SLN 10-K & 10-Q changes, risk factors and insider trading

We are a clinical-stage biopharmaceutical company. As of the date hereof,of this Annual Report, our operations have been primarily limited to developing our siRNA product platform, undertaking basic research around siRNA targets, conducting preclinical and clinical studies and out-licensing some of our intellectual property rights. We have not yet obtained marketing approval for any product candidates and may not for the foreseeable future, if ever. Consequently, any predictions about our future success or viability, or any evaluation of our business and prospects, may not be accurate.

We have incurred net losses in each year since our inception. Our net losses were $88.6 million for the year ended December 31, 2025 and $45.3 million for the year ended December 31, 2024, $54.2 million for the year ended December 31, 2023, and $50.3 million for the year ended December 31, 2022.2024. As of December 31, 2024,2025, we had an accumulated lossdeficit of $474.0$562.6 million. Our losses have resulted primarily from costs related to our research and development programs, including our preclinical and clinical development activities.

We have historically funded our operations through upfront payments and milestones from collaboration agreements, equity offerings and proceeds from private placements, as well as management of expenses and other financing options. As of December 31, 2024,2025, we had cash and cash equivalents and short-termU.S. investmentstreasury bills of $147.3$85.1 million. We expect that our existing cash and cash equivalents will provide sufficient funds to continue to meet our liabilities as they fall due and for at least the next twelve months.months from the issuance of the December 31, 2025 financial statements. However, it is possible that our costs will be higher than expected, that our operating plan may change as a result of many factors currently unknown to us, and that we may need to seek additional funds sooner than planned, through public or private equity or debt financings or other sources, such as strategic collaborations or license and development agreements. In addition, we may seek additional capital due to favorable market conditions or strategic considerations, like we did in February 2024 when we entered into a private placement with certain investors, even if we believe we have sufficient funds for our current or future operating plans.

There is no assurance that we will be successful in obtaining sufficient funding on terms acceptable to us, or if at all. We believe that our current cash and cash equivalents and short-term investments will be able to fund our operations into 2027. The inability to obtain future funding could impact our financial condition and ability to pursue our business strategies, including being required to delay, reduce or eliminate some of our research and development programs, or being unable to continue operations or unable to continue as a going concern.

Further, our focus solely on siRNA technology for developing drugs as opposed to multiple, more proven technologies for drug development increases the risks associated with the ownership of our ordinary shares.securities. If we are not successful in developing any product candidates using siRNA technology, we may be required to change the scope and direction of our product development activities. In that case, we may not be able to identify and successfully implement an alternative product development strategy.

WeIn the past, we have entered into collaborations with other parties, including pharmaceutical and biotechnology companies like Hansoh Pharmaceutical Group Company Limited, or Hansoh, Mallinckrodt plc, or Mallinckrodt, and AstraZeneca PLC, or AstraZeneca, to develop products based on our RNAi technology, and such collaborations and licensing arrangements currently represent a significant portion of our product candidate pipeline. Certain of our collaborations have provided us with important funding for some of our development programs and we expect to receive additional funding under collaborations in the future if certain milestones are achieved although not all of our collaborations may result in funding to us, and certain collaborations, licenses and agreements may result in increased expenditures by us.

Our dependence on collaborators for capabilities and funding means that our business could be adversely affected if any collaborator materially amends or terminates its collaboration agreement with us or fails to perform its obligations under that agreement. Our current or future collaborations, if any, may not be scientifically or commercially successful. Disputes may arise in the future with respect to the ownership of rights to technology or products developed with collaborators, which could have an adverse effect on our ability to develop and commercialize any affected product candidate. Our current collaborations allow, and we expect that any future collaborations will allow, either party to terminate the collaboration for a material breach by the other party. In addition, our collaborators may have additional termination rights for convenience with respect to the collaboration or a particular program under the collaboration, under certain circumstances. For example, we recently concluded our collaboration agreements with Mallinckrodt, AstraZeneca and Hansoh mayin eachDecember be2024. terminated by the respective collaborator at any time upon prior written notice to us. If we were to loseAs a collaborator,result, we may have to attract a new collaborator or develop expanded research and development, sales, distribution and marketing capabilities internally, which would require us to invest significant amounts of financial and management resources.

AEsAdverse effects, or AEs, caused by our product candidates could cause us, other reviewing entities, clinical trial sites or regulatory authorities to interrupt, delay or halt clinical trials and could result in the denial of regulatory approval. Certain oligonucleotide therapeutics have been observed to result in injection site reactions and pro-inflammatory effects and may also lead to impairment of kidney or liver function. There is a risk that our future product candidates may induce similar AEs.

As of December 31, 2024,2025, we had 11686 employees. In the futurefuture, we may expand our employee base to increase our managerial, scientific, operational, commercial, financial and other resources and to hire more consultants and contractors. Future growth would impose significant additional responsibilities on our management, including the need to identify, recruit, maintain, motivate and integrate additional employees, consultants and contractors. Also, our management may need to divert a disproportionate amount of its attention away from its day-to-day activities and devote a substantial amount of time to managing these growth activities. We may not be able to effectively manage the expansion of our operations, which may result in weaknesses in our infrastructure, give rise to operational mistakes, loss of business opportunities, loss of employees and reduced productivity among remaining employees. Our expected growth could require significant capital expenditures and may divert financial resources from other projects, such as the development of additional product candidates. Moreover, if our management is unable to effectively manage our growth, our expenses may increase more than expected, our ability to generate and/or grow revenues could be reduced, and we may not be able to implement our business strategy. Our future financial performance and our ability to commercialize product candidates and compete effectively will depend, in part, on our ability to effectively manage any future growth.

We believe we spend a relatively low amount on technological innovation compared to our larger competitors. There is a risk that competitors will be quicker to develop new technologies, new products for the same gene targets or new delivery methods of nucleic acids into novel cell types, particularly once competitors learn about new gene targets that we or our collaborators have selected for the development of siRNA molecules. We will need to successfully introduce new products to achieve our strategic business objectives. Our successful product development will depend on many factors, including our ability to attract strong talent to lead our research and development efforts, adapt to new technologies, obtain regulatory approvals on a timely basis, demonstrate satisfactory clinical results, manufacture products in an economical and timely manner, obtain appropriate intellectual property protection for our products, gain and maintain market acceptance of our products, and differentiate our products from those of our competitors. In addition, patents attained by others may preclude or delay our commercialization of a product. There can be no assurance that any products now in development or that we may seek to develop in the future will achieve technological feasibility, obtain regulatory approval or gain market acceptance. If we cannot successfully introduce new products or adapt to changing technologies, our products may become obsolete, and our revenue and profitability could suffer.

