Novel Drugs to
Treat Intractable Diseases

Phase 1
Phase 2
Phase 3
  • ARO-AAT (Alpha-1 Liver Disease)
    Alpha-1 Liver Disease
  • ARO-APOC3 (Hypertriglyceridemia)
  • ARO-ANG3 (Dyslipidemia)
  • ARO-HSD (Liver Disease)
    Liver Disease
  • ARO-ENaC (Cystic Fibrosis)
    Cystic Fibrosis
  • ARO-HIF2 (Renal Cell Carcinoma)
    Renal Cell Carcinoma
  • JNJ-3989 (Hepatitis B)
    Hepatitis B
    Partnered with Janssen
  • AMG 890 (Cardiovascular Disease)
    Cardiovascular Disease
    Partnered with Amgen
  • ARO-JNJ1 (Undisclosed)
    Partnered with Janssen
  • Liver
  • Lung
  • Tumor
*Guidance accurate as of August 5, 2019

Pipeline Development Strategy

Arrowhead is focused on developing innovative drugs for diseases with a genetic basis, characterized by the overproduction of one or more proteins. The depth and versatility of our RNAi technologies enable us to address conditions in virtually any therapeutic area and pursue disease targets that are not otherwise druggable by small molecules and biologics.


ARO-AAT is being developed to treat the liver disease associated with alpha-1 antitrypsin deficiency (AATD), a rare genetic disorder that severely damages the liver and lungs of affected individuals.

ARO-AAT is designed to knock down the hepatic production of the mutant alpha-1 antitrypsin (Z-AAT) protein, the cause of progressive liver disease in AATD patients. Reducing production of the inflammatory Z-AAT protein is expected to halt the progression of liver disease and potentially allow it to regenerate and repair.


AATD is a rare genetic disorder associated with liver disease in children and adults and pulmonary disease in adults. AAT is primarily synthesized and secreted by liver hepatocytes. Its function is to inhibit enzymes that can break down normal connective tissue. The most common disease variant, the Z mutant, has a single amino acid substitution that results in improper folding of the protein. The mutant protein cannot be effectively secreted and accumulates in globules inside the hepatocytes. This triggers continuous hepatocyte injury, leading to fibrosis, cirrhosis, and increased risk of hepatocellular carcinoma.

Individuals with the homozygous PiZZ genotype have severe deficiency of functional AAT leading to pulmonary disease and liver disease. Lung disease is frequently treated with AAT augmentation therapy. However, augmentation therapy does nothing to treat liver disease, and there is no specific therapy for hepatic manifestations. There is a significant unmet need as liver transplant, with its attendant morbidity and mortality, is currently the only available cure.

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ARO-APOC3 is designed to reduce production of Apolipoprotein C-III (apoC-III), a component of triglyceride rich lipoproteins (TRLs) including VLDL and chylomicrons and is a key regulator of triglyceride metabolism. The company believes that knocking down the hepatic production of apoC-III may result in reduced VLDL synthesis and assembly, enhanced breakdown of TRLs, and better clearance of VLDL and chylomicron remnants.


Elevated triglyceride levels are an independent risk factor for cardiovascular disease. Severely elevated triglycerides (often over 2,000 mg/dL) in patients with familial chylomicronemia syndrome (FCS), a rare genetic disorder, can result in potentially fatal, acute pancreatitis.

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ARO-ANG3 is designed to reduce production of angiopoietin-like protein 3 (ANGPTL3), a liver synthesized inhibitor of lipoprotein lipase and endothelial lipase. ANGPTL3 inhibition has been shown to lower serum LDL, serum and liver triglyceride and has genetic validation as a novel target for cardiovascular disease.


Hyperlipidemia and hypertriglyceridemia are risk factors for atherosclerotic coronary heart disease and cardiovascular events.

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ARO-HSD is designed to reduce production of HSD17B13, a hydroxysteroid dehydrogenase involved in the metabolism of hormones, fatty acids and bile acids. Human genetic studies indicate that loss-of-function mutations in HSD17B13 provide risk-reduction for development of both alcohol related and non-alcohol related liver disease.


