Financial Performance - The company reported a net loss of £43.3 million for the year ended December 31, 2023, compared to £40.5 million in 2022 and £39.4 million in 2021, with an accumulated loss of £304.6 million as of December 31, 2023[40]. - The company has never generated any revenue from product sales and anticipates continuing to incur significant operating losses for the foreseeable future[42][41]. - The company has a history of net losses and anticipates that it will continue to incur losses for the foreseeable future, requiring additional financial resources for ongoing development[39][46]. - Additional capital will be needed in the future to continue planned operations, including expanded research and development activities and potential commercialization efforts[55]. - As of December 31, 2023, the company had cumulative carryforward tax losses of £155.8 million[202]. Funding and Capital Requirements - In 2023, the company received a $10.0 million milestone payment from the AstraZeneca collaboration and $4 million from the Hansoh collaboration, along with approximately $32.2 million from sales of ADSs under its Sales Agreement[51]. - In January 2024, the company raised an additional $20 million from sales of ADSs under its Sales Agreement[52]. - On February 5, 2024, the company announced a private placement of 5,714,286 ADSs at a price of $21.00 per ADS, aiming for aggregate gross proceeds of $120.0 million[53]. - The company expects to rely primarily on non-dilutive strategic collaboration arrangements and equity or debt financings to fund its operations[48]. - The company may receive future milestone payments of up to $12 million from existing collaboration agreements in the next 12 months, which could extend its ability to fund operations into 2026[54]. Product Development and Regulatory Risks - The company has not yet obtained marketing approval for any product candidates and may not do so in the foreseeable future[39]. - The company faces significant risks related to its financial condition, including the need for additional capital to continue its operations and product development[30][46]. - Clinical trials are expensive and uncertain, with a high risk of failure, which could materially harm the company's business[72]. - Delays in clinical trial processes, including patient enrollment and regulatory approvals, could adversely affect the company's ability to advance product candidates[73][75]. - Regulatory approval for product candidates is uncertain, and delays may occur due to additional studies or regulatory requirements, impacting potential revenue timelines[84]. Intellectual Property and Competition - The company relies on a combination of patents, trade secret protection, and confidentiality agreements to safeguard its intellectual property related to current and future products[152]. - Patent applications may fail to issue or be challenged, potentially impacting the company's ability to commercialize future products[153]. - The company may face claims of intellectual property infringement, which could delay development and commercialization efforts[158]. - The company faces competition from various sources, including major pharmaceutical and biotechnology companies, which may have more resources and experience[105]. - The company may not realize the expected benefits from the Rare Pediatric Disease Designation, as it does not guarantee faster development or regulatory approval[99]. Operational and Compliance Risks - The company is subject to stringent data privacy and security laws, including the EU GDPR and U.K. GDPR, which impose significant compliance obligations and potential fines for violations[125]. - Non-compliance with U.S. healthcare laws and regulations could expose the company to criminal sanctions, civil penalties, and reputational harm[133]. - The company has implemented security measures to protect against cybersecurity incidents, but there is no assurance that these measures will always be effective[117]. - Employee misconduct or improper activities could significantly harm the company, despite the adoption of a code of business conduct and a compliance program[131]. - The evolving regulatory landscape for data privacy and protection could affect the company's business operations and increase operational costs[124]. Corporate Governance and Shareholder Matters - The company has previously identified and remediated material weaknesses in its internal control over financial reporting, but there is no assurance that additional weaknesses will not be identified in the future[181]. - The company is permitted to adopt certain home country practices in corporate governance that may afford less protection to shareholders compared to Nasdaq standards[187]. - Approximately 58% of the company's issued and outstanding ordinary shares are beneficially owned by senior management, directors, and principal shareholders, which may limit new investors' influence on corporate decisions[174]. - The concentration of ownership among existing shareholders may discourage potential acquirers and impede significant corporate transactions[176]. - The company does not anticipate paying any cash dividends on its ordinary shares in the foreseeable future, making capital appreciation the sole source of gains for investors[176].

Full Year 2023 Conference Call March 13, 2024 Forward-Looking Statements 2 The information contained in this presentation is being supplied and communicated to you solely for your information and may not be reproduced, further distributed to any other person or published, in whole or in part, for any purpose. The distribution of this presentation in certain jurisdictions may be restricted by law, and persons into whose possession this presentation comes should inform themselves about, and observe, any such ...

Clinical Study Results - Silence Therapeutics announced positive topline 36-week data from the ALPACAR-360 phase 2 study of zerlasiran, showing highly significant reductions in lipoprotein(a) (Lp(a)) levels[1]. - The study involved 178 subjects with baseline Lp(a) levels at or over 125 nmol/L, indicating a high risk of atherosclerotic cardiovascular disease (ASCVD) events[1]. - Median baseline Lp(a) was approximately 215 nmol/L, with a median percentage reduction in Lp(a) of 90% or greater observed for both 300 mg and 450 mg doses at week 36[2]. - No new safety concerns were identified during the treatment period, supporting the safety profile of zerlasiran[2]. - Silence plans to report topline 48-week data from the study in the second quarter of 2024[4]. - The ongoing 60-week study will evaluate secondary endpoints, including changes in Lp(a) from baseline to 48 weeks and 60 weeks[3]. Company Focus and Collaborations - Silence Therapeutics is focused on developing RNA interference-based medicines to address significant unmet medical needs, particularly in cardiovascular disease[5]. - The company maintains ongoing research collaborations with AstraZeneca and Hansoh Pharma, enhancing its development capabilities[5]. Forward-Looking Statements - Forward-looking statements indicate potential risks and uncertainties regarding clinical and commercial prospects, regulatory approvals, and future data reports[6]. - Silence cautions stakeholders not to place undue reliance on forward-looking statements, which reflect the company's views as of the announcement date[6].