We and the third parties with whom we work are subject to a variety of evolving cybersecurity threats, including but not limited to social-engineering attacks (including through deep fakes, which are increasingly more difficult to identify as fake, and phishing attacks), malicious code (such as viruses and worms), malware (including as a result of advanced persistent threat intrusions), denial-of-service attacks, credential stuffing,stuffing attacks, credential harvesting, personnel misconduct or error, ransomware attacks, supply-chain attacks, software bugs, server malfunctions, software or hardware failures, loss of data or other information technology assets, adware, attacks enhanced or facilitated by AI, fire, storm, flood, power loss, earthquakes, telecommunications failures, physical or software break-ins, software viruses, accidental or malicious insider-action and other similar threats. These events could lead to the unauthorized access, disclosure and use of our sensitive data and information technology systems. The techniques used by criminal elements to attack computer systems arecan be sophisticated, change frequently and may originate from less regulated and remote areas of the world and increasingly involve highly resourced threat actors such as organized criminals and nation states. During times of war and other major conflicts, we, the third parties with whom we work, may be vulnerable to a heightened risk of these attacks, including retaliatory cyber-attacks, that could materially disrupt our systems and operations, supply chain, and ability to produce, sell and distribute our goods and services. In particular, severe ransomware attacks are becoming increasingly prevalent and can lead to significant interruptions in our operations, ability to provide our products or services, loss of sensitive data and income, reputational harm, and diversion of funds. Extortion payments may alleviate the negative impact of a ransomware attack, but we may be unwilling or unable to make such payments due to, for example, applicable laws or regulations prohibiting such payments. It may be difficult and/or costly to detect, investigate, mitigate, contain, and remediate a security incident. Actions taken by us or the third parties with whom we work to detect, investigate, mitigate, contain, and remediate a security incident could result in outages, data losses, and disruptions of our business. Threat actors may also gain access to other networks and systems after a compromise of our networks and systems. For example, threat actors may use an initial compromise of one part of our environment to gain access to other parts of our environment, or leverage a compromise of our networks or systems to gain access to the networks or systems of third parties with whom we work, such as through phishing or supply chain attacks. As a result, we cannot provide assurance that our efforts to address these techniquesthreats proactively or implement adequate preventative measures will always be successful.

Remote work has increased risks to our information technology systems and data, as more of our employees utilize network connections, computers, and devices outside our premises or network, including working at home, while in transit and in public locations. Additionally, future or past business transactions (such as acquisitions or integrations) could expose us to additional cybersecurity risks and vulnerabilities, as our systems could be negatively affected by vulnerabilities present in acquired or integrated entities’ systems and technologies. We may discover security issues that were not found during due diligence of such acquired or integrated entities, and it may be difficult to integrate companies into our information technology environment and security program. In addition, supply-chain attacks have increased in frequency and severity, and we cannot guarantee that third parties’ infrastructure in our supply chain or that of the third parties with whom we work have not been compromised.

We rely on third-party service providers and technologiesthird-parties to operate critical business systems that process sensitive data. Our ability to monitor these third parties’ information security practices is limited, and these third parties may not have adequate information security measures in place. Certain of our third-party service providers have, and may again inIf the future,third parties with whom we work experience a security incident or other interruptioninterruption, thatwe resultscould experience, and in certain cases have experienced, adverse consequences to our operations.consequences. While we may be entitled to damages if ourthe third-partythird serviceparties providerswith whom we work fail to satisfy their privacy or security-related obligations to us, any award may be insufficient to cover our damages, or we may be unable to recover such award.

We take steps designed to detect, mitigate, and remediate vulnerabilities in our information systems (such as our hardware and/or software, including that of third parties with whom we work). We have not and may not, however, detect and remediate all such vulnerabilities including on a timely basis. Further, we may experience delays in deploying remedial measures and patches designed to address identified vulnerabilities. Vulnerabilities could be exploited and result in a security incident.

Any of the previously identified or similar threats could cause a security incident or other interruption that could result in unauthorized, unlawful, or accidental acquisition, modification, destruction, loss, alteration, encryption, disclosure of, or access to our sensitive data or our information technology systems, or those of the third parties with whom we work. A security incident or other interruption could disrupt our ability (and that of third parties with whom we work) to operate our business. We may expend significant resources or modify our business activities (including our clinical trial activities) to try to protect against security incidents. Certain data privacy and security obligations have required us to implement and maintain specific security measures or industry-standard or reasonable security measures designed to protect our information technology systems and sensitive information.

If we (or a third party with whom we work) experience a security incident or are perceived to have experienced a security incident, we could experience material adverse consequences, such as government enforcement actions (for example, investigations, fines, damages,penalties, audits, and inspections), litigation (including class claims) and enforcement actions, additional reporting requirements and/or oversight, restrictions on processing sensitive datainformation (including personal data), indemnification obligations; negative publicity, reputational harm, monetary fund diversions, diversion of management attention, and interruptions in our operations (including availability of clinical trial data)., financial loss, and other similar harms. Security incidents and attendant material consequences may negatively impact our ability to grow and operate our business. In addition, any sustained disruption in internet systems or network access provided by other companies could harm our business. Similarly, if a security incident were to occur, we may be required, or we may voluntarily choose, to notify relevant stakeholders, including affected individuals, customers, regulators, and investors, of security incidents, or to take other actions, such as providing credit monitoring and identity theft protection services. Such disclosures and related actions can be costly, and the disclosure or the failure to comply with such applicable requirements could lead to adverse consequences, including reputational damage, investigations and fines from regulators, as well as litigation. Furthermore, if we are required to disclose the occurrence of a cybersecurity incident, the price of our ADSs may be negatively impacted.

