Silence Therapeutics PLC(SLN) - 2024 Q4 - Annual Report

Part I Business Silence Therapeutics develops siRNA therapeutics using its mRNAi GOLD™ platform, focusing on cardiovascular, hematology, and rare diseases through its pipeline and collaborations - The company focuses on discovering and developing siRNA molecules to inhibit specific target genes using its proprietary mRNAi GOLD™ platform[23] - The wholly-owned pipeline is concentrated in three therapeutic areas: cardiovascular disease, hematology, and rare diseases[23] Our Pipeline The company advances siRNA programs from its mRNAi GOLD™ platform, including clinical-stage Divesiran for PV and Zerlasiran for cardiovascular disease, and a Phase 1 candidate with AstraZeneca - Divesiran (SLN124), a wholly-owned siRNA candidate for polycythemia vera (PV), is in a Phase 2 clinical trial (SANRECO) and has received Fast Track and orphan drug designations from the FDA and Europe[24] - Zerlasiran (SLN360), a wholly-owned siRNA candidate to lower lipoprotein(a) (Lp(a)), completed Phase 1 and 2 trials showing substantial Lp(a) reduction, and the company is seeking a partner for Phase 3 development[25][26] - A third product candidate, developed with AstraZeneca, is in Phase 1 development for an undisclosed indication[27] Collaborations The company maintains strategic collaborations, including a Phase 1 program with AstraZeneca, while partnerships with Mallinckrodt and Hansoh have concluded, with Silence retaining rights for Hansoh targets - The AstraZeneca collaboration covers up to 10 targets, with $60 million in upfront and unconditional payments, a $20 million equity investment, and a $10 million milestone payment triggered by Phase 1 trial initiation, with potential for up to $390 million per target in milestones plus royalties[65][66] - The Mallinckrodt collaboration concluded in March 2024 after Mallinckrodt decided not to pursue further development of SLN501, with Silence having reacquired rights to two other preclinical complement targets in March 2023[67][68] - The Hansoh collaboration concluded in December 2024, with Silence retaining exclusive global rights for all three original targets[70] Intellectual Property The company protects its siRNA platform and product candidates through patents and trade secrets, holding 62 solely owned granted patents and 150 pending applications as of December 31, 2024 Patent Portfolio as of December 31, 2024 | Category | Count | | :--- | :--- | | Solely Owned Granted Patents | 62 (221 including EU validations) | | - U.S. Issued Patents | 14 | | Pending Patent Applications | 150 (138 solely owned) | | - U.S. Pending Applications | 11 (10 solely owned) | - Patent families covering the siRNA chemistry toolbox elements, if granted, are expected to expire no earlier than 2036[84] - Patent families covering the siRNA sequences for product candidates SLN360 and SLN124, if granted, are expected to expire no earlier than 2038[84] Government Regulation and Product Approval The company navigates extensive government regulations for drug approval in the US (FDA), EU (EMA), and UK (MHRA), covering preclinical, clinical, manufacturing, and post-market requirements, with an evolving regulatory landscape - The U.S. drug approval process involves preclinical studies, an effective IND, IRB-approved clinical trials (Phase 1, 2, 3), and NDA submission to the FDA[86] - In the EU, clinical trials are governed by the Clinical Trials Regulation (CTR), streamlining application and assessment through a centralized EU portal[132] - The UK has its own post-Brexit regulatory framework managed by the MHRA, including national authorization procedures and the International Recognition Procedure (IRP) leveraging other trusted regulators' approvals[157][158] Risk Factors The company faces significant risks including historical net losses, capital needs, inherent drug development uncertainties, reliance on third parties, intense competition, intellectual property challenges, and increased compliance costs from its U.S. domestic issuer transition - The company has a history of net losses, with a net loss of $45.3 million in 2024 and an accumulated loss of $474.0 million as of December 31, 2024, anticipating continued significant losses[173] - The company's novel siRNA technology may not lead to marketable products, and its focus on a single technology platform increases inherent development