Agios Enters License Agreement with Alnylam for Novel siRNA for Polycythemia Vera

Rare Daily Staff

Agios Pharmaceuticals said it has entered into an exclusive worldwide license agreement with Alnylam Pharmaceuticals for exclusive worldwide rights to develop and commercialize Alnylam’s novel preclinical siRNA as a potential disease-modifying treatment for patients with the rare blood disease polycythemia vera.

Polycythemia vera (PV) is characterized by excessive production of red blood cells, which leads to increased blood volume and viscosity, and can result in thrombosis, cardiovascular events, and death. There are no disease-modifying treatments for the disease, which affects approximately 100,000 patients in the United States.

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Harnessing the natural biological process of RNAi occurring in our cells gave rise to a new class of medicines known as RNAi therapeutics. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA)—the genetic precursors that encode for disease-causing or disease pathway proteins, thus preventing them from being made.

The siRNA development candidate that Agios licensed targets the knockdown of TMPRSS6, a key driver of red blood cell production. This results in increased hepcidin, reducing iron available to the hematopoietic compartment, thereby reducing red blood cell production. This has the potential to maintain hematocrit within the normal range and reduce the risk of complications in individuals living with PV. TMPRSS6 siRNA has demonstrated low off-target activity, a favorable safety profile in rats, and a 90 percent knockdown of TMPRSS6 mRNA over three months in non-human primates, supporting the potential for an infrequent dosing regimen.

The agreement leverages Agios’ expertise and capabilities in rare hematologic diseases with Alnylam’s siRNA platform and success in RNA therapies.

Under the terms of the agreement, Agios will make an upfront payment of $17.5 million to Alnylam for an exclusive global license to the TMPRSS6 siRNA program. In addition, Alnylam is eligible to receive up to $130 million in potential development and regulatory milestone payments, in addition to sales milestones and tiered royalties. Agios will assume sole responsibility for all development, regulatory, and commercial activities and costs related to the program. Alnylam will provide manufacturing support for phase 1, after which Agios will assume full responsibility for manufacturing.

“This program is highly aligned with our core scientific expertise, clinical development and commercial capabilities in rare hematology as well as our business development strategy to expand beyond our industry-leading pipeline of PK activators,” said Brian Goff, CEO of Agios.

Photo: Brian Goff, CEO of Agios