In addition to experiencing a security incident, third parties may gather, collect, or infer sensitive information about us from public sources, data brokers, or other means that reveals competitively sensitive details about our organization and could be used to undermine our competitive advantage or market position. Additionally, sensitive data of the Company could be leaked, disclosed, or revealed as a result of or in connection with our employees’, personnel’s, or vendors’ use of generative artificial intelligence ("AI"), technologies.

In the ordinary course of business, we collect, receive, store, process, generate, use, transfer, disclose, make accessible, protect, secure, dispose of, transmit, and share (collectively, process) personal data and other sensitive information, including proprietary and confidential business data, trade secrets, intellectual property, data we collect about trial participants in connection with clinical trials, sensitive third-party data, business plans, transactions, clinical trial data and financial information (collectively, sensitive data).

Outside the United States, an increasing number of laws, regulations, guidance and industry standards govern data privacy and security. For example, the European Union’s General Data Protection Regulation ("EU GDPR") and the United Kingdom’s GDPR ("U.K. GDPR") (collectively, “the GDPR”) impose strict requirements for processing personal data (including health data). Under the GDPR, companies may face temporary or definitive bans on data processing and other corrective actions; fines of up to 20 million Euros under the EU GDPR, 17.5 million pounds sterling under the UK GDPR or, in each case, 4% of annual global revenue, whichever is greater; or private litigation related to processing of personal data brought by classes of data subjects or consumer protection organizations authorized at law to represent their interests.

In the ordinary course of business, we may transfer personal data from Europe and other jurisdictions to the United States or other countries. Europe and other jurisdictions have enacted laws requiring data to be localized or limiting the transfer of personal data to other countries. In particular, the European Economic Area (EEA) and the United Kingdom have significantly restricted the transfer of personal data to third countries, including the United States, whose privacy laws it generally believes are inadequate. Other jurisdictions may adopt or have already adopted similarly stringent interpretations of their data localization and cross-border data transfer laws. Although there are currently various mechanisms that may be used to transfer personal data from the EEA and UK to the United States in compliance with law (e.g., the EEA Standard Contractual Clauses, the United Kingdom’s International Data Transfer Agreement / Addendum, and the EU-U.S. Data Privacy Framework and the United Kingdom’s extension thereto (which allows for transfers to relevant U.S.-based organizations who self-certify compliance and participate in the Framework)), these mechanisms are subject to legal challenges, and there is no assurance that we can satisfy or rely on these measures to lawfully transfer personal data to the United States. If there is no lawful manner for us to transfer personal data from the EEA, the UK or other jurisdictions to the United States, or if the requirements for a legally-compliant transfer are too onerous, we could face significant adverse consequences, including the interruption or degradation of our operations, the need to relocate part of or all of our business or data processing activities to other jurisdictions (such as Europe) at significant expense, increased exposure to regulatory actions, substantial fines and penalties, the inability to transfer data and work with partners, vendors and other third parties, and injunctions against our processing or transferring of personal data necessary to operate our business. Additionally, companies that transfer personal data out of the EEA and UK to other jurisdictions, particularly to the United States, are subject to increased scrutiny from regulators, individual litigants, and activist groups. Some European regulators have ordered certain companies to suspend or permanently cease certain transfers out of Europe for allegedly violating the GDPR’s cross-border data transfer limitations. TheAdditionally, Unitedthe StatesU.S. isDepartment alsoof increasinglyJustice scrutinizingissued a rule entitled the Preventing Access to U.S. Sensitive Personal Data and Government-Related Data by Countries of Concern or Covered Persons, which places additional restriction on certain data transferstransactions involving countries of concern (e.g., China, Russia, Iran) and covered persons (i.e., individuals and entities who are designated as such by the U.S. Attorney General or considered “foreign persons” and are majority owned by, organized under the laws of, a primary resident in, or a contractor of, a covered person or country of concern, as applicable) that may impact certain business activities such as vendor engagements, sale or sharing of data, employment of certain individuals, and investor agreements. Violations of the rule could lead to significant civil and criminal fines and penalties. The rule applies regardless of whether data is anonymized, key-coded, pseudonymized, de-identified or encrypted, which presents particular challenges for companies like ours and may alsoimpact imposeour ability engage in transactions or agreements with certain datathird localizationparties requirements,in particularlythe if we transfer personal data to, or process personal data of residents of, high risk or sanctioned jurisdictions.future.

In the United States, federal, state, and local governments have enacted numerous data privacy and security laws, including data breach notification laws, personal data privacy laws, consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act), and other similar laws (e.g., wiretapping laws). Numerous U.S. states have enacted comprehensive privacy laws that impose certain obligations on covered businesses, including providing specific disclosures in privacy notices and affording residents with certain rights concerning their personal data. As applicable, such rights may include the right to access, correct, or delete certain personal data, and to opt-out of certain data processing activities, such as targeted advertising, profiling, and automated decision-making. The exercise of these rights may impact our business and ability to provide our products and services. Certain states also impose stricter requirements for processing certain personal data, including sensitive information, such as conducting data privacy impact assessments. These state laws allow for statutory fines for noncompliance. For example, the California Consumer Privacy Act of 2018 (“CCPA”) requires covered companiesapplies to providethe disclosurespersonal todata California residents, includingof consumers, business representatives, and employees,employees who are California residents and requires businesses to provide specific disclosures in privacy notices and honor requests of Californiasuch residentsindividuals to exercise certain privacy rights. The CCPA provides for statutory fines and allows private litigants affected by certain data breaches to recover significant statutory damages. Although there are limited exemptions for clinical trial data under the CCPA, theThe CCPA may impact (possibly significantly) our business activities, should we become subject to the CCPA in the future. Numerousand other comprehensive U.S. states have also enacted comprehensivestate privacy laws, and similar laws are being considered in several other states, as well as at the federal and local levels. While many of these state laws, like the CCPA, exempt some data processed in the context of clinical trials, these developments further complicate compliance efforts, and increase legal risk and compliance costs for us and the third parties with whom we work.work, should we become subject to such laws in the future. Similar laws are being considered in several other states, as well as at the federal and local levels, and we expect more states to pass similar laws in the future. Failure to comply with federal and state laws in the United States regarding privacy and security of personal data could further expose us to penalties under privacy and data protection laws. Even if we are not determined to have violated these laws, government investigations into these issues typically require the expenditure of significant resources and generate negative publicity, which could harm our business.

