UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13D INFORMATION TO BE INCLUDED IN STATEMENTS FILED PURSUANT TO § 240.13d-1(a) AND AMENDMENTS THERETO FILED PURSUANT TO 240.13d-2(a) UNDER THE SECURITIES EXCHANGE ACT OF 1934 SPERO THERAPEUTICS, INC. (Name of Issuer) Common Stock, Par Value $0.001 (Title of Class of Securities) 84833T 10 3 (CUSIP Number) Victoria A. Whyte GlaxoSmithKline plc 980 Great West Road Brentford, Middlesex TW8 9GS England Telephone: +44 (0)208 047 5000 (Name, Address and Telephone Number of Person Authorized to Receive Notices and Communications) November 6, 2017 (Date of Event which Requires Filing of this Statement) If the filing person has previously filed a statement on Schedule 13G to report the acquisition that is the subject of this Schedule 13D, and is filing this schedule because of §§240.13d-1(e), 240.13d-1(f) or 240.13d-1(g), check the following box. ☐ Note: Schedules filed in paper format shall include a signed original and five copies of the schedule, including all exhibits. See §240.13d-7 for other parties to whom copies are to be sent. * The remainder of this cover page shall be filled out for a reporting person's initial filing on this form with respect to the subject class of securities, and for any subsequent amendment containing information which would alter disclosures provided in a prior cover page. The information required on the remainder of this cover page shall not be deemed to be "filed" for the purpose of Section 18 of the Securities Exchange Act of 1934 ("Act") or otherwise subject to the liabilities of that section of the Act but shall be subject to all other provisions of the Act. Cusip No. 84833T 10 3 13D Page 2 of 9 1. NAMES OF REPORTING PERSONS I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY) GlaxoSmithKline plc 2. CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP (see instructions) (a) ☐ (b) ☐ 3. SEC USE ONLY 4. SOURCE OF FUNDS (see instructions) WC 5. CHECK BOX IF DISCLOSURE OF LEGAL PROCEEDINGS IS REQUIRED PURSUANT TO ITEMS 2(d) or 2(e) ☐ 6. CITIZENSHIP OR PLACE OF ORGANIZATION England and Wales 7. SOLE VOTING POWER 1,854,006 NUMBER OF 8. SHARED VOTING POWER SHARES BENEFICIALLY -0- OWNED BY EACH 9. SOLE DISPOSITIVE POWER REPORTING PERSON WITH 1,854,006 10. SHARED DISPOSITIVE POWER -0- 11. AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON 1,854,006 shares of Common Stock 12. CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (11) EXCLUDES CERTAIN SHARES (see instructions) ☐ 13. PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (11) 13.3% of the shares of Common Stock (1) 14. TYPE OF REPORTING PERSON (see instructions) CO Footnotes: (1) Based on 13,897,684 shares of the Issuer’s common stock outstanding as of November 6, 2017, upon the closing of the Issuer’s initial public offering, as reported in the Issuer’s prospectus dated November 1, 2017 (the “Final Prospectus”) filed with the Securities and Exchange Commission (the “SEC”) on November 2, 2017 pursuant to Rule 424(b)(4) of the Securities Act of 1933, as amended (the “Securities Act”). Cusip No. 84833T 10 3 13D Page 3 of 9 Item 1. Security and Issuer. This statement on Schedule 13D (this “Statement”) relates to the shares of common stock, par value $0.001 per share (the “Common Stock”), of Spero Therapeutics, Inc., a Delaware corporation (the “Issuer”). The Issuer’s principal executive offices are located at 675 Massachusetts Avenue, 14th Floor, Cambridge, Massachusetts 02139. Item 2. Identity and Background. This Statement is being filed on behalf of GlaxoSmithKline plc, a public limited company incorporated under the laws of England and Wales. GlaxoSmithKline plc and its subsidiaries constitute a major global healthcare group engaged in the creation, discovery, development, manufacture and marketing of pharmaceutical and consumer health-related products with its principal offices located at 980 Great West Road, Brentford, Middlesex TW8 9GS, England. Set forth in Schedule 1 to this Statement are the name, business address and present principal occupation or employment and citizenship of each executive officer and director of GlaxoSmithKline plc. The Common