Targeting Innovation

Arrowhead Research Corporation develops novel drugs to treat intractable diseases by silencing the genes that cause them. Using the broadest portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep and durable knockdown of target genes. Arrowhead’s most advanced drug candidate in clinical development is ARC-520, which is designed to treat chronic hepatitis B infection by inhibiting the production of all HBV gene products.  The goal is to reverse the immune suppression that prevents the body from controlling the virus and clearing the disease. Arrowhead’s second clinical candidate is ARC-AAT, a treatment for a rare liver disease associated with a genetic disorder that causes alpha-1 antitrypsin deficiency.

Lead Products

  • ARC-520 is an RNAi-based therapeutic designed to treat chronic hepatitis B virus (HBV) infection.  It is the first clinical-stage drug candidate from Arrowhead’s Dynamic Polyconjugate® delivery platform. It is designed to treat chronic HBV infection by reducing the expression and release of new viral particles and key viral proteins with the goal of achieving a functional cure for HBV.
  • ARC-AAT is a novel unlocked nucleobase analog (UNA)-containing RNAi-based therapeutic for the treatment of liver disease associated with Alpha-1 Antitrypsin Deficiency (AATD), a rare genetic disease that can severely damage the liver and lungs of affected individuals. The goal of treatment with ARC-AAT is to reduce the production of the mutant Z-AAT protein to prevent and potentially reverse accumulation-related liver injury and fibrosis.

Platform Delivery Technology

 The Dynamic Polyconjugate (DPC®) platform is an RNAi delivery system that has been demonstrated to preferentially deliver to hepatocytes, induce efficient endosomal escape, promote high levels of gene knockdown in multiple animal models, and appears to be well tolerated using a variety of RNAi trigger molecules. It is a modular system that can be optimized on a target-by-target basis and may be targeted in the future to address multiple organ systems and cell types.

Pipeline Development Strategy

Arrowhead’s internal drug pipeline is intended to drive value directly through the clinical development of novel therapeutics and to provide proof of concept for our platform technologies. In addition to our two lead product candidates, ARC-520 and ARC-AAT, we intend to nominate additional clinical candidates that utilize the DPC delivery system. Our core areas of focus for expanding our internal pipeline of RNAi therapeutics are: (1) develop intravenous (IV) administered liver-targeted candidates; (2) develop subcutaneously administered liver-targeted candidates; and (3) explore extra-hepatic targets, including oncology.