In addition, on occasion our employees and personnel use generative AI or automated decision-making technologies (collectively, AI technologies) to perform their work, and the disclosure and use of personal data in generative AI technologies is subject to various privacy laws and other privacy obligations. Governments have passed and are likely to pass additional laws regulating generativeAI AI.technologies. Our use of this technology could result in additional compliance costs, regulatory investigations and actions, and lawsuits. If we are unable to use generativeAI AI,technologies, it could make our business less efficient and result in competitive disadvantages.

Obligations related to data privacy and security (and individuals’ data privacy expectations) are quickly changing, becoming increasingly stringent, and creating uncertainty. Additionally, these obligations may be subject to differing applications and interpretations, which may be inconsistent or conflict among jurisdictions. Preparing for and complying with these obligations requires us to devote significant resources, which may necessitate changes to our services, information technologies, systems, and practices and to those of any third parties that process personal data on our behalf. In addition, these obligations may require us to change our business model.

We may at times fail (or be perceived to have failed) in our efforts to comply with our data privacy and security obligations. Moreover, despite our efforts, our personnel or third parties with whom we work may fail to comply with such obligations, which could negatively impact our business operations and compliance posture. For example, any failure by a third party with whom we work to comply with applicable law, regulations, or contractual obligations could result in adverse effects, including inability to or interruption in our ability to operate our business and proceedings against us by governmental entities or others. If we or the third parties with whom we work fail, or are perceived to have failed, to address or comply with applicable data privacy and security obligations, we could face significant consequences, including but not limited to: government enforcement actions (e.g., investigations, fines, penalties, audits, inspections, and similar); litigation (including class-action claims) and mass arbitration demands; additional reporting requirements and/or oversight; bans or restrictions on processing personal data (including clinical trial data); orders to destroy or not use personal data; and imprisonment of company officials. In particular, plaintiffs have become increasingly more active in bringing privacy-related claims against companies, including class claims and mass arbitration demands. Some of these claims allow for the recovery of statutory damages on a per violation basis, and, if viable, carry the potential for monumental statutory damages, depending on the volume of data and the number of violations.

Healthcare providers and third-party payers play a primary role in the recommendation and prescription of any product candidates for which we obtain marketing approval. Our current and future arrangements with healthcare providers, third-party payers and customers may expose us to broadly applicable U.S. federal and state fraud and abuse, transparency, health data privacy, and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we research as well as market, sell and distribute our products for which we obtain marketing approval. If we are found to be in violation of any of any healthcare laws or any other federal or state regulations, we may be subject to significant administrative, civil and/or criminal penalties, damages, fines, disgorgement, imprisonment, exclusion from federal health care programs, additional reporting requirements and/or oversight, and the curtailment or restructuring of our operations. For more information regarding the healthcare laws to which we may be subject, see “Business—Federal and State Fraud and Abuse, Data Privacy and Security, and Transparency Laws and Regulations and Foreign Equivalents”.

In the United States, there have been, and continue to be, legislative and regulatory developments regarding the healthcare system that could prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities, and affect our ability to profitably sell any product candidates for which we obtain marketing approval. Additionally, there has been heightened governmental scrutiny in the United States of pharmaceutical pricing practices in light of the rising cost of prescription drugs and biologics. Such scrutiny has resulted in several recent congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, require direct price negotiations for certain high-expenditure, single-source prescription drugs and biologics covered by the Medicare program, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for products. For example, on July 4, 2025, the annual reconciliation bill, the “One Big Beautiful Bill Act,” or OBBBA, was signed into law which is expected to reduce Medicaid spending and enrollment by implementing work requirements for some beneficiaries, capping state-directed payments, reducing federal funding, and limiting provider taxes used to fund the program. OBBBA also narrows access to Affordable Care Act, or ACA, marketplace exchange enrollment and declines to extend the ACA enhanced advanced premium tax credits, set to expire at the end of 2025, which, among other provisions in the law, are anticipated to reduce the number of Americans with health insurance. In addition, there have been actions and proposals from the Trump administration that include: reducing agency workforce and cutting programs; directing HHS and other agencies to lower prescription drug costs through a variety of initiatives, including by improving upon the Medicare Drug Price Negotiation Program and establishing Most-Favored-Nation pricing for pharmaceutical products; imposing tariffs on imported pharmaceutical products; directing certain federal agencies to enforce existing law regarding hospital and plan price transparency and by standardizing prices across hospitals and health plans; and as part of the Make America Healthy Again (MAHA) Commission’s recent Strategy Report, working across government agencies to increase enforcement on direct-to-consumer pharmaceutical advertising. In addition, on September 30, 2025, the current administration announced the first agreement with a major pharmaceutical company that requires the drug manufacturer to offer, through a direct-to-consumer platform, U.S. patients and Medicaid programs prescription drug Most-Favored Nation pricing equal to or lower than those paid in other developed nations, with additional mandates for direct-to-patient discounts and repatriation of foreign revenues. While anymany of these proposed measures will require authorization through additional legislation to become effective, Congress and the current administration have each indicated that they will continue to seek new legislative and/or administrative measures to control drug costs. At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability or successfully commercialize our drugs.

