Vybion Drug Pipeline
- Huntington's disease affects 5-7 individuals per 100,000 population globally
- Progressively lethal neurodegenerative disease
- No Cure and no effective treatment
- $2.5B annual cost to healthcare
- In US 30,000 patients and 150,000 at risk, 1,550 new cases annually in US
- Mutation in Ht protein: produces aggregate when processed in cell
- Intrabody therapy proven in 4 animal models
Huntington's is an inherited progressive neurological disease that leads to loss of motor and cognitive functions, characterized by the death of specific nerve cells in the brain. Huntington's disease results from a mutation that inserts a large poly glutamine (poly Q) tract in the Huntingtin gene of patients. Aggregation of the Huntingtin protein is the apparent cause of neuron death due to inefficient or defective proteolytic processing. In collaboration with a group at Caltech who developed the first effective Intrabody, Vybion has developed a panel of Intrabodies that restores the processing of the Huntingtin protein protecting affected neurons. A cell-based assay is used to select scFvs that are most effective in correcting this defect. These improved Intrabodies will be tested in animal models of Huntington's disease; these are expected to be superior to the first Caltech Intrabody which reversed clinical disease and increased survival in 30% of animals.
Vybion Intrabodies (INT41)
- Target the Huntingtin mutant protein
- Prevent aggregation of the Huntingtin mutant protein in widely accepted cell-based systems using multiple lines of scientific evidence
- Act with the specificity and efficacy of a Caltech prototype which is similarly effective in cell-based systems and prevents disease progression in widely accepted animal models
- Have solubility characteristics which enable a new mode of delivery to basal ganglion neurons
- INT41, our lead Intrabody, will be tested in the R6/2 animal model in Q1 2012 delivered with AAV2
- Gene therapy in mouse models of huntington disease. Southwell AL, Patterson PH.
Neuroscientist. 2011 Apr;17(2):153-62. Review.
- Perturbation with intrabodies reveals that calpain cleavage is required for degradation of huntingtin exon 1. Southwell AL, Bugg CW, Kaltenbach LS, Dunn D, Butland S, Weiss A, Paganetti P, Lo DC, Patterson PH.
PLoS One. 2011 Jan 31;6(1):e16676.
- Antibody therapy in neurodegenerative disease. Southwell AL, Patterson PH.
Rev Neurosci. 2010;21(4):273-87.
- Intrabody gene therapy ameliorates motor, cognitive, and neuropathological symptoms in multiple mouse models of Huntington's disease. Southwell AL, Ko J, Patterson PH.
J Neurosci. 2009 Oct 28;29(43):13589-602.