8-K: Silence Therapeutics Reports Wider Loss, Advances Pipeline

Silence Therapeutics announced its full year 2025 financial results with a significantly increased net loss, alongside key clinical and pipeline updates.

Summary

• Net loss for the full year ended December 31, 2025, increased to $88.6 million, or $0.63 per share, compared to a net loss of $45.3 million, or $0.33 per share, for 2024.
• Collaboration revenue for 2025 was $0.6 million, a substantial decrease from $43.3 million in 2024, primarily due to the conclusion of the Hansoh collaboration and a $17.4 million decrease from the AstraZeneca collaboration.
• Cash, cash equivalents, and short-term investments stood at $85.1 million as of December 31, 2025.
• Enrollment in the Phase 2 SANRECO trial of divesiran for polycythemia vera (PV) was faster than expected, accelerating topline results to the third quarter of 2026 (formerly 2H 2026).
• Zerlasiran, a Phase 3 ready program for cardiovascular disease due to high Lp(a), has completed core Phase 3 readiness activities and is positioned for a potential third-party partner.
• AstraZeneca notified Silence that it will not pursue further development of SLN312 beyond Phase 1, leading Silence to re-gain exclusive global rights to the asset and evaluate future development plans.
• SLN312 Phase 1 data demonstrated durable dose-dependent reductions in ANGPTL3, triglycerides, and atherogenic lipoproteins, with a strong durability profile supporting infrequent dosing and good tolerability.
• Promising preclinical data were generated for two new mRNAi GOLD platform programs: SLN365 (GPR146 for cholesterol management) and SLN098 (INHBE for obesity).
• Iain Ross was appointed Interim Principal Executive Officer and Chairman of the Board of Directors on December 15, 2025, following the departure of the former CEO, with a search for a new CEO underway.
• James Ede Golightly was reappointed to the Board, and Rhonda Hellums, CFO, was appointed to the Board as an Executive Director in December 2025.

Sentiment

Score: 4

Explanation: StockSavvy.ai views this as a mixed report with significant financial deterioration (increased loss, revenue drop) overshadowing positive clinical progress (divesiran acceleration, promising preclinical data) and the setback with AstraZeneca's exit from SLN312.

Positives

• Accelerated enrollment in the Phase 2 SANRECO trial for divesiran, bringing topline results forward to 3Q 2026.
• Divesiran Phase 1 results demonstrated robust, rapid, and durable efficacy in PV patients, reducing phlebotomy frequency and controlling hematocrit levels with a favorable safety profile.
• Zerlasiran is Phase 3 ready, having completed core activities and is well-positioned for a potential third-party partnership.
• SLN312 Phase 1 data showed a competitive profile with durable, dose-dependent reductions in key lipid markers and good tolerability, offering potential for infrequent dosing.
• Generated promising preclinical data for two new mRNAi GOLD platform programs, SLN365 (GPR146 for cholesterol) and SLN098 (INHBE for obesity), indicating pipeline expansion.
• Advanced extra-hepatic cell targeting leveraging the proprietary siRNA platform, yielding promising preliminary results.
• General and administrative (G&A) expenses decreased by $4.6 million in 2025 due to reduced SEC reporting requirements and other cost-saving initiatives.

Negatives

• Net loss significantly increased to $88.6 million in 2025 from $45.3 million in 2024.
• Collaboration revenue dramatically decreased to $0.6 million in 2025 from $43.3 million in 2024, primarily due to the conclusion of the Hansoh collaboration and a $17.4 million reduction from AstraZeneca.
• AstraZeneca decided not to pursue further development of SLN312 beyond Phase 1, leading to the loss of a partnered asset, despite positive Phase 1 data.
• Incurred restructuring charges of $1.324 million in 2025.
• Experienced a foreign currency loss of $8.467 million in 2025.

Risks

• The company has a history of net operating losses.
• Ability to obtain necessary capital to fund clinical programs is crucial for continued operations.
• Product candidates are in early stages of clinical development, carrying inherent risks.
• Uncertainty in obtaining regulatory approval and successfully commercializing product candidates, either independently or with partners.
• Potential for undesirable side effects or other properties of product candidates.
• Reliance on third-party suppliers and manufacturers for development and production.
• Outcomes of any future collaboration agreements are uncertain.
• Ability to adequately maintain intellectual property rights for product candidates is critical.
• Difficulties inherent in the discovery and development of new products and the design and implementation of pre-clinical and clinical studies, trials, and investigations.
• Delays in and results from studies, trials, and investigations that are inconsistent with previous results and expectations.
• Failure to obtain and maintain required regulatory approvals.
• Product and pricing initiatives by competitors could impact market potential.
• Inability to market existing products effectively.
• Failure to agree beneficial terms with potential partners for any products or the failure of existing partners to perform their obligations.
• Ability to obtain additional financing for operations and the market conditions affecting the availability and terms of such financing.

Future Outlook

The company is focused on clinical execution, particularly advancing divesiran with accelerated Phase 2 topline results expected in 3Q 2026. It aims to secure a third-party partner for the Phase 3 ready zerlasiran program and will evaluate future development plans for SLN312 after regaining global rights. The discovery pipeline continues to advance with promising preclinical data for SLN365 and SLN098, targeting potential IND filings in 2027.