Moreover, in order to obtain reimbursement for our products in some European countries, including some EU Member States, we may be required to compile additional data comparing the cost-effectiveness of our products to other available therapies. This Health Technology Assessment, or HTA, of medicinal products is becoming an increasingly common part of the pricing and reimbursement procedures in some EU Member States, including those representing the larger markets. The HTA process is the procedure to assess therapeutic, economic and societal impact of a given medicinal product in the national healthcare systems of the individual country. The outcome of an HTA will often influence the pricing and reimbursement status granted to these medicinal products by the competent authorities of individual EU Member States. The extent to which pricing and reimbursement decisions are influenced by the HTA of the specific medicinal product currently varies between EU Member States. The HTA Regulation has applied from January 12, 2025, although it will enter into force iteratively and initially apply to new active substances to treat cancer and to all advanced therapy medicinal products (ATMPs), it will then be expanded to orphan medicinal products in January 2028, and to all centrally authorized medicinal products as of 2030. Selected high-risk medical devices will also be assessed under the HTA Regulation as of 2026. The HTA Regulation is intended to harmonize the clinical benefit assessment of HTA across the EU and permits EU Member States to use common HTA tools, methodologies, and procedures across the EU, working together in four main areas, including joint clinical assessment of the innovative health technologies with the most potential impact for patients, joint scientific consultations whereby developers can seek advice from HTA authorities, identification of emerging health technologies to identify promising technologies early, and continuing voluntary cooperation in other areas. However, there is concern that there are insufficient slots available for joint scientific advice during development. If advice is unavailable during development, there is a higher risk of data gaps and therefore delays in access for patients. Individual EU Member States will continue to be responsible for assessing non-clinical (e.g., economic, social, ethical) aspects of health technologies, and making decisions on pricing and reimbursement. If we are unable to maintain favorable pricing and reimbursement status in EU Member States for product candidates that we may successfully develop and for which we may obtain regulatory approval, any anticipated revenue from and growth prospects for those products in the EU could be negatively affected. In light of the fact that the United Kingdom has left the EU, Regulation No 2021/2282 on HTA does not apply in the United Kingdom. However, the UK Medicines and Healthcare products Regulation Agency, or MHRA,MHRA is working with UK HTA bodies and other national organizations, such as the Scottish Medicines Consortium, or SMC, the National Institute for Health and Care Excellence, or NICE, and the All-Wales Medicines Strategy Group, to introduce new pathways supporting innovative approaches to the safe, timely and efficient development of medicinal products, including, effective as of 31 MarchMarch, 2025, relaunching the Innovative Licensing and Access Pathway with more predicable timelines and closer involvement of the National Health Service.

If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, our development plans may be impacted. For more information regarding the healthcare reforms that may affect our business, see “Business—Coverage and Reimbursement in the United States”.

Sales of our product candidates in the U.S.,United States, if approved, will depend, in part, on the extent to which such products will be covered by third-party payers, such as government health care programs, commercial insurance and managed healthcare organizations. These third-party payers are increasingly limiting coverage and/or reducing reimbursements for medical products and services. A third-party payer’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved. Further, one payer’s determination to provide coverage for a drug product does not ensure that other payers will also provide coverage for the drug product. Coverage policies and third-party payer reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained for products for which we receive marketing approval, less favorable coverage policies and reimbursement rates may be implemented in the future. In addition, the U.S. government, state legislatures and foreign governments have continued implementing cost-containment programs, including price controls, restrictions on reimbursement and requirements for substitution of generic products. Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit our net revenue and results. Decreases in third-party payer reimbursement or a decision by a third-party payer to not cover any of our product candidates, if approved, could reduce physician usage of our product candidates, and have a material adverse effect on our sales, results of operations and financial condition. If we are unable to obtain adequate levels of reimbursement, our ability to successfully market and sell any product candidates will be harmed.

The Company'sOur consolidated financial statements are presented in U.S. dollars. The individual financial statements of each subsidiary is prepared in the currency of the primary economic environment in which the entity operates (its functional currency). Our transactions are commonly denominated in U.K pounds sterling,sterling; however we receive payments under our collaboration agreements in U.S. dollars andhowever, we incur a portion of our expenses in other currencies, primarily Euros.U.S. dollars and in the past, we received payments under collaboration agreements in U.S. dollars. As a result, fluctuations in exchange rates, particularly between the pound sterling on the one hand and the U.S. dollar and Euro on the other hand, may adversely affect our reported results of operations and cash flows. Our business and the price of our ADSs may be affected by fluctuations in foreign exchange rates between the pound sterling and these and other currencies, any of which may have a significant impact on our results of operations and cash flows from period to period.

Pursuant to Section 404 of the Sarbanes-Oxley Act, or Section 404, we are required to furnish a report by our management on our internal control over financial reporting. WhenHowever, while we loseremain oura statussmaller asreporting ancompany, “emerging growth company” as of December 31, 2024, our independent registered public accounting firmwe will not be required to attest to the effectiveness of our internal control over financial reporting. At such time as we are required to obtain auditor attestation, if we then haveinclude an unremediatedattestation materialreport weakness, we would receive an adverse opinion regarding ouron internal control over financial reporting fromissued by our independent registered public accounting firm. To achieve compliance with Section 404 within the prescribed period, we willare continue to engageengaged in a process to document and evaluate our internal control over financial reporting, which is both costly and challenging. In this regard, we will need to continue to dedicate or increase internal resources, including through hiring additional financial and accounting personnel, potentially engage outside consultants and adopt a detailed work plan to assess and document the adequacy of internal control over financial reporting, continue steps to improve control processes as appropriate, validate through testing that controls are functioning as documented and implement a continuous reporting and improvement process for internal control over financial reporting. Despite our efforts, there is a risk that we will not be able to conclude, within the prescribed timeframe or at all, that our internal control over financial reporting is effective as required by Section 404. If we identify one or more material weaknesses in our internal control over financial reporting, it could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our financial statements.

commencement of, or involvement in, litigation involving the Companyus;

Some companies that have experienced volatility in the trading price of their sharessecurities have been the subject of securities class action litigation. Any lawsuit to which we are a party, with or without merit, may result in an unfavorable judgment. We also may decide to settle lawsuits on unfavorable terms.

Under the Internal Revenue Code of 1986, as amended, or the Code, we will be a passive foreign investment company, or PFIC, for any taxable year in which (i) 75% or more of our gross income consists of passive income, or (ii) 50% or more of the average quarterly value of our assets consists of assets that produce, or are held for the production of, passive income (including cash). For purposes of these tests, passive income includes dividends, interest, gains from the sale or exchange of investment property and certain rents and royalties. In addition, for purposes of the above calculations, a non-U.S. corporation that directly or indirectly owns at least 25% by value of the shares of another corporation is treated as if it held its proportionate share of the assets and received directly its proportionate share of the income of such other corporation. If we are a PFIC for any taxable year during which a U.S. Holder holds our ADSs, the U.S. Holder may be subject to adverse tax consequences regardless of whether we continue to qualify as a PFIC, including ineligibility for any preferred tax rates on capital gains or on actual or deemed dividends, interest charges on certain taxes treated as deferred, and additional reporting requirements.

