AZ adds gene silencing tech to pipeline with Silence Therapeutics deal

AstraZeneca has announced a collaboration with UK biotech Silence Therapeutics to develop gene silencing drugs for cardiovascular, renal, metabolic and respiratory diseases.

The deal could see AZ adding small interfering RNA (siRNA) technology to its pipeline in one of its main areas of research.

Silence Therapeutics says its technology can selectively inhibit any gene in the genome, specifically silencing the production of disease-causing proteins.

The UK biotech says it has achieved an additional level of accuracy by delivering its therapeutic RNA molecules exclusively to target cells.

siRNA is a technology that showed much promise after biologists Andrew Fire and Craig Mello received the Nobel Prize in Physiology or Medicine for discovering the technology in 2006.

But in 2010 it became apparent that it was harder to convert into a working therapy because of the challenge of delivering therapeutic RNA molecules to target tissues and big pharma quickly lost interest.

But companies like Silence have managed to overcome this hurdle and its rival Alnylam made history in 2018 when its siRNA drug Onpattro was approved by the FDA to treat hereditary transthyretin (hATTR) amyloidosis, which causes the build-up of amyloid protein in nerves and organs.

AZ will pay $60 million up front and invest $20 million in Silence, and will pay up to $400 million in milestone payments plus tiered royalties.

The companies expect to work on five targets within the first three years of the collaboration, and AstraZeneca has the option to extend it to a further five targets.

Silence has technology that can inhibit liver-expressed gene targets and the companies will collaborate to find siRNA molecules to other tissues including the heart, kidney and lung.

The UK biotech will design SiRNA molecules against gene targets selected by AZ, and will manufacture material to support toxicology and phase 1 clinical studies.

AZ and Silence will collaborate during the discovery phase, while AZ will lead clinical trials and marketing.

Silence will have the option to negotiate for co-development of two drugs of their choice starting from phase 2.

AZ will pay an option fee of $10 million for each selected target when a drug candidate is nominated, and Silence could receive up to $140 million in development milestones, and up to $250 million in market milestones.

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