Vybion Drug Pipeline



Vybion Drug Pipeline


Huntington's Disease:

  • Huntington's disease affects 5-7 individuals per 100,000 population globally
  • Progressively lethal neurodegenerative disease
  • $2.5B annual cost to healthcare
  • In US 30,000 patients and 150,000 at risk

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 expands the CAG nucleotide encoding glutamine (Q) in the Huntingtin gene of patients to a length beyond 36 repeats of Q which results in disease. Although the precise function of the Huntingtin protein is unclear, it is involved in vesicle transport.


Vybion Intrabodies (INT41)

  • Binds to specific sequences on the Huntingtin proline rich sequence that influences folding of the polyQ expansion and interacts with critical accessory proteins such as Pascin1.
  • The activity of INT41 is strongly linked to its ability to inhibit specific cell-based Pathology
    • Inhibits the accumulation of mutant Huntingtin protein on membranes.
    • Inhibits the ability of toxic fragments of mutant Huntingtin proteins in the nucleus from binding to chromatin
    • Blocks gene dysregulation characteristic of Huntington's disease in human patients
    • Blocks Huntingtin mutant protein aggregation
    • Preferential binding to polyglutamine degradation fragments

In the acute and rapid disease progression R6/2 transgenic animal model, INT41:

  • Blocks the formation of small aggregates of the Huntingtin mutant protein in the brains of animals treated with rAAV6-INT41.
  • rAAV6-INT41 blocks decline of both motor and cognitive function
    • Female transgenic R6/2 mice treated with rAAV6-INT41 are indistinguishable from normal nontransgenic mice in cognitive function

Vybion has assembled a world class team of experts to guide the Company through the remaining preclinical studies and a proof-of-concept (POC) Phase I human clinical trial. The group includes the Bankiewicz Laboratory for Translational Neuroscience Research at UCSF, the global leader in Convection Enhanced Delivery with extensive Gene Therapy experience in preclinical and human clinical trials for neurodegenerative diseases.


Polyglutamine Diseases:

Several inherited neurologic diseases are caused by polyQ expansion. Nine diseases have been identified: Huntington's disease (HD), Alzheimer’s disease (Tau pathologies) (AD), spinobulbar muscular atrophy (SBMA), dentatorubral and pallidoluysian atrophy, and six types of spinocerebellar ataxia (SCA). All patients with polyQ diseases present with progressive degeneration of a population of neurons in the central nervous system that are involved in motor control. Of these, Huntington’s, SBMA and SCA 1, 3 and 7 have proline rich regions that appear to perform a similar function as in Huntington’s and have multiple sites within that proline rich sequence where INT41 may bind. Tau and some exosome secreted fragments of Tau contain up to 5 target sequences for INT41 binding.