Based on estimatesthe nature of our activities and the composition of our income and assets, and certain assumptions with respect to the characterization of our assets as active or passive, we do not believe we were classified as a PFIC for our taxable year ended December 31, 2024.2025. However, no assurances regarding our PFIC status can be provided for any past, current or future taxable year. The determination of whether we are a PFIC is a fact-intensive determination made on an annual basis and the applicable law is subject to varying interpretation. Accordingly, our U.S. counsel expresses no opinion with respect to our PFIC status for any prior, current or future taxable year.

You should read the following discussion and analysis of our financial condition and results of operations together with our consolidated financial statements and the related notes thereto appearing elsewhere in this Annual Report. Historically, we qualified as a foreign private issuer (as defined in Rule 405 of Regulation C under the Securities Act and Rule 3b-4 under the Exchange Act) and prepared our financial statements in accordance with IFRS as issued by the IASB. On June 30, 2024, the last day of our second fiscal quarter, we determined that we no longer qualified as a foreign private issuer under Rule 3b-4(c) of the Exchange Act. As a result, beginning January 1, 2025, we are required to report with the SEC on domestic forms and comply with domestic company rules in the United States. Therefore, we have now become a domestic issuer and are required under current SEC rules to prepare our financial statements in accordance with U.S. GAAP, as opposed to IFRS. The transition to U.S. GAAP from IFRS was made retrospectively for all periods from our inception. The following discussion is based on our financial information prepared in accordance with U.S. GAAP and regulations of the SEC. Some of the information contained in this discussion and analysis or set forth elsewhere in this Annual Report, including information with respect to our plans and strategy for our business, includes forward-looking statements that involve risks and uncertainties. You should review the section titled “Risk Factors” for a discussion of important factors that could cause actual results to differ materially from the results described in or implied by the forward-looking statements contained in the following discussion and analysis, as well as the section titled “Special Note Regarding Forward-Looking Statements.”

SilenceWe Therapeutics plc (“we”, “us”, “our”, “the Company” or “Silence”) isare a biotechnology company focused on discovering and developing novel molecules incorporating short interfering ribonucleic acid, or siRNA, to inhibit the expression of specific target genes thought to play a role in the pathology of diseases with significant unmet medical need. Our siRNA molecules are designed to harness the body’s natural mechanism of RNA interference, or RNAi,RNAi by specifically binding to and degrading messenger RNA, or mRNA, molecules that encode specific targeted disease-associated proteins in a cell. By degrading the message that encodes the disease-associated protein, the production of that protein is reduced,reduced and its level of activity is lowered. In the field of RNAi therapeutics, this reduction of disease-associated protein production and activity is referred to as “gene silencing.” Our proprietary mRNAi GOLD™ (GalNAc Oligonucleotide Discovery) platform consists of siRNA product candidates designed to precisely target and ‘silence’ specific disease-associated genes in the liver. Using our mRNAi GOLD™ platform, we have generated siRNA product candidates both for our internal development pipeline as well as for out-licensed programs with third-party collaborators. Our wholly owned pipeline is currently focused in three therapeutictargeting areas of high unmet need: cardiovascularacross disease, hematologyrare and rarecommon diseases.diseases where treatments are limited or inadequate.

ZerlasiranCardiometabolic (Cardiovascular Disease)Diseases

Divesiran: Potential first-in-class siRNA for polycythemia vera (Polycythemia VeraPV)

In February 2025, we completed follow-up in the SANRECO Phase 1 clinical trial of divesiran in PV patients. Phase 1 data presentations are planned for medical and research congresses in 2025.2026.

We have incurred significant operating losses and expect to continue to incur significant expenses and operating losses for the near future. These net losses were $45.3 million, $54.2$88.6 million and $50.3$45.3 million,million for the years ended December 31, 2024, 20232025 and 2022,2024, respectively. As of December 31, 2024,2025, our accumulated deficit was $474.0$562.6 million. We expect to continue to incur significant and increasing expenses and to incur operating losses for the foreseeable future, as we advance our product candidates through preclinical and clinical development and seek regulatory approvals, manufacture drug product and drug supply, maintain and expand our intellectual property portfolio, as well as hire additional personnel, pay for further accounting, audit, legal, regulatory and consulting services, and pay costs associated with maintaining compliance with Nasdaq listing rules and the requirements of the U.S. Securities and Exchange Commission, or SEC, director and officer liability insurance, investor and public relations activities and other expenses associated with operating as a public company.

The collaboration coverscovered five targets initially,initially with AstraZeneca having the optionopting to extend the collaboration to a further five targets. AstraZeneca has agreed to pay us $10.0 million upon the exercise of each option to collaborate on an additional target. In May 2023, AstraZeneca nominated the first product candidate under our collaboration, triggering a $10.0 million option fee to us to advance development on an undisclosed program. In February 2024, AstraZeneca initiated a Phase 1 clinical trial for this undisclosed program which triggered another $10.0 million milestone payment to us. In March 2024, we completed our obligations for the second product candidate under the collaboration. For each target selected, we will beare eligible to receive up to $140.0 million in potential milestone payments upon the achievement of milestones relating to the initiation of specified clinical trials, the acceptance of specified regulatory filings and the first commercial sale in specified jurisdictions. For each target selected, we willare also be eligible to receive up to $250.0 million in potential commercial milestone payments, upon the achievement of specified annual net sales levels, as well as tiered royalties as a percentage of net sales ranging from the high single digits to the low double digits.

OnIn October 15, 2021, we announced a collaboration agreement with Hansoh, one of the leading biopharmaceutical companies in China, to develop siRNAs for three undisclosed targets leveraging our proprietary mRNAi GOLD™ platform. Under the terms of the agreement, weHansoh retainhad the exclusive option to license rights to the first two targets in all territories except the China Region (Greater China, Hong Kong, Macau and Taiwan). Hansoh has the exclusive option to license rights to those two targets in the China Region following the completion of phase 1 studies.trials. We willretained beexclusive rights for those two targets in all other territories. We were responsible for all activities up to option exercise and will retainretained responsibility for development outside the China region post phase 1 studies.trials. Hansoh will also havehad the exclusive option to license global rights to a third target at the point of IND filing. Hansoh will bewas responsible for all development activities post option exercise for the third target. Hansoh made a $16 million upfront payment to us in December 2021. We achieved our first $2 million research milestone payment in the Hansoh collaboration in April 2022. In 2023, we achieved two additional preclinical milestones and received $4 million from the collaboration. In 2024, we achieved an additional preclinical milestone andof received $2$2.0 million from the Hansoh collaboration. In December 2024, Hansoh notified us that it will not pursue further development under the Hansoh collaboration. This represented the conclusion of all required development activities and commitments under the terms of the Hansoh Collaboration and we retain exclusive rights globally for all three targets.

