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

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:

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 or connect with Freeline on LinkedIn and Twitter.