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2 April, 2020 - 15:59 By Tony Quested

Silence is golden as AstraZeneca invests in disease discovery suite

AstraZeneca is investing £80 million inSilence Therapeutics to discover, develop and commercialise small interfering RNA (siRNA) therapeutics for the treatment of cardiovascular, renal, metabolic and respiratory diseases. 

The collaboration draws on Silence’s extensive experience as a leader in the discovery, development and delivery of siRNA therapeutics together with AstraZeneca’s industry leading expertise in disease biology and target identification with the aim of developing first-in-class and differentiated therapeutics to address significant unmet need.

AstraZeneca will make an upfront cash payment of $60 million and an equity investment of $20m in Silence. The parties anticipate initiating work on five targets within the first three years of the collaboration with AstraZeneca having the option to extend the collaboration to a further five targets.

Silence will harness its established GalNAc-siRNA platform to inhibit liver expressed gene targets and the companies will collaborate to achieve targeted delivery of siRNA molecules to other tissues including heart, kidney and lung. 

Delivery of siRNA molecules to the liver hepatocytes is an established approach; targeted delivery to these other tissue types represents a new and compelling opportunity to treat cardiovascular, renal, metabolic and respiratory diseases.

Silence will be responsible for designing siRNA molecules against gene targets selected by AstraZeneca and for manufacturing of material to support GLP toxicology studies and Phase I clinical studies. 

AstraZeneca and Silence will collaborate during discovery phase and AZ will lead clinical development and commercialisation of molecules arising from the collaboration. Silence will have the option to negotiate for co-development of two programs of their choice starting from Phase II.

AstraZeneca will pay Silence an option fee of $10m for each selected target at the point of candidate nomination and thereafter for each target selected Silence will be eligible for up to $140m in development milestones and up to $250m in commercialisation milestones as well as tiered royalties on net sales ranging from high single digit to low double digit.

Mene Pangalos, EVP BioPharmaceuticals R&D, AstraZeneca said: “This collaboration with Silence adds an exciting new modality, siRNA, into our drug discovery toolbox.

“Importantly we can apply this drug modality across our key therapy areas in cardiovascular, renal and metabolism and respiratory to target novel pathways not amenable to more traditional drug discovery approaches.”

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