risk[190][192] - Reliance on third parties for manufacturing (CMOs) and clinical research (CROs) introduces risks related to performance, quality, and supply chain disruptions[210][213] - Effective January 1, 2025, the company transitioned to a 'U.S. domestic issuer', resulting in increased compliance costs and reporting requirements under SEC rules[304] Cybersecurity The company manages cybersecurity risks through an information security program overseen by its audit and risk committee, employing threat identification, mitigation measures, and third-party vendor risk management - The company's cybersecurity risk management is overseen by the board's audit and risk committee and managed by the Head of IT[368][369] - The security strategy includes incident detection and response, vulnerability management, disaster recovery, risk assessments, encryption, and employee training[363] - The company relies on third-party service providers for various functions and manages associated cybersecurity risks through vendor assessments and contractual requirements[366] Properties The company leases all its facilities, including corporate headquarters in London, UK, and office/laboratory spaces in Berlin, Germany, and Hoboken, New Jersey, which are deemed adequate for near-term needs - The company leases office and lab space in London (UK), Berlin (Germany), and Hoboken (NJ, USA)[373] Part II Market for Registrant's Common Equity, Related Stockholder Matters, and Issuer Purchases of Equity Securities The company's ADSs trade on Nasdaq under 'SLN' since September 2020, with no dividends paid or intended, as earnings are retained for business development - The company's ADSs (ticker: SLN) began trading on Nasdaq in September 2020, with each ADS representing three ordinary shares[378] - The company has never declared or paid dividends and does not intend to in the foreseeable future, retaining earnings for business growth[380] Management's Discussion and Analysis of Financial Condition and Results of Operations For 2024, the company reported $43.3 million in revenue and a net loss of $45.3 million, with R&D expenses increasing to $67.9 million, and ended the year with $147.3 million in cash after significant capital raises Results of Operations For 2024, revenue increased to $43.3 million due to the Hansoh collaboration, while R&D expenses rose to $67.9 million, resulting in an improved net loss of $45.3 million Consolidated Results of Operations (in thousands) | | 2024 | 2023 | 2022 | | :--- | :--- | :--- | :--- | | Revenue | $43,258 | $31,643 | $21,655 | | Gross profit | 31,448 | 18,776 | 8,192 | | Research and development costs | (67,883) | (56,937) | (43,550) | | General and administrative expenses | (26,884) | (26,222) | (25,682) | | Operating loss | (63,319) | (64,383) | (61,040) | | Net Loss | $(45,309) | $(54,228) | $(50,334) | | Loss per share (basic and diluted) | $(0.33) | $(0.49) | $(0.52) | - Revenue increased to $43.3 million in 2024 from $31.6 million in 2023, primarily due to recognizing $24.6 million from the Hansoh Collaboration upon its conclusion[430] - Research and development expenses increased by $11.0 million year-over-year to $67.9 million in 2024, driven by additional clinical trials and increased contract manufacturing for proprietary programs[436] Liquidity and Capital Resources As of December 31, 2024, the company held $147.3 million in cash and investments, bolstered by $120.0 million from a private placement and $27.7 million from ATM sales, with net cash outflow from operations at $67.6 million - As of December 31, 2024, the company had cash, cash equivalents, and short-term investments of $147.3 million[443] - In February 2024, the company raised approximately $120.0 million in gross proceeds through a private placement of ADSs[445] - In 2024, the company raised $27.7 million in proceeds (before fees) from sales of ADSs under its Open Market Sale Agreement (ATM facility)[444] Summary of Cash Flows (in thousands) | | 2024 | 2023 | 2022 | | :--- | :--- | :--- | :--- | | Net cash outflow from operating activities | $(67,640) | $(49,462) | $(57,044) | | Net cash (outflow)/inflow from investing activities | $(21,966) | $19,294 | $(20,498) | | Net cash inflow from financing activities | $142,087 | $31,937 | $52,581 | Controls and Procedures Management concluded that disclosure controls and internal control over financial