X0306 4 2021-12-20 0 0001761612 BICYCLE THERAPEUTICS plc BCYC 0001391045 Legault Pierre C/O BICYCLE THERAPEUTICS PLC B900, BABRAHAM RESEARCH CAMPUS CAMBRIDGE X0 CB22 3AT UNITED KINGDOM 1 0 0 0 Ordinary Shares 2021-12-20 4 M 0 7603 8.41 A 7603 D Ordinary Shares 2021-12-20 4 S 0 7603 57.02 D 0 D Ordinary Shares 2021-12-21 4 M 0 44537 8.44 A 44537 D Ordinary Shares 2021-12-21 4 S 0 44537 57.11 D 0 D Ordinary Shares 2021-12-22 4 M 0 97860 8.48 A 97860 D Ordinary Shares 2021-12-22 4 S 0 97860 58.01 D 0 D Stock Option (Right to Buy) 8.41 2021-12-20 4 M 0 7603 0.00 D 2029-04-25 Ordinary Shares 7603 165709 D Stock Option (Right to Buy) 8.44 2021-12-21 4 M 0 44537 0.00 D 2029-04-25 Ordinary Shares 44537 121172 D Stock Option (Right to Buy) 8.48 2021-12-22 4 M 0 97860 0.00 D 2029-04-25 Ordinary Shares 97860 23312 D This exercise price is in US Dollars and reflects the conversion of GBP to USD at an exchange rate of $1.319915 to GBP 1.00 as of December 20, 2021. Shares were sold pursuant to a Rule 10b5-1 trading plan. The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $57.00 to $57.05 inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares sold at each separate price within the ranges set forth in footnotes (3), (5) and (7). This exercise price is in US Dollars and reflects the conversion of GBP to USD at an exchange rate of $1.324735 to GBP 1.00 as of December 21, 2021. The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $57.02 to $57.55 inclusive. This exercise price is in US Dollars and reflects the conversion of GBP to USD at an exchange rate of $1.331495 to GBP 1.00 as of December 22, 2021. The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $57.51 to $58.50 inclusive. This option shall vest in 36 equal monthly installments and shall be fully vested on March 15, 2022. /s/ Lee Kalowski, Attorney-in-Fact 2021-12-22