Financial Data and Key Metrics Changes - The company's net loss for the full year 2022 was £40.5 million compared to a net loss of £39.4 million in 2021, reflecting an increase in R&D expenses due to advancing clinical programs [17] - Revenue for the year ended December 31, 2022, was £17.5 million, up from £12.4 million in 2021, driven by advancements in partnered programs [28] - Cash and cash equivalents were £71.1 million (approximately US$86 million) at the end of December 2022, with an estimated cash runway through the first quarter of 2024 [17][50] Business Line Data and Key Metrics Changes - The SLN360 program, now known as Zerlasiran, reported up to 98% efficacy in the APOLLO study, with strong durability after a single dose [25] - The SLN124 program is progressing in the clinic, with encouraging preliminary safety results reported in the GEMINI II Phase I thalassemia study [14][21] Market Data and Key Metrics Changes - Elevated Lp(a) levels are recognized to affect up to 1.4 billion people worldwide, representing a significant unaddressed health issue [31] - The company is focusing on a target population with Lp(a) levels greater than or equal to 125 nmol per liter for the Phase II study, which is a lower threshold than in the Phase I study [20][39] Company Strategy and Development Direction - The company aims to differentiate its products in the market, particularly in the statin-sized market for cardiovascular treatments [10] - The focus is on advancing clinical programs across both proprietary and partnered pipelines, with expectations for strong execution in 2023 [27][35] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in achieving key milestones by year-end, including top-line data from multiple ongoing studies [2][47] - There is a growing recognition of Lp(a) as a key cardiovascular risk factor, with increased awareness and testing among major societies [51] Other Important Information - The company has received FDA fast track and orphan drug designations for SLN124, indicating regulatory support for its development in rare diseases [33] - The company anticipates receiving up to $14 million in potential milestone payments from existing partnerships within the next 12 months [45] Q&A Session Summary Question: What kind of MACE reduction is needed for investor excitement regarding Lp(a)? - Management indicated that a 70% reduction in Lp(a) is generally needed to demonstrate therapeutic benefit, with current data showing higher reductions [37] Question: What insights are expected from the MAD portion of the Phase I trial? - The MAD portion will provide interim data that could optimize dosing for future studies, although it will not impact the ongoing Phase II trial [41] Question: What potential additional indications are being considered for SLN124? - Management noted that while both polycythemia vera and beta-thalassemia involve hepcidin, the underlying mechanisms differ, and they are exploring relevant indications for SLN124 [43]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 Form 20-F (Mark One) ☐ REGISTRATION STATEMENT PURSUANT TO SECTION 12(b) OR (g) OF THE SECURITIES EXCHANGE ACT OF 1934 OR ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2022 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to OR ☐ SHELL COMPANY REPORT PURSUANT TO SECTION 13 OR 15(d) OF ...

Company Vision and Strategy - Silence Therapeutics aims to transform lives by silencing diseases with precision medicines, leveraging its mRNAi GOLD™ platform through a hybrid business model[11] - The company's partnered pipeline has a potential of ~$7.5 billion in milestones plus royalties[13] - Silence Therapeutics' proforma cash balance is approximately $110 million, expected to fund the company into Q2 2024[13] - The company's market capitalization is approximately $367 million as of September 9, 2022[14] Clinical Program Highlights - SLN360 (Cardiovascular Disease) showed up to 98% Lp(a) reduction in a Phase 1 study after a single dose[55] - SLN124 (Hematological Disorders) showed an average hepcidin increase of up to ~4-fold in a Phase 1 study after a single dose[55] - Approximately 10% of the global population has >90 mg/dL Lp(a), indicating a 2-3x increased heart attack risk[58] - SLN124 increased average hepcidin up to ~4-fold and reduced serum iron ~50% after a single dose in healthy volunteers[101] Partnerships - AstraZeneca deal includes up to $4 billion in potential milestones plus tiered royalties for 10 targets[43] - Mallinckrodt collaboration includes up to $2 billion in potential milestones plus royalties for 3 targets[43] - Hansoh collaboration includes up to $1.3 billion in potential milestones plus royalties for undisclosed targets[43]

Silence Therapeutics September 2022 Forward-Looking Statements The information contained in this presentation is being supplied and communicated to you solely for your information and may not be reproduced, further distributed to any other person or published, in whole or in part, for any purpose. The distribution of this presentation in certain jurisdictions may be restricted by law, and persons into whose possession this presentation comes should inform themselves about, and observe, any such restrictions ...

Silence Therapeutics July 13, 2022 Forward-Looking Statements The information contained in this presentation is being supplied and communicated to you solely for your information and may not be reproduced, further distributed to any other person or published, in whole or in part, for any purpose. The distribution of this presentation in certain jurisdictions may be restricted by law, and persons into whose possession this presentation comes should inform themselves about, and observe, any such restrictions. ...

Silence Therapeutics plc (NASDAQ:SLN) Q4 2021 Earnings Conference Call March 17, 2022 8:00 AM ET Company Participants Gem Hopkins - Head of Investor Relations and Corporate Communications Craig Tooman - President and Chief Executive Officer Rhonda Hellums - Chief Financial Officer Giles Campion - Head of R&D Conference Call Participants Tom Shrader - BTIG Patrick Trucchio - H.C. Wainright Myles Minter - William Blair Operator Good day, ladies and gentlemen, and welcome to the Silence Therapeutics Full Year ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 Form 20-F (Mark One) ☐ REGISTRATION STATEMENT PURSUANT TO SECTION 12(b) OR (g) OF THE SECURITIES EXCHANGE ACT OF 1934 OR ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2021 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to OR ☐ SHELL COMPANY REPORT PURSUANT TO SECTION 13 OR 15(d) OF ...