BCYC / Bicycle Therapeutics plc - Depositary Receipt (Common Stock) - Документы SEC, Годовой отчет, Доверенное заявление

30,323,301 Ordinary Shares Represented by 30,323,301 American Depositary Shares

TABLE OF CONTENTS   Pursuant to Rule 424(b)(3)  Registration No. 333-289423 PROSPECTUS 30,323,301 Ordinary Shares Represented by 30,323,301 American Depositary Shares This prospectus relates to the resale or other disposition by the selling securityholders identified in this prospectus, or the selling securityholders, of 30,323,301 of our ordinary shares, nominal value £0.01 per share, represented

Bicycle Therapeutics Reports Recent Business Progress and Second Quarter 2025 Financial Results Continued advancement across research and development pipeline, with key program updates expected in 2H 2025 Phase 1/2 Duravelo-4 trial for zelenectide pe

Exhibit 99.1 Bicycle Therapeutics Reports Recent Business Progress and Second Quarter 2025 Financial Results Continued advancement across research and development pipeline, with key program updates expected in 2H 2025 Phase 1/2 Duravelo-4 trial for zelenectide pevedotin in NECTIN4-amplified non-small cell lung cancer open and actively recruiting patients Strengthened clinical leadership and bolste

Amended and Restated Employment Agreement, dated March 25, 2025, by and between Eric Westin and Bicycle Therapeutics Inc.

Exhibit 10.1 AMENDED AND RESTATED EMPLOYMENT AGREEMENT This Amended and Restated Employment Agreement (the “Agreement”) is entered into as of March 25, 2025, by and between Eric Westin (“Executive”) and Bicycle Therapeutics Inc. (the “Company”). The Company desires to employ Executive on a full time bases (i.e., 40 hours per week) and, in connection therewith, to compensate Executive for Executive

Amendment No. 1 to the Amended and Restated 2020 Equity Incentive Plan.

Exhibit 10.3 AMENDMENT NO. 1 TO THE AMENDED AND RESTATED 2020 EQUITY INCENTIVE PLAN In accordance with Section 10.4 of Bicycle Therapeutics, plc (the “Company”) Amended and Restated 2020 Equity Incentive Plan (the “Plan”), the Plan is hereby amended as follows, subject to approval of the Company’s shareholders: 1. Section 4.1 of the Plan is hereby deleted and replaced as follows: Subject to adjust

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 August 6, 2025 Date of Report (Date of earliest event reported) Bicycle Therapeutic

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 August 6, 2025 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

Non-Employee Director Compensation Policy, as amended as of June 18, 2025.

Exhibit 10.2 Bicycle Therapeutics plc Non-Employee Director Compensation Policy As amended through June 18, 2025 This Non-Employee Director Compensation Policy (the “Policy”) has been established in order to attract and retain non-employee directors who have the knowledge, skills and experience to serve as a member of the Board of Directors (the “Board”) of Bicycle Therapeutics plc (the “Company”)

Filing Fee Table

Calculation of Filing Fee Tables S-3 BICYCLE THERAPEUTICS PLC Table 1: Newly Registered and Carry Forward Securities ☐Not Applicable Security Type Security Class Title Fee Calculation or Carry Forward Rule Amount Registered Proposed Maximum Offering Price Per Unit Maximum Aggregate Offering Price Fee Rate Amount of Registration Fee Carry Forward Form Type Carry Forward File Number Carry Forward Initial Effective Date Filing Fee Previously Paid in Connection with Unsold Securities to be Carried Forward Newly Registered Securities Equity Ordinary Shares, nominal value GBP0.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2025 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38916 Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) England and Wales Not Applicable (State or other jurisdiction of incorporation or organization) (I.

Bicycle Therapeutics plc, Issuer AND [TRUSTEE], Trustee INDENTURE Dated as of [·], 20__ Debt Securities TABLE OF CONTENTS

Exhibit 4.3 Bicycle Therapeutics plc, Issuer AND [TRUSTEE], Trustee INDENTURE Dated as of [·], 20 Debt Securities TABLE OF CONTENTS PAGE article 1 DEFINITIONS 1 Section 1.01 Definitions of Terms 1 article 2 ISSUE, DESCRIPTION, TERMS, EXECUTION, REGISTRATION AND EXCHANGE OF SECURITIES 5 Section 2.01 Designation and Terms of Securities 5 Section 2.02 Form of Securities and Trustee’s Certificate 7 Se

As filed with the Securities and Exchange Commission on August 8, 2025

TABLE OF CONTENTS As filed with the Securities and Exchange Commission on August 8, 2025 Registration No.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 June 17, 2025 Date of Report (Date of earliest event reported) Bicycle Therapeutics

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 June 17, 2025 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

Consulting Agreement, dated March 24, 2025, between the Company and Santiago Arroyo.

Exhibit 10.1 CONSULTING AGREEMENT THIS CONSULTING AGREEMENT (the “Agreement”) is made by and between Bicycle Therapeutics Inc. (“Company”) and Santiago Arroyo (“Consultant”), effective as of March 24, 2025 (the “Effective Date”). 1.ENGAGEMENT OF SERVICES. Subject to the terms of this Agreement, Consultant agrees to provide consulting services to Company as described in Exhibit A hereto (the “Servi

Consulting Agreement, dated March 15, 2019, between the Company and Stone Sunny Isles Inc., as amended by the Amendment to Consulting Agreement, executed March 26, 2025 and effective as of June 17, 2025, between the Company and Stone Atlanta Estates LLC (successor-in-interest to Stone Sunny Isles Inc.).

Exhibit 10.3 CONSULTING AGREEMENT This “Agreement” is made and entered into as of March 15, 2019 (the “Effective Date”) by and between Stone Sunny Isles Inc. (“Consultant”) and Bicycle Therapeutics, Inc. (the “Company”) (each a “Party” and collectively the “Parties”). The Company and Consultant hereby agree as follows: 1.Services. The Company hereby engages Consultant to provide to the Company, it

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2025 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38916 Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) England and Wales Not Applicable (State or other jurisdiction of incorporation or organization) (I.

Separation Agreement, dated March 24, 2025, between the Company and Santiago Arroyo.

Exhibit 10.2 Bicycle Therapeutics, Inc. March 24, 2025 Santiago Arroyo Dear Santiago: This letter confirms the end of your employment with Bicycle Therapeutics, Inc. (the “Company”) based on your resignation from employment, effective March 24, 2025 (the “Separation Date”), and we desire to resolve any and all issues relating to your employment and the conclusion of your employment with the Compan

Consulting Agreement, executed March 26, 2025 and effective as of June 17, 2025, between the Company and Richard Kender.

Exhibit 10.4 CONSULTING AGREEMENT THIS CONSULTING AGREEMENT (the “Agreement”) is made by and between Bicycle Therapeutics Inc. (“Company”) and Kender Consulting LLC (“Consultant”), effective as of June 17, 2025 (the “Effective Date”). 1.ENGAGEMENT OF SERVICES. Subject to the terms of this Agreement, Consultant agrees to provide consulting services to Company as described in Exhibit A hereto (the “

Bicycle Therapeutics Reports Recent Business Progress and First Quarter 2025 Financial Results Multiple abstracts accepted for presentation at 2025 ASCO and AACR annual meetings underscore breadth of Bicycle® technology and potential of oncology pipe

Exhibit 99.1 Bicycle Therapeutics Reports Recent Business Progress and First Quarter 2025 Financial Results Multiple abstracts accepted for presentation at 2025 ASCO and AACR annual meetings underscore breadth of Bicycle® technology and potential of oncology pipeline Phase 1/2 Duravelo-3 trial for zelenectide pevedotin in NECTIN4-amplified breast cancer open and actively recruiting patients Bolste

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 May 1, 2025 Date of Report (Date of earliest event reported) Bicycle Therapeutics p

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 May 1, 2025 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation) (C

Bicycle Therapeutics Announces Presentation of Additional Human Radiopharmaceutical Imaging Data for MT1-MMP at the American Association for Cancer Research Annual Meeting 2025 Data continue to validate the potential of MT1-MMP as a novel cancer targ

Exhibit 99.1 Bicycle Therapeutics Announces Presentation of Additional Human Radiopharmaceutical Imaging Data for MT1-MMP at the American Association for Cancer Research Annual Meeting 2025 Data continue to validate the potential of MT1-MMP as a novel cancer target and further underscore the applicability of Bicycle® Radioconjugates (BRC®) for radiopharmaceutical imaging Data are representative of

Regulation FD Disclosure, Financial Statements and Exhibits

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 April 29, 2025 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. )

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. ) Filed by the Registrant ⌧ Filed by a Party other than the Registrant ◻ Check the appropriate box: ◻ Preliminary Proxy Statement ◻ Confidential, for Use of the Commission Only (as permitte

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. )

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. ) Filed by the Registrant ⌧ Filed by a Party other than the Registrant ◻ Check the appropriate box: ⌧ Preliminary Proxy Statement ◻ Confidential, for Use of the Commission Only (as permitte

Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers, Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 March 21, 2025 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

Bicycle Therapeutics Announces New Board and Key Clinical Leadership Appointments Felix J. Baker, Ph.D., to become chairman of Board of Directors Alessandro Riva, M.D., joins Board of Directors and Fabrice André, M.D., Ph.D., joins Clinical Advisory

Exhibit 99.1 Bicycle Therapeutics Announces New Board and Key Clinical Leadership Appointments Felix J. Baker, Ph.D., to become chairman of Board of Directors Alessandro Riva, M.D., joins Board of Directors and Fabrice André, M.D., Ph.D., joins Clinical Advisory Board Eric Westin, M.D., promoted to chief medical officer and Jim MacDonald-Clink promoted to senior vice president, head of business de

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 March 12, 2025 Date of Report (Date of earliest event reported) Bicycle Therapeutic

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 March 12, 2025 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

Form of Option Grant Notice and Agreement (for employees) for the 2020 Plan.

Exhibit 10.7 OPTION GRANT NOTICE BICYCLE THERAPEUTICS PLC 2020 EQUITY INCENTIVE PLAN Capitalized terms not specifically defined in this Option Grant Notice (the “Grant Notice”) have the meanings given to them in the 2020 Equity Incentive Plan (as amended from time to time, the “Plan”) of Bicycle Therapeutics Plc (the “Company”). The Company has granted to the participant listed below (“Participant

Form of Amended and Restated Restricted Share Unit Grant Notice and Agreement (regular settlement for directors) for the 2020 Plan.

Exhibit 10.12 AMENDED AND RESTATED RESTRICTED SHARE UNIT GRANT NOTICE BICYCLE THERAPEUTICS PLC 2020 EQUITY INCENTIVE PLAN: NON-EMPLOYEE SUB-PLAN Capitalized terms not specifically defined in this Amended and Restated Restricted Share Unit Grant Notice (the “Grant Notice”) have the meanings given to them in the 2020 Equity Incentive Plan: Non-Employee Sub-Plan (as amended from time to time, the “Pl

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-8 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Bicycle Therapeutics plc (Exact name of registrant as specified in its charter)

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-8 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales (State or other jurisdiction of incorporation or organization) Not applicable (I.R.S. Employer Identification No.) Blocks A & B, Portway Building Granta Park, Great

Amended and Restated Insider Trading Policy, as amended (adopted September 26, 2019 and amended September 27, 2023).

Exhibit 19.1 Bicycle Therapeutics plc Amended and Restated Insider Trading Policy, as Amended (adopted September 26, 2019 and Amended September 27, 2023) Introduction During the course of your relationship with Bicycle Therapeutics plc (the “Company”), you may receive material information that is not yet publicly available (“material nonpublic information”) about the Company or other publicly trad

Form of Restricted Share Unit Grant Notice and Agreement (deferred settlement for directors) for the 2020 Plan.

