CERO THERAPEUTICS HOLDINGS, INC.

As filed with the Securities and Exchange Commission on December 5, 2025.

Registration No. 333-

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORMS-1

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

**CERO THERAPEUTICS HOLDINGS, INC. **

(Exact name of registrant as specified in its charter)

201 Haskins Way, Suite 230

South San Francisco, CA 94080

(650) 407-2376

(Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices)

Chris Ehrlich

Chief Executive Officer

CERo Therapeutics Holdings, Inc.

201 Haskins Way, Suite 230

South San Francisco, CA 94080

Telephone: (650) 407-2376

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

Copies to:

Stephen M. Davis

Jeffrey A. Letalien

Goodwin Procter LLP

620 Eighth Avenue

New York, NY 10018

(212) 813-8800

Approximate date of commencement of proposed sale to the public: From time to time after this Registration Statement becomes effective.

If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933 check the following box.☒

If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, please check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.☐

If this Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.☐

If this Form is a post-effective amendment filed pursuant to Rule 462(d) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.☐

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.☐

The registrant hereby amends this registration statement on such date or dates as may be necessary to delay its effective date until the registrant shall file a further amendment which specifically states that this registration statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act of 1933 or until this registration statement shall become effective on such date as the Securities and Exchange Commission, acting pursuant to said Section 8(a), may determine.

The information in this preliminary prospectus is not complete and may be changed. These securities may not be issued until the registration statement filed with the U.S. Securities and Exchange Commission is effective. This preliminary prospectus is not an offer to sell these securities and does not constitute the solicitation of an offer to buy these securities in any jurisdiction where the offer or sale is not permitted.

SUBJECT TO COMPLETION, DATED DECEMBER 5, 2025

PRELIMINARY PROSPECTUS

Up to 729,596,950 Shares of Common Stock

This prospectus relates to the potential offer and sale from time to time by Keystone Capital Partners, LLC (“Keystone”) of up to 729,596,950 shares of common stock, par value $0.0001 per share (the “Common Stock”), that have been or may be issued by us to Keystone, consisting of 729,596,950 shares of Common Stock that we may elect, in our sole discretion, to issue and sell to Keystone, from time to time from and after the Keystone Commencement Date (as defined below) pursuant to a Common Stock Purchase Agreement, dated as of November 26, 2025, by and between us and Keystone (the “New Keystone Purchase Agreement”). We have separately registered the resale pursuant to the Prior Registration Statements (as defined below) of 12,612,270 shares of Common Stock (the “Old Keystone Purchase Shares”) for aggregate proceeds of approximately $10,408,061, consisting of (i) 100,581 shares of Common Stock that have been issued to Keystone, as of November 24, 2025, pursuant to a Common Stock Purchase Agreement, dated as of November 8, 2024, by and between us and Keystone (the “November 2024 Keystone Purchase Agreement,”), (ii) 11,689 shares of Common Stock that have been issued to Keystone, as of November 24, 2025, pursuant to a Common Stock Purchase Agreement, dated as of February 14, 2024, by and between us and Keystone (the “February 2024 Keystone Purchase Agreement”) and (iii) 12,500,000 shares of Common Stock that have been issued to Keystone, as of November 24, 2025, pursuant to a Common Stock Purchase Agreement, dated as of July 11, 2025, by and between us and Keystone (the “July 2025 Keystone Purchase Agreement,” together with the New Keystone Purchase Agreement, February 2024 Keystone Purchase Agreement, and the November 2024 Keystone Purchase Agreement, the “Keystone Purchase Agreements”), as consideration for it establishing an equity line of credit (the “Keystone Equity Financing”).

We previously filed a registration statement on Form S-1 (File No. 333-278603), which was declared effective by the Securities and Exchange Commission (the “SEC”) on May 1, 2024, and remains in effect, with respect to up to (i) 12,500 Keystone Purchase Shares (as defined below) and (ii) 310 Keystone Commitment Shares (as defined below), a registration statement on Form S-1 (File No. 333-283492), which was declared effective by the SEC on December 5, 2024, and remains in effect, with respect to (i) 104,318 Keystone Purchase Shares and (ii) 682 Keystone Commitment Shares and a registration statement on Form S-1 (File No. 333-288816), which was declared effective by the SEC on July 29, 2025, and remains in effect, with respect to 12,500,000 Keystone Purchase Shares (collectively, the “Prior Registration Statements”).

