Skye Bioscience, Inc.

Director and Officer Trading Arrangements

On December 12, 2025, 5AM Partners II, LLC (the general partner of 5AM Ventures II, L.P. and 5AM Co-Investors II, L.P.)adopted a Rule 10b5-1 trading plan with Piper Sandler & Co. (“Piper Sandler”). 5AM Partners II, LLC’s Rule 10b5-1 trading plan (the “10b5-1 Plan”) is intended to satisfy the affirmative defense conditions of Rule 10b5-1(c) and provides for the potential sale by Piper Sandler of up to 1,514,557 shares of the Company’s common stock from the 10b5-1 Plan’s effective date of January 11, 2026 until its termination date of November 16, 2026, subject to earlier termination in accordance with the terms of the 10b5-1 Plan and applicable laws, rules and regulations. Andrew Schwab is a member of the Board of Directors of the Company and a managing member of 5AM Partners II, LLC, with shared voting and investment power over the shares in the 10b5-1 Plan. Mr. Schwab disclaims beneficial ownership of such shares except to the extent of his pecuniary interest therein.

Except as set forth above, none of our directors or officers adopted or terminated a Rule 10b5-1 trading arrangement or a non-Rule 10b5-1 trading arrangement (as defined in Item 408(c) of Regulation S-K) during the fourth quarter of 2024.