AstraZeneca forms $2bn gene silencing pact with Silence Tx

UK biotech Silence Therapeutics has added to its growing stable of pharma partnerships with a wide-ranging collaboration with AstraZeneca in cardiovascular, renal, metabolic and respiratory diseases.

The deal is focused on using Silence’s small interfering RNA (siRNA) platform to develop drugs that can target the liver in the first instance, with the project also expected to extend to include targeted delivery to the heart, lung and kidney.

London-based Silence will get $60m upfront from AZ in cash plus a $20m equity investment, plus $400m in milestone payments apiece for up to five targets over an initial three-year period, giving a total deal value of up to $2.06bn.

There’s also an option to expand the number of targets to ten if the programme goes well, according to Silence, which saw its AIM-listed shares rocket more than 22% in morning trading today. The biotech company has retained co-development rights to two programmes in the partnership.

AZ will pay another $10m option fee for each nominated drug candidate, plus $140m in development milestones and $250m tied to commercial performance.

AZ’s head of biopharma R&D Mene Pangalos said the alliance “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,” he added.

It’s not the first time the two companies have worked together, however. Back in 2007, they formed a $400m collaboration in the respiratory area, and extended that three years later to include oncology targets.

siRNA drugs work by switching off the expression of specific genes, specifically by causing messenger RNA to be degraded, preventing translation into proteins. Silence’s GalNAc-siRNA platform allows it to direct these effects directly to cells in the liver, and with AZ it will now try to develop new ways to target other tissues.

This is the second $2bn-plus alliance for Silence, coming after Irish drugmaker Mallinckrodt paid $25m upfront last year for a project that will develop siRNA drugs targeting the complement cascade, part of the immune system.

Silence received its first $2m research milestone from that alliance last September after lead candidate SLN500 – which targets complement C3 – cleared some preclinical studies.  Meanwhile, the UK company has also signed a smaller technical evaluation agreement with Takeda for preliminary work on an undisclosed drug target.

It is also working on its own in-house projects, namely SLN124 for beta thalassaemia, which is in phase 1b testing, and SLN360 which targets Lp(a) and is in early development for cardiovascular diseases, with trials due to start later this year.