The actual number of shares of our Common Stock issuable will vary depending on the then-current market price of shares of our Common Stock sold to Keystone under the Keystone Purchase Agreements, but will not exceed the number set forth in the preceding sentences unless we file an additional registration statement under the Securities Act of 1933, as amended (the “Securities Act”), with the SEC. See “The Committed Equity Financing” for a description of the Keystone Purchase Agreements and “Selling Securityholder” for additional information regarding Keystone.

We are not selling any securities under this prospectus and will not receive any of the proceeds from the sale of the shares of our Common Stock by Keystone. Additionally, we will not receive any proceeds from the issuance or sale of the Keystone Commitment Shares. We may receive up to $25 million in aggregate gross proceeds from Keystone under the Keystone Purchase Agreements in connection with sales of the shares of our Common Stock to Keystone pursuant to the Keystone Purchase Agreements, including the Old Keystone Purchase Shares and any shares of our Common Stock sold after the date of this prospectus. However, the actual proceeds from Keystone may be less than this amount depending on the number of shares of our Common Stock sold and the price at which the shares of our Common Stock are sold.

As of November 24, 2025, there were 172,373,412 shares of Common Stock outstanding on a fully-diluted basis after giving effect to the conversion of all outstanding Preferred Shares (as defined below), the exercise of all outstanding Warrants and options, and options available for issuance pursuant to our 2024 Plan and 2024 ESPP Plan, as amended from time to time, of which 172,241,636 shares were held by non-affiliates (without taking into account beneficial ownership or stock exchange limitations). If all of the 729,596,950 shares of our Common Stock offered for resale by Keystone under this prospectus were issued and outstanding as of November 24, 2025 (without taking into account beneficial ownership or stock exchange limitations), such shares would represent approximately 80.89% of total number of shares of our fully-diluted Common Stock outstanding and approximately 80.90% of the total number of shares of our fully-diluted Common Stock outstanding held by non-affiliates.

This prospectus provides you with a general description of such securities and the general manner in which Keystone may offer or sell the securities. More specific terms of any securities that Keystone may offer or sell may be provided in a prospectus supplement that describes, among other things, the specific amounts and prices of the securities being offered and the terms of the offering. The prospectus supplement may also add, update or change information contained in this prospectus.

Keystone may offer, sell or distribute all or a portion of the shares of our Common Stock acquired under the Keystone Purchase Agreements and hereby registered publicly or through private transactions at prevailing market prices or at negotiated prices. We will bear all costs, expenses and fees in connection with the registration of the shares of our Common Stock, including with regard to compliance with state securities or “blue sky” laws. The timing and amount of any sales are within the sole discretion of Keystone. Keystone is an underwriter under the Securities Act with respect to the resale of shares held by it. Although Keystone is obligated to purchase shares of our Common Stock under the terms and subject to the conditions and limitations of the Keystone Purchase Agreements to the extent we choose to sell such shares of our Common Stock to it (subject to certain conditions), there can be no assurances that we will choose to sell any shares of our Common Stock to Keystone, or that Keystone will sell any or all of the shares of our Common Stock, if any, purchased under the Keystone Purchase Agreements pursuant to this prospectus. Keystone will bear all commissions and discounts, if any, attributable to its sale of shares of our Common Stock. See “Plan of Distribution.”

You should read this prospectus and any prospectus supplement or amendment carefully before you invest in our securities.

Our Common Stock is traded on OTCQB under the symbol “CERO.” On December 4, 2025, the last quoted bid price for the shares of our Common Stock as reported on the OTCQB was $0.113 per share.

We are an “emerging growth company” and a “smaller reporting company” under applicable federal securities laws and will be subject to reduced public company reporting requirements for so long as we remain an emerging growth company or a smaller reporting company.

Investing in our securities involves a high degree of risk. Before buying any securities, you should carefully read the discussion of the risks of investing in our securities in “Risk Factors” beginning on page 10 of this prospectus.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of the securities to be issued under this prospectus or determined if this prospectus is truthful or complete. Any representation to the contrary is a criminal offense.

The date of this prospectus is , 2025.

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