As filed with the Securities and Exchange Commission on May 22, 2019 Registration No. 333-231422

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

PRE-EFFECTIVE AMENDMENT NO. 1 TO FORM F-6

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933 FOR AMERICAN DEPOSITARY SHARES EVIDENCED BY

AMERICAN DEPOSITARY RECEIPTS

BICYCLE THERAPEUTICS PLC

(Exact name of issuer of deposited securities as specified in its charter)

[N/A] 

(Translation of issuer’s name into English)

England and Wales 

(Jurisdiction of incorporation or organization of issuer)

CITIBANK, N.A. 

(Exact name of depositary as specified in its charter)

388 Greenwich Street

New York, New York 10013

(877) 248-4237 

(Address, including zip code, and telephone number, including area code, of depositary’s principal executive offices)

Lee Kalowski
Bicycle Therapeutics Inc.
4 Hartwell Place
Lexington, Massachusetts 02421

617-945-8155

(Address, including zip code, and telephone number, including area code, of agent for service)

Copies to:

Kristopher D. Brown
James Xu
Jonathan A. Schur
Goodwin Procter LLP
620 Eighth Avenue
New York, NY  10018
(212) 813-8800 Herman H. Raspé, Esq. Patterson Belknap Webb & Tyler LLP
1133 Avenue of the Americas
New York, NY 10036
(212) 336-2301  

It is proposed that this filing become effective under Rule 466:	☐	immediately upon filing.
	☐	on (Date) at (Time).

If a separate registration statement has been filed to register the deposited shares, check the following box: ☒

CALCULATION OF REGISTRATION FEE

Title of Each Class of Securities to be Registered	Amount to be Registered	Proposed Maximum Aggregate Price Per Unit*	Proposed Maximum Aggregate Offering Price**	Amount of Registration Fee
American Depositary Shares (ADS(s)), each ADS representing  the right to receive one (1) Ordinary Share of Bicycle Therapeutics plc (the “Company”)	N/A	N/A	N/A	N/A
*     Each unit represents 100 ADSs. **   Estimated solely for the purpose of calculating the registration fee. Pursuant to Rule 457(k), such estimate is computed on the basis of the maximum aggregate fees or charges to be imposed in connection with the issuance of ADSs.
The Registrant hereby amends this Registration Statement on such date or dates as may be necessary to delay its effective date until the Registrant shall file a further amendment which specifically states that this Registration Statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act of 1933, or until this Registration Statement shall become effective on such date as the Commission, acting pursuant to said Section 8(a), may determine.

This Pre-Effective Amendment No. 1 to Registration Statement may be executed in any number of counterparts, each of which shall be deemed an original, and all of such counterparts together shall constitute one and the same instrument.

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PART I

INFORMATION REQUIRED IN PROSPECTUS

Cross Reference Sheet

Item 1. DESCRIPTION OF SECURITIES TO BE REGISTERED

Item Number and Caption			Location in Form of American Depositary Receipt (“Receipt”) Filed Herewith as Prospectus
1.	Name of Depositary and address of its principal executive office		Face of Receipt -  Introductory Article.
2.	Title of Receipts and identity of deposited securities		Face of Receipt  - Top Center.
Terms of Deposit:
	(i)	The amount of deposited securities represented by one American Depositary Share ("ADSs")	Face of Receipt  - Upper right corner.
	(ii)	The procedure for voting, if any, the deposited securities	Reverse of Receipt  - Paragraphs (17) and (18).
	(iii)	The collection and distribution of dividends	Reverse of Receipt - Paragraph (15).
	(iv)	The transmission of notices, reports and proxy soliciting material	Face of Receipt  - Paragraph (14); Reverse of Receipt - Paragraph (18).
	(v)	The sale or exercise of rights	Reverse of Receipt – Paragraphs (15) and (17).
	(vi)	The deposit or sale of securities resulting from dividends, splits or plans of reorganization	Face of Receipt - Paragraphs (3) and (6); Reverse of Receipt - Paragraphs (15) and (17).
	(vii)	Amendment, extension or termination of the deposit agreement	Reverse of Receipt - Paragraphs (23) and (24) (no provision for extensions).
	(viii)	Rights of holders of Receipts to inspect the transfer books of the Depositary and the list of holders of ADSs	Face of Receipt - Paragraph (14).

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Item Number and Caption			Location in Form of American Depositary Receipt (“Receipt”) Filed Herewith as Prospectus
	(ix)	Restrictions upon the right to deposit or withdraw the underlying securities	Face of Receipt – Paragraphs (2), (3), (4), (6), (7), (9) and (10).
	(x)	Limitation upon the liability of the Depositary	Face of Receipt - Paragraph (8); Reverse of Receipt - Paragraphs (20) and (21).
3.	Fees and charges which may be imposed directly or indirectly on holders of ADSs		Face of Receipt - Paragraph (11).
Item 2.		AVAILABLE INFORMATION	Face of Receipt - Paragraph (14).

