10-K: Silence Therapeutics Reports $88.6M Loss, AstraZeneca Exits SLN312

Silence Therapeutics reported a significant net loss of $88.6 million for 2025, alongside AstraZeneca's decision to discontinue further development of SLN312 beyond Phase 1.

Summary

• Silence Therapeutics incurred a net loss of $88.6 million for the fiscal year ended December 31, 2025, an increase from $45.3 million in 2024.
• The company's accumulated deficit reached $562.6 million as of December 31, 2025.
• Cash, cash equivalents, and U.S. treasury bills totaled $85.1 million as of December 31, 2025, projected to fund operations into 2028.
• AstraZeneca notified Silence Therapeutics on March 4, 2026, that it will not pursue further development of SLN312 beyond Phase 1, returning full rights to Silence.
• Divesiran (SLN124), a potential first-in-class siRNA for polycythemia vera (PV), is in Phase 2 development, with topline results anticipated in Q3 2026, accelerated due to faster enrollment.
• Zerlasiran (SLN360), a Phase 3 ready siRNA for cardiovascular disease due to high Lp(a), has completed core Phase 3 readiness activities and is seeking a third-party partner.
• Promising preclinical data was generated for two new mRNAi GOLD platform programs: SLN365 for cholesterol management and SLN098 for obesity.
• The Hansoh collaboration concluded in December 2024, with Silence Therapeutics retaining exclusive global rights for all three targets evaluated under the agreement.
• Research and development costs remained stable at $67.8 million in 2025, while general and administrative expenses decreased to $22.3 million.
• A non-recurring restructuring charge of $1.3 million was incurred in June 2025 due to a limited reduction in workforce.

Sentiment

Score: 4

Explanation: StockSavvy.ai views this filing with a cautious sentiment. While pipeline assets like divesiran and zerlasiran show promise and preclinical programs are advancing, the significant increase in net loss and the termination of a key collaboration (SLN312 with AstraZeneca) indicate substantial financial and operational challenges, despite the company's stated liquidity runway.

Positives

• Topline results for the Phase 2 SANRECO trial of divesiran in PV are anticipated in Q3 2026, an acceleration from prior guidance due to faster than expected enrollment.
• Zerlasiran, a Phase 3 ready program for cardiovascular disease, has completed core Phase 3 readiness activities, positioning it for potential partnership.
• Divesiran has received Fast Track and orphan drug designations from the FDA and orphan drug designation from the European Commission for PV.
• SLN365 and SLN098, new mRNAi GOLD platform programs, have generated promising preclinical data, with additional data anticipated in Q2 2026.
• The company believes its existing cash, cash equivalents, and U.S. treasury bills of $85.1 million are sufficient to fund operating expenses and capital expenditure requirements into 2028.

Negatives

• Net loss significantly increased to $88.6 million for the year ended December 31, 2025, compared to $45.3 million in 2024.
• AstraZeneca notified Silence Therapeutics on March 4, 2026, that it will not pursue further development of SLN312 beyond Phase 1, leading to the re-gaining of rights by Silence.
• The Hansoh collaboration concluded in December 2024, resulting in no revenue recognition from this agreement in 2025, compared to $24.6 million in 2024.
• Revenue from the AstraZeneca collaboration decreased significantly to $0.6 million in 2025 from $18.0 million in 2024, with no milestone payments achieved in 2025.
• A non-recurring restructuring charge of $1.3 million was incurred in June 2025 due to a limited reduction in workforce.
• The company has a history of net losses and anticipates continuing to incur significant losses for the foreseeable future.

