LONDON, October 4, 2022 – Freeline Therapeutics Holdings plc (Nasdaq: FRLN) today announced that the first patient has been dosed in the second dose cohort of the Phase 1/2 MARVEL-1 clinical trial of FLT190 in Fabry disease, a debilitating inherited disorder that leads to progressive organ damage and can result in early death as a result of a harmful build-up of fat in cells due to an enzyme deficiency.
“We believe FLT190 has the potential to be a life-changing therapy for people with Fabry disease by providing durable enzyme activity above the normal range with a one-time treatment, and we are excited to have initiated this cohort in MARVEL-1,” said Pamela Foulds, MD, Chief Medical Officer at Freeline. “We have multiple trial sites now open across five countries with more expected to open by year-end. We look forward to reporting updated safety and efficacy data in the first half of next year.”
Freeline recently reached alignment with the U.S. Food and Drug Administration to dose patients in MARVEL-1 in the United States. Efficacy and safety data from the first dose cohort of MARVEL-1 (in which patients received 7.5e11 vg/kg of FLT190) supported progression to the second, mid-dose cohort (1.5e12 vg/kg).
MARVEL-1 is an international, multicenter, adaptive dose-escalation and dose-expansion Phase 1/2 clinical trial in adult men (≥ 18 years) with classic Fabry disease. The trial is evaluating the safety and efficacy of one-time treatment with FLT190 in up to four dose cohorts. Efficacy measures include α-Gal A activity levels and clearance of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) as measured in plasma and urine. In the dose-escalation part, patient dosing is staggered to allow for adequate monitoring of both safety and efficacy. Patients will be monitored for nine months after dosing and will be eligible to participate in a long-term follow-up study for at least five years (MARVEL-2).
About Fabry Disease
Fabry disease is caused by a mutation in the GLA gene, which encodes for the enzyme α-galactosidase A (α-Gal A) that is required to metabolize a certain type of fat called globotriaosylceramide 3 (Gb3). As a result of deficient α-Gal A production or function, Gb3 accumulates in the lysosome of various cell types and causes damage, commonly leading to a variety of painful and debilitating renal, cardiac, skin, neurological, and gastrointestinal conditions. A Gb3 metabolite, called lyso-Gb3, is considered a good biomarker for Fabry disease and may contribute to disease pathogenesis. Fabry disease can lead to 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 and Japan.
About FLT190 for Fabry Disease
FLT190 is a gene therapy candidate designed to generate durable plasma α-Gal A levels above the normal range to enable sufficient enzyme activity in relevant tissues with a one-time treatment. FLT190 uses Freeline’s proprietary AAVS3 capsid to introduce a functional GLA gene into liver cells to produce functional α-Gal A. AAVS3 has been rationally designed to enable effective liver cell transduction and strong and durable enzyme production at low doses and with a good safety profile. From the liver, α-Gal A can circulate in the blood and be taken up by various tissues in the body, where it is transported to the cells and lysosomes and can break down Gb3.
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 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 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.
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 therapy for people with Fabry disease by providing durable enzyme activity above the normal range with a one-time treatment and that the Company expects to open more sites in its MARVEL-1 clinical trial by year end and plans to report updated safety and efficacy data from such trial in the first half of next year, are forward-looking statements. 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Arne Naeveke, PhD
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