AYTU BIOPHARMA, INC

Our Board of Directors (the “Board”) has adopted, subject to stockholder approval, the Aytu BioPharma, Inc. 2027 Employee Stock Purchase Plan (the “2027 ESPP” or the “ESPP”). The Board adopted the 2027 ESPP on October 16, 2026. Although the 2027 ESPP became effective upon its adoption by the Board, no purchase rights may be exercised under the ESPP unless and until it is approved by our stockholders. If this proposal is approved, the first offering period under the 2027 ESPP will begin on the first trading day on or after July 1, 2027, and a total of 500,000 shares of our common stock will be reserved for issuance under the 2027 ESPP.

The 2027 ESPP is intended to qualify as an “employee stock purchase plan” under Section 423 of the Internal Revenue Code of 1986, as amended (the “Code”). Stockholder approval is required to satisfy the listing rules of Nasdaq and to permit the ESPP to qualify for the favorable tax treatment available under Section 423, which requires stockholder approval within 12 months before or after the date the plan is adopted by the Board.

The Company does not currently maintain an employee stock purchase plan. Accordingly, approval of the 2027 ESPP would establish this benefit for the first time. The following summary of the principal features of the 2027 ESPP is qualified in its entirety by reference to the full text of the 2027 ESPP, a copy of which is attached to this proxy statement as Appendix B.