Stock which is the subject of this Statement is held of record by S.R. One, Limited (“S.R. One”), a wholly-owned indirect subsidiary of GlaxoSmithKline plc. On September 30, 2016, GlaxoSmithKline plc agreed to a settlement with the SEC relating to an investigation into the commercial practices of certain subsidiaries of GlaxoSmithKline plc in China. The SEC’s order found that GlaxoSmithKline plc violated the internal controls and books and records provisions of the U.S. Foreign Corrupt Practices Act (the “FCPA”). GlaxoSmithKline plc consented to the order without admitting or denying the findings, and agreed to pay a $20 million civil penalty. GlaxoSmithKline plc also agreed to provide status reports to the SEC for the next two years on its remediation and implementation of anti-corruption compliance measures. Other than as set forth above in this Item 2, during the last five years prior to the date hereof, neither GlaxoSmithKline plc nor, to the best knowledge of GlaxoSmithKline plc, any of the other persons with respect to whom information is given in response to this Item 2 has been convicted in a criminal proceeding or been a party to a civil proceeding ending in a judgment, decree or final order enjoining future violations of, or prohibiting or mandating activities subject to, federal or state securities laws, or finding any violation with respect to such laws. Item 3. Source or Amount of Funds or Other Consideration. GlaxoSmithKline plc, through its wholly-owned indirect subsidiary S.R. One, acquired from the Issuer 428,571 shares of Common Stock on November 6, 2017 in the Issuer’s initial public offering (the “IPO”) at the public offering price of $14.00 per share. The total consideration paid by S.R. One for these shares was $5,999,994, and such consideration was obtained from the working capital of S.R. One. S.R. One also acquired 1,425,435 shares of Common Stock on November 1, 2017 upon conversion of (i) 1,483,784 shares of Junior preferred stock of the Issuer (the “Junior Preferred”) into 244,147 shares of Common Stock, (ii) 982,906 shares of Series A preferred stock of the Issuer (the “Series A Preferred”) into 246,272 shares of Common Stock, (iii) 1,250,000 shares of Series B preferred stock of the Issuer (the “Series B Preferred”) into 328,992 shares of Common Stock; (iv) 3,683,045 shares of Series C preferred stock of the Issuer (the “Series C Preferred” and, together with the Junior Preferred, the Series A Preferred and the Series B Preferred, the “Preferred Stock”) into 606,024 shares of Common Stock. The amount of underlying securities reflects the application of the applicable conversion ratio as set forth in the Issuer’s Amended and Restated Certificate of Incorporation in effect immediately prior to the closing of the initial public offering (as adjusted by the 1-for-6.0774 reverse stock split of the Issuer’s common stock effected on October 20, 2017). The conversion of the Preferred Stock into shares of Common Stock occurred automatically upon the closing of the IPO without payment of consideration. The consideration for each of the Junior Preferred, Series A Preferred, Series B Preferred and Series C Preferred was obtained from the working capital of S.R. One. Item 4. Purpose of Transaction. S.R. One appointed Vikas Goyal, a Principal at S.R. One and an employee of GlaxoSmithKline LLC, an indirect, wholly-owned subsidiary of GlaxoSmithKline plc, to the board of the Issuer in September 2013. Mr. Goyal continues to serve on the board of directors of the Issuer. On June 30, 2017, the Issuer, S.R. One and certain other investors of preferred stock entered into the Investors’ Rights Agreement, a copy of which is attached hereto as Exhibit 1. Pursuant to the Investors’ Rights Agreement, S.R. One (i) has the right to require the Issuer to register the shares of Common Stock held by it under the Securities Act under specified circumstances and subject to certain limitations, (ii) has piggyback registration rights, subject to specified exceptions, if the Issuer proposes to file a registration statement to register any of its securities under the Securities Act, either for the Issuer’s own .