SYRE · Spyre Therapeutics, Inc.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on November 10, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $88.17 to $89.01, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range.

Includes 67,476 restricted stock units ("RSUs"). Each RSU represents a contingent right to receive, upon vesting, one share of Common Stock. The RSUs vest in two equal installments on each of September 1, 2026 and 2027, subject to the Reporting Person's continued employment with the Issuer.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on November 10, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $87.13 to $88.05, 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 (the "SEC"), upon request, full information regarding the number of shares sold at each separate price within the range.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $87.82 to $88.75, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range.

Includes 72,623 shares of common stock that vest in monthly installments through November 2026, subject to the continuing service of the Reporting Person on each vesting date.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $88.86 to $88.98, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range.

Includes 72,623 shares of common stock that vest in monthly installments through November 2026, subject to the continuing service of the Reporting Person on each vesting date.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $86.82 to $87.81, 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 (the "SEC"), upon request, full information regarding the number of shares sold at each separate price within the range.

Includes 72,623 shares of common stock that vest in monthly installments through November 2026, subject to the continuing service of the Reporting Person on each vesting date.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

This option represents the right to purchase 400,000 shares of the Issuer's common stock, one quarter of which vested and became exercisable on October 1, 2025, with the remaining three quarters vesting in monthly installments over the following three years, subject to the Reporting Person's continued employment with the Issuer.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $88.03 to $88.95, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on November 10, 2025.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on November 10, 2025.

This option represents a right to purchase 404,857 shares of the Issuer's common stock (which have been adjusted to reflect the Issuer's 1-for-25 reverse stock split on September 8, 2023), one quarter of which vested and became exercisable on September 1, 2024, with the remaining three quarters vesting in monthly installments over the following three years, subject to the Reporting Person's continued employment with the Issuer.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $87.03 to $87.99, 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 (the "SEC"), upon request, full information regarding the number of shares sold at each separate price within the range.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $86.78 to $87.43, 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 (the "SEC"), upon request, full information regarding the number of shares sold at each separate price within the range.

Includes 67,476 restricted stock units ("RSUs"). Each RSU represents a contingent right to receive, upon vesting, one share of Common Stock. The RSUs vest in two equal installments on each of September 1, 2026 and 2027, subject to the Reporting Person's continued employment with the Issuer.

This option represents a right to purchase 404,857 shares of the Issuer's common stock (which have been adjusted to reflect the Issuer's 1-for-25 reverse stock split on September 8, 2023), one quarter of which vested and became exercisable on September 1, 2024, with the remaining three quarters vesting in monthly installments over the following three years, subject to the Reporting Person's continued employment with the Issuer.

Each share of Series B Preferred Stock is convertible at the option of the holder into 40 shares of Common Stock, subject to certain beneficial ownership limitations, including that a holder of Series B Preferred Stock is prohibited from converting shares of Series B Preferred Stock into shares of Common Stock if, as a result of such conversion, such holder, together with its affiliates, would beneficially own more than 9.99% of the total number of shares of Common Stock issued and outstanding immediately after giving effect to such conversion. On June 23, 2026, the Reporting Persons converted 16,667 shares of Series B Preferred Stock into 666,680 shares of Common Stock for no cash consideration, in accordance with the Certificate of Designations for the Series B Convertible Preferred Stock.

Fairmount Funds Management LLC ("Fairmount") is the investment manager for Fairmount Healthcare Fund II L.P. The managers of Fairmount are Peter Harwin and Tomas Kiselak. Fairmount, Mr. Harwin, and Mr. Kiselak disclaim beneficial ownership of any of the reported securities, except to the extent of their pecuniary interest therein.

Fairmount Funds Management LLC ("Fairmount") is the investment manager for Fairmount Healthcare Fund II L.P. The managers of Fairmount are Peter Harwin and Tomas Kiselak. Fairmount, Mr. Harwin, and Mr. Kiselak disclaim beneficial ownership of any of the reported securities, except to the extent of their pecuniary interest therein.

Each share of Series B Preferred Stock is convertible at the option of the holder into 40 shares of Common Stock, subject to certain beneficial ownership limitations, including that a holder of Series B Preferred Stock is prohibited from converting shares of Series B Preferred Stock into shares of Common Stock if, as a result of such conversion, such holder, together with its affiliates, would beneficially own more than 9.99% of the total number of shares of Common Stock issued and outstanding immediately after giving effect to such conversion. On June 23, 2026, the Reporting Persons converted 16,667 shares of Series B Preferred Stock into 666,680 shares of Common Stock for no cash consideration, in accordance with the Certificate of Designations for the Series B Convertible Preferred Stock.

Fairmount Funds Management LLC ("Fairmount") is the investment manager for Fairmount Healthcare Fund II L.P. The managers of Fairmount are Peter Harwin and Tomas Kiselak. Fairmount, Mr. Harwin, and Mr. Kiselak disclaim beneficial ownership of any of the reported securities, except to the extent of their pecuniary interest therein.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on February 6, 2026.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

This option represents the right to purchase 400,000 shares of the Issuer's common stock, one quarter of which vested and became exercisable on October 1, 2025, with the remaining three quarters vesting in monthly installments over the following three years, subject to the Reporting Person's continued employment with the Issuer.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on November 10, 2025.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on November 10, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $69.37 to $70.36, 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 (the "SEC"), upon request, full information regarding the number of shares sold at each separate price within the range.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $69.96 to $70.95, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range.

