Juan Ruiz

Gene Therapy for Krabbe Disease

Juan Ruiz
Senior Vicepresident, Medical Affairs. Forge Biologics

Krabbe disease (KD) is a devastating neurodegenerative disease caused by a lack of
functional galactosylceramidase (GALC) enzyme leading to cytotoxic build-up of
metabolites such as psychosine. Myelin-producing cells are particularly sensitive to
these toxic metabolites, resulting in rapid loss of white matter in the central nervous
system (CNS) and progressive demyelination in the peripheral nervous
system (PNS). Infantile KD usually results in death by age 2. There is currently no
cure for KD. The standard of care for patients with presymptomatic or minimally
symptomatic KD (diagnosed by newborn screening or family history)
is hematopoietic stem cell transplantation (HSCT) which addresses demyelination of
cells in the brain, but motor function continues to decline due to progressive
peripheral neuropathy with death by teen years.

Forge Biologics is developing FBX-101, an AAVrh.10 vector expressing human
GALC, that is systemically delivered by intravenous administration, to correct the
peripheral nerve disease and increase GALC expression in patients with KD that
received HSCT. Two clinical trials, RESKUE and REKLAIM, are ongoing to test the
safety and efficacy of FBX-101 administered during the myeloablation phase post-
HSCT (RESKUE) or at different timepoints post-HSCT (REKLAIM)