Arrowhead Pharmaceuticals, Inc.

Casi M Schienebeck

Tao Pei

Anthony Nicholas

Zhi-Ming Ding

Xiaokai Li

Zhao Xu

Erik W Bush

Grigoriy Shekhtman

Yichen Wang

Teng Ai

Susan Phan

Susan Ramos-Hunter

Jonathan Van Dyke

The present disclosure relates to RNAi agents able to inhibit Complement Factor B (CFB) gene expression. Also disclosed are pharmaceutical compositions that include CFB RNAi agents and methods of use thereof. The CFB RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that comprise N-acetyl-galactosanine, to facilitate the in vivo delivery to hepatocyte cells. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by CFB gene expression, including IgA nephropathy (IgAN), C3 glomerulopathy (C3G), immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN), lupus nephritis (LN), Anti-Glomerular Basement Membrane disease (anti-GBM), ischemia reperfusion injury and T-cell mediated rejection (TCMR) in kidney transplantation, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, age-related macular degeneration (AMD), including early and/or intermediate AMD, geographic atrophy (GA), glaucoma, Doyne honeycomb retinal dystrophy, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), pre-eclampsia, rheumatoid arthritis (RA), and/or other complement-mediated diseases.

RNAi agents for inhibiting expression of complement factor B (CFB), pharmaceutical compositions thereof, and methods of use

Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a Mucin 5AC (MUC5AC) gene. The MUC5AC RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an MUC5AC gene. Pharmaceutical compositions that include one or more MUC5AC RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described MUC5AC RNAi agents to pulmonary epithelial cells, in vivo, provides for inhibition of MUC5AC gene expression and a reduction in MUC5AC production, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including mucoobstructive lung disease such as severe asthma and various cancers.

RNAi agents for inhibiting expression of mucin 5AC (MUC5AC), compositions thereof, and methods of use

Described are RNAi agents, e.g., double stranded RNAi agents, for inhibiting patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene expression. Also disclosed are pharmaceutical compositions that include PNPLA3 RNAi agents and methods of use thereof. The PNPLA3 RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the PNPLA3 RNAi agents in vivo provides for inhibition of PNPLA3 gene expression. The RNAi agents can be used in methods of treatment of PNPLA3-related diseases and disorders, including non-alcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), hepatic fibrosis, and alcoholic or non-alcoholic liver diseases, including cirrhosis.

RNAi agents for inhibiting expression of PNPLA3, pharmaceutical compositions thereof, and methods of use

Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a double homeobox 4 (DUX4) gene. The DUX4 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of a DUX4 gene. Pharmaceutical compositions that include one or more DUX4 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described DUX4 RNAi agents to skeletal muscle cells in vivo, provides for inhibition of DUX4 gene expression and a reduction in DUX4 levels, which can provide a therapeutic benefit to subjects, including human subjects, suffering from certain skeletal muscle-related diseases or disorders including Facioscapulohumeral Muscular Dystrophy (FSHD).

RNAi agents for inhibiting expression of DUX4, compositions thereof, and methods of use

Growing community of inventors

Deerfield, WI, United States of America

Casi M Schienebeck