SILENCE THERAPEUTICS PLC (Exact Name of Registrant As Specified in Its Charter)

Table of Contents As filed with the Securities and Exchange Commission on April 8, 2021 Registration No. 333-248203 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Post-Effective Amendment No. 2 to Form F-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 SILENCE THERAPEUTICS PLC (Exact Name of Registrant as Specified in its Charter) Not Applicable (Translation of Registrant’s Name into English) England and Wales 2834 Not Applicable (State or other Jurisdiction of (Primary Standard Industrial (I.R.S. Employer Incorporation or Organization) Classification Code Number) Identification Number) 72 Hammersmith Road London W14 8TH United Kingdom Tel: +44 20 3457 6900 (Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices) Silence Therapeutics Inc. 434 West 33rd Street, Office 814 New York, New York 10001 Tel: +1 917 374 0372 (Name, address, including zip code, and telephone number, including area code, of agent for service) Copies of all communications, including communications sent to agent for service, should be sent to: Joshua A. Kaufman Claire A. Keast-Butler Divakar Gupta Cooley (UK) LLP Brian F. Leaf Dashwood Cooley LLP 69 Old Broad Street 55 Hudson Yards London EC2M 1QS New York, New York 10001 United Kingdom +1 212 479—6000 +44 20 7785 9355 Approximate date of commencement of proposed sale to the public: From time to time after the effective date of this Registration Statement If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933, check the following box. ☒ If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐ If this Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐ If this Form is a post-effective amendment filed pursuant to Rule 462(d) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐ Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933. Emerging growth company ☒ If an emerging growth company that prepares its financial statements in accordance with U.S. GAAP, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act of 1933. ☐ † The term “new or revised financial accounting standards” refers to any update issued by the Financial Accounting Standards Board to its Accounting Standards Codification after April 5, 2012. This filing constitutes Post-Effective Amendment No. 2 to the Registration Statement on Form F-1 (File No. 333-248203), which was initially declared effective on September 4, 2020. This Post-Effective Amendment No. 2 shall hereafter become effective in accordance with Section 8(c) of the Securities Act of 1933, as amended (the “Securities Act”), on such date as the Securities and Exchange Commission, acting pursuant to Section 8(c) of the Securities Act, may determine. Table of Contents Explanatory Note This Post-Effective Amendment No. 2 to the Registration Statement on Form F-1 (File No. 333-248203), or the Registration Statement, of Silence Therapeutics plc, or the Company, is being filed (i) pursuant to the undertakings in Item 9 of the Registration Statement to update the information contained in the Registration Statement, as originally declared effective by the Securities and Exchange Commission, or the SEC, on September 4, 2020, to include the Company’s audited financial statements for the year ended December 31, 2020, and (ii) to update certain other information in the Registration Statement. The information included in this filing updates the Registration Statement and the prospectus contained therein. No additional securities are being registered under this Post-Effective Amendment No. 2. All applicable registration fees were paid at the time of the original filing of the Registration Statement. Table of Contents The information contained in this prospectus is not complete and may be changed. No securities may be sold pursuant to this prospectus until the registration statement filed with the Securities and Exchange Commission with respect to such securities has been declared effective. This prospectus is not an offer to sell these securities and no offers to buy these securities are being solicited in any jurisdiction where their offer or sale is not permitted. SUBJECT TO COMPLETION, DATED APRIL 8, 2021 PRELIMINARY PROSPECTUS 49,106,988 Ordinary Shares Represented by approximately 16,368,996 American Depositary Shares SILENCE THERAPEUTICS PLC Our American Depositary Shares, or ADSs, each representing three ordinary shares of Silence Therapeutics plc, are listed on the Nasdaq Capital Market, or Nasdaq, under the symbol “SLN”. The ADSs began trading on September 8, 2020. Our ordinary shares are currently traded on AIM, a market operated by the