Kineta has discovered a novel class of broad spectrum small molecule antivirals that function through a host directed mechanism. These compounds have demonstrated an innovative mechanism of action and target several high priority pathogens that are commercially valuable. The lead chromenone-based candidates have potency in the nM range, inhibit multiple viruses including influenza, coronavirus, West Nile, ebola, and dengue virus in vitro and in animal models, have an attractive pharmacologic profile, and are well tolerated in vivo. In this application, we will perform lead optimization and preclinical development of the lead series. The major milestone of the project is to select one or more nominated drug candidates for formal IND-enabling development towards an oral therapeutic for broad respiratory viral infections. Drug treatment to stimulate the host innate immune response is increasingly appreciated as a strategy for therapeutic intervention and has the potential to redefine the paradigm of antiviral drug development. The need for effective antivirals is great, and our approach to stimulate innate immunity in the presence of diverse viral countermeasures has yielded promising leads that are effective against a broad range of RNA and DNA viruses. We have assembled a highly qualified development team that includes the Kineta scientists responsible for the antiviral discovery work and Prof Michael Gale, Jr. of the University of Washington, an expert in innate immunity and the antiviral response.
Public Health Relevance Statement: Public Health Relevance: We have utilized a unique drug discovery strategy to identify potential new antiviral drugs that work by activating a faster, more potent immune response to fight off virus infection. Our goal is to develop lead candidates as oral antiviral drugs for a varety of viruses, including influenza virus, RSV, coronaviruses, and flaviviruses. The lead drugs have shown broad spectrum activity and in vivo efficacy against broad respiratory viruses. The confirmed drug mechanism of action is an innate immune response and they are predicted to be more effective and less prone viral resistance than conventional direct acting therapeutics.
Project Terms: ADME Study; Animal Model; Antiviral Agents; Antiviral Response; Antiviral Therapy; aqueous; Back; base; Biochemical; Biological Assay; Biological Availability; Body Weight decreased; Cells; Characteristics; Chemicals; Clinical; Coronavirus; Data; Dengue Virus; Development; DNA Viruses; Dose; drug candidate; drug development; drug discovery; Drug Kinetics; drug mechanism; Drug or chemical Tissue Distribution; Drug resistance; Ebola virus; efficacy testing; Evaluation; Exhibits; fighting; Flavivirus; Frequencies; Genetic; Goals; Immune response; In Vitro; in vivo; Infection; Influenza; influenzavirus; innovation; Isoflavones; Lead; lead series; Mediating; meetings; Metabolic; Modification; mouse model; Mus; Natural Immunity; Nature; novel; Oral; Organ; pathogen; Pathogenesis; Permeability; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; pre-clinical; Pre-Clinical Model; product development; Property; public health relevance; Qualifying; Resistance; resistant strain; Respiratory Syncytial Virus Infections; respiratory virus; RNA Viruses; Safety; scaffold; Scientist; small molecule; Solubility; Specificity; Staging; Therapeutic; Therapeutic Index; Therapeutic Intervention; Toxicology; Universities; Viral; viral DNA; viral resistance; Viral Respiratory Tract Infection; virology; Virus; Virus Diseases; Virus Replication; Washington; West Nile virus; Work