The Company is subject to the periodic reporting requirements of the United States Securities Exchange Act of 1934, as amended, and, accordingly, files certain reports with, and submits certain reports to, the United States Securities and Exchange Commission (the “Commission”). These reports can be retrieved from the Commission’s internet website (www.sec.gov), and can be inspected and copied at the public reference facilities maintained by the Commission at 100 F Street, N.E., Washington D.C. 20549.

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PROSPECTUS

The Prospectus consists of the proposed form of American Depositary Receipt included as Exhibit A to the Form of Deposit Agreement filed as Exhibit (a) to this Pre-Effective Amendment No. 1 to Registration Statement on Form F-6 and is incorporated herein by reference. 

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PART II

INFORMATION NOT REQUIRED IN PROSPECTUS

Item 3. EXHIBITS

(a) Form of Deposit Agreement, by and among Bicycle Therapeutics plc (the “Company”), Citibank, N.A., as depositary (the “Depositary”), and all Holders and Beneficial Owners of American Depositary Shares issued thereunder (“Deposit Agreement”). ^___ Filed herewith as Exhibit (a).

(b) Any other agreement to which the Depositary is a party relating to the issuance of the American Depositary Shares registered hereunder or the custody of the deposited securities represented thereby. ^___ None.

(c) Every material contract relating to the deposited securities between the Depositary and the issuer of the deposited securities in effect at any time within the last three years. ^___ None.

(d) Opinion of counsel for the Depositary as to the legality of the securities to be registered. ^___ Previously filed as exhibit (d) to Registration Statement on Form F-6 (Reg. No. 333-231422) with the Commission on May 13, 2019, and incorporated herein by reference .

(e) Certificate under Rule 466. ^___ None.

(f) Powers of Attorney for certain officers and directors and the authorized representative of the Company. ^___ Previously filed.

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Item 4. UNDERTAKINGS

(a) The Depositary undertakes to make available at the principal office of the Depositary in the United States, for inspection by holders of ADSs, any reports and communications received from the issuer of the deposited securities which are both (1) received by the Depositary as the holder of the deposited securities, and (2) made generally available to the holders of the underlying securities by the issuer.

(b) If the amount of fees charged is not disclosed in the prospectus, the Depositary undertakes to prepare a separate document stating the amount of any fee charged and describing the service for which it is charged and to deliver promptly a copy of such fee schedule without charge to anyone upon request. The Depositary undertakes to notify each registered holder of an ADS thirty (30) days before any change in the fee schedule.

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SIGNATURES

Pursuant to the requirements of the Securities Act of 1933, as amended, Citibank, N.A., acting solely on behalf of the legal entity to be created by the Deposit Agreement, by and among Bicycle Therapeutics plc, Citibank, N.A., as depositary, and all Holders and Beneficial Owners from time to time of American Depositary Shares to be issued thereunder, certifies that it has reasonable grounds to believe that all the requirements for filing on Form F-6 are met and has duly caused this Pre-Effective Amendment No. 1 to Registration Statement on Form F-6 to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of New York, State of New York, on the 22nd day of May, 2019.

Legal entity created by the Deposit Agreement under which the American Depositary Shares registered hereunder are to be issued, each American Depositary Share representing the right to receive one (1) ordinary share of Bicycle Therapeutics plc.
CITIBANK, N.A., solely in its capacity as Depositary
By:	/s/ Leslie DeLuca
	Name: Leslie DeLuca
	Title:   Attorney-in-Fact

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SIGNATURES

Pursuant to the requirements of the Securities Act of 1933, as amended, Bicycle Therapeutics plc certifies that it has reasonable grounds to believe that all the requirements for filing on Form F-6 are met and has duly caused this Pre-Effective Amendment No. 1 to Registration Statement on Form F-6 to be signed on its behalf by the undersigned thereunto duly authorized, in Cambridge, United Kingdom, on May 22, 2019.

BICYCLE THERAPEUTICS PLC
By:	/s/ Kevin Lee
	Name: Kevin Lee, Ph.D., MBA
	Title:   Chief Executive Officer

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Pursuant to the requirements of the Securities Act of 1933, as amended, this Pre-Effective Amendment No. 1 to Registration Statement on Form F-6 has been signed by the following persons in the following capacities on May 22, 2019.

Signature	Title
/s/ Kevin Lee	Chief Executive Officer and Member of the Board
Kevin Lee, Ph.D., MBA	(Principal Executive Officer)
/s/ Lee Kalowski	Chief Financial Officer (Principal Financial
Lee Kalowski, MBA	Officer and Principal Accounting Officer)
*	Chairman and Director
Pierre Legault, MBA, CPA
*	Director
Michael Anstey, DPhil
*	Director
Catherine Bingham, MBA

*	Director
Deborah Harland, Ph.D., MBA
*	Director
Anja König, Ph.D.
*	Director
Eashwar Krishnan
*	Director
Carolyn Ng, Ph.D.
*	Director
Jason Rhodes, MBA
*	Director
Sir Gregory Winter, FRS
/s/ Lee Kalowski	Authorized Representative in the U.S.
Lee Kalowski

*By:	/s/ Lee Kalowski
	Name: Lee Kalowski
	Title: Attorney-in-Fact

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Index to Exhibits

Exhibit	Document	Sequentially Numbered Page
(a)	Form of Deposit Agreement

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