Metagenomi reports new dose range finding data from MGX-001 hemophilia A program

Metagenomi (MGX) reported new dose range finding data from the company’s MGX-001 hemophilia A program. The data demonstrated curative factor VIII activity in non-human primates and informs a clinical dose regimen strategy for a therapy with treatment potential. Metagenomi intends to advance MGX-001 into clinical development. In this preclinical dose range finding study, a single dose of AAV containing a B-domain deleted human FVIII gene was administered to 24 NHPs in six dose cohorts at varying doses from 5.0e11 vg/kg to 4.0e13 vg/kg followed by a single dose of LNP delivering the proprietary MG29-1 nuclease mRNA and associated guide RNA at either 0.2, 0.6 or 2.0 mg/kg. Each animal received a single dose of corticosteroids prior to both AAV and LNP doses. Therapeutically relevant levels of FVIII activity were achieved in the five highest AAV doses of the six dose cohorts. At a proposed clinical dose of AAV at 5e12 vg/kg and LNP at 0.6 mg/kg, MGX-001 achieved average FVIII activity of 49% within a range of 29.3%-59.5%. The new data demonstrated improved FVIII activity with reduced variability, building upon previously announced results with the B-domain deleted FVIII construct that demonstrated durable FVIII activity over an approximately 19-month study. This earlier NHP study used a cynomolgus version of the FVIII gene to avoid the confounding effects of anti-human FVIII antibodies. MGX-001 has also shown no identifiable off-target editing in a series of orthogonal assays employed to discover and validate potential off-target sites.