Exhibit 10.13 RESTRICTED SHARE UNIT GRANT NOTICE (DEFERRED SETTLEMENT) BICYCLE THERAPEUTICS PLC 2020 EQUITY INCENTIVE PLAN: NON-EMPLOYEE SUB-PLAN Capitalized terms not specifically defined in this Restricted Share Unit Grant Notice (the “Grant Notice”) have the meanings given to them in the 2020 Equity Incentive Plan: Non-Employee Sub-Plan (as amended from time to time, the “Plan”) of Bicycle Ther

Exhibit 4.6

Exhibit 4.6 DESCRIPTION OF THE REGISTRANT'S SECURITIES The following describes certain material terms and provisions of the ordinary shares with nominal value of £0.01 per share of Bicycle Therapeutics plc (“Bicycle,” the “company,” “we,” “our,” or “us”) which are represented by American Depositary Shares (“ADSs”) with each ADS representing one ordinary share that are registered under Section 12 o

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ⌧ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2024 OR ◻ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number 001-389

Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 February 25, 2025 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporati

Form of Amended and Restated Restricted Share Unit Grant Notice and Agreement (deferred settlement for directors) for the 2020 Plan.

Exhibit 10.14 AMENDED AND RESTATED RESTRICTED SHARE UNIT GRANT NOTICE (DEFERRED SETTLEMENT) BICYCLE THERAPEUTICS PLC 2020 EQUITY INCENTIVE PLAN: NON-EMPLOYEE SUB-PLAN Capitalized terms not specifically defined in this Amended and Restated Restricted Share Unit Grant Notice (the “Grant Notice”) have the meanings given to them in the 2020 Equity Incentive Plan: Non-Employee Sub-Plan (as amended from

Form of Amended and Restated Restricted Share Unit Grant Notice and Agreement (for employees) for the 2020 Plan.

Exhibit 10.10 AMENDED & RESTATED RESTRICTED SHARE UNIT GRANT NOTICE BICYCLE THERAPEUTICS PLC 2020 EQUITY INCENTIVE PLAN Capitalized terms not specifically defined in this Amended & Restated Restricted Share Unit Grant Notice (the “Grant Notice”) have the meanings given to them in the 2020 Equity Incentive Plan (as amended from time to time, the “Plan”) of Bicycle Therapeutics Plc (the “Company”).

Form of Restricted Share Unit Grant Notice and Agreement (regular settlement for directors) for the 2020 Plan.

Exhibit 10.11 RESTRICTED SHARE UNIT GRANT NOTICE BICYCLE THERAPEUTICS PLC 2020 EQUITY INCENTIVE PLAN: NON-EMPLOYEE SUB-PLAN Capitalized terms not specifically defined in this Restricted Share Unit Grant Notice (the “Grant Notice”) have the meanings given to them in the 2020 Equity Incentive Plan: Non-Employee Sub-Plan (as amended from time to time, the “Plan”) of Bicycle Therapeutics Plc (the “Com

Bicycle Therapeutics Reports Recent Business Progress and Fourth Quarter and Full Year 2024 Financial Results Updated topline Phase 1 combination data for zelenectide pevedotin plus pembrolizumab continue to show promising anti-tumor activity and a d

Exhibit 99.1 Bicycle Therapeutics Reports Recent Business Progress and Fourth Quarter and Full Year 2024 Financial Results Updated topline Phase 1 combination data for zelenectide pevedotin plus pembrolizumab continue to show promising anti-tumor activity and a differentiated safety profile in first-line metastatic urothelial cancer; Duravelo-2 dose selection data expected in 2H 2025 Enhanced resp

Filing Fee Table

Calculation of Filing Fee Tables S-8 BICYCLE THERAPEUTICS PLC Table 1: Newly Registered Securities Security Type Security Class Title Fee Calculation Rule Amount Registered Proposed Maximum Offering Price Per Unit Maximum Aggregate Offering Price Fee Rate Amount of Registration Fee 1 Equity Ordinary shares, nominal value GBP0.

Form of Restricted Share Unit Grant Notice and Agreement (for employees) for the 2020 Plan.

Exhibit 10.9 RESTRICTED SHARE UNIT GRANT NOTICE BICYCLE THERAPEUTICS PLC 2020 EQUITY INCENTIVE PLAN Capitalized terms not specifically defined in this Restricted Share Unit Grant Notice (the “Grant Notice”) have the meanings given to them in the 2020 Equity Incentive Plan (as amended from time to time, the “Plan”) of Bicycle Therapeutics Plc (the “Company”). The Company has granted to the particip

Non-Employee Director Compensation Policy, as amended as of December 12, 2024.

Exhibit 10.36 Bicycle Therapeutics plc Non-Employee Director Compensation Policy As amended through December 12, 2024 This Non-Employee Director Compensation Policy (the “Policy”) has been established in order to attract and retain non-employee directors who have the knowledge, skills and experience to serve as a member of the Board of Directors (the “Board”) of Bicycle Therapeutics plc (the “Comp

Form of Option Grant Notice and Agreement (for non-employees) for the 2020 Plan.

Exhibit 10.8 OPTION GRANT NOTICE BICYCLE THERAPEUTICS PLC 2020 EQUITY INCENTIVE PLAN: NON-EMPLOYEE SUB-PLAN Capitalized terms not specifically defined in this Option Grant Notice (the “Grant Notice”) have the meanings given to them in the 2020 Equity Incentive Plan: Non-Employee Sub-Plan (as amended from time to time, the “Plan”) of Bicycle Therapeutics Plc (the “Company”). The Company has granted

Regulation FD Disclosure, Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 January 13, 2025 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporatio

Bicycle Therapeutics Announces Updated Topline Zelenectide Pevedotin Data and Highlights 2025 Strategic Priorities and Milestones Updated topline Phase 1 combination data for zelenectide pevedotin plus pembrolizumab continue to show promising anti-tu

Exhibit 99.1 Bicycle Therapeutics Announces Updated Topline Zelenectide Pevedotin Data and Highlights 2025 Strategic Priorities and Milestones Updated topline Phase 1 combination data for zelenectide pevedotin plus pembrolizumab continue to show promising anti-tumor activity and a differentiated safety profile in first-line cisplatin-ineligible metastatic urothelial cancer NECTIN4 gene amplificati

JOINT ACQUISITION STATEMENT PURSUANT TO RULE 13d-1(k)

EXHIBIT 99.1 JOINT ACQUISITION STATEMENT PURSUANT TO RULE 13d-1(k) The undersigned acknowledge and agree that the foregoing statement on Schedule 13G is filed on behalf of each of the undersigned and that all subsequent amendments to this statement on Schedule 13G shall be filed on behalf of each of the undersigned without the necessity of filing additional joint filing agreements. The undersigned

BCYC / Bicycle Therapeutics plc - Depositary Receipt (Common Stock) / BAKER BROS. ADVISORS LP - SC 13D/A Activist Investment

SC 13D/A 1 tm2431383d3sc13da.htm SC 13D/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 SCHEDULE 13D Under the Securities Exchange Act of 1934 (Amendment No. 2)* Bicycle Therapeutics plc (Name of Issuer) Ordinary Shares, nominal value £0.01 per share (Title of Class of Securities) 088786108** (CUSIP number) Alexandra A. Toohey Chief Financial Officer Baker Bros. Advisors LP

Bicycle Therapeutics Announces Data Updates Across Zelenectide Pevedotin Program and Development Strategy Leveraging NECTIN4 Gene Amplification Topline combination data for zelenectide pevedotin plus pembrolizumab in first-line metastatic urothelial

Exhibit 99.1 Bicycle Therapeutics Announces Data Updates Across Zelenectide Pevedotin Program and Development Strategy Leveraging NECTIN4 Gene Amplification Topline combination data for zelenectide pevedotin plus pembrolizumab in first-line metastatic urothelial cancer demonstrated a 60% overall response rate, in line with existing therapies Dose selection and topline data from Phase 2/3 Duravelo-

Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 December 13, 2024 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporati

BCYC / Bicycle Therapeutics plc - Depositary Receipt (Common Stock) / RA CAPITAL MANAGEMENT, L.P. - SC 13G/A Passive Investment

SC 13G/A 1 tm2427451d19sc13ga.htm SC 13G/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 SCHEDULE 13G/A Under the Securities Exchange Act of 1934 (Amendment No. 1)* Bicycle Therapeutics plc (Name of Issuer) Ordinary Shares, nominal value £0.01 per share (Title of Class of Securities) 088786108** (CUSIP Number) September 30, 2024 (Date of Event Which Requires Filing of thi

BCYC / Bicycle Therapeutics plc - Depositary Receipt (Common Stock) / Paradigm Biocapital Advisors LP - SC 13G/A Passive Investment

SC 13G/A 1 tm2427604d4sc13ga.htm SC 13G/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. 2)* Bicycle Therapeutics plc (Name of Issuer) Ordinary Shares, nominal value £0.01 per share** (Title of Class of Securities) 088786108*** (CUSIP Number) September 30, 2024 (Date of Event Which Requires Filing of thi

Joint Filing Agreement

EX-99.1 2 tm2427451d19ex1.htm EXHIBIT 1 EXHIBIT 1 AGREEMENT This Joint Filing Agreement, dated as of November 14, 2024 is by and among RA Capital Management, L.P., Peter Kolchinsky, Rajeev Shah, and RA Capital Healthcare Fund, L.P. (the foregoing are collectively referred to herein as the “Filers”). Each of the Filers may be required to file with the United States Securities and Exchange Commissio

BCYC / Bicycle Therapeutics plc - Depositary Receipt (Common Stock) / Jefferies Financial Group Inc. - SC 13G/A Passive Investment

SC 13G/A 1 ef20038551sc13ga.htm SC 13G/A SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. 1)* Bicycle Therapeutics plc (Name of Issuer) Ordinary Shares, nominal value £0.01 per share (Title of Class of Securities) 088786108** (CUSIP Number) September 30, 2024 (Date of Event Which Requires Filing of this Statement) Check

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2024 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38916 Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) England and Wales Not Applicable (State or other jurisdiction of incorporation or organization) (I.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 October 31, 2024 Date of Report (Date of earliest event reported) Bicycle Therapeut

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 October 31, 2024 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporatio

Bicycle Therapeutics Reports Recent Business Progress and Third Quarter 2024 Financial Results Presented updated clinical results across oncology pipeline, including a 45% overall response rate (ORR) for zelenectide pevedotin monotherapy and a 45% OR

Exhibit 99.1 Bicycle Therapeutics Reports Recent Business Progress and Third Quarter 2024 Financial Results Presented updated clinical results across oncology pipeline, including a 45% overall response rate (ORR) for zelenectide pevedotin monotherapy and a 45% ORR for BT5528 6.5 mg/m2 every two weeks monotherapy, both in metastatic urothelial cancer Progressed radiopharmaceuticals pipeline with fi

Financial Statements and Exhibits

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 October 23, 2024 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporatio

Bicycle Therapeutics Announces First Human Imaging Data from European Association of Nuclear Medicine 2024 Congress and Outlines Strategy for Leadership in Next-Generation Radiopharmaceuticals First human imaging data validate the potential of MT1-MM

Exhibit 99.1 Bicycle Therapeutics Announces First Human Imaging Data from European Association of Nuclear Medicine 2024 Congress and Outlines Strategy for Leadership in Next-Generation Radiopharmaceuticals First human imaging data validate the potential of MT1-MMP as a novel target in the treatment of cancer and demonstrate positive properties of Bicycle Radionuclide Conjugates (BRC®) for radiopha

Bicycle Therapeutics Presents Updated Clinical Results Across Oncology Pipeline at ESMO Congress 2024 Updated monotherapy data for Nectin-4 targeting zelenectide pevedotin in metastatic urothelial cancer (mUC) showed a promising 45% overall response

Exhibit 99.1 Bicycle Therapeutics Presents Updated Clinical Results Across Oncology Pipeline at ESMO Congress 2024 Updated monotherapy data for Nectin-4 targeting zelenectide pevedotin in metastatic urothelial cancer (mUC) showed a promising 45% overall response rate (ORR), 11.1 months median duration of response and a generally well-tolerated safety profile EphA2-targeting BT5528 demonstrated an

Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 September 14, 2024 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporat

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2024 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38916 Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) England and Wales Not Applicable (State or other jurisdiction of incorporation or organization) (I.

