Silence's divesiran bet ends in a $20 cash offer

The technology

Silence Therapeutics builds small interfering RNA (siRNA) drugs on its mRNAi GOLD platform that switch off disease-related genes in the liver. Its lead drug, divesiran, silences TMPRSS6, a liver protein that suppresses hepcidin, the hormone that controls iron. More hepcidin means less iron reaches the bone marrow and fewer red blood cells are made, which is the core problem in polycythemia vera (PV).

The phase 2 SANRECO trial gave the platform its clearest proof. In 48 phlebotomy-dependent patients, 88% responded on divesiran against 19% on placebo over weeks 18 to 36, and the every-12-weeks arm reached 81.3%. Mean phlebotomies fell to 0.2 from 2.1. Safety was clean, with two cases of grade 1 anemia.

The rest of the pipeline is thinner. Zerlasiran, for high lipoprotein(a), finished phase 3 readiness work but was waiting for a partner to run phase 3. AstraZeneca said in March it would not take SLN312 past phase 1. SLN365 and SLN098 are preclinical, aimed at IND filings in 2027.

The odds

Divesiran has cleared the stage where most drugs fail. The BIO, Informa and QLS study of 2011 to 2020 found that only 28.9% of programs move from phase 2 to phase 3. For rare disease drugs that reach phase 3, 60.4% go on to a filing and 93.6% of filings are approved. Multiplied together, that is roughly 57% from phase 3 to approval. Hematology programs had a 23.9% chance of approval from phase 1, against 7.9% across all diseases.

Two facts push divesiran above the base rate. Its phase 2 effect was large and statistically clear (p<0.0001). And FDA approved Takeda and Protagonist's Mimrylo on August 28 on a similar phlebotomy-based response endpoint, so the regulatory path is mapped. The open clinical question is whether the 12-week arm's 81.3% holds up in a larger phase 3, planned to start in the first half of 2027.

The money

Silence ended June with $72.1 million in cash and a quarterly net loss of $12.3 million. It then raised about $175 million at $13.50 per ADS on August 11.

On October 19, Merck KGaA agreed to pay $20.00 in cash per ADS, an equity value of about $1.3 billion and an enterprise value of $1.1 billion. The price is a 130% premium to the October 16 close and 82% above the 30-day volume-weighted average of $10.99. Holders of about 14% of the voting power signed agreements to vote in favor.

The risks

The first risk is that the deal does not close. It needs Silence shareholder approval, sanction by the High Court of England and Wales and regulatory clearances, with closing expected in the first quarter of 2027.

If it fell apart, Silence would be back to a one-drug story. Divesiran would face phase 3 risk and a market where Mimrylo, a once-weekly injection, had a head start. William Blair analyst Myles Minter said the deal "takes the execution risk off the table in an increasingly competitive space," according to Reuters.

Minter also said "the deal valuation does appear inexpensive", pointing to Mimrylo. Some holders may raise that at the vote, though the 14% support agreement and the competitive sale process described by chairman Iain Ross make a rejection less likely.

Our read

Silence played a weak hand well. Its CEO left in December, AstraZeneca stepped back from SLN312 in March, and zerlasiran had no partner. The company put its weight behind one phase 2 readout, pulled that readout forward, and got a strong result. It raised money into the rally, which removed any need to sell cheaply, and then ran a sale.

For shareholders, the outcome now turns on deal steps, not PV data. The scientific bet on 12-week dosing moves to Merck, which would run the phase 3 and compete with Mimrylo for patients. The dates to track are the shareholder meeting, the court hearing and any regulatory reviews, all ahead of a first-quarter 2027 close.