PLUS THERAPEUTICS, INC.

As filed with the Securities and Exchange Commission on Ja

nua

ry 9, 2026.

Registration

No. 333-

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

Form

REGISTRATION STATEMENT

Under

The Securities Act of 1933

(Exact name of Registrant as specified in its charter)

6420 Levit Green Boulevard, Suite 310

Houston, Texas 77021

(737)

255-7194

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

Andrew Sims

Chief Financial Officer

Plus Therapeutics, Inc.

6420 Levit Green Boulevard, Suite 310

Houston, Texas 77021

(737)

255-7194

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

Approximate date of commencement of proposed sale to the public

: As soon as practic

able

after this registration statement is declared 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, 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 the provisions of Section 8(a) of the Securities Act of 1933 or until the Registration Statement shall become effective on such date as the Commission, acting pursuant to said Section 8(a), may determine.

The information in this prospectus is not complete and may be changed. We may not sell these securities until the registration statement filed with Securities and Exchange Commission is effective. This prospectus is not an offer to sell these securities and is not soliciting an offer to buy these securities in any state where the offer or sale is not permitted.

PRELIMINARY PROSPECTUS

(Subject to Completion, dated January 9, 2026)

22,321,429 Units, Each Consisting of One Share of Common Stock and One Warrant to

Purchase One Share of Common Stock

22,321,429 Pre-Funded Units, Each Consisting of One Pre-Funded Warrant to Purchase One Share of Common Stock and One Warrant to Purchase One Share of Common Stock

22,321,429 Shares of Common Stock Underlying the Warrants

22,321,429 Shares of Common Stock Underlying the Pre-Funded Warrants

We are offering, in a firm commitment underwritten offering, 22,321,429 units, with each unit consisting of (i) one share of our common stock, and (ii) one warrant to purchase one share of our common stock at an assumed public offering price of $0.56 per Unit, the last reported sale price of our common stock as reported on The Nasdaq Capital Market on January 6, 2026. The actual public offering price per Unit will be determined between us and the underwriter at the time of pricing and may be at a discount to this assumed offering price. Therefore, the assumed public offering price used throughout this prospectus may not be indicative of the actual public offering price.

We are also offering 22,321,429 pre-funded units, with each pre-funded unit consisting of (i) one pre-funded warrant to purchase one share of our common stock and (ii) one warrant to purchase one share of our common stock, to those purchasers whose purchase of Units in this offering would otherwise result in the purchaser, together with its affiliates and certain related parties, beneficially owning more than 4.99% (or, at the election of the purchaser, 9.99%) of our outstanding shares of common stock immediately following the consummation of this offering. The purchase price of eachpre-funded unit is equal to the price per unit being sold to the public in this offering, minus $0.001.

Each warrant will entitle the holder to purchase one share of common stock at an assumed exercise price of $0.56 (representing 100% of the assumed public offering price of $0.56 per unit, the last reported sale price of our common stock as reported on The Nasdaq Capital Market on January 6, 2026) and expire five (5) years from date of issuance. Eachpre-funded warrant will be immediately exercisable and may be exercised at any time until all of the pre-funded warrants are exercised in full. For eachpre-funded unit we sell, the number of units that we are offering will be decreased on aone-for-one basis.

The shares of common stock and pre-funded warrants, as the case may be, and the accompanying warrants, can only be purchased together in this offering but will be issued separately and will be immediately separable upon issuance. Pursuant to the registration statement of which this prospectus forms a part, we are also registering the shares of common stock issuable upon exercise of the warrants and pre-funded warrants included in the units and pre-funded units offered hereby.

Neither the pre-funded warrants nor the warrants will be listed on the Nasdaq Capital Market or trade in any market. However, we anticipate that the shares of our common stock to be issued upon exercise of thepre-funded warrants and the warrants will trade on the Nasdaq Capital Market. This prospectus also relates to the shares of common stock issuable upon the exercise of thepre-funded warrants and the warrants.

We have engaged Lake Street Capital Markets, LLC to act as our underwriter in connection with this offering. We have agreed to pay to the underwriter the underwriting fees set forth in the table below. Further, any proceeds from the sale of securities offered by us will be available for our immediate use, despite uncertainty about whether we would be able to use such funds to effectively implement our business plan. See the section entitled “Risk Factors” for more information. We will bear all costs associated with the offering. See “Underwriting” on page of this prospectus for more information regarding these arrangements.

Our common stock is listed on the Nasdaq Capital Market under the symbol “PSTV.” The closing price of our common stock on the Nasdaq Stock Market on January 6, 2026, was $0.56 per share.

There is no established trading market for thepre-funded warrants or the warrants, and we do not expect a market to develop. We do not intend to apply for a listing of thepre-funded warrants or the warrants on any securities exchange or other nationally recognized trading system. Without an active trading market, the liquidity of thepre-funded warrants and the warrants will be limited.

Investing in our securities involves a high degree of risk. These risks are described in the “Risk Factors” section on page 6 of this prospectus. You should also consider the risk factors described or referred to in any applicable prospectus supplement, before investing in these securities.

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

We have also granted the underwriter an option to purchase up to 3,348,214 additional shares of common stock and/or up to 3,348,214 additional pre-funded warrants and/or up to 3,348,214 additional Warrants, or any combination thereof, solely to cover over-allotments, if any. The underwriter may exercise this option at any time and from time to time during the 30-day period from the date of this prospectus.

Delivery of the securities offered hereby is expected to be made on or about , 2026.

Lake Street

The date of this prospectus is , 2026