Under our collaboration agreement with AstraZeneca, we received an upfront cash payment of $20.0 million in May 2020 and an additional payment of $40.0 million in May 2021. We are also eligible to receive specified development and commercial milestone payments as well as tiered royalties on net sales, if any. During the year ended December 31, 2023,2024, we receivedachieved milestone payments totaling $10.0 million. During the year ended December 31, 2024,2025, we receiveddid not achieve any milestone payments totaling $10.0 million.payments. We recognize the upfront payment and milestone payments over time. During the year ended December 31, 2024,2025, we recognized a total of $18.0$0.6 million in revenue under the AstraZeneca agreement.

Divesiran (SLN124) is our potential first-in-class siRNA in Phase 2 development for polycythemia vera, or PV. PV is a rare myeloproliferative neoplasm characterized by the overproduction of red blood cells, or RBCs. Elevated hematocrit, or HCT, - an index of RBC mass - is a hallmark of the disease and HCT levels above 45% increase the risk of thrombotic and cardiovascular events. The current standard of care in all PV patients to control HCT is phlebotomy, daily low-dose aspirin therapy, sometimes in combination with cytoreductive therapies. PV patients have low levels of hepcidin the body’s master regulator of iron. Divesiran works by "silencing" the TMPRSS6 gene, lifting the natural brake on hepcidin - the body's master iron regulator. When TMPRSS6 is turned down in people living with PV, hepcidin levels rise, reducing iron availability to the bone marrow. With less iron available, the overproduction of RBCs seen in PV is reduced. This helps keep HCT levels in a safer range and can reduce or eliminate the need for phlebotomies. Additionally, siRNA therapies have a highly potent and durable effect - enabling less frequent and more convenient dosing. In the Phase 1 part of the SANRECO clinical trial evaluating divesiran treatment in 21 PV patients, divesiran produced durable HCT control and substantially reduced phlebotomy use following infrequent dosing (Q6W). Based on the strong durability observed in Phase 1, the ongoing Phase 2 part of the SANRECO trial is evaluating both a Q6W and Q12W dosing interval. The SANRECO Phase 2 trial iscompleted fullypatient enrolleddosing in June 2026 and topline results are anticipated in August 2026. The U.S. Food and Drug Administration, or FDA, has granted divesiran Fast Track and orphan drug designations for PV. Divesiran has also been granted orphan drug designation by the European Commission for PV in Europe. While our initial focus is on PV, divesiran has shown the potential in preclinical studies to address multiple hematological conditions through the unifying mechanism of elevating hepcidin in conditions with dysregulation of iron homeostasis.

SLN365 is our potential first-in-class siRNA product candidate that works by "silencing" GPR146, a novel mechanism of action for the management of cholesterol levels in patients, independent of LDLR function. Hypercholesterolemia is a highly prevalent indication with an estimated one in 300 individuals worldwide living with the familial form HeFH (heterozygous) and around one in 300,000 individuals suffering from the form HoFH (homozygous) globally. SLN365 has demonstrated promising preclinical results in non-human primates and wethe anticipateprogram additionalis preclinicalwell datapositioned for a potential IND filing in the second quarter of 2026.2027.

SLN098 is our siRNA product candidate that works by "silencing" INHBE, a novel target for obesity supported by human genetics, strong preclinical data and emerging third-party clinical data demonstrating early efficacy and safety. Despite recent advances in obesity treatment, limitations of current standards of care leave millions at risk of further complications. Around one billion patients worldwide are affected by obesity and associated co-morbidities. Current obesity treatments offer weight loss around 15-20% which plateaus after 12-24 months and are associated with up to 40% lean muscle mass loss. More than two thirds of weight loss is regained within the first year after discontinuation of treatment. There is also poor tolerability and compliance with up to 30% of patients discontinuing GLP/GIP agonists treatment. SLN098 has the opportunity to address unmet needs including increasing fat loss, preventing muscle mass loss and slowing weight regain. SLN098 has demonstrated deep and durable knockdown in nonhuman primates and wethe anticipateprogram additionalis diseasewell modelpositioned datafor a potential IND filing in the second quarter of 2026 to further validate the mechanism of action.2027. We believe there is an opportunity to develop SLN098 either as a monotherapy or add-on to GLP/GIP agonists or as a weight maintenance treatment.

FirstSecond Quarter 2026 and Recent Business Developments

Divesiran: First-in-class siRNA silencing TMPRSS6 for PV

SANRECOPresented follow-up data from the Phase 1 SANRECO study abstract accepted for poster presentation at the European Hematology Association (EHA) 2026 Annual Congress taking placein June 11-14,demonstrating 2026.durable efficacy and potential best-in-class profile for divesiran in PV.

AbstractCompleted #PF886,dosing Posterin Session 1 on Friday, June 12 (6:45-7:45 p.m. CEST) SANRECOthe Phase 2 SANRECO double-blind, placebo-controlled trial evaluating divesiran 6 mg (Q6W and Q12W dosing intervals) in 48 phlebotomy-dependent PV patients is ongoing with topline results on-track for the third quarter of 2026.patients.

SLN312 (AZD1705): Phase 1 siRNA silencing ANGPTL3 with a competitive profile for dyslipidemia

Under the AstraZeneca collaboration, we received an upfront cash payment of $20.0 million and an additional payment of $40.0 million in May 2021. We are also eligible to receive specified development and commercial milestone payments as well as tiered royalties on net sales, if any. We recognize the upfront payment and milestone payments over time. DuringThere was no revenue for the three months ended MarchJune 31,30, 2026 (three months ended June 30, 2025: $0.2 million). During the six months ended June 30, 2026, we recognized a total of $0.4 million in revenue under the AstraZeneca collaboration (threesix months ended MarchJune 31,30, 2025: $0.1$0.4 million).

Foreign exchange gains and losses primarily relate to cash and short-term investments held in foreign currencies (primarily USDGBP and Euros).

