Silence Therapeutics: Clinical Wins Clash with Financial Headwinds

LONDON, UK – March 05, 2026 – Silence Therapeutics (Nasdaq: SLN) presented a starkly mixed picture in its full-year 2025 financial report, showcasing significant clinical momentum for its lead drug candidate while simultaneously revealing major financial pressures and a pivotal shift in a key partnership with AstraZeneca. The developments place the siRNA-focused biotechnology company at a critical juncture, where promising science is contending with the harsh realities of drug development costs and strategic dependencies.

At the heart of the company's update is a blend of progress and pragmatism. While an accelerated timeline for its lead asset, divesiran, offers a near-term catalyst, the unexpected return of a promising drug from partner AstraZeneca, coupled with a dramatic fall in revenue and a widening net loss, underscores the challenges ahead. The ongoing search for a permanent CEO adds another layer of uncertainty to a company navigating a crucial period of transition.

Divesiran's Momentum Offers a Glimmer of Hope

The most significant positive news from Silence is the accelerated development of divesiran, its first-in-class siRNA therapy for polycythemia vera (PV), a rare blood cancer that causes an overproduction of red blood cells. The company announced that due to faster-than-expected enrollment in its Phase 2 SANRECO trial, it now anticipates reporting topline results in the third quarter of 2026, ahead of its previous second-half 2026 guidance.

“The past year was focused on clinical execution, demonstrated by the expedited enrollment in the Phase 2 SANRECO trial of divesiran in PV which is on-track for topline results in third quarter of 2026,” said Iain Ross, Chairman and Interim Principal Executive Officer at Silence. “Divesiran is a first-in-class siRNA product candidate in PV with broad potential in blood disorders and this program is our highest priority.”

Divesiran works by silencing the TMPRSS6 gene, which in turn increases levels of hepcidin, the body's master regulator of iron. This novel mechanism aims to restrict the iron supply needed for excessive red blood cell production, addressing the root cause of the disease. Positive Phase 1 data showed the drug could potentially eliminate the need for phlebotomies (therapeutic blood draws), the current physically taxing standard of care. With FDA Fast Track and Orphan Drug designations, divesiran is positioned as a key value driver for the company, though it faces competition from other novel agents like Takeda's rusfertide.

AstraZeneca's Pivot Creates a New Hurdle

Contrasting with the clinical progress of divesiran is the strategic setback involving SLN312, an siRNA therapy for dyslipidemia discovered using Silence's proprietary mRNAi GOLD™ platform. AstraZeneca, which was developing the drug, has decided to return the exclusive global rights to Silence following the completion of Phase 1 studies.

The decision is particularly noteworthy because the Phase 1 trial results were positive. Data showed SLN312 was well-tolerated and produced durable, dose-dependent reductions in ANGPTL3, triglycerides, and other lipoproteins linked to heart disease. The move by AstraZeneca is widely seen not as a reflection on the drug's scientific merit or the validity of Silence's platform, but rather as a strategic pipeline reprioritization by the pharmaceutical giant.

While this validates the science behind Silence's platform, it leaves the smaller biotech with a valuable but unfunded mid-stage asset. Silence now faces the choice of seeking a new partner for SLN312 or funding further development itself—a daunting prospect given its current financial situation. The decision also directly contributed to a severe drop in collaboration revenue for 2025.

The High-Stakes Hunt for a Partner

The company's strategy for its other major asset, zerlasiran, underscores its financial constraints. Zerlasiran is an siRNA therapy designed to lower high levels of lipoprotein(a), or Lp(a), a genetic risk factor for cardiovascular disease. Having completed core Phase 3 readiness activities and received positive feedback on its trial design from global regulators, the program is essentially shovel-ready.

However, Silence has made the pragmatic decision to not initiate the costly, large-scale Phase 3 cardiovascular outcomes study until it secures a third-party partner. This move conserves cash and extends the company's financial runway but also makes the drug's path to market entirely dependent on a future deal. With strong Phase 2 data showing a greater than 90% reduction in Lp(a) levels, zerlasiran is an attractive asset. Yet, the Lp(a) space is competitive, with giants like Novartis advancing their own candidates, making the timing and terms of any potential partnership critical.

Decoding the Financial Reality

The financial results for 2025 lay bare the company's challenges. Collaboration revenue plummeted to just $0.6 million for the year, a stark contrast to the $43.3 million reported in 2024. This precipitous drop was primarily caused by the conclusion of a collaboration with Hansoh Pharma and a significant decrease in revenue from the AstraZeneca partnership.

The revenue collapse had a direct impact on the bottom line. Silence reported a net loss of $88.6 million for 2025, nearly double the $45.3 million loss from the previous year. While the company managed to slightly reduce its general and administrative expenses through cost-saving initiatives, its R&D expenses remained flat at $67.8 million, reflecting its continued investment in its pipeline.

The company ended the year with $85.1 million in cash, cash equivalents, and short-term investments. While the decision to pause the zerlasiran trial is a key part of its cash preservation strategy, the widening losses and near-total evaporation of collaboration revenue highlight an urgent need to secure new funding sources, either through partnerships or financing, to support its ambitious clinical goals and preclinical programs, which include novel candidates for cholesterol management and obesity.

Awaiting New Leadership at a Pivotal Moment

Overseeing this complex period is an interim leadership team. In December 2025, Chairman Iain Ross stepped in as Interim Principal Executive Officer following the departure of the former CEO. The company is actively searching for a permanent replacement.

This leadership transition comes at a critical time. The new CEO will inherit a promising scientific platform and a pipeline with clear potential but will also be tasked with shoring up the company's finances, securing a vital partnership for zerlasiran, and charting a new path forward for the newly returned SLN312. For Silence Therapeutics, the coming months will be crucial in determining whether it can translate its scientific promise into sustainable long-term value.