Freeline Therapeutics Holdings plc 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. 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 a-galactosidase A (a-Gal A), the enzyme that is deficient in Fabry disease; Increases in a-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. The company 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.