Tissue-specific KO’s of “Phs1” Phosphatase Prevents NASH

• Validity of Therapeutic Hypothesis:
  • Mouse: global KO protects against high-fat diet (“HFD”)-induced NASH
  • Mouse: liver-specific KO protects against HFD-induced NASH Mouse: liver-specific KO on CDAA diet - Phs1 required to develop NASH (a)
  • Mouse: liver-specific KO protects against HFD-induced NASH (b), elevated liver triglycerides (c), reduces PPARγ and SERP1c mRNAs (d)
  • Mouse: genetically obese (ob/ob) Phs1 KO are protected against NASH (e)
• Drugability of Class: Allosteric site identified and successfully targeted for the structurallyrelated Phs-5 Phosphatase.
  • Commercial: “Phs5” program for multiple fibrosis indications partnered with a top Pharma.
• Faculty Resources:
  • Validated primary and secondary screens established Library of Phs family allosteric scaffolds available for medicinal chemistry
  • Cell lines, mouse models, assays, commercial experience
• IP/Assets: diverse expertise, models, cocrystal structures, published biology and pathway understanding, proven team