Novel DFG out inhibitors of Abl-kinases to treat PML

DESCRIPTION provided by applicant Inhibikase Therapeutics is a clinical stage biopharmaceutical company that has developed a host targeted mechanism of action to treat AIDS related and drug induced progressive multifocal leukoencephalopathy PML PML is a demyelinating disease of the central nervous system and was rarely seen clinically until the era of the HIV epidemic began in the mid s During the height of the epidemic the rate of PML occurrence rose fold with of patients with a diagnosis of clinical AIDS afflicted by the disease Indeed the PML became the first clinical syndrome associated with the AIDS epidemic With the introduction of immunosuppressive monoclonal antibodies mAb PML has become a growing concern for most mAb therapies in addition to its occurrence in patients with AIDS PML results from pathogenic conversion of the polyomavirus JC a virus that persistently infects adult humans When a patient becomes immunocompromised however JC undergoes a genomic rearrangement converting the virus to a pathogenic form with tropism for brain oligodendrocytes Once infecting brain the infection is lytic and leads to severe dementia loss of limb function and death Despite numerous clinical efforts no polyoma antiviral has been identified a failure that is largely due to the sparse testing landscape for drug discovery and no permissive non human host for JC Inhibikase Therapeutics has taken a different approach and identified host targets that can disrupt JC reproduction in host cells The Company has demonstrated that host Abl kinase inhibition can disrupt JC polyomavirus entry using the anti cancer agent Gleevec as a proof of principle drug substance to define the mechanism of action Gleevec however cannot reach the effective concentration in humans to achieve this effect Chemical library synthesis has discovered agents with up to fold higher antiviral potency and the present proposal will complete the optimization of these compounds to advance them to IND enabling studies in preparation for FDA engagement PUBLIC HEALTH RELEVANCE Inhibikase Therapeutics is a clinical stage biopharmaceutical company developing a novel strategy for treating a fatal infectious disease progressive multifocal leukoencephalopathy that occurs in patients treated with monoclonal antibodies for cancer and autoimmune disease The Companyandapos s products will treat this viral infection and save up to lives and protect more than patients from becoming at risk for this fatal disorder