UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549

SCHEDULE 13D/A

(Amendment No. 4) *

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

BICYCLE THERAPEUTICS PLC

(Name of Issuer)

Ordinary Shares, par value £0.01
(Title of Class of Securities)

088786 108

(CUSIP Number)

Victoria A. Whyte

(Name, Address and Telephone Number of Person
Authorized to Receive Notices and Communications)

August 5, 2021

(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.

Item 1.       Security and Issuer.

This Amendment No. 4 to Schedule 13D (this “Statement”) amends and supplements the statement on Schedule 13D originally filed on June 7, 2019, and amended on February 14, 2020, December 7, 2020 and April 16, 2021 (the “Schedule 13D”) with respect to the ordinary shares, nominal value £0.01 per share (the “Ordinary Shares”) of Bicycle Therapeutics plc, a public limited company incorporated under the laws of England and Wales (the “Issuer”). GlaxoSmithKline plc is filing this amendment to disclose its new percentage beneficial ownership in the Issuer, which has been decreased as a result of (1) the disposition of American Depositary Shares representing Ordinary Shares by the Reporting Person and (2) an increase in the outstanding Ordinary Shares of the Issuer. The Issuer’s principal executive offices are located at B900, Babraham Research Campus, Cambridge, CB22 3AT, United Kingdom.

Item 2.      Identity and Background.

The response set forth in Item 2 of the Schedule 13D is hereby amended by deleting Schedule 1 in its entirety and replacing it with Schedule 1 attached.

Item 5.      Interest in Securities of the Issuer.

The response set forth in Items 5 (a) , (b) and (c) of the Schedule 13D is hereby amended by deleting the previous response in its entirety and replacing it with the following:

(a), (b) The information contained in rows 7, 8, 9, 10, 11, and 13 on each of the cover pages of this Statement is incorporated by reference in its entirety into this Item 5.

(c) Except as described herein, no transaction in Ordinary Shares were effected during the past 60 days by GlaxoSmithKline plc

SIGNATURE

After reasonable inquiry and to the best of my knowledge and belief, I certify that the information set forth in this statement is true, complete and correct.

Date: September 16, 2021

GLAXOSMITHKLINE PLC

By: /s/ Victoria A. Whyte

Name: Victoria A. Whyte
Title: Authorized Signatory

Schedule 1