reporting were effective as of December 31, 2024, with PricewaterhouseCoopers LLP issuing an unqualified opinion on internal controls - Management concluded that the company's disclosure controls and procedures were effective as of December 31, 2024[489] - Management assessed internal control over financial reporting as effective as of December 31, 2024, based on the COSO framework[492] - The independent registered public accounting firm, PricewaterhouseCoopers LLP, issued an unqualified opinion on the effectiveness of the company's internal control over financial reporting as of December 31, 2024[494] Part III Information for Items 10 through 14, covering Directors, Executive Officers, Corporate Governance, Executive Compensation, Security Ownership, and Related Transactions, is incorporated by reference from the company's 2025 Proxy Statement Directors, Executive Officers and Corporate Governance Information for this item is incorporated by reference from the company's 2025 Proxy Statement, which also details the adopted Code of Business Conduct and Ethics and Insider Trading Policy - Information for this item is incorporated by reference from the Proxy Statement for the 2025 Annual General Meeting of Shareholders[500] Executive Compensation Information regarding executive compensation is incorporated by reference from the company's 2025 Proxy Statement - Information for this item is incorporated by reference from the Proxy Statement for the 2025 Annual General Meeting of Shareholders[503] Part IV Exhibits and Financial Statement Schedules This section lists the financial statements and exhibits filed as part of the Annual Report on Form 10-K, including auditor reports, consolidated financial statements, and various corporate governance documents Financial Statements Report of Independent Registered Public Accounting Firm PricewaterhouseCoopers LLP issued an unqualified opinion on the consolidated financial statements and internal control over financial reporting, identifying R&D accruals as a Critical Audit Matter - The auditor, PricewaterhouseCoopers LLP, issued an unqualified (clean) opinion on both the consolidated financial statements and the effectiveness of internal control over financial reporting[525] - A Critical Audit Matter (CAM) was identified concerning the accuracy of management's assessment of accruals and prepayments for third-party research and development contracts, due to the significant judgment required to estimate the stage of completion[533][534] Consolidated Financial Statements The consolidated financial statements show total assets of $202.6 million and total liabilities of $68.6 million as of December 31, 2024, with a net loss of $45.3 million on $43.3 million in revenue for the year Consolidated Balance Sheet Data (in thousands) | | Dec 31, 2024 | Dec 31, 2023 | | :--- | :--- | :--- | | Cash and cash equivalents | $121,330 | $68,789 | | Total current assets | $187,366 | $103,151 | | Total assets | $202,635 | $119,448 | | Total current liabilities | $(16,822) | $(22,336) | | Total liabilities | $(68,612) | $(97,455) | | Total shareholders' equity | $(134,023) | $(21,993) | Consolidated Income Statement Data (in thousands) | | Year ended Dec 31, 2024 | Year ended Dec 31, 2023 | Year ended Dec 31, 2022 | | :--- | :--- | :--- | :--- | | Revenue | $43,258 | $31,643 | $21,655 | | Operating loss | $(63,319) | $(64,383) | $(61,040) | | Net Loss | $(45,309) | $(54,228) | $(50,334) | Notes to the Consolidated Financial Statements The notes detail accounting policies, including U.S. GAAP transition and revenue recognition, with significant 2024 contributions from AstraZeneca and Hansoh collaborations, and provide insights into equity changes and share-based compensation expenses - The company transitioned from IFRS to U.S. GAAP, applied retrospectively, due to the loss of its 'foreign private issuer' status[551] - Revenue from collaboration agreements is recognized over time using a cost-to-cost input method, as the license and R&D services are considered a single performance obligation per target[568] - In 2024, the company raised gross proceeds of $120.0 million from a private placement and $27.7 million from its ATM sales agreement[657][658] - Share-based compensation expense for 2024 was $16.3 million, with $29.1 million of total unrecognized compensation cost related to unvested stock options as of year-end[665][667]