ARO-ENaC is designed to reduce production of the epithelial sodium channel alpha subunit (αENaC) in the airways of the lung. In cystic fibrosis patients, increased ENaC activity contributes to airway dehydration and reduced mucociliary transport.


Cystic fibrosis (CF) is a rare disease caused by a genetic mutation that leads to mucus buildup in the lungs and pancreas. In CF lung disease, patients can have difficulty breathing and experience frequent and persistent lung infections.

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ARO-HIF2 is being developed as a promising new drug candidate for the treatment of clear cell renal cell carcinoma (ccRCC). ARO-HIF2 is designed to inhibit the production of HIF-2α, which has been linked to tumor progression and metastasis in ccRCC. Arrowhead believes it is an attractive target for intervention because over 90% of ccRCC tumors express a mutant form of the Von Hippel-Landau protein that is unable to degrade HIF-2α, leading to its accumulation during tumor hypoxia and promoting tumor growth.

ARO-HIF2 is Arrowhead’s first therapeutic candidate delivered using a new extra-hepatic delivery vehicle.


Renal cell carcinoma is a type of kidney cancer that originates in the cells that line the small tubes that filter waste material from the blood. RCC is the most common type of kidney cancer accounting for more than 90% of cases with approximately 50,000 diagnoses in the U.S. each year.

Unfortunately, patients with advanced stages of RCC have a 5-year survival rate of only 12-25%. Surgical resection is the mainstay of current treatment while chemotherapy and radiation have not been successful at prolonging survival. The treatment options for patients with metastatic disease are extremely limited.

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JNJ-3989, formerly ARO-HBV, is being developed in collaboration with Janssen Pharmaceuticals, Inc. to be a potentially curative therapy for patients with chronic hepatitis B infection. JNJ-3989 silences all HBV gene products and intervenes upstream of the reverse transcription process where current standard-of-care nucleotide and nucleoside analogues act. The company believes this will allow the body’s natural immune defenses to clear the virus and lead to a functional cure.


Chronic hepatitis B infection is the most common serious liver infection. Current drugs suppress viral replication but rarely lead to a cure and therefore must be taken indefinitely. Developing curative therapy is a priority.

There are 16 million people with chronic hepatitis B in the U.S. and Western Europe and 300 million people worldwide. In the immune tolerant phase of chronic infection, which can last for many years, the infected person typically produces very high levels of viral DNA and viral antigens. However, the infection is not cytotoxic and the carrier may have no symptoms of illness. Over time, the ongoing production of viral antigens causes inflammation and necrosis, leading to cirrhosis and liver cancer (HCC). Hepatitis B is responsible for 80% of primary liver cancers.

The current standard of care for treatment of chronic HBV infection is a daily oral dose of nucleotide/nucleoside analogs (NUCs) or a regimen of interferon injections for approximately one year. NUCs are generally well tolerated, but patients may need lifetime treatment because viral replication often rebounds upon cessation of treatment. Interferon therapeutics can result in a functional cure in around 10% of some patient types, but treatment is often associated with significant side effects, including severe flu-like symptoms, bone marrow suppression, and autoimmune disorders.

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AMG 890

AMG 890 (formerly ARO-LPA) is designed to reduce production of apolipoprotein A, a key component of lipoprotein(a), which has been genetically linked with increased risk of cardiovascular diseases, independent of cholesterol and LDL levels. Amgen acquired a worldwide, exclusive license in September 2016, to develop and commercialize AMG 890.


Elevated lipoprotein(a), or Lp(a), is widely viewed as a key risk factor for cardiovascular diseases, including coronary artery disease, atherosclerosis, thrombosis and stroke.

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ARO-JNJ1 is being developed against an undisclosed liver-expressed target as part of a research collaboration and option agreement with Janssen Pharmaceuticals, Inc.