Bicycle Therapeutics Reports Recent Business Progress and Second Quarter 2024 Financial Results Four abstracts containing data updates across clinical pipeline accepted for poster presentation at ESMO Congress 2024 Focused R&D pipeline on clinical pr

Exhibit 99.1 Bicycle Therapeutics Reports Recent Business Progress and Second Quarter 2024 Financial Results Four abstracts containing data updates across clinical pipeline accepted for poster presentation at ESMO Congress 2024 Focused R&D pipeline on clinical programs and research areas that have the highest potential to maximize value creation Streamlined leadership team to better align with str

Form of Option Grant Notice and Option Agreement for the 2024 Plan (incorporated by reference to Exhibit 99.2 to the Registration Statement on Form S-8 (File No. 333-281304), filed with the Securities and Exchange Commission on August 6, 2024).

Exhibit 99.2 Bicycle Therapeutics plc 2024 Inducement Plan Option Grant Notice Bicycle Therapeutics plc (the “Company”), pursuant to its 2024 Inducement Plan (the “Plan”), hereby grants to Optionholder the option described in this grant notice at the exercise price set forth below (the “Option”). This Option is subject to all of the terms and conditions as set forth in this Option Grant Notice (th

Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 August 6, 2024 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

Bicycle Therapeutics plc 2024 Inducement Plan.

Exhibit 99.1 Bicycle Therapeutics plc 2024 Inducement Plan Approved by the Board: July 24, 2024 1.            General. (a)            Eligible Award Recipients. The only persons eligible to receive grants of Awards under this Plan are individuals who satisfy the standards for inducement grants under Nasdaq Marketplace Rule 5635(c)(4) or 5635(c)(3), if applicable, and the related guidance under Nas

Form of RSU Grant Notice and RSU Agreement for the 2024 Plan (incorporated by reference to Exhibit 99.3 to the Registration Statement on Form S-8 (File No. 333-281304), filed with the Securities and Exchange Commission on August 6, 2024).

Exhibit 99.3 Bicycle Therapeutics plc 2024 Inducement Plan Restricted Share Unit Grant Notice Bicycle Therapeutics plc (the “Company”), pursuant to Section 6(a) of the Company’s 2024 Inducement Plan (the “Plan”), hereby awards to Participant Restricted Share Units (“RSUs” or “Restricted Share Units”) described below (sometimes referred to as the “Award”). The Award is subject to all of the terms a

Service Agreement, dated March 18, 2024, by and between BicycleTx Ltd. and Michael Charles Ferguson Hannay.

Exhibit 10.4 DATED 18 March 2024 BICYCLETX LIMITED and MICHAEL CHARLES FERGUSON HANNAY SERVICE AGREEMENT CONTENTS Clause Page 1. COMMENCEMENT OF EMPLOYMENT 1 2. JOB TITLE 1 3. PLACE OF WORK 2 4. REMUNERATION 2 5. BENEFITS 3 6. EXPENSES 3 7. HOURS OF WORK 3 8. HOLIDAYS 4 9. SICKNESS AND OTHER ABSENCE 4 10. GARDEN LEAVE 5 11. NOTICE 6 12. DISCIPLINARY, DISMISSAL AND GRIEVANCE PROCEDURES 9 13. OUTSID

Articles of Association, dated May 16, 2024 (incorporated by reference to Exhibit 3.1 to the Quarterly Report on Form 10-Q (File No. 001-38916) filed with the Securities and Exchange Commission on August 6, 2024).

DATED 16 MAY 2024 The Companies Act 2006 Public Company Limited by shares ARTICLES OF ASSOCIATION of BICYCLE THERAPEUTICS PLC TABLE OF CONTENTS Clause‌Page 1.

Filing Fee Table

Calculation of Filing Fee Tables S-8 BICYCLE THERAPEUTICS PLC Table 1: Newly Registered Securities Security Type Security Class Title Fee Calculation Rule Amount Registered Proposed Maximum Offering Price Per Unit Maximum Aggregate Offering Price Fee Rate Amount of Registration Fee 1 Equity Ordinary shares, nominal value GBP 0.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-8 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Bicycle Therapeutics plc (Exact name of registrant as specified in its charter)

As filed with the Securities and Exchange Commission on August 6, 2024 Registration No.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 July 9, 2024 Date of Report (Date of earliest event reported) Bicycle Therapeutics

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 July 9, 2024 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation) (

Calculation of Filing Fee Tables (Form Type) Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) Table 1: Newly Registered Securities

EX-FILING FEES Calculation of Filing Fee Tables 424(b)(7) (Form Type) Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) Table 1: Newly Registered Securities Security Type Security Class Title Fee Calculation Rule Amount Registered(1) Proposed Maximum Offering Price Per Share Maximum Aggregate Offering Price Fee Rate Amount of Registration Fee Fees to Be Paid Equity Ordinary Shares, nominal value £0.

37,656,764 Ordinary Shares Represented by 37,656,764 American Depositary Shares

TABLE OF CONTENTS  As Filed Pursuant to Rule 424(b)(7)  Registration No. 333-272248 PROSPECTUS SUPPLEMENT (To Prospectus Dated May 26, 2023) 37,656,764 Ordinary Shares Represented by 37,656,764 American Depositary Shares This prospectus supplement relates to the resale or other disposition by the selling securityholders identified in this prospectus supplement, or the selling securityholders, of 3

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 June 18, 2024 Date of Report (Date of earliest event reported) Bicycle Therapeutics

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 June 18, 2024 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

BCYC / Bicycle Therapeutics plc - Depositary Receipt (Common Stock) / RA CAPITAL MANAGEMENT, L.P. - SC 13G Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. )* Bicycle Therapeutics plc (Name of Issuer) Ordinary Shares, nominal value £0.01 per share (Title of Class of Securities) 088786108** (CUSIP Number) May 28, 2024 (Date of Event Which Requires Filing of this Statement) Check the appropriate box to designate

Joint Filing Agreement

EX-99.1 2 tm2416767d1ex1.htm EXHIBIT 1 EXHIBIT 1 AGREEMENT This Joint Filing Agreement, dated as of June 7, 2024 is by and among RA Capital Management, L.P., Peter Kolchinsky, Rajeev Shah, and RA Capital Healthcare Fund, L.P. (the foregoing are collectively referred to herein as the “Filers”). Each of the Filers may be required to file with the United States Securities and Exchange Commission a st

BCYC / Bicycle Therapeutics plc - Depositary Receipt (Common Stock) / BAKER BROS. ADVISORS LP - SC 13D/A Activist Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 SCHEDULE 13D Under the Securities Exchange Act of 1934 (Amendment No.

Entry into a Material Definitive Agreement, Unregistered Sales of Equity Securities, Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 May 23, 2024 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation) (

Form of Securities Purchase Agreement.

  Exhibit 10.1   SECURITIES PURCHASE AGREEMENT   This SECURITIES PURCHASE AGREEMENT (this “Agreement”) is made and entered into as of May 23, 2024, by and among Bicycle Therapeutics plc, a public limited company incorporated under the laws of England and Wales (the “Company”), and the Investors identified on Exhibit A attached hereto (each an “Investor,” and collectively the “Investors”).   Recita

BICYCLE THERAPEUTICS PLC

Exhibit (b)(i) BICYCLE THERAPEUTICS PLC July 1, 2020 Citibank, N.A. – ADR Department 388 Greenwich Street New York, NY 10013 Attn: Susanna Ansala Program ADSs (CUSIP No.: 088786108) Ladies and Gentlemen: Reference is made to the Deposit Agreement, dated as of May 28, 2019, as amended and supplemented from time to time (the “Deposit Agreement”), by and among Bicycle Therapeutics plc, a public limit

AMENDMENT TO LETTER AGREEMENT

Exhibit (b)(ii) AMENDMENT TO LETTER AGREEMENT This Amendment to Letter Agreement (this “Amendment”) is effective as of October 27, 2020, by and between Bicycle Therapeutics plc, a public limited company incorporated under the laws of England and Wales (the “Company”), and Citibank, N.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 May 16, 2024 Date of Report (Date of earliest event reported) Bicycle Therapeutics

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 May 16, 2024 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation) (

Exhibit (d)

Exhibit (d) May 16, 2024 Citibank, N.A. – ADR Department 388 Greenwich Street New York, New York 10013 Ladies and Gentlemen: We refer to the Registration Statement on Form F-6 (the “Registration Statement”) to be filed with the Securities and Exchange Commission (the “SEC”) by the legal entity created by the Deposit Agreement (as hereinafter defined) for the purpose of registering under the United

Bicycle Therapeutics plc

Exhibit (b)(iv) Bicycle Therapeutics plc As of March 7, 2022 Citibank, N.A. - ADR Department 388 Greenwich Street New York, New York 10013 Re: Restricted ADSs (CUSIP No.: 088786991) Ladies and Gentlemen: Reference is made to the Deposit Agreement, dated as of May 28, 2019, as amended and supplemented from time to time (the “Deposit Agreement”), by and among Bicycle Therapeutics plc, a public limit

SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM F-6 REGISTRATION STATEMENT THE SECURITIES ACT OF 1933 FOR AMERICAN DEPOSITARY SHARES EVIDENCED BY AMERICAN DEPOSITARY RECEIPTS BICYCLE THERAPEUTICS PLC (Exact name of issuer of deposited

As filed with the Securities and Exchange Commission on May 16, 2024 Registration No.

Rule 466 Certification

Exhibit (e) Rule 466 Certification The depositary, Citibank, N.A., represents and certifies the following: (i) That it previously had filed a registration statement on Form F-6 (Registration No. 333-231422), which the U.S. Securities and Exchange Commission declared effective, with terms of deposit identical to the terms of deposit of this Form F-6 Registration Statement except for the number of s

DEPOSIT AGREEMENT by and among BICYCLE THERAPEUTICS PLC CITIBANK, N.A., as Depositary, THE HOLDERS AND BENEFICIAL OWNERS OF AMERICAN DEPOSITARY SHARES ISSUED HEREUNDER Dated as of May 28, 2019 TABLE OF CONTENTS

Exhibit (a) DEPOSIT AGREEMENT by and among BICYCLE THERAPEUTICS PLC and CITIBANK, N.

AMENDMENT TO LETTER AGREEMENT

Exhibit (b)(ii) AMENDMENT TO LETTER AGREEMENT This Amendment to Letter Agreement (this “Amendment”) is effective as of May 24, 2021, by and between Bicycle Therapeutics plc, a public limited company incorporated under the laws of England and Wales (the “Company”), and Citibank, N.

AMENDMENT to letter agreement

Exhibit (b)(v) AMENDMENT to letter agreement This Amendment to Letter Agreement (this “Amendment”) is effective as of May 26, 2023, by and between Bicycle Therapeutics plc, a public limited company incorporated under the laws of England and Wales (the “Company”), and Citibank, N.

Amendment No. 4 to Collaboration and License Agreement, dated January 17, 2024, between BicycleTx Limited and Ionis Pharmaceuticals, Inc.

CONFIDENTIAL AMENDMENT NO. 4 TO COLLABORATION AND LICENSE AGREEMENT This Amendment No. 4 to Collaboration and License Agreement (“Fourth Amendment”) is made and entered into effective as of January 17, 2024 (“Fourth Amendment Effective Date”) by and between BicycleTx Limited, a company incorporated in England and Wales with a place of business at Blocks A & B, Portway Building Granta Park, Great A

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2024 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38916 Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) England and Wales Not Applicable (State or other jurisdiction of incorporation or organization) (I.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 May 2, 2024 Date of Report (Date of earliest event reported) Bicycle Therapeutics p

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 May 2, 2024 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation) (C

Bicycle Therapeutics Reports Recent Business Progress and First Quarter 2024 Financial Results Multiple preclinical and clinical abstracts accepted for presentation at 2024 ASCO Annual Meeting and AACR Annual Meeting underscore breadth of Bicycle® pl

Exhibit 99.1 Bicycle Therapeutics Reports Recent Business Progress and First Quarter 2024 Financial Results Multiple preclinical and clinical abstracts accepted for presentation at 2024 ASCO Annual Meeting and AACR Annual Meeting underscore breadth of Bicycle® platform technology and pipeline Continued progress across research and development (R&D) pipeline, with numerous clinical data readouts an

BCYC / Bicycle Therapeutics plc - Depositary Receipt (Common Stock) / BAKER BROS. ADVISORS LP - SC 13D Activist Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 SCHEDULE 13D Under the Securities Exchange Act of 1934 (Amendment No.