Risks

• A history of net losses and anticipation of continued significant losses for the foreseeable future.
• No revenue generated from product sales to date, with profitability uncertain.
• Requirement for additional financial resources to continue product candidate development and business objectives, with no assurance of obtaining them on acceptable terms.
• Raising additional capital may cause dilution to shareholders, restrict operations, or require relinquishing rights to technologies or product candidates.
• The siRNA drug discovery and development approach is novel and may not lead to marketable products.
• Reliance on third parties for manufacturing, research, and development activities, with risks of unsatisfactory performance or agreement termination.
• Uncertainty regarding regulatory approval timing for product candidates, impacting future revenue.
• Extensive and evolving regulatory requirements even if product candidates obtain approval.
• Intense competition from other companies developing novel drugs and technology platforms, including those using similar siRNA technologies.
• Risk of failure to introduce new products or keep pace with advances in technology.
• Potential product liability and other claims, which could result in substantial liability and costs.
• Cybersecurity risks and the failure to maintain confidentiality, integrity, and availability of information systems and data.
• Subject to stringent and evolving U.S. and foreign data privacy and security laws, regulations, and contractual obligations, with potential for regulatory actions, litigation, fines, and reputational harm.
• Inability to obtain or protect intellectual property rights related to current or future products and product candidates.
• Involvement in expensive, time-consuming, and potentially unsuccessful lawsuits to protect or enforce patents.
• Increased costs and management time devoted to compliance initiatives and corporate governance practices as a public company.
• Volatility in the trading price of ADSs, with potential for loss of investment.
• Future sales, or the possibility of future sales, of a substantial number of ADSs could adversely affect the price.
• Potential for identifying material weaknesses in internal control over financial reporting.
• Holders of ADSs have fewer rights than ordinary shareholders and must act through the depositary.
• Potential adverse U.S. federal income tax consequences to U.S. Holders if classified as a passive foreign investment company (PFIC).
• Inability to use U.K. carryforward tax losses to reduce future tax payments or benefit from favorable U.K. tax legislation.
• Uncertainty related to pricing, coverage, and reimbursement for product candidates.
• Exchange rate fluctuations may adversely affect results of operations and cash flows.
• Potential for claims that employees, consultants, or independent contractors have wrongfully used or disclosed confidential information of third parties.
• Protections under the U.K. City Code on Takeovers and Mergers will not apply if the place of management and control remains outside the United Kingdom.
• Claims of U.S. civil liabilities may not be enforceable against the company due to incorporation under English law and assets located outside the U.S.

Future Outlook

The company anticipates topline results for the Phase 2 SANRECO trial of divesiran in Q3 2026 and additional preclinical data for SLN365 and SLN098 in Q2 2026. Phase 1 data presentations for SLN312 are planned for medical and research congresses in 2026. The company expects to continue incurring significant operating losses for the foreseeable future and will need additional capital to fund operations beyond 2028, relying on potential future milestone payments from collaborations, equity, or debt financings.

Management Comments

• Iain Ross, Interim Principal Executive Officer and Chairman of the Board of Directors, certified the accuracy of the Annual Report on Form 10-K.
• Rhonda Hellums, Chief Financial Officer, certified the accuracy of the Annual Report on Form 10-K.

Industry Context

StockSavvy.ai notes that Silence Therapeutics operates in the highly competitive and rapidly advancing RNAi therapeutics space, a novel drug development approach. The termination of the AstraZeneca collaboration for SLN312, despite positive Phase 1 results, highlights the inherent risks and high attrition rates in pharmaceutical partnerships, particularly in early-stage development. The company's focus on rare diseases like polycythemia vera and prevalent cardiometabolic conditions like high Lp(a) positions it in areas with significant unmet medical needs, but also intense competition from larger pharmaceutical and biotechnology companies with greater resources. The shift to regain full rights for SLN312 and seek new partners for zerlasiran indicates a strategic pivot to manage pipeline assets independently or through new collaborations, a common strategy for smaller biotechs navigating development costs and market access.

