BICYCLE THERAPEUTICS PLC

Report of Independent Registered Public Accounting Firm

To** the **Board of Directors and Shareholders of Bicycle Therapeutics plc

Opinion on the Financial Statements

We have audited the accompanying consolidated** balance sheets of Bicycle Therapeutics plc and its subsidiaries (the “Company”) as of December 31, 2025 and 2024, and the related consolidated statements of operations and comprehensive loss, of shareholders’ equity and of cash flows for each of the three years in the period ended December 31, 2025, including the related notes (collectively referred to as the “consolidated financial statements”). In our opinion, the consolidated financial statements present fairly, in all material respects, the financial position of the Company as of December 31, 2025 and 2024, and the results of its operations and its cash flows for each of the three years in the period ended December 31, 2025 **in conformity with accounting principles generally accepted in the United States of America.

Basis for Opinion

These consolidated** **financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on the Company’s consolidated financial statements based on our audits. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States) (PCAOB) and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.

We conducted our audits of these consolidated** **financial statements in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audits to obtain reasonable assurance about whether the consolidated financial statements are free of material misstatement, whether due to error or fraud. The Company is not required to have, nor were we engaged to perform, an audit of its internal control over financial reporting. As part of our audits we are required to obtain an understanding of internal control over financial reporting but not for the purpose of expressing an opinion on the effectiveness of the Company's internal control over financial reporting. Accordingly, we express no such opinion.

Our audits included performing procedures to assess the risks of material misstatement of the consolidated** financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the consolidated financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the consolidated **financial statements. We believe that our audits provide a reasonable basis for our opinion.

Critical Audit Matters

The critical audit matters communicated below are matters arising from the current period audit of the consolidated financial statements that were communicated or required to be communicated to the audit committee and that (i) relate to accounts or disclosures that are material to the** consolidated financial statements and (ii) involved our especially challenging, subjective, or complex judgments. The communication of critical audit matters does not alter in any way our opinion on the consolidated **financial statements, taken as a whole, and we are not, by communicating the critical audit matters below, providing separate opinions on the critical audit matters or on the accounts or disclosures to which they relate.

External research and development expenses

As described in Note 2 and 5 to the consolidated financial statements, research and development expenses were $240.3 million for the year ended December 31, 2025, of which a significant portion related to external research and development expense. Accrued external research and development expenses were $20.5 million as of December 31, 2025. The Company has entered into various research and development and manufacturing contracts, including contracts with respect to preclinical studies and clinical trials. Research and development costs are expensed as incurred. Significant judgments and estimates are made by management in estimating external research and development expenses incurred and associated accrued balance at the end of the reporting period.

For estimating accrued external research and development expenses, management analyzes the progress of the research and development and manufacturing activities, including the level of service performed and associated cost incurred, invoices received and contracted costs.

The principal considerations for our determination that performing procedures relating to external research and development expenses is a critical audit matter are (i) the significant judgment by management in developing the estimate of the accrued external research and development expenses; and (ii) a high degree of auditor judgment, subjectivity and effort in performing procedures and evaluating management’s significant assumption related to the level of service performed.

Addressing the matter involved performing procedures and evaluating audit evidence in connection with forming our overall opinion on the consolidated financial statements. These procedures included, among others (i) reading significant research and development and manufacturing contracts; (ii) testing the external research and development expenses incurred, on a sample basis, by tracing information to the underlying contracts, purchase orders, invoices and information received from the research institutions or vendors, as applicable; (iii) testing management’s process for estimating the accrued external research and development expenses; (iv) testing the completeness and accuracy of underlying data used by management; and (v) evaluating the reasonableness of the significant assumption used by management in estimating of the level of service performed on a sample of contracts. Evaluating management’s assumption related to the level of service performed involved obtaining and examining a sample of third party contracts to evaluate the completeness and consistency of the costs and milestones in the contract with those used in developing the estimate, testing the associated cost incurred based on underlying contracts and other information received from research organizations and re-calculating the level of service performed for a study or research and development activity.

Accounting for termination of Novartis Collaboration Agreement

As described in Note 9 to the consolidated financial statements, in November 2025, Novartis Pharma AG (“Novartis”) provided the Company with a notice of termination of the Novartis Collaboration Agreement in its entirety, effective in February 2026. Management exercised significant judgment in concluding that the notice of termination should be accounted for as a contract modification in the fourth quarter of 2025 as it reduces the scope of the arrangement. Management concluded that the notice of termination substantively removes all remaining performance obligations, including remaining material rights, as of the date of the notice as Novartis will not benefit from any remaining activities performed during the notice period and the likelihood of exercising any remaining options is remote. As a result, the Company recognized the remaining unrecognized transaction price of $41.9 million as revenue on the date of the notice of termination.

The principal considerations for our determination that performing procedures relating to accounting for the termination of Novartis Collaboration Agreement is a critical audit matter are (i) the significant judgment by management in determining the timing of accounting for the termination of collaboration agreement, and (ii) a high degree of auditor judgment, subjectivity and effort in performing procedures related to accounting for the termination of Novartis Collaboration Agreement.

Addressing the matter involved performing procedures and evaluating audit evidence in connection with forming our overall opinion on the consolidated financial statements. These procedures included, among others (i) reading the Novartis Collaboration Agreement and the notice of termination; (ii) evaluating management’s assessment of the accounting for the termination of the Novartis Collaboration Agreement; (iii) evaluating the reasonableness of significant judgment used by management related to the determination that Novartis will not benefit from any remaining activities performed during the notice period and the likelihood of exercising any remaining options is remote by evaluating its consistency with the contractual terms and considering the progress of the research as of the date of termination; and (iv) evaluating the sufficiency of the disclosures in the consolidated financial statements.

/s/PricewaterhouseCoopers LLP

Cambridge, United Kingdom

March 17, 2026

We have served as the Company’s auditor since 2010.