SCHEDULE 13G/A 0001104659-24-113067 0001346824 XXXXXXXX LIVE 2 Common Stock, par value $0.001 per share 09/30/2025 0001645469 Monopar Therapeutics Inc. 61023L207 1000 Skokie Blvd., Suite 350 Wilmette IL 60091 Rule 13d-1(c) RA Capital Management, L.P. DE 0.00 742861.00 0.00 742861.00 742861.00 9.9 IA PN Peter Kolchinsky X1 0.00 742861.00 0.00 742861.00 742861.00 9.9 HC IN Rajeev Shah X1 0.00 742861.00 0.00 742861.00 742861.00 9.9 HC IN RA Capital Healthcare Fund, L.P. DE 0.00 742861.00 0.00 742861.00 742861.00 9.9 PN Monopar Therapeutics Inc. 1000 Skokie Blvd., Suite 350, Wilmette, IL, 60091. The names of the persons filing this report (collectively, the "Reporting Persons") are: RA Capital Management, L.P. ("RA Capital") Peter Kolchinsky Rajeev Shah RA Capital Healthcare Fund, L.P. (the "Fund") The Reporting Persons expressly disclaim status as a "group" for purposes of this Schedule 13G. The address of the principal business office of each of the Reporting Persons is: c/o RA Capital Management, L.P., 200 Berkeley Street, 18th Floor, Boston MA 02116 RA Capital and the Fund are Delaware limited partnerships. Dr. Kolchinsky and Mr. Shah are United States citizens. Y Row 9 of each Reporting Person's cover page to this Schedule 13G sets forth the aggregate number of securities of the Issuer beneficially owned by such Reporting Person as of September 30, 2025 and is incorporated by reference. The Fund directly holds 511,207 shares of Common Stock and pre-funded warrants ("Pre-Funded Warrants") exercisable for up to 1,621,640 shares of Common Stock. The Pre-Funded Warrants contain a provision (the "Beneficial Ownership Blocker"), which precludes the exercise of the Pre-Funded Warrants to the extent that, following exercise, the Fund, together with its affiliates and other attribution parties, would own more than 9.99% of the Common Stock outstanding. The Fund is currently prohibited from exercising a portion of the Pre-Funded Warrants to the extent that such exercise would result in beneficial ownership of more than 742,861 shares of Common Stock. RA Capital Healthcare Fund GP, LLC is the general partner of the Fund. The general partner of RA Capital is RA Capital Management GP, LLC, of which Dr. Kolchinsky and Mr. Shah are the controlling persons. RA Capital serves as investment adviser for the Fund and may be deemed a beneficial owner, for purposes of Section 13(d) of the Act, of any securities of the Issuer held by the Fund. The Fund has delegated to RA Capital the sole power to vote and the sole power to dispose of all securities held in the Fund's portfolio, including the shares of the Issuer's Common Stock reported herein. Because the Fund has divested voting and investment power over the reported securities it holds and may not revoke that delegation on less than 61 days' notice, the Fund disclaims beneficial ownership of the securities it holds for purposes of Section 13(d) of the Act. As managers of RA Capital, Dr. Kolchinsky and Mr. Shah may be deemed beneficial owners, for purposes of Section 13(d) of the Act, of any securities of the Issuer beneficially owned by RA Capital. RA Capital, Dr. Kolchinsky, and Mr. Shah disclaim beneficial ownership of the securities reported in this Schedule 13G other than for the purpose of determining their obligations under Section 13(d) of the Act, and the filing of this Schedule 13G shall not be deemed an admission that either RA Capital, Dr. Kolchinsky, or Mr. Shah is the beneficial owner of such securities for any other purpose. Due to the Beneficial Ownership Blocker listed in the Pre-Funded Warrants, each Reporting Person's beneficial ownership percentage was 9.99% as of September 30, 2025. Such percentage is based upon the sum of (i) 6,169,961 shares of the Issuer's Common Stock outstanding as of July 31, 2025, as reported in the Issuer's Quarter Report on Form 10-Q, filed with the Securities and Exchange Commission (the "SEC") on August 12, 2025, (ii) 1,034,433 shares of Common Stock that were sold by the Issuer in connection with its public offering as described in the Issuer's Prospectus Supplement filed with the SEC pursuant to Rule 424(b)(5) on September 24, 2025 and (iii) 231,654 shares of Common Stock issuable upon the exercise of the Pre-Funded Warrants. Due to field limitations of the EDGAR filing system, the percentages listed in Row 11 of the Reporting Persons' cover pages have been rounded down to 9.9%. Row 5 of each Reporting Person's cover page to this Schedule 13G sets forth the sole power to vote or to direct the vote of securities of the Issuer beneficially owned by such Reporting Person as of September 30, 2025 and is incorporated by reference. Row 6 of each Reporting Person's cover page to this Schedule 13G sets forth the shared power to vote or to direct the vote of securities of the Issuer beneficially owned by such Reporting Person as of September 30, 2025 and is incorporated by reference. Row 7 of each Reporting Person's cover page to this Schedule 13G sets forth the sole power to dispose or to direct the disposition of securities of the Issuer beneficially owned by such Reporting Person as of September 30, 2025 and is incorporated by reference. Row 8 of each Reporting Person's cover page to this Schedule 13G sets forth the shared power to dispose or to direct the disposition of securities of the Issuer beneficially owned by such Reporting Person as of September 30, 2025 and is incorporated by reference. Y Y Y Y Y N By signing below I certify that, to the best of my knowledge and belief, the securities referred to above were not acquired and are not held for the purpose of or with the effect of changing or influencing the control of the issuer of the securities and were not acquired and are not held in connection with or as a participant in any transaction having that purpose or effect, other than activities solely in connection with a nomination under ?? 240.14a-11. Exhibit 99.1 Joint Filing Agreement (incorporated by reference to Exhibit 99.1 to Schedule 13G/A filed on February 14, 2025) RA Capital Management, L.P. /s/ Peter Kolchinsky 11/14/2025 Peter Kolchinsky /s/ Peter Kolchinsky 11/14/2025 Rajeev Shah /s/ Rajeev Shah 11/14/2025 RA Capital Healthcare Fund, L.P. /s/ Peter Kolchinsky 11/14/2025