Troy Messick

Troy Messick (The Wistar Institute, USA)
"Development of an EBNA1 Inhibitor for the Treatment of NPC: Toward First-in-Human Studies"

• EBNA1 is master regulator of ENBV latency
• ENA1 is the only viral protein expressed in all EBV cancers
• EBNA1 is required for cell transformation and tumorigenesius
• EBNA1 structure is now and druggable
• No EBNA1 orthologs in human proteome predicates a high therapeutic index
• EBNA1 is a druggable target selected 100 fragments, soaked 5 compounds for each crystal
• Collected data
• Candidate selection campaign
• - 90+high quality structure
• Biochemical assay IC50=299 nM
• VK1727, VK
• Xenografts (NSG). VK-2019 10 mpk IP
• C666-1
• MutiLCL
• C15-PDX NPC (Morocco)
• C17-PDX NPC ()
• VK-2019 is effective in NPC-PDX

• 3 mpk, 30, 100 mpk
• Combination of VK2019 and RT (radiotherapy)
• Target engagement studies
• - TGFb are affected by treatment
• - EBV qPCR for C15-PDX (EBNA1 and Bam-HI W
• - EBER-ISH time course expertment
• - Toxicology studies prior to IND
• - Maximum tolerated does (MTD)
• - Dose range finding
• Summary
• - no toxicology findings that preclude further development
• - Observe excellent exposure
• - No severe toxicity observed
• Exposure summary

2016 GRC NPC

Troy Messick (The Wistar Institute, USA) "Development of Small Molecule Inhibitors of EBNA1 for the Treatment of Nasopharyngeal Carcinoma" (Tuesday Poster # 18)

Link to 2016 GRC NPC PA Lieberman page