Sec Form 3 Filing - BAKER BROS. ADVISORS LP @ BICYCLE THERAPEUTICS plc - 2024-04-18

FORM 3 Check this box if no longer subject to Section 16. Form 4 or Form 5 obligations may continue. See Instruction 1(b).

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 STATEMENT OF CHANGES IN BENEFICIAL OWNERSHIP Filed pursuant to Section 16(a) of the Securities Exchange Act of 1934, Section 17(a) of the Public Utility Holding Company Act of 1935 or Section 30(h) of the Investment Company Act of 1940

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1. Name and Address of Reporting Person BAKER BROS. ADVISORS LP 2. Issuer Name and Ticker or Trading Symbol BICYCLE THERAPEUTICS plc [ BCYC] 5. Relationship of Reporting Person(s) to Issuer (Check all applicable) X __ Director X __ 10% Owner _____ Officer (give title below) _____ Other (specify below) (Last) (First) (Middle) 860 WASHINGTON STREET, 3RD FLOOR 3. Date of Earliest Transaction (MM/DD/YY) 04/18/2024 (Street) NEW YORK, NY10014 4. If Amendment, Date Original Filed (MM/DD/YY) 6. Individual or Joint/Group Filing (Check Applicable Line) _____ Form filed by One Reporting Person __ X __ Form filed by More than One Reporting Person (City) (State) (Zip)

Table I - Non-Derivative Securities Acquired, Disposed of, or Beneficially Owned 1.Title of Security (Instr. 3) 2. Transaction Date (MM/DD/YY) 2A. Deemed Execution Date, if any (MM/DD/YY) 3. Transaction Code (Instr. 8) 4. Securities Acquired (A) or Disposed of (D) (Instr. 3, 4 and 5) 5. Amount of Securities Beneficially Owned Following Reported Transaction(s) (Instr. 3 and 4) 6. Ownership Form: Direct (D) or Indirect (I) (Instr. 4) 7. Nature of Indirect Beneficial Ownership (Instr. 4) Code V Amount (A) or (D) Price American Depositary Shares 579,856 I See Footnotes ( 1 ) ( 2 ) ( 3 ) ( 4 ) American Depositary Shares 6,437,320 I See Footnotes ( 1 ) ( 3 ) ( 4 ) ( 5 )

Table II - Derivative Securities Acquired, Disposed of, or Beneficially Owned ( e.g. , puts, calls, warrants, options, convertible securities) 1. Title of Derivative Security (Instr. 3) 2. Conversion or Exercise Price of Derivative Security 3. Transaction Date (MM/DD/YY) 3A. Deemed Execution Date, if any (MM/DD/YY) 4. Transaction Code (Instr. 8) 5. Number of Derivative Securities Acquired (A) or Disposed of (D) (Instr. 3, 4, and 5) 6. Date Exercisable and Expiration Date (MM/DD/YY) 7. Title and Amount of Underlying Securities (Instr. 3 and 4) 8. Price of Derivative Security (Instr. 5) 9. Number of Derivative Securities Beneficially Owned Following Reported Transaction(s) (Instr. 4) 10. Ownership Form of Derivative Security: Direct (D) or Indirect (I) (Instr. 4) 11. Nature of Indirect Beneficial Ownership (Instr. 4) Code V (A) (D) Date Exercisable Expiration Date Title Amount or Number of Shares Non-Voting Ordinary Shares ( 6 ) ( 6 ) ( 6 )( 7 ) ( 6 ) Ordinary Shares 363,453 I See Footnotes ( 2 ) ( 3 ) ( 4 ) Non-Voting Ordinary Shares ( 6 ) ( 6 ) ( 6 )( 7 ) ( 6 ) Ordinary Shares 4,342,429 I See Footnotes ( 3 ) ( 4 ) ( 5 )

Reporting Owners Reporting Owner Name / Address Relationships Director 10% Owner Officer Other BAKER BROS. ADVISORS LP 860 WASHINGTON STREET, 3RD FLOOR NEW YORK, NY10014 X X 667, L.P. 860 WASHINGTON STREET, 3RD FLOOR NEW YORK, NY10014 X X Baker Bros. Advisors (GP) LLC 860 WASHINGTON STREET, 3RD FLOOR NEW YORK, NY10014 X X Baker Brothers Life Sciences LP 860 WASHINGTON STREET, 3RD FLOOR NEW YORK, NY10014 X X BAKER FELIX 860 WASHINGTON STREET, 3RD FLOOR NEW YORK, NY10014 X X BAKER JULIAN 860 WASHINGTON STREET, 3RD FLOOR NEW YORK, NY10014 X X Signatures By: Baker Bros. Advisors LP, Name: Scott L. Lessing, Title: President /s/ Scott L. Lessing 04/18/2024 Signature of Reporting Person Date Baker Bros. Advisors LP, Mgmt. Co. and Inv. Adviser to 667, L.P., pursuant to authority granted by Baker Biotech Capital, L.P., GP to 667, L.P. Name: Scott L. Lessing, Title: President /s/ Scott L. Lessing 04/18/2024 Signature of Reporting Person Date By: Baker Bros. Advisors (GP) LLC, Name: Scott L. Lessing, Title: President /s/ Scott L. Lessing 04/18/2024 Signature of Reporting Person Date Baker Bros. Advisors LP, Mgmt. Co. and Inv. Adviser to BAKER BROTHERS LIFE SCIENCES, L.P., pursuant to authority grantedby Baker Brothers Life Sciences Capital, L.P., GP to Baker Brothers Life Sciences, L.P., Name: Scott L. Lessing, Title: President /s/ 04/18/2024 Signature of Reporting Person Date /s/ Felix J. Baker 04/18/2024 Signature of Reporting Person Date /s/ Julian C. Baker 04/18/2024 Signature of Reporting Person Date

