Pasadena Pharmaceuticals Company Collaborates on Billion-Dollar Deal To Develop New Liver Disease Treatment

Takeda Pharmaceutical Co. and Pasadena-based Arrowhead Pharmaceuticals have announced a collaboration and licensing agreement to develop a new treatment for liver disease and other deadly afflictions. 

The partnership, if approved, would net Arrowhead up to $1.04 billion, including an upfront payment of $300 million and potential development, regulatory and commercial milestones up to $740 million, according to a report appearing at businesswire.com.

The deal hinges on ARO-AAT, a Phase 2 investigational RNA interference therapy in development to treat alpha-1 antitrypsin-associated liver disease (AATLD). ARO-AAT is a potential first-in-class therapy designed to reduce the production of mutant alpha-1 antitrypsin protein, the cause of AATLD progression.

Under terms of the agreement, Takeda and Arrowhead will co-develop ARO-AAT which, if approved, will be co-commercialized in the United States under a 50/50 profit-sharing structure. 

Outside the United States, Takeda will lead the global commercialization strategy and receive an exclusive license to commercialize ARO-AAT, with Arrowhead eligible to receive tiered royalties of 20-25 percent on net sales. 

Closing of the transaction is contingent on completion of review under U.S. antitrust laws, including the Hart-Scott-Rodino Antitrust Improvements Act of 1976.

“AAT-associated liver disease is a devastating condition for which there are no approved therapies. With its RNAi-based mechanism of action, ARO-AAT has the potential to treat the underlying cause of AATLD, thereby helping patients avoid the need for liver transplantation and associated co-morbidities,” said Dr. Asit Parikh, head of the Gastroenterology Therapeutic Area Unit at Takeda in a prepared statement.

“We are excited to collaborate with Arrowhead to bring forward this exciting late-stage liver asset for the Alpha-1 community as part of our growing GI portfolio,” Parikh said. 

“Takeda’s global presence and experience with payers and regulators in the rare disease and GI therapy space, combined with its long history serving the Alpha-1 community make it the ideal partner for ARO-AAT. It is well-positioned to work with the patient and medical community to help meet the severe unmet need of patients with Alpha-1 liver disease,” said Arrowhead President and CEO Christopher Anzalone. 

“This agreement also supports our strategy of using partnering selectively to continue to invest in our Targeted RNAi Molecule (TRiMTM) platform and the growing pipeline of RNAi therapeutics targeting diverse tissue types, while focusing our commercial organization on opportunities in two key areas of cardiometabolic and pulmonary,” Anzalone said.

Alpha-1 Antitrypsin-Associated Deficiency (AATD) is a rare genetic disorder associated with liver disease in children and adults and pulmonary disease in adults. AATD is estimated to affect 1 per 3,000-5,000 people in the United States and 1 per 2,500 in Europe. The protein AAT is primarily synthesized and secreted by liver hepatocytes, cells of the main parenchymal tissue of the liver which make up 80 percent of the liver’s mass. 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.

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.

Researchers at Osaka-based Takeda believe gastro-intestinal (GI) and liver diseases are not just life disrupting conditions, but diseases that can impact a patient’s quality of life. Beyond a fundamental need for effective treatment options, Takeda physicians understand that improving patients’ lives also depends on their needs being recognized. 

With nearly 30 years of experience in gastroenterology, Takeda has made significant strides in addressing GI patient needs with treatments for inflammatory bowel disease (IBD), acid-related Arrowhead Pharmaceuticals, based in Pasadena, 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. 

Takeda Pharmaceutical Co. Ltd. is a global, values-based, research and development-driven biopharmaceutical leader headquartered in Japan, committed to bringing better health and a brighter future to patients by translating science into highly-innovative medicines. Takeda focuses its R&D efforts on four therapeutic areas: oncology, rare diseases, neuroscience, and gastroenterology. 

For more information about Takeda Pharmaceutical Co., visit https://www.takeda.com. For more on Arrowhead Pharmaceuticals, visit www.arrowheadpharma.com, or follow the company  on Twitter @ArrowheadPharma. 

Investors may access a live audio webcast on the company’s website at http://ir.arrowheadpharma.com/events.cfm. For analysts that wish to participate in the conference call, please dial 855-215-6159 or 315-625-6887 and provide Conference ID 1790033.A replay of the webcast will be available on the company’s website approximately two hours after the conclusion of the call and will remain available for 90 days. An audio replay will also be available approximately two hours after the conclusion of the call and will be available for 3 days. To access the audio replay, dial 855-859-2056 or 404-537-3406 and provide Conference ID 1790033.