Agreement Regarding the Joint Filing of Schedule 13D by and among the Reporting Persons.

Exhibit 99.1 JOINT FILING AGREEMENT Pursuant to Rule 13d-1(k)(1) under the Securities Exchange Act of 1934, as amended, the undersigned hereby agree that only one statement containing the information required by Schedule 13D need be filed with respect to the ownership by each of the undersigned of the Ordinary Shares of Bicycle Therapeutics plc This Agreement may be executed in any number of count

Consulting Agreement, dated April 17, 2024, by and between the Company and Veronica Jordan

Exhibit 10.1 CONSULTING AGREEMENT This Consulting Agreement (the “Agreement”) is made by and between Bicycle Therapeutics Inc. (“Company”) and Veronica Jordan (“Consultant”), effective as of April 17, 2024 (the “Effective Date”). 1. Engagement of Services. Subject to the terms of this Agreement, Consultant agrees to provide consulting services to Company as described in Exhibit A hereto (the “Serv

Registration Rights Agreement, dated April 18, 2024, by and among the Company and 667, L.P. and Baker Brothers Life Sciences, L.P.

Exhibit 10.2 Execution Version REGISTRATION RIGHTS AGREEMENT This Registration Rights Agreement (this “Agreement”) is made as of April 18, 2024 by and between Bicycle Therapeutics plc, a public limited company incorporated under the laws of England and Wales (the “Company”), and the persons listed on the attached Schedule A who are signatories to this Agreement (collectively, the “Investors”). Unl

Registration Rights Agreement by and among Bicycle Therapeutics plc, 667, L.P., and Baker Brothers Life Sciences, L.P., dated as of April 18, 2024 (incorporated by reference to Exhibit 10.2 to the Issuer’s Current Report on Form 8-K, filed with the SEC on April 18, 2024).

Exhibit 10.2 Execution Version REGISTRATION RIGHTS AGREEMENT This Registration Rights Agreement (this “Agreement”) is made as of April 18, 2024 by and between Bicycle Therapeutics plc, a public limited company incorporated under the laws of England and Wales (the “Company”), and the persons listed on the attached Schedule A who are signatories to this Agreement (collectively, the “Investors”). Unl

Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers, Entry into a Material Definitive Agreement, Financial Statements and Exhibits

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 April 16, 2024 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

Consulting Agreement, dated April 17, 2024, by and between the Company and Veronica Jordan

Exhibit 10.1 CONSULTING AGREEMENT This Consulting Agreement (the “Agreement”) is made by and between Bicycle Therapeutics Inc. (“Company”) and Veronica Jordan (“Consultant”), effective as of April 17, 2024 (the “Effective Date”). 1. Engagement of Services. Subject to the terms of this Agreement, Consultant agrees to provide consulting services to Company as described in Exhibit A hereto (the “Serv

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. )

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. ) Filed by the Registrant x Filed by a Party other than the Registrant ¨ Check the appropriate box: ¨ Preliminary Proxy Statement ¨ Confidential, for Use of the Commission Only (as permitted by Rule 14a-6(e)

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. )

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. ) Filed by the Registrant ⌧ Filed by a Party other than the Registrant ◻ Check the appropriate box: ◻ Preliminary Proxy Statement ◻ Confidential, for Use of the Commission Only (as permitte

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. )

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. ) Filed by the Registrant ⌧ Filed by a Party other than the Registrant ◻ Check the appropriate box: ⌧ Preliminary Proxy Statement ◻ Confidential, for Use of the Commission Only (as permitte

Filing Fee Table

Exhibit 107 Calculation of Filing Fee Tables Form S-8 (Form Type) Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) Table 1: Newly Registered Securities Security Type Security Class Title Fee Calculation Rule Amount Registered Proposed Maximum Offering Price Per Unit Maximum Aggregate Offering Price Fee Rate Amount of Registration Fee Equity Ordinary shares, nominal value £0.

Description of Securities.

Exhibit 4.6 DESCRIPTION OF THE REGISTRANT'S SECURITIES The following describes certain material terms and provisions of the ordinary shares with nominal value of £0.01 per share of Bicycle Therapeutics plc (“Bicycle,” the “company,” “we,” “our,” or “us”) which are represented by American Depositary Shares (“ADSs”) with each ADS representing one ordinary share that are registered under Section 12 o

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-8 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Bicycle Therapeutics plc (Exact name of registrant as specified in its charter)

As filed with the Securities and Exchange Commission on February 20, 2024 Registration No.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ⌧ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2023 OR ◻ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number 001-389

Bicycle Therapeutics Reports Recent Business Progress and Fourth Quarter and Full Year 2023 Financial Results Catalyst-rich 2024 with multiple clinical data readouts and updates expected for pipeline and discovery programs Phase 2/3 Duravelo-2 regist

Exhibit 99.1 Bicycle Therapeutics Reports Recent Business Progress and Fourth Quarter and Full Year 2023 Financial Results Catalyst-rich 2024 with multiple clinical data readouts and updates expected for pipeline and discovery programs Phase 2/3 Duravelo-2 registrational trial for BT8009 in metastatic urothelial cancer now active and recruiting patients BT8009 initial clinical data showed a promis

Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers, Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 February 20, 2024 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporati

Incentive Compensation Recoupment Policy.

Exhibit 97.1 Bicycle Therapeutics plc Incentive Compensation Recoupment Policy 1. Introduction The Compensation Committee (the “Compensation Committee”) of the Board of Directors (the “Board”) of Bicycle Therapeutics plc, a public limited company incorporated under the laws of England and Wales (the “Company”), has determined that it is in the best interests of the Company and its shareholders to

Non-Employee Director Compensation Policy, as amended as of December 13, 2023.

Exhibit 10.25 Bicycle Therapeutics plc Non-Employee Director Compensation Policy As amended through December 13, 2023 This Non-Employee Director Compensation Policy (the “Policy”) has been established in order to attract and retain non-employee directors who have the knowledge, skills and experience to serve as a member of the Board of Directors (the “Board”) of Bicycle Therapeutics plc (the “Comp

BCYC / Bicycle Therapeutics plc - Depositary Receipt (Common Stock) / Ridgeback Capital Investments L.P. - SC 13G/A Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 SCHEDULE 13G (Amendment No.

BCYC / Bicycle Therapeutics plc - Depositary Receipt (Common Stock) / Paradigm Biocapital Advisors LP - SC 13G/A Passive Investment

SC 13G/A 1 tm245955d4sc13ga.htm SC 13G/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. 1)* Bicycle Therapeutics plc (Name of Issuer) Ordinary Shares, nominal value £0.01 per share** (Title of Class of Securities) 088786108*** (CUSIP Number) December 31, 2023 (Date of Event Which Requires Filing of this

BCYC / Bicycle Therapeutics plc - Depositary Receipt (Common Stock) / Jefferies Financial Group Inc. - SC 13G Passive Investment

SC 13G 1 ef20021679sc13g.htm SC 13G SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No.)* Bicycle Therapeutics plc (Name of Issuer) Ordinary Shares, nominal value £0.01 per share (Title of Class of Securities) 088786108** (CUSIP Number) December 31, 2023 (Date of Event Which Requires Filing of this Statement) Check the app

BCYC / Bicycle Therapeutics plc - Depositary Receipt (Common Stock) / Deep Track Capital, LP Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 SCHEDULE 13G/A Under the Securities Exchange Act of 1934 (Amendment No.

AGREEMENT

EX-99.1 2 tm245479d1ex99-1.htm EXHIBIT 99.1 EXHIBIT 99.1 AGREEMENT In accordance with Rule 13d-1(k)(1) under the Securities Exchange Act of 1934, as amended, the undersigned hereby agree that this Statement on Schedule 13G relating to the Ordinary Shares of Bicycle Therapeutics plc is being filed with the Securities and Exchange Commission on behalf of each of them. February 12, 2024 BAKER BROS. A

BCYC / Bicycle Therapeutics plc - Depositary Receipt (Common Stock) / BAKER BROS. ADVISORS LP - SC 13G Passive Investment

SCHEDULE 13G SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 Under the Securities Exchange Act of 1934 (Amendment No.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 December 14, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeu

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 December 14, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporati

Bicycle Therapeutics Provides Data Updates for Three Clinical Programs and Strategy Overview at First R&D Day Nectin-4 portfolio comprised of BT8009 and BT7480 represents potential opportunity to become leader in treating Nectin-4-driven cancers, sta

Exhibit 99.1 Bicycle Therapeutics Provides Data Updates for Three Clinical Programs and Strategy Overview at First R&D Day Nectin-4 portfolio comprised of BT8009 and BT7480 represents potential opportunity to become leader in treating Nectin-4-driven cancers, starting with metastatic urothelial cancer (mUC) Updated BT8009 clinical data continue to support promising response and differentiated safe

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2023 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38916 Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) England and Wales Not Applicable (State or other jurisdiction of incorporation or organization) (I.

Amendment No. 1 to Service Agreement, dated July 24, 2023, by and between BicycleTx Limited and Kevin Lee (incorporated by reference to Exhibit 10.1 to the Quarterly Report on Form 10-Q (File No. 001-38916) filed with the Securities and Exchange Commission on November 2, 2023).

Exhibit 10.1 24 July 2023 Amendment No. 1 to Service Agreement This Amendment No. 1 (“Amendment No. 1”) to Service Agreement, dated 26 September 2019, between BicycleTX Limited (the “Company”) and Dr Kevin Lee (“you”) (the “Service Agreement”), is entered into by the Company and you (collectively the “Parties”), to amend certain terms of the Service Agreement, as agreed by the Parties. Amendments

Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 November 2, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporatio

Bicycle Therapeutics Reports Recent Business Progress and Third Quarter 2023 Financial Results and Announces Upcoming R&D Day R&D Day on December 14 to provide clinical updates for BT8009, BT5528 and BT7480, and highlight broad capabilities of novel

Exhibit 99.1 Bicycle Therapeutics Reports Recent Business Progress and Third Quarter 2023 Financial Results and Announces Upcoming R&D Day R&D Day on December 14 to provide clinical updates for BT8009, BT5528 and BT7480, and highlight broad capabilities of novel Bicycle® technology Alignment with FDA on expedited development and design of Phase 2/3 registrational trial for BT8009 in metastatic bla

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 September 11, 2023 Date of Report (Date of earliest event reported) Bicycle Therape

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 September 11, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporat

Bicycle Therapeutics Announces Expedited Development Plan for BT8009 in Metastatic Bladder Cancer Alignment with U.S. FDA on design of Phase 2/3 registrational trial, to be initiated in 1Q 2024 Innovative study design allows for potential accelerated

Exhibit 99.1 Bicycle Therapeutics Announces Expedited Development Plan for BT8009 in Metastatic Bladder Cancer Alignment with U.S. FDA on design of Phase 2/3 registrational trial, to be initiated in 1Q 2024 Innovative study design allows for potential accelerated approval in untreated (first-line) and previously treated (second-line plus) metastatic bladder cancer Conference call and webcast today

Employment Agreement, dated June 22, 2023, by and between Bicycle Therapeutics Inc. and Alethia Young (incorporated by reference to Exhibit 10.1 to Quarterly Report on Form 10-Q (File No. 001-38916), filed with the Securities and Exchange Commission on August 3, 2023).

Exhibit 10.1 EMPLOYMENT AGREEMENT This Employment Agreement (the “Agreement”) is entered into effective as of June 22, 2023 (the “Effective Date”), by and between Alethia Young (“Executive”) and Bicycle Therapeutics Inc. (the “Company”). The Company desires to employ Executive and, in connection therewith, to compensate Executive for Executive’s personal services to the Company; and Executive wish

Third Amendment to Loan and Security Agreement, dated as of May 15, 2023, by and among Bicycle Therapeutics plc and each of its Subsidiaries, the Lenders, and Hercules Capital, Inc., as Agent.

