Portfolio

Our portfolio is a result of high-throuput screening of a diverse library containing lead-like and drug-like compounds to discover small molecule inhibitors of accumulation of insoluble glycogen or polyglucosan bodies, using an APBD patient skin fibroblast cell-based assay. As all Glycogen Storage Diseases (GSDs) share the etiology of excessive normal or malconstructed glycogen, we believe that APBD represents a prototypical GSD and thus development of pharmaceutical inhibitors of glycogen accumulation is likely to benefit most GSDs.

Ex-vivo High-Throughput Screening

Cell-based assay to detect inhibition of polyglucosan accumulation with library of small molecules.
Assay readout: Amylase-resistant fluorescence of Periodic Acid Schiff’s reagent (PAS) staining.
Use of APBD patient derived fibroblasts for screening Software-based analysis of cell images.
Focus on ADMET-compatible (novel and ‘lead-like’) compounds.

APBD patient fibroblasts

Solmesky et al (2017)

Healthy control fibroblasts

The selected compounds were further investigated in vitro and in vivo.

In an APBD mouse model (Gbe^ys/ys), our lead compound, GHF-201 (Compound A), was effective in lowering polyglucosan bodies, improving motility and , carbohydrate burn and lifespan extension.

Furthermore, our extensive cell and in vitro analyses show that GHF-201 targets the lysosomal protein LAMP1 and enhances autophagic flux as well as respiratory and glycolytic ATP production, transforming the adversely excessive glycogen into a useful fuel source.

First In Human – GHF-201 was approved for an Urgent Compassionate Use program in Israel limited to 3 APBD patients.

GHF partnered with LDS to formulate GHF-201 in a highly-bioavailable non-aqueous oral solution, to be administered daily.

The program, led by Prof. Alexander Lossos and his team at Hadassah University Hospital–Ein Kerem, Jerusalem, Israel, enrolled 3 APBD patients, totaling over 8 patient-years, and has shown promising clinical improvements.

The growing knowledge and evidence about GHF-201 suggest that it may offers a new, safe, and efficacious approach to treat APBD and additional glycogen and lysosomal storage disorders, as well as diseases with greater prevalence.

Research and Development

GHF-201 reduces glycogen in target organs of APBD mouse*

*Homozygous for the human mutated GBE gene Gbe^ys/ys

GHF-201 improves motility in APBD mouse*

*Homozygous for the human mutated GBE gene Gbeys/ys

GHF-201 extends survival in the APBD mouse*

*Homozygous for the human mutated GBE gene Gbeys/ys

Vaknin et al, 2021

GHF-201 Mechanism of Action is Known*

GHF-201 modulates lysosomal and autophagy genes

LAMP1 has a pivotal role in lysosome integrity and function

*Determined by NPOT technology

Vaknin et al, 2021

GHF-201 Mechanism of Action is Known*

GHF-201 is a novel compound capable of degrading polyglucans and over-accumulated glycogen
In vivo proof of concept for use of GHF-201 in treating APBD and other glycogen storage disorders
GHF-201 activates auto-lysosomal catabolism
Potential to treat lysosomal storage disorders (LSDs), such as Mucopolysaccharidosis type I (MPS I) and Gaucher disease
GHF-201 reduces nuclear & cellular levels of glycogen