Explanation of Responses:

( 1 )American Depositary Shares ("ADS") of Bicycle Therapeutics plc (the "Issuer") each represent 1 Ordinary Share ("Ordinary Shares") of the Issuer. ( 2 )As a result of their ownership interest in (i) Baker Biotech Capital, L.P. and (ii) 667, L.P. ("667"), Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in the securities reported in column 2 of Table I and column 3 of Table II held directly by 667, a limited partnership of which the sole general partner is Baker Biotech Capital, L.P., a limited partnership of which the sole general partner is Baker Biotech Capital (GP), LLC, due to their interest in 667 and Baker Biotech Capital, L.P.'s right to receive an allocation of a portion of the profits from 667. ( 3 )Baker Bros. Advisors LP (the "Adviser") serves as the investment adviser to 667 and Baker Brothers Life Sciences, L.P. ("Life Sciences" and together with 667, the "Funds"). In connection with the services provided by the Adviser, the Adviser receives an asset-based management fee that does not confer any pecuniary interest in the securities held directly by the Funds. Baker Bros. Advisors (GP) LLC (the "Adviser GP") is the Adviser's sole general partner. Julian C. Baker and Felix J. Baker are managing members of the Adviser GP. The Adviser has complete and unlimited discretion and authority with respect to the investment and voting power of the securities held directly by the Funds. The general partners of the Funds relinquished to the Adviser all discretion and authority with respect to the investment and voting power of the securities held directly by the Funds. ( 4 )Julian C. Baker, Felix J. Baker, the Adviser GP and the Adviser disclaim beneficial ownership of the securities held directly by the Funds or for the benefit of the Funds except to the extent of their pecuniary interest therein, and this report shall not be deemed an admission that any of Julian C. Baker, Felix J. Baker, the Adviser GP or the Adviser is a beneficial owner of such securities for purposes of Section 16 or any otherpurpose. ( 5 )As a result of their ownership interest in (i) Baker Brothers Life Sciences Capital, L.P. and (ii) Life Sciences, Julian C. Baker and Felix J. Baker each may be deemed to have an indirect pecuniary interest in the securities reported in column 2 of Table I and column 3 of Table II held directly by Life Sciences, a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital, L.P., a limited partnership of which the sole general partner is Baker Brothers Life Sciences Capital (GP), LLC, due to their interest in Life Sciences and Baker Brothers Life Sciences Capital, L.P.'s right to receive an allocation of a portion of the profits from Life Sciences. ( 6 )These securities consist of non-voting ordinary shares of the Issuer ("Non-Voting Ordinary Shares") convertible at any time at the option of the holder on a 1-for-1 basis without consideration into Ordinary Shares to the extent that immediately prior to or after giving effect to such conversion the holders thereof, together with their affiliates and any members of a Section 13(d) group with such holders, would beneficially own, for purposes of Rule 13d-3 under the Securities Act of 1934, as amended, no more than 9.99% of the outstanding Ordinary Shares (the "Beneficial Ownership Limitation") following such conversion. The Non-Voting Ordinary Shares have no expiration date. ( 7 )By written notice to the Issuer, the Funds may from time to time increase or decrease the Beneficial Ownership Limitation applicable to that Fund to any other percentage not in excess of 19.9%. Any such increase will not be effective until the 61st day after such notice is delivered to the Issuer. The Funds notified the Issuer of an increase in the Beneficial Ownership Limitation from 9.99% to 19.9% on April 16, 2024. This increase in the Beneficial Ownership Limitation will be effective on June 16, 2024.

Remarks: Felix J. Baker, a managing member of Baker Bros. Advisors (GP) LLC, was appointed as director on April 18, 2024 of Bicycle Therapeutics plc (the "Issuer"). By virtue of their representation on the board of directors of the Issuer, for purposes of Section 16 of the Securities Exchange Act of 1934, as amended, the reporting persons other than Felix J. Baker are deemed directors by deputization of the Issuer.

Reminder: Report on a separate line for each class of securities beneficially owned directly or indirectly.

* If the form is filed by more than one reporting person, see Instruction 4(b)(v).

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