Assess the safety, tolerability and efficacy of GHF-201 in 3 patients with Adult Polyglucosan Body Disease (APBD) in a Compassionate Use program.

APBD is a frequently misdiagnosed rare neurodegenerative disorder beginning in the 5-6^th decade of life. APBD is caused by mutations in the GBE1 gene, encoding Glycogen Branching Enzyme (GBE1), which endows glycogen its solubility and metabolization. GBE1 deficiency leads to accumulation of polyglucosan bodies (PBs) in various tissues, including neurons and astrocytes, causing progressive neurological symptoms. GHF-201 is an autophagy-inducing agent identified by its ability to reduce PBs in APBD models.

Three APBD patients were dosed with a novel GHF-201 oral formulation (210 mg BID) as part of a Compassionate Use program initiated in June 2021 under strict supervision. Safety measures, including laboratory tests, electrocardiograms, efficacy parameters, including muscle force measured by the Medical Research Council (MRC) scale, and biomarkers (PBs in fibroblasts and PBMC and neurofilament light chain- NfLC in plasma) indicative of disease progression, are analyzed periodically.

Patients were dosed with GHF-201 for over 10 patient years.  GHF-201 was well tolerated with no major safety issues. GHF-201 treatment demonstrated encouraging clinically meaningful improvement over time in muscle force and mobility. These results were corroborated by a statistically significant ~81% reduction in PBs accumulation in skin fibroblasts (p<0.001; two-tailed T-test), 91% reduction in lymphocytes PBs (p<0.0001; two-tailed T-test),  and ~80% reduction in plasma NfLC levels, a quantifiable biomarker for neurodegeneration, were observed  between treatment initiation and the latest assessments for each patient (p<0.0001; ANOVA).

These initial findings indicate that GHF-201 is safe and may have a meaningful positive impact in APBD. The data support advancement to a pivotal study following completion of a Phase I trial.  GHF-201 may have a therapeutic potential in other neurodegenerative disorders involving noxious aggregates.