As filed with the Securities and Exchange Commission on March 29, 2024

Registration No. 333-       

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM S-8

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

Palisade Bio, Inc.

(Exact name of registrant as specified in its charter)

Palisade Bio, Inc. 2021 Equity Incentive Plan

Palisade Bio, Inc. 2021 Employee Stock Purchase Plan

(Full titles of the plans)

J.D. Finley

Chief Executive Officer

Palisade Bio, Inc.

7750 El Camino Real, Suite 2A

Carlsbad, California 92009

(858) 704-4900

(Name, address, including zip code, and telephone number, including area code, of agent for service)

Copies to:

Raul Silvestre, Esq.

Dennis Gluck, Esq.

Silvestre Law Group

2629 Townsgate Rd., Suite 215

Westlake Village, California 91361

(818) 597-7552

Indicate by check mark whether the Registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

If an emerging growth company, indicate by check mark if the Registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ☐

EXPLANATORY NOTE

This Registration Statement on Form S-8 is filed by Palisade Bio, Inc., a Delaware corporation (“Palisade” or “Registrant”), for the purpose of registering an additional 927,089 shares (“Additional Securities”) of its common stock, par value $0.01 per share (the “Common Stock”), that are issuable to eligible employees, consultants, contractors, and directors of the Registrant and its affiliates under the Registrant’s: (i) Palisade Bio, Inc. 2021 Equity Incentive Plan, as amended (the “2021 Plan”); and (ii) Palisade Bio, Inc. 2021 Employee Stock Purchase Plan, as amended (the “2021 ESPP”) (collectively “the Plans”). The Registrant previously registered an aggregate of 1,011,834 shares of Common Stock underlying the Plans that are issuable to eligible employees, consultants, contractors, and directors of the Registrant and its affiliates, consisting of: (i) 32,363 shares on Form S-8 (File No. 333-259553) filed on September 15, 2021, (ii) 14,239 shares on Form S-8 (File No. 333-263706) filed on March 18, 2022, and (iii) 965,231 shares on Form S-8 (File No. 333-274522 filed on September 14, 2023 (collectively the “Prior Registration Statements”). All share amounts reflected in this Registration Statement on Form S-8 give effect to the 1-for-50 reverse stock split that became effective November 16, 2022.

This Registration Statement relates to securities of the same class as registered on the Prior Registration Statements and is submitted in accordance with General Instruction E to Form S-8 regarding Registration of the Additional Securities. Pursuant to Instruction E of Form S-8, the Prior Registration Statements are incorporated by reference and made part of this Registration Statement, except to the extent supplemented, amended or superseded by the information set forth herein.

USE OF COMBINED PROSPECTUS

Pursuant to Rule 429(a) of the Securities Act of 1933, as amended, the prospectus that will be used in connection with the offer and sale of the securities covered by this Registration Statement and issued pursuant to the Plans (the “Combined Prospectus”) will also be used in connection with the sale of securities covered by the Prior Registration Statement.

PART II. INFORMATION REQUIRED IN REGISTRATION STATEMENT

ITEM 8. EXHIBITS.

* Filed herein

SIGNATURES

Pursuant to the requirements of the Securities Act of 1933, as amended, the Registrant certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-8 and has duly caused this Registration Statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Carlsbad, State of California, on March 29, 2024.

POWER OF ATTORNEY

KNOW ALL BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints J.D. Finley, as his or her true and lawful attorneys-in-fact and agents, with the full power of substitution, for him or her and in his or her name, place or stead, in any and all capacities, to sign any and all amendments to this Registration Statement (including post-effective amendments), and to file the same, with exhibits thereto and other documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorneys-in-fact and agent, full power and authority to do and perform each and every act and thing requisite and necessary to be done in and about the premises, as fully to all intents and purposes as he or she might or could do in person, hereby ratifying and confirming that said attorneys-in-fact and agents, or his substitute or substitutes, may lawfully do or cause to be done by virtue hereof.

