and is one of only a handful of institutions rated as having the strongest academic reputation and the broadest research impact. UCL has a progressive and integrated approach to teaching and research – championing innovation, creativity and cross-disciplinary working. UCL teaches its students how to think, not what to think, and sees them as partners, collaborators and contributors. For almost 200 years, UCL is proud to have opened higher education to students from a wide range of backgrounds and to change the way it creates and shares knowledge. UCL was the first in England to welcome women to university education and that courageous attitude and disruptive spirit is still alive today.

Forward-Looking Statements

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 potential of FLT180a to protect people with hemophilia B from bleeding and the need for lifelong FIX replacement, the potential of the Company’s proprietary AAVS3 capsid to enable strong and durable gene expression at low vector doses to effectively treat debilitating inherited diseases with a good safety profile, and the potential of gene therapy to free patients from the challenges of having to adhere to lifelong therapy or provide treatment where none exists today. In some cases, you can identify such forward-looking statements by terminology such as “anticipate,” “intend,” “believe,” “estimate,” “plan,” “seek,” “project” or “expect,” “may,” “will,” “would,” “could” or “should,” the negative of these terms or similar expressions. Forward-looking statements are based on management’s current beliefs and assumptions and on information currently available to the Company, and you should not place undue reliance on such statements. Forward-looking statements are subject to many risks and uncertainties, including the Company’s recurring losses from operations; the uncertainties inherent in research and development of the Company’s product candidates, including statements regarding the timing of initiation, completion and the outcome of clinical studies or trials and related preparatory work and regulatory review, regulatory submission dates, regulatory approval dates and/or launch dates, as well as risks associated with preclinical and clinical data, including the possibility of unfavorable new preclinical, clinical or safety data and further analyses of existing preclinical, clinical or safety data; the Company’s ability to design and implement successful clinical trials for its product candidates; whether the Company’s cash resources will be sufficient to fund the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements for the Company’s expected timeline; the potential for a pandemic, epidemic or outbreak of infectious diseases in the United States, United Kingdom or European Union, including the COVID-19 pandemic, to disrupt and delay the Company’s clinical trial pipeline; the Company’s failure to demonstrate the safety and efficacy of its product candidates; the fact that results obtained in earlier stage clinical testing may not be indicative of results in future clinical trials; the Company’s ability to enroll patients in clinical trials for its product candidates; the possibility that one or more of the Company’s product candidates may cause serious adverse, undesirable or unacceptable side effects or have other properties that could delay or prevent their regulatory approval or limit their commercial potential; the Company’s ability to obtain and maintain regulatory approval of its product candidates; the Company’s limited manufacturing experience, which could result in delays in the development, regulatory approval or commercialization of its product candidates; and the Company’s ability to identify or discover additional product candidates, or failure to capitalize on programs or product candidates. 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, 2021 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. Risk factors.” Many of these risks are outside of the Company’s control and could cause its actual results to differ materially from those it thought would occur. The forward-looking statements included in this press release are made only as of the date hereof. The Company does not undertake, and specifically declines, any obligation to update any such statements or to publicly announce the results of any revisions to any such statements to reflect future events or developments, except as required by law. For further information, please reference the Company’s reports and documents filed with the U.S. Securities and Exchange Commission (the “SEC”). You may review these documents by visiting EDGAR on the SEC website at

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


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