Comparison to Industry Standards

• The siRNA approach, while novel, has seen successes with companies like Alnylam Pharmaceuticals, which Silence Therapeutics previously settled patent litigation with regarding ONPATTRO. This suggests a competitive landscape where intellectual property and clinical superiority are critical.
• The substantial reduction in Lp(a) levels (up to 99% in APOLLO Phase 1, over 80% in ALPACAR-360 Phase 2) for zerlasiran compares favorably to non-specific lipid-lowering agents like ezetimibe (7%), niacin (23%), CETP inhibitors (25-60%), and PCSK9 inhibitors (20-30%), which achieve more modest reductions. This positions zerlasiran as potentially clinically superior for high Lp(a) if approved.
• Current obesity treatments, such as GLP/GIP agonists, offer 15-20% weight loss that plateaus and is associated with up to 40% lean muscle mass loss and poor tolerability. SLN098's opportunity to address unmet needs like increasing fat loss and preventing muscle mass loss could differentiate it in a crowded and rapidly evolving obesity market, potentially competing with or complementing therapies from companies like Novo Nordisk (Wegovy, Ozempic) and Eli Lilly (Zepbound, Mounjaro).

Management Changes

Corporate Governance

Legal Proceedings

• No pending litigation that, separately or in the aggregate, would have a material adverse effect on results of operations, financial condition, or cash flows.

Related Party Transactions

• No related party transactions in 2024 or 2025.

Stakeholder Impact

• **Shareholders:** Face increased net losses and potential dilution from future capital raises. The termination of key collaborations (AstraZeneca for SLN312, Hansoh) could impact future revenue and stock performance. However, accelerated timelines for divesiran and progress on other pipeline candidates offer future potential.
• **Employees:** Experienced a limited reduction in workforce in June 2025, leading to restructuring charges. Management changes, including an Interim PEO and new board appointments, indicate organizational shifts. Share-based compensation remains a key incentive.
• **Customers/Patients:** Potential for new therapies in areas of high unmet medical need (PV, high Lp(a), hypercholesterolemia, obesity) if product candidates successfully complete trials and gain regulatory approval. The acceleration of divesiran trial results is positive for patients awaiting treatment.
• **Collaboration Partners:** AstraZeneca's decision to exit SLN312 development highlights the risks of pharmaceutical partnerships, while the company actively seeks new partners for zerlasiran and other assets.
• **Creditors:** The company's cash position is expected to fund operations into 2028, but the need for additional capital beyond that period could be a consideration.

Next Steps

• Anticipate topline results for the Phase 2 SANRECO trial of divesiran in PV in Q3 2026.
• Anticipate additional preclinical data for SLN365 (GPR146) in Q2 2026.
• Anticipate additional preclinical data for SLN098 (INHBE) in Q2 2026.
• Plan Phase 1 data presentations for SLN312 at medical and research congresses in 2026.
• Evaluate plans for further clinical development of SLN312 after regaining full rights from AstraZeneca.
• Seek a third-party partner for potential Phase 3 development and future commercialization of zerlasiran.
• Continue to identify, recruit, retain, incentivize, and integrate additional employees to support growth.
• Renew shareholder authorization for allotting new shares and disapplying preemptive rights upon expiration (at least every five years).

Key Dates

Recommendation

Silence Therapeutics presents a mixed bag for investors. The significant increase in net loss and the termination of the AstraZeneca collaboration for SLN312 are clear negatives, impacting near-term revenue and partnership prospects. However, the acceleration of divesiran's Phase 2 results and the Phase 3 readiness of zerlasiran, coupled with promising preclinical data for SLN365 and SLN098, demonstrate continued pipeline progress in areas of high unmet medical need. The company's cash runway into 2028 provides some stability, but future capital raises are anticipated. Given the high-risk, high-reward nature of clinical-stage biotech and the recent setbacks balanced by pipeline advancements, a 'hold' recommendation is appropriate. Investors should monitor upcoming clinical data, progress on new partnerships, and the company's ability to secure additional funding without excessive dilution.

Keywords

siRNA, RNAi therapeutics, biotechnology, drug development, polycythemia vera, cardiovascular disease, Lp(a), dyslipidemia, obesity, hypercholesterolemia, clinical trials, preclinical studies, gene silencing, pharmaceutical, SEC filing, 10-K