Exhibit 10.4 THIRD AMENDMENT TO LOAN AND SECURITY AGREEMENT THIS THIRD AMENDMENT TO LOAN AND SECURITY AGREEMENT (this “Amendment”), dated as of May 15, 2023, is entered into by and among BICYCLE THERAPEUTICS PLC, a public limited company organized under the laws of England and Wales (“Parent”), BICYCLETX LIMITED, a private company limited by shares organized under the laws of England and Wales (“B

Amendment No. 3 to Collaboration and License Agreement, dated April 27, 2023, between BicycleTx Limited and Ionis Pharmaceuticals, Inc. (incorporated by reference to Exhibit 10.3 to the Quarterly Report on Form 10-Q (File No. 001-38916), filed with the Securities and Exchange Commission on May 4, 2023).

CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED BECAUSE IT IS BOTH (I) NOT MATERIAL AND (II) WOULD BE COMPETITIVELY HARMFUL IF PUBLICLY DISCLOSED.

Bicycle Therapeutics Reports Second Quarter 2023 Financial Results and Provides Corporate Update Continued progress across pipeline, including advancing BT8009, BT5528, and BT7480 in ongoing clinical trials; clinical and regulatory updates remain on

Exhibit 99.1 Bicycle Therapeutics Reports Second Quarter 2023 Financial Results and Provides Corporate Update Continued progress across pipeline, including advancing BT8009, BT5528, and BT7480 in ongoing clinical trials; clinical and regulatory updates remain on track for BT8009 in 2H23 Entered into strategic collaborations with Novartis, Bayer, and broadened an ongoing collaboration with DKFZ in

Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 August 3, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

Collaboration and Licence Agreement, dated May 4, 2023, by and between BicycleTx Limited and Bayer Consumer Care AG (incorporated by reference to Exhibit 10.2 to the Quarterly Report on Form 10-Q (File No. 001-38916) filed with the Securities and Exchange Commission on August 3, 2023).

CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED BECAUSE IT IS BOTH (I) NOT MATERIAL AND (II) WOULD BE COMPETITIVELY HARMFUL IF PUBLICLY DISCLOSED.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2023 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38916 Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) England and Wales Not Applicable (State or other jurisdiction of incorporation or organization) (I.

BCYC / Bicycle Therapeutics Plc - ADR / GLAXOSMITHKLINE PLC - AMENDMENT TO FORM SC 13D Activist Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13D/A (Amendment No. 5) * 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

4,705,884 American Depositary Shares Representing Ordinary Shares 4,705,882 Non-Voting Ordinary Shares

TABLE OF CONTENTS  Filed Pursuant to Rule 424(b)(5)  Registration No. 333-272248 Prospectus Supplement (to Prospectus dated May 26, 2023) 4,705,884 American Depositary Shares Representing Ordinary Shares 4,705,882 Non-Voting Ordinary Shares We are offering 9,411,766 American Depositary Shares, or ADSs, each representing one ordinary share, nominal value £0.01 per share, and, in lieu of ADSs to inv

Description of Non-Voting Ordinary Shares.

Exhibit 4.1 The below supplements the description of the Company's securities filed as Exhibit 4.4 to the Company’s Annual Report on Form 10-K, filed with the Securities and Exchange Commission on March 10, 2020. Description of the Non-Voting Ordinary Shares Pursuant to the terms of issue of the non-voting ordinary shares approved by our board of directors, the non-voting ordinary shares have the

Calculation of Filing Fee Tables 424(b)5 (Form Type) bicycle therapeutics PLC (Exact Name of Registrant as Specified in its Charter) Table I: Newly Registered and Carry Forward Securities

Exhibit 107 Calculation of Filing Fee Tables 424(b)5 (Form Type) bicycle therapeutics PLC (Exact Name of Registrant as Specified in its Charter) Table I: Newly Registered and Carry Forward Securities Security Type Security Class Title Fee Calculation or Carry Forward Rule Amount Registered Proposed Maximum Offering Price Per Unit Maximum Aggregate Offering Price Fee Rate Amount of Registration Fee(3) Carry Forward Form Type Carry Forward File Number Carry Forward Initial Effective Date Filing Fee Previously Paid in Connection with Unsold Securities to be Carried Forward Newly Registered Securities Fees to be Paid Equity Ordinary Shares, nominal value £0.

Underwriting Agreement, dated July 12, 2023, by and among the Company, Goldman Sachs & Co. LLC, Jefferies LLC and SVB Securities LLC, as the Representatives of the several underwriters named therein.

Exhibit 1.1 Execution Version Bicycle Therapeutics plc 4,705,884 American Depositary Shares representing 4,705,884 Ordinary Shares, nominal value £0.01 per share 4,705,882 Non-Voting Ordinary Shares, nominal value £0.01 per share Underwriting Agreement July 12, 2023 Goldman Sachs & Co. LLC Jefferies LLC SVB Securities LLC As representatives (the “Representatives”) of the several Underwriters named

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 July 12, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 July 12, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

Subject to Completion, Dated July 12, 2023

TABLE OF CONTENTS The information in this preliminary prospectus supplement and the accompanying prospectus is not complete and may be changed.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 June 22, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 June 22, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 June 13, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 June 13, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

Calculation of Filing Fee Tables 424(b)(5) (Form Type) bicycle therapeutics PLC (Exact Name of Registrant as Specified in its Charter) Table 1: Newly Registered and Carry Forward Securities

EX-FILING FEES 2 tm2317110d5ex-filingfees.htm EX-FILING FEES Exhibit 107 Calculation of Filing Fee Tables 424(b)(5) (Form Type) bicycle therapeutics PLC (Exact Name of Registrant as Specified in its Charter) Table 1: Newly Registered and Carry Forward Securities Security Type Security Class Title Fee Calculation or Carry Forward Rule Amount Registered Proposed Maximum Offering Price Per Unit Maxim

Form of Debt Securities Warrant Agreement and Warrant Certificate.

Exhibit 4.7 BICYCLE THERAPEUTICS PLC and , As Warrant Agent Form of Debt Securities Warrant Agreement Dated As Of 1 Bicycle Therapeutics plc Form of Debt Securities Warrant Agreement This Debt Securities Warrant Agreement (this “Agreement”), dated as of [●], between Bicycle Therapeutics plc, a public limited company incorporated under the laws of England and Wales (the “Company”), and [●], a [corp

Filing Fee Table

EX-FILING FEES 9 tm2317110d2ex-filingfees.htm EX-FILING FEES Exhibit 107 Calculation of Filing Fee Tables Form S-3 (Form Type) bicycle therapeutics PLC (Exact Name of Registrant as Specified in its Charter) Table I: Newly Registered and Carry Forward Securities Security Type Security Class Title Fee Calculation or Carry Forward Rule Amount Registered Proposed Maximum Offering Price Per Unit Maximu

Form of Indenture.

Exhibit 4.3 Bicycle Therapeutics plc, Issuer AND [TRUSTEE], Trustee INDENTURE Dated as of [·], 20 Debt Securities TABLE OF CONTENTS PAGE article 1 DEFINITIONS 1 Section 1.01 Definitions of Terms 1 article 2 ISSUE, DESCRIPTION, TERMS, EXECUTION, REGISTRATION AND EXCHANGE OF SECURITIES 5 Section 2.01 Designation and Terms of Securities 5 Section 2.02 Form of Securities and Trustee’s Certificate 7 Se

Up to $150,000,000 American Depositary Shares representing Ordinary Shares

TABLE OF CONTENTS   Filed Pursuant to Rule 424(b)(5)   Registration No. 333-272248 PROSPECTUS SUPPLEMENT (To Prospectus Dated May 26, 2023) Up to $150,000,000 American Depositary Shares representing Ordinary Shares In accordance with the terms of the Controlled Equity OfferingSM Sales Agreement, or Sales Agreement, dated as of June 5, 2020, with Cantor Fitzgerald & Co. and Oppenheimer & Co. Inc.,

Form of Preference Share Warrant Agreement and Warrant Certificate.

Exhibit 4.6 Bicycle Therapeutics plc and , As Warrant Agent Form of Preference Shares Warrant Agreement Dated As Of Bicycle Therapeutics plc Form of preference Shares Warrant Agreement This Preference Shares Warrant Agreement (this “Agreement”), dated as of [●], between Bicycle Therapeutics plc, a public limited company incorporated under the laws of England and Wales (the “Company”), and [●], a [

Form of Ordinary Share Warrant Agreement and Warrant Certificate.

Exhibit 4.5 BICYCLE THERAPEUTICS PLC and , As Warrant Agent Form of Ordinary Shares Warrant Agreement Dated As Of Bicycle Therapeutics plc Form of Ordinary Shares Warrant Agreement This Ordinary Shares Warrant Agreement (this “Agreement”), dated as of [●], between Bicycle Therapeutics plc, a public limited company incorporated under the laws of England and Wales (the “Company”), and [●], a [corpor

Form S-3ASR (File No. 333-272248)

TABLE OF CONTENTS As filed with the Securities and Exchange Commission on May 26, 2023 Registration No.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 May 26, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 May 26, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation) (

Bayer and Bicycle Therapeutics Enter Strategic Collaboration for Development of Novel Targeted Radionuclide Therapies in Oncology

Exhibit 99.1 Bayer AG Communications 51368 Leverkusen Germany Phone +49 214 30-1 www.bayer.com/en/media News Release Bayer and Bicycle Therapeutics Enter Strategic Collaboration for Development of Novel Targeted Radionuclide Therapies in Oncology · Collaboration will leverage Bicycle Therapeutic’s synthetic peptides for the discovery and development of multiple targeted radioconjugates of the comp

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 May 4, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics p

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 May 4, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation) (C

Bicycle Therapeutics Reports First Quarter 2023 Financial Results and Provides Corporate Update -          Continued progress across pipeline, including encouraging BT8009 Phase I dose escalation results presented in Q1’23 -          Entered into a s

Exhibit 99.1 Bicycle Therapeutics Reports First Quarter 2023 Financial Results and Provides Corporate Update -          Continued progress across pipeline, including encouraging BT8009 Phase I dose escalation results presented in Q1’23 -          Entered into a strategic collaboration with Novartis and expanded separate collaboration with the Division of Radiopharmaceutical Chemistry, German Cance

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 May 4, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics p

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 May 4, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation) (C

Amendment No. 1 to Amended and Restated Employment Agreement, dated February 20, 2023, by and between Bicycle Therapeutics Inc. and Nicholas Keen.

Exhibit 10.3 Date: February 20, 2023 Amendment No. 1 to Amended and Restated Employment Agreement This Amendment No. 1 (“Amendment No. 1”) to Amended and Restated Employment Agreement, effective as of September 26, 2019 (the “Employment Agreement”) is entered into by the following Parties: Bicycle Therapeutics Inc. (the “Company”) and Nicholas Keen (“Executive”) (collectively the “Parties”), to pr

Collaboration and Licence Agreement, dated March 27, 2023, by and between BicycleTx Limited and Novartis Pharma AG (incorporated by reference to Exhibit 10.8 to the Quarterly Report on Form 10-Q (File No. 001-38916) filed with the Securities and Exchange Commission on May 4, 2023).

CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED BECAUSE IT IS BOTH (I) NOT MATERIAL AND (II) WOULD BE COMPETITIVELY HARMFUL IF PUBLICLY DISCLOSED.

Amendment No. 2 to Service Agreement, dated February 20, 2023, by and between BicycleTx Limited and Michael Skynner (incorporated by reference to Exhibit 10.2 to the Quarterly Report on Form 10-Q (File No. 001-38916), filed with the Securities and Exchange Commission on May 4, 2023).

Exhibit 10.2 20th February, 2023 Amendment No. 2 to Service Agreement This Amendment No. 2 (“Amendment No. 2”) to Service Agreement dated 26 September 2019, as amended on 5 January 2022 (the “Employment Agreement”) is entered into by the following Parties: BicycleTX Limited (the “Company”) and Dr. Michael Skynner (“you”) (collectively the “Parties”), to provide clarity and define new terms agreed

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2023 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38916 Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) England and Wales Not Applicable (State or other jurisdiction of incorporation or organization) (I.