London Stock Exchange, under the symbol “SLN”. The closing price of our ordinary shares on AIM on April 1, 2021 was £5.90 per ordinary share, which is equivalent to a price of $8.12 per share based on the noon buying rate of the Federal Reserve Bank of New York on March 26, 2021, or $24.36 per ADS, after giving effect to the ratio of one ADS for every three ordinary shares. We have appointed The Bank of New York Mellon to act as the depositary for the ADSs representing our ordinary shares, including the Registered Shares, as defined below. Holders of ordinary shares registered hereby may deposit such ordinary shares with the depositary in exchange for ADSs representing such ordinary shares at the ratio referred to in the first sentence of this paragraph. ADSs representing the ordinary shares registered hereby will be freely tradeable on Nasdaq. We filed the registration statement of which this prospectus forms a part with respect to an aggregate of 49,106,988 ordinary shares held by the shareholders identified herein. Holders of all such ordinary shares are identified in this prospectus as the Registered Holders and the aggregate of 49,106,988 ordinary shares registered hereby as the Registered Shares. Any Registered Shares offered and sold in the United States by the Registered Holders will be in the form of ADSs. The Registered Holders are also permitted to sell ordinary shares not represented by ADSs in private transactions, including on AIM, which resales are not covered by this prospectus. The Registered Holders are offering their securities in order to create and maintain a public trading market for our equity securities in the United States. However, unlike an initial public offering, any disposition by the Registered Holders of the Registered Shares represented by ADSs is not being underwritten by any investment bank. The Registered Holders may, or may not, elect to dispose of Registered Shares represented by ADSs as and to the extent that they may individually determine. Such dispositions, if any, will be made through brokerage transactions on Nasdaq or other securities exchanges in the United States at prevailing market prices. See the section entitled “Plan of Distribution.” We will not receive proceeds from any disposition of Registered Shares in the form of ADSs by Registered Holders. We are an “emerging growth company” and a “foreign private issuer,” each as defined under the federal securities laws, and, as such, we are subject to reduced public company reporting requirements. See the section entitled “Summary — Implications of Being an Emerging Growth Company and a Foreign Private Issuer.” Neither the U.S. Securities and Exchange Commission nor any other regulatory body has approved or disapproved of these securities or passed upon the adequacy or accuracy of this prospectus. Any representation to the contrary is a criminal offense. Investing in ADSs representing our ordinary shares involves a high degree of risk. Before buying any ADSs representing our ordinary shares you should carefully read the discussion of material risks of investing in such securities in “Risk Factors” beginning on page 13 of this prospectus. The date of this prospectus is , 2021 Table of Contents TABLE OF CONTENTS ABOUT THIS PROSPECTUS ii PRESENTATION OF FINANCIAL AND SHARE INFORMATION ii SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS 1 PROSPECTUS SUMMARY 3 THE REGISTERED SHARES 9 SUMMARY CONSOLIDATED FINANCIAL DATA 11 RISK FACTORS 13 INDUSTRY AND MARKET DATA 51 USE OF PROCEEDS 51 DIVIDEND POLICY 51 CAPITALIZATION 52 MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS 53 BUSINESS 67 MANAGEMENT 97 RELATED PARTY TRANSACTIONS 113 PRINCIPAL SHAREHOLDERS 114 REGISTERED HOLDERS 116 DESCRIPTION OF SHARE CAPITAL AND ARTICLES OF ASSOCIATION 118 DESCRIPTION OF AMERICAN DEPOSITARY SHARES 138 ORDINARY SHARES AND ADSS ELIGIBLE FOR FUTURE SALE 147 MATERIAL INCOME TAX CONSIDERATIONS 148 PLAN OF DISTRIBUTION 156 EXPENSES OF THIS OFFERING 159 LEGAL MATTERS 159 EXPERTS 159 SERVICE OF PROCESS AND ENFORCEMENT OF LIABILITIES 159 WHERE YOU CAN FIND ADDITIONAL INFORMATION 161 INDEX TO FINANCIAL STATEMENTS F-1 i Table of Contents We and the Registered Holders are responsible for the information contained in this prospectus and any free writing prospectus that we may prepare or authorize. Neither we nor the Registered Holders have authorized anyone to provide you with different or additional information, and neither we nor they take any responsibility for, or provide any assurance as to the reliability of, any other information that others may give you.

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