Treatment of NAFLD and NASH

Inventors

Roberts, Brian • Wang, Xueyan • CHOI, YUN-JUNG • Karpf, David • Martin, Robert • McWherter, Charles

Assignees

CymaBay Therapeutics Inc

Abstract

Treatment of NAFLD and NASH by therapy with MBX-8025 or an MBX-8025 salt.

Core Innovation

The document describes an unmet clinical need for therapies for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), and proposes administering MBX-8025 (seladelpar) or a salt thereof to address that need. The background establishes that NAFLD/NASH are associated with dyslipidemia and metabolic and inflammatory abnormalities, motivating treatment goals that include reductions in hepatic fat and circulating biomarkers.

The core treatment concept is the use of seladelpar (MBX-8025), including salt forms such as seladelpar L-lysine dihydrate salt, to provide oral PPARδ agonism. The document characterizes seladelpar as having oral activity as a PPARδ agonist and summarizes previously reported lipid/inflammatory and metabolic effects relevant to NAFLD/NASH.

The document links administration of seladelpar to expected NAFLD/NASH benefits through reductions in hepatic fat by MRI, liver transaminases, inflammatory cytokines, and an apoptosis marker CK18, and to improved lipid and glycemic parameters. It also includes definitions of therapeutically effective amount, allowable salt forms, and describes assessing treatment effects using hepatic fat and biomarker measurements over a time period with reported dose-related improvement.

Claims Coverage

The independent claims provide inventive coverage for administering seladelpar or specific salt forms to subjects with NAFLD or NASH to reduce at least one of LDL-C and triglycerides (TGs), with oral administration and, for the salt-specific independent claim, explicit selection of seladelpar L-lysine dihydrate salt. Across the independent claims, the key inventive features are selection of the compound or salt, selection of the patient population, and selection of the lipid endpoints.

Overall, the claim set covers methods of reducing LDL-C and/or triglycerides in subjects with NAFLD or NASH by administering seladelpar, including salt forms. One independent claim covers the general administration of seladelpar or a salt thereof, while other independent coverage emphasizes oral administration and specifically selects seladelpar L-lysine dihydrate salt.

Stated Advantages

Documented Applications