Amendment No. 1 to Service Agreement, dated February 20, 2023, by and between BicycleTx Limited and Alistair Milnes (incorporated by reference to Exhibit 10.6 to the Quarterly Report on Form 10-Q (File No. 001-38916), filed with the Securities and Exchange Commission on May 4, 2023).

Exhibit 10.6 20th February, 2023 Amendment No. 1 to Service Agreement This Amendment No. 1 (“Amendment No. 1”) to Service Agreement dated 5 January 2022 (the “Employment Agreement”) is entered into by the following Parties: BicycleTX Limited (the “Company”) and Alistair Milnes (“you”) (collectively the “Parties”), to provide clarity and define new terms agreed to by the Parties. Amendments to Clau

Amendment No. 1 to Service Agreement, dated February 27, 2023, by and between BicycleTx Limited and Dominic Smethurst.

Exhibit 10.5 27th February, 2023 Amendment No. 1 to Service Agreement This Amendment No. 1 (“Amendment No. 1”) to Service Agreement dated 9 July 2020 (the “Employment Agreement”) is entered into by the following Parties: BicycleTX Limited (the “Company”) and Dominic Smethurst (“you”) (collectively the “Parties”), to provide clarity and define new terms agreed to by the Parties. Amendments to Claus

Amendment No. 1 to Amended and Restated Employment Agreement, dated March 29, 2023, by and between Bicycle Therapeutics Inc. and Lee Kalowski.

Exhibit 10.1 Date: March 29, 2023 Amendment No. 1 to Amended and Restated Employment Agreement This Amendment No. 1 (“Amendment No. 1”) to Amended and Restated Employment Agreement, effective as of September 26, 2019 (the “Employment Agreement”) is entered into by the following Parties: Bicycle Therapeutics Inc. (the “Company”) and Lee Kalowski (“Executive”) (collectively the “Parties”), to provid

Amendment No. 1 to Service Agreement, dated February 20, 2023, by and between BicycleTx Limited and Nigel Crockett (incorporated by reference to Exhibit 10.4 to the Quarterly Report on Form 10-Q (File No. 001-38916), filed with the Securities and Exchange Commission on May 4, 2023).

Exhibit 10.4 20th February, 2023 Amendment No. 1 to Service Agreement This Amendment No. 1 (“Amendment No. 1”) to Service Agreement dated 26 September 2019 (the “Employment Agreement”) is entered into by the following Parties: BicycleTX Limited (the “Company”) and Nigel Crockett (“you”) (collectively the “Parties”), to provide clarity and define new terms agreed to by the Parties. Amendments to Cl

Employment Agreement, dated March 31, 2023, by and between Bicycle Therapeutics Inc. and Santiago Arroyo (incorporated by reference to Exhibit 10.7 to the Quarterly Report on Form 10-Q (File No. 001-38916), filed with the Securities and Exchange Commission on May 4, 2023).

Exhibit 10.7 EMPLOYMENT AGREEMENT This Employment Agreement (the “Agreement”) is entered into effective as of 31st March 2023 (the “Effective Date”), by and between Santiago Arroyo (“Executive”) and Bicycle Therapeutics Inc. (the “Company”). The Company desires to employ Executive and, in connection therewith, to compensate Executive for Executive’s personal services to the Company; and Executive

Definitive Proxy Statement on Schedule 14A, filed with the SEC on April 28, 2023

DEF 14A 1 tmb-20230613xdef14a.htm DEF 14A Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. ) Filed by the Registrant ⌧ Filed by a Party other than the Registrant ◻ Check the appropriate box: ◻ Preliminary Proxy Statement ◻ Confidential, f

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. )

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. ) Filed by the Registrant ⌧ Filed by a Party other than the Registrant ◻ Check the appropriate box: ⌧ Preliminary Proxy Statement ◻ Confidential, for Use of the Commission Only (as permitte

Bicycle Therapeutics Enhances Leadership Team with Key Appointments - Santiago Arroyo, M.D., Ph.D., appointed Chief Development Officer - Jennifer Perry, Pharm.D., promoted to Senior Vice President, Commercial

Exhibit 99.1 Bicycle Therapeutics Enhances Leadership Team with Key Appointments - Santiago Arroyo, M.D., Ph.D., appointed Chief Development Officer - Jennifer Perry, Pharm.D., promoted to Senior Vice President, Commercial CAMBRIDGE, England & BOSTON, April 3, 2023 – Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 March 31, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutic

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 March 31, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 March 27, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutic

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 March 27, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

Bicycle Therapeutics Announces a Strategic Collaboration with Novartis to Discover, Develop and Commercialize Bicycle® Radio-Conjugates

Exhibit 99.1 Bicycle Therapeutics Announces a Strategic Collaboration with Novartis to Discover, Develop and Commercialize Bicycle® Radio-Conjugates - Bicycle and Novartis will collaborate on the discovery and development of multiple targeted radioligand therapies in oncology - - Bicycle will receive a $50 million upfront payment as well as potential milestones and tiered commercial royalties CAMB

Filing Fee Table

Exhibit 107 Calculation of Filing Fee Tables Form S-8 (Form Type) Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) Table 1: Newly Registered Securities Security Type Security Class Title Fee Calculation Rule Amount Registered Proposed Maximum Offering Price Per Unit Maximum Aggregate Offering Price Fee Rate Amount of Registration Fee Equity Ordinary shares, nominal value £0.

Amended and Restated Bicycle Therapeutics plc 2020 Equity Incentive Plan and forms of award thereunder (incorporated by reference to Exhibit 10.6 to the Registrant’s Annual Report on Form 10-K (File No. 001-38916), filed with the Commission on February 28, 2023).

BICYCLE THERAPEUTICS PLC 2020 EQUITY INCENTIVE PLAN Adopted by the Board on April 23, 2020 and approved by Shareholders on June 29, 2020 Amended and Restated by the Board on April 14, 2022 and approved by Shareholders on June 27, 2022 Cooley (UK) LLP, 22 BISHOPSGATE, London EC2N 4BQ, UK T: +44 (0) 20 7583 4055 F: +44 (0) 20 7785 9355 www.

Third Amendment to the Discovery Collaboration and License Agreement, dated October 26, 2022, by and between Genentech, Inc. and BicycleTx Limited (incorporated by reference to Exhibit 10.25 to the Annual Report on Form 10-K (File No. 001-38916), filed with the Securities and Exchange Commission on February 28, 2023).

EX-10.25 4 bcyc-20221231xex10d25.htm EX-10.25 Execution Version [*] = Certain confidential information contained in this document, marked by brackets, has been omitted because it is both (i) not material and (ii) would be competitively harmful if publicly disclosed. Third Amendment to the Discovery Collaboration and License Agreement between Genentech, Inc. 1 DNA Way, South San Francisco, Californ

Non-employee Director Compensation Policy, as amended as of December 8, 2022.

EX-10.20 3 bcyc-20221231xex10d20.htm EX-10.20 Bicycle Therapeutics plc Non-Employee Director Compensation Policy As amended through December 8, 2022 This Non-Employee Director Compensation Policy (the “Policy”) has been established in order to attract and retain non-employee directors who have the knowledge, skills and experience to serve as a member of the Board of Directors (the “Board”) of Bicy

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 February 28, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeu

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 February 28, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporati

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ⌧ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2022 OR ◻ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number 001-389

As filed with the Securities and Exchange Commission on February 28, 2023

As filed with the Securities and Exchange Commission on February 28, 2023 Registration No.

Bicycle Therapeutics Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Corporate Update - Significant progress across pipeline including advancing BT8009, BT5528, and BT7480 in ongoing clinical trials - BT8009 granted Fast Trac

Exhibit 99.1 Bicycle Therapeutics Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Corporate Update - Significant progress across pipeline including advancing BT8009, BT5528, and BT7480 in ongoing clinical trials - BT8009 granted Fast Track Designation by the U.S. Food and Drug Administration; completed Phase I results presented at ASCO GU Cancers Symposium - Cash position

BCYC / Bicycle Therapeutics Plc - ADR / Paradigm Biocapital Advisors LP - SC 13G Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. )* Bicycle Therapeutics plc (Name of Issuer) Common Stock, £0.01 par value per share (Title of Class of Securities) 088786108 (CUSIP Number) February 14, 2023 (Date of Event Which Requires Filing of this statement) Check the appropriate box to designate the

JOINT FILING AGREEMENT

Exhibit 1 JOINT FILING AGREEMENT In accordance with Rule 13d-1(k) under the Securities Exchange Act of 1934, as amended, the persons named below agree to the joint filing on behalf of each of them of a statement on Schedule 13G (including amendments thereto) with respect to the Common Stock, £0.

BCYC / Bicycle Therapeutics plc / Ridgeback Capital Investments L.P. - SCHEDULE 13G/A Passive Investment

SC 13G/A 1 tm234702d1sc13ga.htm SCHEDULE 13G/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 SCHEDULE 13G (Amendment No. 3) UNDER THE SECURITIES EXCHANGE ACT OF 19341 Bicycle Therapeutics plc (Name of Issuer) Ordinary Shares, nominal value £0.01 (Title of Class of Securities) 088786 10 8 (CUSIP Number) December 31, 2022 (Date of Event Which Requires Filing of this Statement

Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 February 14, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporati

BCYC / Bicycle Therapeutics plc / Deep Track Capital, LP Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 SCHEDULE 13G/A Under the Securities Exchange Act of 1934 (Amendment No.

Bicycle Therapeutics Announces Phase I Dose Escalation Results from Ongoing Phase I/II Study of BT8009 50% overall response rate (ORR) and 75% clinical benefit rate, including one complete response in urothelial cancer at the 5 mg/m2 dose on an inten

Exhibit 99.1 Bicycle Therapeutics Announces Phase I Dose Escalation Results from Ongoing Phase I/II Study of BT8009 50% overall response rate (ORR) and 75% clinical benefit rate, including one complete response in urothelial cancer at the 5 mg/m2 dose on an intent-to-treat (ITT) basis As of January 2023, median duration of response (mDOR) is estimated to be approximately 14 months among urothelial

BCYC / Bicycle Therapeutics plc / Logos Global Management LP Passive Investment

SC 13G/A 1 bicyclethera13ga1.htm UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. 1) Bicycle Therapeutics plc (Name of Issuer) Ordinary Shares, nominal value £0.01 per share (Title of Class of Securities) 0887861081 (CUSIP Number) December 31, 2022 (Date of Event Which Requires Filing of this Statement) Ch

JOINT FILING AGREEMENT

EX-99.1 2 pt7213gab.htm JOINT FILING AGREEMENT Exhibit 99.1 JOINT FILING AGREEMENT The undersigned hereby agree that the foregoing statement on Schedule 13G is filed on behalf of each of the undersigned in accordance with the provisions of Rule 13d-1(k) under the Securities Exchange Act of 1934, as amended, and that all subsequent amendments to this statement on Schedule 13G may be filed on behalf

BCYC / Bicycle Therapeutics plc / Ridgeback Capital Investments L.P. - SCHEDULE 13G/A Passive Investment

SC 13G/A 1 tm234702d1sc13ga.htm SCHEDULE 13G/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 SCHEDULE 13G (Amendment No. 3) UNDER THE SECURITIES EXCHANGE ACT OF 19341 Bicycle Therapeutics plc (Name of Issuer) Ordinary Shares, nominal value £0.01 (Title of Class of Securities) 088786 10 8 (CUSIP Number) December 31, 2022 (Date of Event Which Requires Filing of this Statement

BCYC / Bicycle Therapeutics plc / Point72 Asset Management, L.P. - SCHEDULE 13G/A, AMENDMENT #1 Passive Investment

SC 13G/A 1 pt7213gaa.htm SCHEDULE 13G/A, AMENDMENT #1 240.13d-102 Schedule 13G - Information to be included in statements filed pursuant to 240.13d-1(b), (c), and (d) and amendments thereto filed pursuant to 240.13d-2. Securities and Exchange Commission, Washington, D.C. 20549 Schedule 13G Under the Securities Exchange Act of 1934 (Amendment No. 3)* (Name of Issuer) Bicycle Therapeutics plc (Title

