Freeline Publishes Preclinical Proof-of-Concept Data for FLT190, its AAV Gene Therapy Candidate for Fabry Disease, in the Nature Journal Gene Therapy

Data show increased enzyme activity and reduction of harmful substrate, an established biomarker of efficacy in Fabry disease, in key tissues and organs

FLT190 currently being investigated in MARVEL-1 Phase 1/2 clinical trial

LONDON, Jan. 19, 2023 (GLOBE NEWSWIRE) — Freeline Therapeutics Holdings plc (Nasdaq: FRLN) today announced the publication of preclinical proof-of-concept data for its gene therapy candidate for Fabry disease, FLT190, in the Nature journal Gene Therapy. Fabry disease is a debilitating genetic disorder in which an enzyme deficiency leads to a harmful build-up of fat in the cells that causes progressive organ damage and can result in early death.

“People living with Fabry disease can experience debilitating symptoms and disease progression, even with current treatments. There is a pressing need for therapies with more lasting efficacy that are less burdensome on Fabry families,” said Pamela Foulds, M.D., Chief Medical Officer at Freeline. “We are encouraged by these preclinical data that support our ongoing Phase 1/2 clinical trial of FLT190 and our belief in FLT190 as a potential life-changing, one-time therapy for people with Fabry disease.”

Key findings that support development of FLT190 based on the preclinical evaluation in a Fabry mouse model and non-human primates following a single intravenous dose include:

  • Stable and robust long-term expression of α-galactosidase A (α-Gal A), the enzyme that is deficient in Fabry disease.
  • Increases in α-Gal A in plasma and in key tissues, including the kidney and heart.
  • Reduction of globotriaosylsphingosine (lyso-Gb3) to normal levels in plasma, kidney and heart, and reduction of globotriaosylceramide (Gb3) to normal levels in plasma, heart and urine, as well as significant clearance of Gb3 in kidney.
    • Lyso-Gb3 and Gb3 are harmful substrates that accumulate in cells of Fabry patients.
  • No observed toxicities or adverse events related to FLT190.

A link to the publication, “Preclinical evaluation of FLT190, a liver-directed AAV gene therapy for Fabry disease,” can be found here: https://www.nature.com/articles/s41434-022-00381-y

Freeline is currently enrolling patients in the second dose cohort of MARVEL-1, an international, multicenter, adaptive dose-escalation and dose-expansion Phase 1/2 clinical trial in adult men (≥ 18 years) with classic Fabry disease. The company expects to share initial safety and efficacy data from the second dose cohort of MARVEL-1, as well as updated data from the first cohort, in the first half of 2023.

About Fabry Disease
Fabry disease is caused by a mutation in the GLA gene that results in the absence or deficient activity of α-galactosidase A (α-Gal A), an enzyme needed to metabolize a type of fat called globotriaosylceramide (Gb3). As a result of the deficiency, Gb3 accumulates in the lysosome of various cell types, leading to progressive damage to organs, including the kidney, heart and vasculature. Globotriaosylsphingosine (lyso-Gb3), a Gb3 degradation product and substrate of α-Gal A, may also contribute to disease pathology and is an established biomarker for the diagnosis and treatment of Fabry disease. Despite existing therapies, people with Fabry disease can continue to experience debilitating symptoms and even premature death, with renal failure and cardiac disease being the most common causes of death. Fabry disease affects approximately 16,000 people in the United States, European Union, United Kingdom and Japan.

About FLT190
FLT190 is an adeno-associated virus (AAV) gene therapy candidate that is currently being investigated in the MARVEL-1 Phase 1/2 clinical trial in adults with Fabry disease. FLT190 is designed to generate durable increases in α-Gal A levels and reduce substrate accumulation, with the aim of providing a one-time treatment that can stop disease progression and improve outcomes. FLT190 uses Freeline’s proprietary AAVS3 capsid to introduce a functional GLA gene into liver cells to produce α-Gal A. AAVS3 has been rationally designed to enable highly efficient liver cell transduction and durable enzyme production at low doses with a good safety profile. From the liver, α-Gal A can then circulate in the blood to be taken up by various tissues and transported to the cells and lysosomes to break down Gb3.

About Freeline Therapeutics
Freeline is a clinical-stage biotechnology company developing transformative adeno-associated virus (AAV) vector-mediated gene therapies. The company is dedicated to improving patient lives through innovative, one-time treatments for chronic debilitating diseases. Freeline uses its proprietary, rationally designed AAV vector and capsid (AAVS3), 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 is advancing clinical programs in Fabry disease and Gaucher disease Type 1. Freeline is headquartered in the UK and has operations in the United States and Germany. For more information about the company, visit www.freeline.life or connect with Freeline on LinkedIn and Twitter.

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. All statements, other than historical facts, including statements regarding FLT190’s potential to be a life-changing, one-time therapy for people with Fabry disease and that the Company expects to share initial safety and efficacy data from the second dose cohort of the MARVEL-1 Phase 1/2 clinical trial of FLT190, as well as updated data from the first dose cohort, in the first half of 2023, are forward-looking statements. In some cases, you can identify such forward-looking statements by terminology such as “anticipate,” “intend,” “believe,” “estimate,” “plan,” “seek,” “project,” “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, enrollment, continuation, 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; business interruptions resulting from geopolitical actions, including global hostilities, war and terrorism, global pandemics or natural disasters, including earthquakes, typhoons, floods and fires; 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 history, 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. The Company 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 www.sec.gov

Media and Investor Contact:

Naomi Aoki
[email protected]
Senior Vice President, Head of Investor Relations & Communications
+ 1 617 283 4298

error: Content is protected !!