12,962,963 American Depositary Shares Representing 38,888,889 Ordinary Shares We are offering American Depositary Shares, or ADSs, representing ordinary shares, nominal value £0.05 each, of Silence Therapeuticsplc offered by this prospectus supplement. Each ADS represents three ordinary shares. The ADSs are listed on the Nasdaq Global Market under the symbol “SLN”. On August11, 2026, the closing price of our ADSs,as reported on The Nasdaq Global Market, was $14.72per ADS. We are a “smaller reporting company” as defined under the federal securities laws and, as such, have elected to comply withcertain reduced public company disclosure and reporting requirements. (1)See “Underwriting” for additional disclosure regarding the underwriting commissions and estimated offering expenses. We have granted the underwriters the option to purchase up to 1,944,444 additional ADSs from us at the offering price, less underwritingdiscounts and commissions. The underwriters may exercise this right at any time, in whole or in part, within 30 days following the date ofthis prospectus supplement. Investing in these securities involves a high degree of risk. You should review carefully the risks and uncertainties describedunder the heading “Risk Factors” on page S-5 of this prospectus supplement and under similar headings in the otherdocuments that are incorporated by reference into this prospectus supplement. Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of thesesecurities or determined if this prospectus supplement or the accompanying prospectus is truthful or complete. Anyrepresentation to the contrary is a criminal offense. The underwriters expect to deliver the ADSs to purchasers on or about August13, 2026. Joint Bookrunners JEFFERIESMORGANSTANLEY WILLIAMBLAIR CANTOR Table of Contents TABLE OF CONTENTS Prospectus Supplement ABOUT THIS PROSPECTUSMARKET, INDUSTRY AND OTHER DATAPROSPECTUS SUPPLEMENT SUMMARYTHE OFFERINGRISK FACTORSSPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTSUSE OF PROCEEDSDIVIDEND POLICYDILUTIONUNDERWRITINGMATERIAL TAX CONSIDERATIONSLEGAL MATTERSEXPERTSSERVICE OF PROCESS AND ENFORCEMENT OF LIABILITIESWHERE YOU CAN FIND ADDITIONAL INFORMATIONINCORPORATION BY REFERENCE Prospectus PAGEABOUT THIS PROSPECTUSiiTRADEMARKSivPROSPECTUS SUMMARY1RISK FACTORS4SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS6USE OF PROCEEDS8DESCRIPTION OF SHARE CAPITAL AND ARTICLES OF ASSOCIATION11DESCRIPTION OF AMERICAN DEPOSITARY SHARES30MATERIAL TAX CONSIDERATIONS39LEGAL MATTERS40EXPERTS40SERVICE OF PROCESS AND ENFORCEMENT OF LIABILITIES41WHERE YOU CAN FIND ADDITIONAL INFORMATION43INCORPORATION BY REFERENCE44 Table of Contents ABOUT THIS PROSPECTUS This document is part of the registration statement that we filed with the SEC using a “shelf” registration process and consists of two parts. Thefirst part is this prospectus supplement, including the documents incorporated by reference, which describes the specific terms of this offering andalso adds to and updates information contained in the accompanying prospectus. The second part, the accompanying prospectus, including thedocuments incorporated by reference, gives more general information, some of which may not be applicable to this offering. Generally, when werefer to the prospectus, we are referring to this prospectus supplement and the accompanying prospectus combined. This prospectus supplement and the documents incorporated into this prospectus supplement by reference include important information aboutus, the securities being offered and other information you should know before investing in our securities. To the extent there is a conflict betweenthe information contained in this prospectus supplement, on the one hand, and the information contained in any document incorporated byreference into this prospectus that was filed with the SEC before the date of this prospectus supplement, on the other hand, you should rely onthe information in this prospectus supplement. If any statement in one of these documents is inconsistent with a statement in another documenthaving a later date (for example, a document incorporated by reference in this prospectus supplement), the statement in the document having thelater date modifies or supersedes the earlier statement. Any statement so modified or superseded will not be deemed, except as so modified orsuperseded, to constitute a part of this prospectus supplement. You should rely only on the information contained in or incorporated by reference in this prospectus supplement and in any free writing prospectusthat we have authorized for use in connection with this offering. We have not, and the underwriters have not, authorized anyone to provide youwith different information. If anyone provides you with different or inconsistent information, you should not rely on it. We are not, and theunderwriters are not, making an offer to sell these securities in any