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 January 17, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeut

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 January 17, 2023 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporatio

Bicycle Therapeutics Announces First Patient Dosed in BT8009 Phase II Expansion Cohorts and Provides Program Update The Phase II multi-center, open label trial will evaluate BT8009 administered at the recommended Phase II doses of 5mg/m2 and 7.5mg/m2

Exhibit 99.1 Bicycle Therapeutics Announces First Patient Dosed in BT8009 Phase II Expansion Cohorts and Provides Program Update The Phase II multi-center, open label trial will evaluate BT8009 administered at the recommended Phase II doses of 5mg/m2 and 7.5mg/m2 Phase I dose escalation cohorts complete; results to be presented at a medical conference in 1H 2023 Confirmed RECIST response in a non-

Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 November 8, 2022 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporatio

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 November 3, 2022 Date of Report (Date of earliest event reported) Bicycle Therapeut

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 November 3, 2022 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporatio

Bicycle Therapeutics Reports Third Quarter 2022 Financial Results and Provides Corporate Update - Continued clinical progress across pipeline including BT5528 end of Phase I dose escalation update; completion of enrollment in BT5528 initial dose expa

Exhibit 99.1 Bicycle Therapeutics Reports Third Quarter 2022 Financial Results and Provides Corporate Update - Continued clinical progress across pipeline including BT5528 end of Phase I dose escalation update; completion of enrollment in BT5528 initial dose expansion cohorts expected in Q4 - BT8009 clinical update remains on-track for Q4 - Received $10 million option fee payment from Genentech th

Amendment No. 2 to Collaboration and License Agreement, dated August 1, 2022, between BicycleTx Limited and Ionis Pharmaceuticals, Inc. (incorporated by reference to Exhibit 10.1 to Form 10-Q (File No. 001-38916), filed with the Securities and Exchange Commission on November 3, 2022).

Execution Version ? [*] = Certain confidential information contained in this document, marked by brackets, has been omitted because it is both (i) not material and (ii) would be competitively harmful if publicly disclosed.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

Table of Contents ? ? UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ? QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2022 OR ? TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38916 Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) ? ? ? ? England and Wales Not Applicable (State or other jurisdiction of incorporation or organization) ? (I.

Bicycle Therapeutics Announces BT5528 Phase I Dose Escalation Results in Patients with Advanced Solid Tumors Anti-tumor activity observed in heavily pre-treated patients with EphA2-positive ovarian and urothelial cancers; overall response rates of 22

Exhibit 99.1 Bicycle Therapeutics Announces BT5528 Phase I Dose Escalation Results in Patients with Advanced Solid Tumors Anti-tumor activity observed in heavily pre-treated patients with EphA2-positive ovarian and urothelial cancers; overall response rates of 22% (including one complete response) and 67%, respectively Emergent safety profile of BT5528 suggests notable differentiation from current

Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 September 7, 2022 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporati

Second Amendment to the Discovery Collaboration and License Agreement, dated June 27, 2022, by and between Genentech, Inc. and BicycleTx Limited (incorporated by reference to Exhibit 10.2 to Form 10-Q (File No. 001-38916), filed with the Securities and Exchange Commission on August 4, 2022).

? Second Amendment to the Discovery Collaboration and License Agreement ? ? between ? Genentech, Inc.

Financial Statements and Exhibits, Results of Operations and Financial Condition, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 August 4, 2022 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

- Continued clinical progress across pipeline, including dosing of the first patient in expansion cohorts of Phase I/II study of BT5528 - Expansion of Genentech exclusive strategic collaboration, triggering a $10 million payment to Bicycle in Q3 - Ca

Exhibit 99.1 Bicycle Therapeutics Reports Second Quarter 2022 Financial Results and Provides Corporate Update - Continued clinical progress across pipeline, including dosing of the first patient in expansion cohorts of Phase I/II study of BT5528 - Expansion of Genentech exclusive strategic collaboration, triggering a $10 million payment to Bicycle in Q3 - Cash and cash equivalents of $372.8 millio

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

Table of Contents ? ? UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ? QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2022 OR ? TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38916 Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) ? ? ? ? England and Wales Not Applicable (State or other jurisdiction of incorporation or organization) ? (I.

First Amendment to the Discovery Collaboration and License Agreement, dated November 5, 2021, by and between Genentech, Inc. and BicycleTx Limited (incorporated by reference to Exhibit 10.1 to Form 10-Q (File No. 001-38916), filed with the Securities and Exchange Commission on August 4, 2022).

? Confidential ? ? ? First Amendment to the Discovery Collaboration and License Agreement ? ? between ? Genentech, Inc.

Entry into a Material Definitive Agreement, Financial Statements and Exhibits

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 July 15, 2022 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

Second Amendment to Loan and Security Agreement, dated as of July 15, 2022, by and among Bicycle Therapeutics plc and each of its Subsidiaries, the Lenders, and Hercules Capital, Inc., as Agent (incorporated by reference to Exhibit 10.1 to the Form 8-K (File No. 001-38916) filed with the Securities and Exchange Commission on July 15, 2022).

Exhibit 10.1 SECOND AMENDMENT TO LOAN AND SECURITY AGREEMENT THIS SECOND AMENDMENT TO LOAN AND SECURITY AGREEMENT (this ?Amendment?), dated as of July 15, 2022, is entered into by and among BICYCLE THERAPEUTICS PLC, a public limited company organized under the laws of England and Wales (?Parent?), BICYCLETX LIMITED, a private company limited by shares organized under the laws of England and Wales

Bicycle Therapeutics Announces Further Expansion of Genentech Immuno-Oncology Collaboration Genentech exercises second option to initiate an additional program under the 2020 collaboration agreement

Exhibit 99.1 Bicycle Therapeutics Announces Further Expansion of Genentech Immuno-Oncology Collaboration Genentech exercises second option to initiate an additional program under the 2020 collaboration agreement CAMBRIDGE, England, & BOSTON, July 12, 2022 ? Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its propri

Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 July 12, 2022 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

Submission of Matters to a Vote of Security Holders

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 June 27, 2022 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

Regulation FD Disclosure, Financial Statements and Exhibits, Results of Operations and Financial Condition, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 May 5, 2022 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation) (C

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

Table of Contents ? ? UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ? QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2022 OR ? TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38916 Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) ? ? ? ? England and Wales Not Applicable (State or other jurisdiction of incorporation or organization) ? (I.

Bicycle Therapeutics Reports First Quarter 2022 Financial Results and Provides Corporate Update - Continued clinical progress across pipeline, including interim BT8009 Phase I clinical data - Cash and cash equivalents of $407.4 million as of March 31

Exhibit 99.1 Bicycle Therapeutics Reports First Quarter 2022 Financial Results and Provides Corporate Update - Continued clinical progress across pipeline, including interim BT8009 Phase I clinical data - Cash and cash equivalents of $407.4 million as of March 31, 2022 expected to provide financial runway through 2024 CAMBRIDGE, England, & BOSTON, May 5, 2022 ? Bicycle Therapeutics plc (NASDAQ: BC

BCYC / Bicycle Therapeutics plc / Logos Global Management LP Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. ) Bicycle Therapeutics plc (Name of Issuer) Ordinary Shares, nominal value £0.01 per share (Title of Class of Securities) 0887861081 (CUSIP Number) April 20, 2022 (Date of Event Which Requires Filing of this Statement) Check the appropriate box to designate

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. )

DEF 14A 1 tmb-20220627xdef14a.htm DEF 14A Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. ) Filed by the Registrant ⌧ Filed by a Party other than the Registrant ◻ Check the appropriate box: ◻ Preliminary Proxy Statement ◻ Confidential, f

SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. )

PRE 14A 1 tmb-20220627xpre14a.htm PRE 14A Table of Contents SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. ) Filed by the Registrant ⌧ Filed by a Party other than the Registrant ◻ Check the appropriate box: ⌧ Preliminary Proxy Statement ◻ Confidential, for Use of the Commission Only (as permitted by Rule 14a-6(e)(2)) ◻ Defin

Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 April 11, 2022 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

This presentation may contain forward - looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 . These statements may be identified by words such as “aims,” “anticipates,” “believes,” “c

Exhibit 99.2 BT8009 clinical trial update NASDAQ: BCYC April 2022 Exhibit 992 SP1 This presentation may contain forward - looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 . These statements may be identified by words such as ?aims,? ?anticipates,? ?believes,? ?could,? ?estimates,? ?expects,? ?forecasts?, ?goal,? ?intends,? ?may?

Bicycle Therapeutics Announces Interim BT8009 Phase I Clinical Trial Results at the 2022 AACR Annual Meeting - 50% confirmed overall response rate, including one (13%) confirmed complete response in eight urothelial cancer patients dosed at 5.0mg/m2

Exhibit 99.1 Bicycle Therapeutics Announces Interim BT8009 Phase I Clinical Trial Results at the 2022 AACR Annual Meeting - 50% confirmed overall response rate, including one (13%) confirmed complete response in eight urothelial cancer patients dosed at 5.0mg/m2 weekly - Median duration of response not yet reached in the 2.5mg/m2 and 5.0mg/m2 weekly cohorts; four of five responders in these cohort

BCYC / Bicycle Therapeutics plc / TYBOURNE CAPITAL MANAGEMENT (HK) LTD - AMENDMENT NO. 3 Activist Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13D Under the Securities Exchange Act of 1934 (Amendment No. 3)* Bicycle Therapeutics Limited (Name of Issuer) Ordinary Shares (Title of Class of Securities) 088786108 ** (CUSIP Number) Catherine Cheung Tybourne Capital Management (HK) Limited 30/F, AIA Central 1 Connaught Road Central Hong Kong, K3 Tel. No.: 852-3983

Amendment No. 1 to Collaboration and License Agreement, dated December 17, 2021, between BicycleTx Limited and Ionis Pharmaceuticals, Inc. (incorporated by reference to Exhibit 10.25 to the Annual Report on Form 10-K (File No. 001-38916), filed with the Securities and Exchange Commission on March 1, 2022).

Exhibit 10.25 ? CERTAIN PORTIONS OF THIS EXHIBIT (MARKED BY [***]) HAVE BEEN OMITTED BECAUSE THE IDENTIFIED INFORMATION IS NOT MATERIAL AND IS THE TYPE THAT THE REGISTRANT TREATS AS PRIVATE OR CONFIDENTIAL. ? AMENDMENT NO. 1 TO COLLABORATION AND LICENSE AGREEMENT This Amendment No. 1 to Collaboration and License Agreement (?First Amendment?) is made and entered into effective as of December 17, 20

Filing Fee Table

Exhibit 107 Calculation of Filing Fee Tables Form S-8 (Form Type) Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) Table 1: Newly Registered Securities Security Type Security Class Title Fee Calculation Rule Amount Registered Proposed Maximum Offering Price Per Unit Maximum Aggregate Offering Price Fee Rate Amount of Registration Fee Equity Ordinary shares, nominal value ?0.

Bicycle Therapeutics Reports Fourth Quarter and Full Year 2021 Financial Results and Provides Corporate Update - Continued clinical progress across pipeline of Bicycle Toxin Conjugates® (BTCs) and Bicycle tumor-targeted immune cell agonists (Bicycle

Exhibit 99.1 Bicycle Therapeutics Reports Fourth Quarter and Full Year 2021 Financial Results and Provides Corporate Update - Continued clinical progress across pipeline of Bicycle Toxin Conjugates? (BTCs) and Bicycle tumor-targeted immune cell agonists (Bicycle TICAs) - Cash of $438.7 million at December 31, 2021 expected to provide financial runway through 2024 CAMBRIDGE, England, & BOSTON, Marc

Amended and Restated Employment Agreement, dated January 6, 2022, by and between BicycleTx Ltd. And Michael Skynner, Ph.D. (incorporated by reference to Exhibit 10.11 to the Annual Report on Form 10-K (File No. 001-38916), filed with the Securities and Exchange Commission on March 1, 2022).