Includes 87,138 shares of common stock that vest in monthly installments through November 2026, subject to the continuing service of the Reporting Person on each vesting date.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $68.96 to $69.86, 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 (the "SEC"), upon request, full information regarding the number of shares sold at each separate price within the range.

Includes 87,138 shares of common stock that vest in monthly installments through November 2026, subject to the continuing service of the Reporting Person on each vesting date.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $70.97 to $71.93, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range.

Includes 87,138 shares of common stock that vest in monthly installments through November 2026, subject to the continuing service of the Reporting Person on each vesting date.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on November 10, 2025.

This option represents a right to purchase 404,857 shares of the Issuer's common stock (which have been adjusted to reflect the Issuer's 1-for-25 reverse stock split on September 8, 2023), one quarter of which vested and became exercisable on September 1, 2024, with the remaining three quarters vesting in monthly installments over the following three years, subject to the Reporting Person's continued employment with the Issuer.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on November 10, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $70.38 to $71.34, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on November 10, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $71.54 to $72.14, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range.

Includes 67,476 restricted stock units ("RSUs"). Each RSU represents a contingent right to receive, upon vesting, one share of Common Stock. The RSUs vest in two equal installments on each of September 1, 2026 and 2027, subject to the Reporting Person's continued employment with the Issuer.

This option represents a right to purchase 8,026 shares of the Issuer's common stock, which will vest and become fully exercisable upon the earlier of May 27, 2027 or the date of the Issuer's 2027 annual meeting of stockholders, subject to the Reporting Person's continuous service to the Issuer through the applicable vesting date.

This option represents a right to purchase 8,026 shares of the Issuer's common stock, which will vest and become fully exercisable upon the earlier of May 27, 2027 or the date of the Issuer's 2027 annual meeting of stockholders, subject to the Reporting Person's continuous service to the Issuer through the applicable vesting date.

This option represents a right to purchase 8,026 shares of the Issuer's common stock, which will vest and become fully exercisable upon the earlier of May 27, 2027 or the date of the Issuer's 2027 annual meeting of stockholders, subject to Tomas Kiselak's continuous service to the Issuer through the applicable vesting date.

Under Mr. Kiselak's arrangement with Fairmount Funds Management LLC (the "Adviser"), Mr. Kiselak holds the option for one or more investment vehicles managed by the Adviser (each, a "Fairmount Fund"). Mr. Kiselak is obligated to turn over to the Adviser any net cash or stock received from the option for the benefit of such Fairmount Fund. Mr. Kiselak therefore disclaims beneficial ownership of the option and underlying common stock, except to the extent of his pecuniary interest therein.

This option represents a right to purchase 8,026 shares of the Issuer's common stock, which will vest and become fully exercisable upon the earlier of May 27, 2027 or the date of the Issuer's 2027 annual meeting of stockholders, subject to the Reporting Person's continuous service to the Issuer through the applicable vesting date.

This option represents a right to purchase 8,026 shares of the Issuer's common stock, which will vest and become fully exercisable upon the earlier of May 27, 2027 or the date of the Issuer's 2027 annual meeting of stockholders, subject to the Reporting Person's continuous service to the Issuer through the applicable vesting date.

This option represents a right to purchase 8,026 shares of the Issuer's common stock, which will vest and become fully exercisable upon the earlier of May 27, 2027 or the date of the Issuer's 2027 annual meeting of stockholders, subject to the Reporting Person's continuous service to the Issuer through the applicable vesting date.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on February 6, 2026.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $72.03 to $73.00, 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 (the "SEC"), upon request, full information regarding the number of shares sold at each separate price within the range.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on February 6, 2026.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $75.15 to $75.71, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on February 6, 2026.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $74.15 to $75.14, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on February 6, 2026.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $73.15 to $74.14, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $70.21 to $71.20, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $74.95 to $74.96, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range.

Includes 101,653 shares of common stock that vest in monthly installments through November 2026, subject to the continuing service of the Reporting Person on each vesting date.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $72.21 to $73.20, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on November 10, 2025.

Includes 67,476 restricted stock units ("RSUs"). Each RSU represents a contingent right to receive, upon vesting, one share of Common Stock. The RSUs vest in two equal installments on each of September 1, 2026 and 2027, subject to the Reporting Person's continued employment with the Issuer.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $74.21 to $74.96, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $70.30 to $71.28, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range.

Includes 101,653 shares of common stock that vest in monthly installments through November 2026, subject to the continuing service of the Reporting Person on each vesting date.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on November 10, 2025.

This transaction was executed pursuant to a Rule 10b5-1 trading plan adopted on June 20, 2025.

The price reported above is a weighted average price. The shares were sold in multiple transactions at prices ranging from $73.21 to $74.20, inclusive. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range.