In Vivo Agonist Intervention in Established Disease

• Validity of Therapeutic Hypothesis:
  • Human: Smokers have decreased circulating MIF (A)
  • Patient Selection: Genotypic (MIF CATT allele) & serum MIF; low MIF expression is more common in COPD patients
  • Mouse: MIF-deficiency results in spontaneous COPD (B)
• Demonstrated Efficacy:
  • Mouse: Over-expression of MIF prevents spontaneous COPD
  • Mouse: Established smoke-induced COPD is treated by daily oral administration of MIF-20 (C); 3 months
• Chemistry: Multiple MIF agonist compositions of matter; enhanced MIF to CD74 binding