Filed pursuant to Rule 424(b)(5)
File No. 333-278861
Supplement No. 5 dated June 27, 2025
To
Prospectus Supplement dated May 23, 2024
(To Prospectus Dated May 1, 2024)
JAGUAR HEALTH, INC.
Up to $3,378,239
Shares
of Common Stock
This supplement No. 5 (this Supplement) amends and supplements certain information contained in the prospectus supplement, dated
May 23, 2024, and as amended by the supplement No. 1, dated July 17, 2024, the supplement No. 2, dated November 13, 2024, supplement No. 3, dated May 5, 2025 and supplement No. 4, dated May 21, 2025 (the
ATM Prospectus Supplement), and the accompanying prospectus, dated May 1, 2024 (the Base Prospectus, and together with the ATM Prospectus Supplement, any supplement thereto, and the documents deemed incorporated by
reference in each, the Prospectus), filed as part of our registration statement on Form S-3 (File No. 333-278861) (the Registration
Statement), which relate to the offer and sale of shares of voting common stock of Jaguar Health, Inc. (we, us or the Company), par value $0.0001 per share (the Common Stock), in an at-the-market offering (the ATM Program) pursuant to the ATM Agreement (as defined below). The terms Company, we,
us, and our refer to Jaguar Health, Inc. and its subsidiaries, unless indicated otherwise.
You should carefully
read the entire Prospectus and this Supplement before investing in our Common Stock. This Supplement should be read in conjunction with the Prospectus, and is qualified by reference thereto, except to the extent that the information herein amends or
supersedes the information contained in the Prospectus. This Supplement is not complete without, and may only be delivered or utilized in connection with the Prospectus and any future amendments or supplements thereto.
Under the Prospectus, we registered shares of our Common Stock having an aggregate offering price of up to $75,000,000 for offer and sale from
time to time through Ladenburg Thalmann & Co. Inc. (Ladenburg) and Lucid Capital Markets, LLC (Lucid and, together with Ladenburg, the Managers), acting as the Companys sales agents, pursuant to an
At The Market Offering Agreement, dated December 10, 2021, between us and Ladenburg, as amended on each of February 2, 2022 and May 23, 2024 by and between the Company and Ladenburg, and on each of July 17, 2024,
November 13, 2024 and February 4, 2025 by and among the Company, Ladenburg and Lucid Capital Markets, LLC (the ATM Agreement). Sales of our Common Stock under the Prospectus, as supplemented by this Supplement, may be made in
sales deemed to be an at-the-market offering as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as amended (Securities
Act).
As previously reported, on March 31, 2025, we became subject to General Instruction I.B.6 of Form S-3, which limits the amounts that we may sell under the Registration Statement of which this Supplement and the Prospectus are a part. The aggregate market value of our Common Stock held by non-affiliates as of June 26, 2025 pursuant to General Instruction I.B.6 of Form S-3 is approximately $19.0 million, which was calculated based on 1,463,644
outstanding shares of our Common Stock held by non-affiliates at a price of $12.98 per share, which was the closing price of our Common Stock on May 2, 2025. As of the date hereof, we have sold an
aggregate of approximately $2.95 million worth of shares of our Common Stock pursuant to General Instruction I.B.6 of Form S-3 during the prior 12-month calendar
period that ends on and includes the date hereof. As a result of the limitations of General Instruction I.B.6 of Form S-3 and the sales to date under the Prospectus, and in accordance with the terms of the ATM
Agreement, the aggregate offering price of the shares of Common Stock that we may sell from time to time through the Managers pursuant to the Prospectus has been reduced to $3,378,239.