Unsurrendered U.K. tax losses may be carried forward indefinitely to be offset against future taxable profits, subject to numerous utilization criteria and restrictions. The amount that can be offset each year is limited to $6.5 million (£5.0 million) plus an incremental 50% of U.K. taxable profits. After accounting for tax credits receivable, we had accumulated tax losses for carry forward in the United Kingdom of $237.0$248.2 million as of MarchJune 31,30, 2026 ($187.7$214.7 million as of MarchJune 31,30, 2025). However, in the event of a change in ownership of a U.K. company, certain provisions may apply to restrict the utilization of carried forward tax losses in future periods. These provisions apply where there is a major change in the nature or conduct of a trade in connection with the change in ownership. For the avoidance of doubt, we do not recognize a deferred tax asset in respect of the accumulated tax losses. In addition to our accumulated tax losses in the United Kingdom, we also had $50.5$48.4 million of accumulated tax losses as of MarchJune 31,30, 2026 ($48.7$52.6 million as of MarchJune 31,30, 2025), related to our operations in Germany for corporate income taxes. We also had $48.9$47.3 million of accumulated losses related to trade taxes in our German entity ($47.2$50.9 million as of MarchJune 31,30, 2025). We had a foreign tax expense in Germany of nil for the threesix months ended MarchJune 31,30, 2026 (threesix months ended MarchJune 31,30, 2025: nil). Tax losses in the United States were negligible.

Comparison of the three and six months ended MarchJune 31,30, 2026, and 2025

The following table summarizes the results of our operations for the three months and six months ended MarchJune 31,30, 2026, and 2025 (in thousands).

Revenue for the three months ended MarchJune 31,30, 2026 was $0.4 million,nil, reflecting ana increasedecrease of $0.3$0.2 million as compared to the same period in 2025 due to a reduction in activity associated with the AstraZeneca collaboration.

Cost of sales movement was negligibleRevenue for the threesix months ended MarchJune 31,30, 2026,2026 was $0.4 million, reflecting a negligible increase as compared to the same period in 2025. The change was2025 due to activity associated with our collaboration agreements, which fluctuates based on the timingAstraZeneca of activities and project progression.collaboration.

The following table summarizes our research and development costs for the three and six months ended MarchJune 31,30, 2026 and 2025, based on their classification (in thousands).

Research and development costs for the three months ended MarchJune 31,30, 2026 decreased by $11.7$8.5 millionmillion, as compared to $9.1the million.same period in 2025. This change was mainly due to a decrease in contracted development costs of $10.3$7.5 million associated with the Phase 3 readiness for zerlasiran in 20252025, as well as a decrease in personnel costs of $1.4$0.8 million mainly due to reduced headcount.

Contracted development costs for the three months ended MarchJune 31,30, 2026 decreased by $10.3$7.5 million and $17.8 million for the six months ended June 30, 2026, compared to $4.3the million.same periods in 2025. The decrease was largely due to a decrease in costs related to contract manufacturing activities related to our zerlasiran Phase 3 readiness completed in 2025. The remaining decrease is due to the timing of clinical manufacturing and clinical studies for divesiran.

General and administrative expenses decreased by $0.7$0.4 million for the three months ended MarchJune 31,30, 2026 and $1.1 million for the six months ended June 30, 2026, compared to the same periodperiods in 2025. These decreases were mainly due to an effort to reduce administrative costs.

As of January 1, 2026, the functional currency of our U.K. entity changed to USD and as a result, foreign currency activity included in net incomegain of $0.2 million for the three months ended MarchJune 31,30, 2026 wasand a net loss of $0.5$0.3 million.million for the six months ended June 30, 2026. In the prior year, foreign exchange gains and losses included in net income resulted primarily from foreign currency (USD and EUR) denominated bank accounts. The foreign exchange losses for the three and six months ended MarchJune 31,30, 2025 were primarily due to remeasurement of U.S. treasury bills held in USD to the related functional currency.

As of MarchJune 31,30, 2026, we had cash,cash and cash equivalents, and short-term investmentsequivalents of $70.1$72.1 million. We believe that our cash,cash and cash equivalents, and short-term investmentsequivalents will be sufficient to fund our anticipated operating and capital expenditure requirements into 2028.

The following table summarizes the results of our cash flows for the threesix months ended MarchJune 31,30, 2026 and 2025.

Net cash outflow from operating activities increaseddecreased by $3.3$20.0 million for the threesix months ended MarchJune 31,30, 2026, as compared with the same period in 2025. This increasedecrease was mainly due to the receipt of $11.0 million related to the 2023 R&D benefitreduction in the three months ended March 31, 2025, while no related claim was received in 2026. This was offset by a reduction inour research and development spend in 2026.

Net cash inflow from investing activities relates to $139.4 million redemptions of U.S. treasury bills, offset by $64.4 million in purchases for the threesix months ended MarchJune 31,30, 2026. The same period in 2025 reflected $70.1$72.4 million in purchases of U.S. treasury bills offset by $25.7$26.6 million in redemptions.

Cash flows from financing activities were negligible for the periods ended MarchJune 31,30, 2026 and 2025.

The following table summarizes our contractual commitments and obligations as of MarchJune 31,30, 2026 and December 31, 2025.

At MarchJune 31,30, 2026, we had a gross commitment on our office rental in Berlin, Germany and in the United States equal to an aggregate of $0.6 million in the next year. No amounts are payable after more than one year.

During the threesix months ended MarchJune 31,30, 2026 and 2025, our revenue from collaboration agreements was derived from the AstraZeneca collaboration.

For the threesix months ended MarchJune 31,30, 2026 and 2025, we determined actual costs and forecast costs for the remainder of the contract. We calculated total contract costs across the contract term, including costs that will be reimbursed to us, and costs incurred to date as a percentage of total contract costs. We multiplied this percentage by the consideration deemed highly probable of not having a significant reversal, calculating the cumulative revenue to be recognized. When variable consideration increases due to a further milestone becoming highly probable that a significant reversal of revenue will not occur, a catch-up in revenue is recorded to reflect efforts already expended by us up to that point. In the threesix months ended MarchJune 31,30, 2026, the estimated forecasted cost for partnered programs was not material and the related judgment was not significant.