Pursuant to the requirements of the Securities Act of 1933, as amended, this Registration Statement has been signed by the following persons in the capacities and on the dates indicated.

Exhibit 5.1

SILVESTRE LAW GROUP, P.C.

2629 Townsgate Road, Suite 215

Westlake Village, CA 91361

(818) 597-7552

Fax (805) 553-9783

March 29, 2024

Palisade Bio, Inc.

7750 El Camino Real, Suite 2A

Carlsbad, CA 92009

Ladies and Gentlemen:

We have acted as counsel to Palisade Bio, Inc., a Delaware corporation (the “Company”), in connection with the filing of a registration statement on Form S-8 (the “Registration Statement”) with the Securities and Exchange Commission (the “Commission”) covering the offering of up to 927,089 shares (the “Shares”) of the Company’s Common Stock, par value $0.01 per share (“Common Stock”) consisting of (a) 695,317 shares of Common Stock issuable pursuant to the Company’s 2021 Equity Incentive Plan, as amended (the “2021 Plan”) and (b) 231,772 shares of Common Stock issuable pursuant to the Company’s 2021 Employee Stock Purchase Plan, as amended (“2021 ESPP”) (collectively, the 2021 Plan and 2021 ESPP are referred to herein as the “Plans”).

In connection with this opinion, we have examined and relied upon the Registration Statement and related prospectuses, the Plans, the Company’s Amended and Restated Certificate of Incorporation, as amended and the Amended and Restated Bylaws, each as currently in effect, and originals or copies certified to our satisfaction of such other records, documents, certificates, memoranda and other instruments as in our judgment are necessary or appropriate to enable us to render the opinion expressed below. We have assumed the genuineness of all signatures, the authenticity of all documents submitted to us as originals, the conformity to originals of all documents submitted to us as copies, the accuracy, completeness and authenticity of certificates of public officials, and the due authorization, execution and delivery of all documents by all persons other than by the Company where authorization, execution and delivery are prerequisites to the effectiveness thereof. As to certain factual matters, we have relied upon a certificate of an officer of the Company and have not independently verified such matters.

Our opinion is expressed only with respect to the General Corporation Law of the State of Delaware. We express no opinion to the extent that any other laws are applicable to the subject matter hereof and express no opinion and provide no assurance as to compliance with any federal or state securities law, rule or regulation.

On the basis of the foregoing, and in reliance thereon, we are of the opinion that the Shares, when sold and issued in accordance with the Plans, the Registration Statement and related prospectuses, will be validly issued, fully paid, and nonassessable (except as to Shares issued pursuant to certain deferred payment arrangements, which will be fully paid and nonassessable when such deferred payments are made in full).

We hereby consent to the use of our name in the prospectus constituting a part of the Registration Statement and in any prospectus supplements related thereto under the heading “Legal Matters” and to the use of this opinion as a part (Exhibit 5.1) of the Registration Statement. In giving such consent, we do not thereby admit that we are within the category of persons whose consent is required under Section 7 of the Securities Act of 1933, as amended, or the Rules and Regulations of the Commission thereunder. The opinion expressed herein is rendered on and as of the date hereof, and we assume no obligation to advise you, or to make any investigations, as to any legal developments or factual matters arising subsequent to the date hereof that might affect the opinion expressed herein.

SILVESTRE LAW GROUP, P.C.

Very truly yours,

SILVESTRE LAW GROUP, P.C.

Exhibit 23.1

CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM

We consent to the incorporation by reference in this Registration Statement on Form S-8 of our report dated March 26, 2024, relating to the consolidated financial statements of Palisade Bio, Inc., which appears in the Company’s Annual Report on Form 10-K for the year ended December 31, 2023. Our report includes an explanatory paragraph relating to the Company’s ability to continue as a going concern.

/s/ Baker Tilly US, LLP

Tewksbury, Massachusetts

March 29, 2024

Exhibit 107

Calculation of Filing Fee Table

Form S-8

(Form Type)

Palisade Bio, Inc.

(Exact Name of Registrant as Specified in its Charter)

Table 1: Newly Registered Securities