AstraZeneca pays Silence $60M to take siRNA beyond the liver

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Shares in Silence rose more than 20% following the news AstraZeneca is paying it to work on siRNA therapies. (jam_90s/CC BY 2.0)

AstraZeneca is set to pay Silence Therapeutics $60 million (€55 million) to work on siRNA therapies against cardiovascular, renal, metabolic and respiratory disease targets. The upfront cash fee is part of a suite of payments that could see Silence reel in billions of dollars through the deal. 

In recent years, Silence has made headlines as much for its legal scrap with Alnylam, which ultimately netted it a small, time-limited cut of European Onpattro sales, as for its own R&D activities. That is now poised to change, with the interest of AstraZeneca positioning Silence to take multiple therapies forward in the coming years.

AstraZeneca is paying $60 million—made up of $20 million now and $40 million within 12 months—and taking a $20 million stake in Silence to get the deal up and running. In return, Silence will design siRNA molecules against targets picked by AstraZeneca. The partners plan to start work on five targets over the next three years.

RNA therapeutics are best established in the treatment of diseases affecting the liver, but Silence and AstraZeneca hope to expand the field into other organs. Specifically, the partners aim to create drugs aimed at tissues including the heart and lung, building on Silence’s use of its GalNAc-siRNA platform to zero in on gene targets in the liver. 

Mene Pangalos, executive vice president of biopharmaceuticals R&D at AstraZeneca, thinks the collaboration will give his company access to an expanded drug discovery toolkit capable of targeting once-inaccessible pathways. 

“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,” Pangalos said in a statement.

Silence will design the siRNA molecules and produce materials for GLP toxicology studies and phase 1 trials. AstraZeneca will collaborate with Silence during the discovery stage before stepping up to lead clinical development and commercialization. 

If assets make it that far, Silence is in line to receive a substantial sum of money. AstraZeneca will pay a $10 million option fee for each selected target at the candidate nomination stage. Beyond that, the Big Pharma is on the hook for up to $140 million in development milestones and up to $250 million in commercialization payments.

At $400 million per target, the first stage of the collaboration is worth up to $2 billion in milestones. AstraZeneca has an option to extend the collaboration to another five targets, thereby doubling the maximum value of the deal. 

The upfront cash injection provided by the deal led Silence to reprioritize its internal assets. Having moved SLN124 into the human testing in beta-thalassaemia and myelodysplastic syndrome patients late last year, Silence is now switching its focus to a Lp(a) targeting siRNA, SLN360, that it sees as a potential treatment for cardiovascular disease.

Silence framed the decision to make SLN360 its top priority as a consequence of the unmet need the drug addresses, the preclinical profile and the “significant strengthening” of its balance sheet. Yet the shift is also in line with the difficulties SLN124, as a clinical asset, will face in the coming months. 

In light of the COVID-19 pandemic, Silence has paused enrollment in the phase 1 trial of SLN124. The biotech plans to resume enrollment “under a new and broader protocol when appropriate.” An interim data readout is currently penciled in for the first half of next year. 

Shares in Silence rose more than 20% following the news.