3-HKA Analogs for the Treatment of Autoimmune Diseases

Background & Unmet Need

• Autoimmune disease is the 4th largest cause of disability among women in the United States
• Autoimmune disease has an incidence rate of 4% worldwide, or 300 million individuals, and increasing
• IDO1 catalyzes the first, rate-limiting step of the kynurenine pathway, and is highly expressed in antigen-presenting cells (APCs) in inflammatory conditions dominated by interferon γ (IFN-γ)
• Targeting the kynurenine pathway may help control autoimmune and chronic inflammatory diseases, but which kynurenine to target remains unclear
• Unmet Need: Improved understanding of kynurenine pathway to inform targeted therapy for autoimmune diseases

Technology Overview

• The Technology: Method to treat autoimmune diseases using 3-HKA and its analogs
• The Discovery: 3-hydroxykynurenine (3-HKA) is a previously undescribed biogenic amine with anti-inflammatory and immunosuppressive capabilities in vivo and in vitro
• PoC Data: 3-HKA inhibits the IFN-g-receptor and NF-kB activation (pro-inflammatory cytokines) and decreases inflammatory T-cell proliferation in mouse models of psoriasis, nephrotoxic lupus, and Chron’s disease
• IDO1 knockout (which thus abolishes 3-HKA production) leads to an increase in inflammation, and exacerbates psoriasis in mice models
• The inventors also showed that 3-HKA is the most abundant Trp metabolite in multiple solid tumor types, suggesting antagonism of 3-HKA may have therapeutic applications in cancer immunotherapy

Technology Applications

• Development of 3-HKA and its analogs as potent treatments of autoimmune diseases
• Antagonism of 3-HKA may have therapeutic applications in cancer immunotherapy

Technology Advantages

• Demonstrated efficacy across multiple indications (psoriasis, nephrotoxic lupus, and Chron’s disease)
• 3-HKA is a naturally-occurring metabolite with no known toxicity