Exhibit 10.11 ? Dr Michael Skynner ? ? ? January 5, 2022 ? Dear Michael, Amendment to your service agreement with BicycleTX Limited (the ?Company?) dated 26 September 2019 (the ?Service Agreement?) Following our recent discussions regarding a move from the Chief Operating Officer role to the new Chief Technology Officer role, I am happy to write to you to confirm this agreed move and to confirm th

Non-employee Director Compensation Policy, amended as of December 14, 2021.

?Exhibit 10.21 Bicycle Therapeutics plc Non-Employee Director Compensation Policy As amended through December 14, 2021 ? This Non-Employee Director Compensation Policy (the ?Policy?) has been established in order to attract and retain non-employee directors who have the knowledge, skills and experience to serve as a member of the Board of Directors (the ?Board?) of Bicycle Therapeutics plc (the ?C

Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 March 1, 2022 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation)

As filed with the Securities and Exchange Commission on March 1, 2022

As filed with the Securities and Exchange Commission on March 1, 2022 Registration No.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K

Table of Contents ? ? UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.

Service Agreement, dated January 5, 2022, by and between BicycleTx Ltd. and Alistair Milnes (incorporated by reference to Exhibit 10.17 to the Annual Report on Form 10-K (File No. 001-38916), filed with the Securities and Exchange Commission on March 1, 2022).

EX-10.17 3 bcyc-20211231xex10d17.htm EX-10.17 Exhibit 10.17 DATED January 5, 2022 BICYCLETX LIMITED and ALISTAIR MILNES SERVICE AGREEMENT 8548359 v5 Exhibit 10.17 CONTENTS Clause‌Page 1. COMMENCEMENT OF EMPLOYMENT‌1 2. JOB TITLE‌1 3. PLACE OF WORK‌2 4. REMUNERATION‌2 5. BENEFITS‌3 6. EXPENSES‌3 7. HOURS OF WORK‌3 8. HOLIDAYS‌4 9. SICKNESS AND OTHER ABSENCE‌4 10. GARDEN LEAVE‌5 11. NOTICE‌6 12. DIS

BCYC / Bicycle Therapeutics plc / Logos Global Management LP Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. 1) Bicycle Therapeutics plc (Name of Issuer) Ordinary Shares, nominal value ?0.01 per share (Title of Class of Securities) 0887861081 (CUSIP Number) December 31, 2021 (Date of Event Which Requires Filing of this Statement) Check the appropriate box to design

BCYC / Bicycle Therapeutics plc / Ridgeback Capital Investments L.P. - SC 13G/A Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 SCHEDULE 13G (Amendment No.

BCYC / Bicycle Therapeutics plc / Point72 Asset Management, L.P. - SCHEDULE 13G (AMENDMENT NO. 2) Passive Investment

SC 13G/A 1 b020822a.htm SCHEDULE 13G (AMENDMENT NO. 2) 240.13d-102 Schedule 13G - Information to be included in statements filed pursuant to 240.13d-1(b), (c), and (d) and amendments thereto filed pursuant to 240.13d-2. Securities and Exchange Commission, Washington, D.C. 20549 Schedule 13G Under the Securities Exchange Act of 1934 (Amendment No. 2)* (Name of Issuer) Bicycle Therapeutics plc. (Tit

Joint Filing Agreement

EXHIBIT 99.3 Joint Filing Agreement In accordance with Rule 13d-1(k) under the Securities Exchange Act of 1934, as amended, the undersigned agree to the joint filing on behalf of each of them of a Statement on Schedule 13G (including amendments thereto) with respect to the Ordinary Shares, nominal value ?0.001 per share, of Bicycle Therapeutics plc, a public limited company incorporated under the

BCYC / Bicycle Therapeutics plc / Novartis Bioventures Ltd - SCHEDULE 13G/A Passive Investment

SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No.

BCYC / Bicycle Therapeutics plc / Deep Track Capital, LP Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No.

Bicycle Therapeutics Announces Continued Clinical Progress and Updates to Management Team

Exhibit 99.1 Bicycle Therapeutics Announces Continued Clinical Progress and Updates to Management Team CAMBRIDGE, England, & BOSTON, January 5, 2022 ? Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle?) technology, today announced continued progress in its ongoing Phase I/II

Regulation FD Disclosure, Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers, Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 January 3, 2022 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporation

Regulation FD Disclosure

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 November 8, 2021 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporatio

Financial Statements and Exhibits, Results of Operations and Financial Condition, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 November 4, 2021 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporatio

Bicycle Therapeutics Announces First Patient Dosed in Phase I/II Trial of Bicycle® Tumor-targeted Immune Cell Agonist™ BT7480 in Patients with Advanced Solid Tumors Associated with Nectin-4 Expression - BT7480 is the Company’s Fourth Product Candidat

Exhibit 99.2 Bicycle Therapeutics Announces First Patient Dosed in Phase I/II Trial of Bicycle? Tumor-targeted Immune Cell Agonist? BT7480 in Patients with Advanced Solid Tumors Associated with Nectin-4 Expression - BT7480 is the Company?s Fourth Product Candidate to Enter the Clinic in the Past Four Years - This is Bicycle?s First Immuno-oncology Asset to Enter the Clinic CAMBRIDGE, England, & BO

Collaboration and License Agreement, dated as of July 9, 2021, between BicycleTx Limited and Ionis Pharmaceuticals, Inc.

Exhibit 10.1 ? [***] = CERTAIN IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THIS DOCUMENT BECAUSE IT IS BOTH NOT MATERIAL AND IS OF THE TYPE THAT THE REGISTRANT TREATS AS PRIVATE AND CONFIDENTIAL. ? COLLABORATION AND LICENSE AGREEMENT between BICYCLETX LIMITED and IONIS PHARMACEUTICALS, INC. Dated as of July 9, 2021 ? ? ? ? ? ? ? ? ? ? TABLE OF CONTENTS Article 1 DEFINITIONS?1 Article 2 GRANT OF

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

Table of Contents ? ? UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ? QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2021 OR ? TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38916 Bicycle Therapeutics plc (Exact Name of Registrant as Specified in its Charter) ? ? ? ? England and Wales Not Applicable (State or other jurisdiction of incorporation or organization) ? (I.

Share Purchase Agreement, dated as of July 9, 2021, between Bicycle Therapeutics plc and Ionis Pharmaceuticals, Inc.

Exhibit 10.2 ? Execution Version ? SHARE PURCHASE AGREEMENT THIS SHARE PURCHASE AGREEMENT (?Agreement?) is entered into as of July 9, 2021 (the ?Execution Date?), by and between Bicycle Therapeutics plc, a company incorporated under the laws of England and Wales having an office at Building 900, Babraham Research Campus, Cambridge, United Kingdom CB22 3AT (the ?Company?), and Ionis Pharmaceuticals

Bicycle Therapeutics Reports Third Quarter 2021 Financial Results and Provides Corporate Update

Exhibit 99.1 Bicycle Therapeutics Reports Third Quarter 2021 Financial Results and Provides Corporate Update - Announced interim BT5528 Phase I clinical trial results and preliminary results from ongoing BT8009 Phase I clinical trial - First Patient Dosed in Phase I/II Trial of Bicycle? Tumor-targeted Immune Cell Agonist? BT7480 in Patients with Advanced Solid Tumors Associated with Nectin-4 Expre

Bicycle Therapeutics Announces Expansion of Genentech Immuno-Oncology Collaboration Genentech exercised an option to initiate an additional program under the 2020 collaboration agreement

Exhibit 99.1 Bicycle Therapeutics Announces Expansion of Genentech Immuno-Oncology Collaboration Genentech exercised an option to initiate an additional program under the 2020 collaboration agreement CAMBRIDGE, England, & BOSTON, October 26, 2021 ? Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bic

Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 October 26, 2021 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporatio

Underwriting Agreement, dated October 12, 2021, by and among the Company, Goldman Sachs & Co. LLC, Morgan Stanley & Co. LLC and SVB Leerink LLC, as the Representatives of the several underwriters named therein.

Exhibit 1.1 Execution Version Bicycle Therapeutics plc 3,240,741 American Depositary Shares representing 3,240,741 Ordinary Shares, nominal value ?0.01 per share Underwriting Agreement October 12, 2021 Goldman Sachs & Co. LLC Morgan Stanley & Co. LLC SVB Leerink LLC As representatives (the ?Representatives?) of the several Underwriters named in Schedule I hereto c/o Goldman Sachs & Co. LLC 200 Wes

Entry into a Material Definitive Agreement, Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 October 12, 2021 Date of Report (Date of earliest event reported) Bicycle Therapeutics plc (Exact name of registrant as specified in its charter) England and Wales 001-38916 Not applicable (State or other jurisdiction of incorporatio

CALCULATION OF REGISTRATION FEE

TABLE OF CONTENTS Filed Pursuant to Rule 424(b)(5) Registration No. 333-260179? CALCULATION OF REGISTRATION FEE ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? Title of Each Class of Securities to be Registered ? ? ? Amount to be Registered ? ? ? Proposed Maximum Offering Price Per Unit ? ? ? Proposed Maximum Aggregate Offering Price ? ? ? Amount of Registration Fee(1) ? Ordinary Share

Form of Senior Indenture.

Exhibit 4.3 BICYCLE THERAPEUTICS PLC, Issuer AND [ ], Trustee INDENTURE Dated as of [ ], 20[ ] Senior Debt Securities Table Of Contents Page article 1 DEFINITIONS 1 Section 1.01 Definitions of Terms 1 article 2 ISSUE, DESCRIPTION, TERMS, EXECUTION, REGISTRATION AND EXCHANGE OF SECURITIES 5 Section 2.01 Designation and Terms of Securities 5 Section 2.02 Form of Securities and Trustee?s Certificate

Form of Preference Share Warrant Agreement and Warrant Certificate.

Exhibit 4.7 Bicycle Therapeutics plc and , As Warrant Agent Form of Preference Shares Warrant Agreement Dated As Of Bicycle Therapeutics plc Form of preference Shares Warrant Agreement This Preference Shares Warrant Agreement (this ?Agreement?), dated as of [?], between Bicycle Therapeutics plc, a public limited company incorporated under the laws of England and Wales (the ?Company?), and [?], a [

Form of Debt Securities Warrant Agreement and Warrant Certificate.

Exhibit 4.8 BICYCLE THERAPEUTICS PLC and , As Warrant Agent Form of Debt Securities Warrant Agreement Dated As Of 1 Bicycle Therapeutics plc Form of Debt Securities Warrant Agreement This Debt Securities Warrant Agreement (this ?Agreement?), dated as of [?], between Bicycle Therapeutics plc, a public limited company incorporated under the laws of England and Wales (the ?Company?), and [?], a [corp

Form S-3 (File No. 333-260179) that we filed with the Securities and Exchange Commission, or SEC, on October 12, 2021

TABLE OF CONTENTS As filed with the Securities and Exchange Commission on October 12, 2021 Registration No.

Form of Subordinated Indenture.

Exhibit 4.4 BICYCLE THERAPEUTICS PLC, Issuer AND [ ], Trustee INDENTURE Dated as of [ ], 20[ ] Subordinated Debt Securities Table Of Contents Page article 1 DEFINITIONS 1 Section 1.01 Definitions of Terms 1 article 2 ISSUE, DESCRIPTION, TERMS, EXECUTION, REGISTRATION AND EXCHANGE OF SECURITIES 5 Section 2.01 Designation and Terms of Securities 5 Section 2.02 Form of Securities and Trustee?s Certif

SUBJECT TO COMPLETION, DATED OCTOBER 12, 2021

TABLE OF CONTENTS The information in this preliminary prospectus supplement and the accompanying prospectus is not complete and may be changed.

Form of Ordinary Share Warrant Agreement and Warrant Certificate.

Exhibit 4.6 BICYCLE THERAPEUTICS PLC and , As Warrant Agent Form of Ordinary Shares Warrant Agreement Dated As Of Bicycle Therapeutics plc Form of Ordinary Shares Warrant Agreement This Ordinary Shares Warrant Agreement (this ?Agreement?), dated as of [?], between Bicycle Therapeutics plc, a public limited company incorporated under the laws of England and Wales (the ?Company?), and [?], a [corpor