Management Comments

• Iain Ross, Chairman and Interim Principal Executive Officer, stated, '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.'
• Ross emphasized, 'Divesiran is a first-in-class siRNA product candidate in PV with broad potential in blood disorders and this program is our highest priority.'
• Ross also commented, 'We believe we are well positioned today with excellent optionality and multiple near-term value drivers ahead.'

Industry Context

StockSavvy.ai notes that the siRNA therapy space is highly competitive, with several companies developing similar gene-silencing technologies. The decision by AstraZeneca to discontinue SLN312 development, despite positive Phase 1 data, highlights the high bar for partnership and the strategic shifts large pharmaceutical companies make in their pipelines. However, regaining full rights to SLN312 offers Silence Therapeutics an opportunity to seek new partners or pursue development independently, potentially leveraging its competitive profile in dyslipidemia. The acceleration of the divesiran trial and promising preclinical data for SLN365 and SLN098 demonstrate continued innovation within the company's mRNAi GOLD platform, crucial for maintaining relevance in a rapidly evolving therapeutic landscape.

Comparison to Industry Standards

• Divesiran's Phase 1 results showing sustained HCT control and elimination of phlebotomy needs in PV patients are competitive, especially with Q6W dosing, compared to existing treatments that often lead to inconsistent HCT control and iron deficiency.
• Zerlasiran's over 90% Lp(a) reductions persisting for 60 weeks with Q16W and Q24W dosing are comparable to or potentially better than other investigational Lp(a)-lowering therapies, positioning it well for a partnership in the significant cardiovascular disease market.
• SLN312's robust, dose-dependent reductions in ANGPTL3, triglycerides, and atherogenic lipoproteins, with potential for infrequent dosing, align with the efficacy seen in other ANGPTL3 inhibitors in development, such as those from Regeneron or Amgen, suggesting a competitive profile despite AstraZeneca's exit.
• The preclinical data for SLN365 (GPR146) showing >80% mRNA knockdown and significant reductions in cholesterol and triglycerides in murine models suggests a novel mechanism of action for cholesterol management, potentially differentiating it from statins or PCSK9 inhibitors by targeting an LDL-C receptor-independent pathway.
• SLN098 (INHBE) for obesity, with its potential to enhance fat loss and preserve muscle mass, aims to address limitations of current GLP/GIP agonists which often result in significant lean muscle mass loss and weight regain. This could offer a differentiated approach in a rapidly growing market dominated by drugs like Ozempic (semaglutide) and Wegovy (semaglutide) from Novo Nordisk, or Mounjaro (tirzepatide) from Eli Lilly.

Management Changes

Stakeholder Impact

• Shareholders: Significant net loss and revenue decline could negatively impact investor confidence, but clinical progress and pipeline updates offer long-term potential. The need for future capital raises could lead to dilution.
• Employees: Management changes (Interim CEO, new board appointments) indicate strategic adjustments. Restructuring charges suggest some impact on workforce or operations.
• Customers/Patients: Positive clinical trial updates for divesiran, zerlasiran, and preclinical programs offer hope for new therapeutic options in areas of high unmet need (PV, high Lp(a), dyslipidemia, cholesterol management, obesity).
• Partners (AstraZeneca): AstraZeneca's decision to drop SLN312 beyond Phase 1 impacts the existing collaboration for that specific asset, though the broader collaboration remains.
• Creditors: The cash position and burn rate will be a factor in assessing creditworthiness, though not explicitly detailed.

Next Steps

• Topline results for Phase 2 SANRECO trial of divesiran in 3Q 2026.
• Additional preclinical data for SLN365 (GPR146) in 2Q 2026.
• Additional preclinical data for SLN098 (INHBE) in 2Q 2026.
• Phase 1 data presentations for SLN312 at medical and research congresses in 2026.
• Seeking potential third-party partners for Zerlasiran Phase 3 development.
• Evaluating plans for further development of SLN312 after regaining global rights.
• Potential IND filing for SLN365 in 1H 2027.
• Potential IND filing for SLN098 by 2027 year-end.
• Search for a new CEO is underway.

Key Dates

Recommendation

The substantial increase in net loss and dramatic drop in collaboration revenue are significant concerns, indicating a challenging financial year. However, the company maintains a solid cash position for the near term and has made notable clinical progress, including accelerated enrollment for divesiran and promising preclinical data for new assets. The regaining of SLN312 rights offers optionality. The mixed bag of financial setbacks and clinical advancements suggests a 'Hold' recommendation, as investors should monitor the upcoming clinical readouts and the company's strategy for SLN312 and future financing.

Keywords

siRNA, Silence Therapeutics, SLN, Polycythemia Vera, Divesiran, Zerlasiran, Lp(a), Dyslipidemia, SLN312, ANGPTL3, GPR146, SLN365, INHBE, SLN098, mRNAi GOLD platform, Biotechnology, Clinical-stage, Financial results, Drug development, Cardiovascular disease, Obesity, Cholesterol management