Arrowhead Pharmaceuticals, Inc.

Matthew Fowler-Watters

Zhen Li

Jeffrey Carlson

Anthony Nicholas

Erik W Bush

Tao Pei

Agnieszka Glebocka

Rui Zhu

Aaron Almeida

Xiaokai Li

Erich Altenhofer

Dongxu Shu

So Wong

Jonathan D Benson

Patrick Shao

Bo Chen

Angieszka Glebocka

The present disclosure relates to RNAi agents, for example, double stranded RNAi agents, able to inhibit HIF-2 alpha (EPAS1) gene expression. Also disclosed are pharmaceutical compositions that include HIF-2 alpha RNAi agents and methods of use thereof. The HIF-2 alpha RNAi agents disclosed herein may be linked or conjugated to targeting ligands (such as compounds that have affinity for integrins, including alpha-v-beta-3 and alpha-v-beta-5 integrins) and pharmacokinetic (PK) enhancers, to facilitate the delivery to cells and tissues, including to clear cell renal cell carcinoma (ccRCC) cells and tumors. Delivery of compositions comprising the HIF-2 alpha RNAi agents in vivo provides for inhibition of HIF-2 alpha gene expression. The HIF-2 alpha RNAi agents can be used in methods of treatment of various diseases and disorders, including ccRCC.

RNAi agents for inhibiting expression of HIF-2 alpha (), compositions thereof, and methods of use

Integrin ligands having serum stability and affinity for αvβ6 integrins are described. Compositions comprising αvβ6 integrin ligands having serum stability and having affinity for αvβ6 integrins and methods of using them are also described.

Alpha-v beta-6 integrin ligands and uses thereof

Described are improved linking agents that are useful for facilitating the attachment of targeting groups, pharmacokinetic (PK) enhancers or modifiers, or other delivery agents to oligonucleotides. The described linking agents may exhibit improved reaction yields, stability, and biological activity, particularly when used in connection with oligonucleotide-based compounds, such as RNA interference (RNAi) agents.

Trialkyne linking agents and methods of use

Synthetic &#x3b1;v&#x3b2;6 integrin ligands of Formula I having serum stability and affinity for integrin &#x3b1;v&#x3b2;6, which is a receptor expressed in a variety of cell types, are described. The described ligands are useful for delivering cargo molecules, such as RNAi agents or other oligonucleotide-based compounds, to cells that express integrin &#x3b1;v&#x3b2;6, and thereby facilitating the uptake of the cargo molecules into these cells. Compositions that include &#x3b1;v&#x3b2;6 integrin ligands and methods of use are also described. 

Integrin ligands and uses thereof

Integrin ligands having serum stability and affinity for &#x3b1;v&#x3b2;6 integrins are described. Compositions comprising &#x3b1;v&#x3b2;6 integrin ligands having serum stability and having affinity for &#x3b1;v&#x3b2;6 integrins and methods of using them are also described.

Growing community of inventors

Madison, WI, United States of America

Matthew Fowler-Watters