Arrowhead Pharmaceuticals utilizes innovative RNA interference (RNAi) technology to develop targeted therapies aimed at silencing disease-causing genes. Their proprietary TRiM™ platform harnesses a natural biological pathway to effectively reduce the expression of specific proteins linked to various diseases. One of their leading drug candidates, Plozasiran (formerly ARO-APOC3), is designed to lower the production of Apolipoprotein-CIII (ApoC3), a protein that plays a critical role in lipid metabolism and is associated with severe hypertriglyceridemia. By inhibiting ApoC3, Plozasiran aims to restore lipid levels to normal, addressing significant unmet medical needs in patients suffering from conditions like familial chylomicronemia syndrome and severe hypertriglyceridemia.

In addition to Plozasiran, Arrowhead is advancing other candidates such as Zodasiran (ARO-ANG3), which targets angiopoietin-like protein 3 (ANGPTL3) to manage dyslipidemia. The company is committed to accelerating the development of its therapies through strategic collaborations and a focus on clinical trials, with a goal of having 20 products in clinical trials or on the market by 2025. Their approach emphasizes not only the scientific exploration of RNAi technology but also the importance of collaboration in reimagining therapeutic development and delivery, ultimately aiming to provide meaningful solutions for patients in need.

United States

Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad 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. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing.

Cardiovascular Diseases

Endocrine System Diseases

Genetic Diseases

Immune System Diseases

Liver Diseases

Lung Diseases

Metabolic Diseases

Musculoskeletal Diseases

Nervous System Diseases

Arrowhead Pharmaceuticals 

Familial chylomicronemia syndrome

ARO-APOC3 is designed to reduce production of Apolipoprotein C-III &nbsp;(apoC-III), a component of triglyceride rich lipoproteins (TRLs) &nbsp;including VLDL and chylomicrons and is a key regulator of triglyceride &nbsp;metabolism. The company believes that knocking down the hepatic &nbsp;production of apoC-III may result in reduced VLDL synthesis and &nbsp;assembly, enhanced breakdown of TRLs, and better clearance of VLDL and &nbsp;chylomicron remnants.
<a href="https://arrowheadpharma.com/pipeline/">Source</a>

Plozasiran (ARO-APOC3)

Liver disease

Severe alpha-1 antitrypsin deficiency

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.
<a href="https://arrowheadpharma.com/pipeline/">Source</a>

Fazirsiran (ARO-AAT) (TAK-999)

Severe hypertriglyceridemia

Plozasiran (ARO-APOC3) 

Dyslipidemia

Plozasiran (ARO-APOC3)  

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.
<a href="https://arrowheadpharma.com/pipeline/">Source</a>

ARO-ANG3 

Zodasiran (ARO-ANG3)

Lung disease

Muco-Obstructive Lung Diseases

ARO-MUC5AC

Asthma

Inflammatory disease

ARO-RAGE is designed to reduce production of the Receptor for Advanced Glycation End products (RAGE) as a potential treatment for various muco-obstructive and inflammatory pulmonary diseases.

ARO-RAGE

C3 Glomerulopathy

IgA nephropathy

Paroxysmal nocturnal hemoglobinuria

Renal disease

ARO-C3, the company’s investigational RNA interference (RNAi) therapeutic is designed to reduce production of complement component 3 (C3). RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein.

ARO-C3 (RNAi)

Idiopathic pulmonary fibrosis

ARO-MMP7 is designed to the reduce expression of matrix metalloproteinase 7 (MMP7) as a potential treatment for idiopathic pulmonary fibrosis (IPF).

ARO-MMP7

Facioscapulohumeral muscular dystrophy

ARO-DUX4 is an investigational RNAi therapeutic designed to reduce expression of the gene that encodes the human double homeobox 4 (DUX4) protein as a potential treatment for FSHD. FSHD is an autosomal dominant disease associated with the failure to maintain complete epigenetic suppression of DUX4 expression in differentiated skeletal muscle, leading to overexpression of DUX4, which is myotoxic and can lead to muscle degeneration. Expression of downstream DUX4 associated genes over time leads to muscle fatty infiltration and progressive muscle weakness. As DUX4 overexpression is the cause of muscle pathology in FSHD patients, it is expected that the selective knockdown of DUX4 messenger RNA transcripts using RNA interference will inhibit DUX4 translation, thereby preventing or reversing downstream myotoxicity and allowing muscle repair and partial or complete return of normal muscle function in patients.

ARO-DUX4

Myotonic Dystrophy Type 1

ARO-DM1

Complement mediated diseases

Kidney disease

ARO-CFB, the company’s investigational RNA interference (RNAi) therapeutic; ARO-CFB is designed to reduce hepatic expression of complement factor B (CFB), which plays an important regulatory role in amplifying complement alternative pathway activation and has been identified as a promising therapeutic target. ARO-CFB is being developed as a potential treatment for complement mediated kidney diseases such as immunoglobulin A nephropathy (IgAN), which is the most common glomerular disease worldwide and carries a high lifetime risk of progression to end-stage renal disease. Additionally, ARO-CFB may have clinical applications in non-renal diseases involving complement activation.

ARO-CFB

Metabolic disorder

Obesity

ARO-INHBE, the company’s investigational RNA interference (RNAi) therapeutic being developed as a potential treatment for obesity.ARO-INHBE is designed to reduce the hepatic expression of the INHBE gene and its secreted gene product, Activin E. INHBE is a promising genetically validated target in which loss-of-function INHBE variants in humans are associated with lower risk of obesity and metabolic diseases, such as type 2 diabetes. Activin E acts as a ligand in a pathway that regulates energy homeostasis in adipose tissue​. Intervening in this pathway with investigational ARO-INHBE treatment has the potential to increase lipolysis, and reduce adipose hypertrophy and dysfunction, visceral adiposity, and insulin resistance.

ARO-INHBE

ARO-ALK7 is designed to silence adipocyte expression of the ACVR1C gene to reduce production of Activin receptor-like kinase 7 (ALK7), which acts as a receptor in a pathway that regulates energy homeostasis in adipose tissue. In large genetic datasets, reduced ACVR1C expression has been associated with healthier adipose distribution and reduced risk of obesity-related metabolic complications. Treatment with investigational ARO-ALK7 has the potential to reduce visceral adiposity and improve lipid and glycemic parameters.

ARO-ALK7

Hepatitis B

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, when used in combination with other direct antivirals. JNJ-3989 is a sub-cutaneous, ribonucleic acid interference (RNAi) therapy candidate which is designed to silence 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 may allow the body’s natural immune defenses to clear the virus and potentially lead to a functional cure.
<a href="https://arrowheadpharma.com/pipeline/">Source</a>

JNJ-3989 (ARO-HBV)

Non-alcoholic steatohepatitis

ARO-HSD is designed to reduce production of HSD17B13, a &nbsp;hydroxysteroid dehydrogenase involved in the metabolism of hormones, &nbsp;fatty acids and bile acids. Human genetic studies indicate that &nbsp;loss-of-function mutations in HSD17B13 provide risk-reduction for &nbsp;development of both alcohol related and non-alcohol related liver &nbsp;disease.
<a href="https://arrowheadpharma.com/pipeline/">Source</a>

Arrowhead Pharmaceuticals

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