6-Ethylthioinosine for the Treatment of Cancers that Overexpress Adenosine Kinase (ADK)

Background & Unmet Need

• The γ-herpesvirus KSHV, also called HHV-8, is the etiological agent of Kaposi’s sarcoma (KS), multicentric Castleman’s disease, and primary effusion lymphoma (PEL)
• KS, the most common malignancy in AIDS patients, is often treatable by antiviral therapy and radiation or chemotherapy
• PEL is a rare HIV-associated non-Hodgkin’s lymphoma (NHL) that is largely a highly aggressive and intractable disease, with rapid progression to death
• Unmet Need: Specific and effective therapeutics for diseases caused by KSHV

Technology Overview

• The Technology: Identification of 6-ethylthioinosine (6-ETI) as a potent inhibitor of cancers that overexpress adenosine kinase (ADK)
• 6-ETI was identified through a high throughput screen of compounds that selectively inhibit NF-κB in a KSHV-infected PEL cell line (LC50=50nM)
• The inventors then demonstrated that 6-ETI is converted into phosphor-6-ETI by ADK, which is commonly overexpressed in several cancers
• PoC Data: 6-ETI is highly effective in both PEL and disseminated multiple myeloma (MM) xenograft mouse models, with significant reduction in tumor burden and prolonged survival
• 6-ETI was also demonstrated to be effective against solid tumors that overexpress ADK, including those with resistance to 1L therapies
• 6-ETI is therefore a promising lead compound for targeted treatment of ADK positive cancers

Technology Applications

• Treatment of plasma cell malignancies including PEL, PBL, and MM
• Treatment of solid tumors with ADK overexpression, such as NSCLC, colorectal, and pancreatic

Technology Advantages

• Precision medicine approach
• Applicable to multiple tumor types
• Demonstrated efficacy in PEL and MM xenograft models
• Overcomes treatment resistance to gemcitabine and erlotinib in pancreatic and NSCLC cancer