Company: PSTV
Filing Date: 2025-04-11
Form Type: POS AM
Source: 0001193125-25-079109
Chunk: 2

Company: PLUS THERAPEUTICS, INC.
Filing Date: 2025-04-11
Form: POS AM
Chunk 2
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; (ii) 2,151,544 shares of common stock issuable upon exercise of pre-funded warrants; (iii)
3,591,532 shares of common stock issuable upon exercise of Series A common stock warrants; and (iv) 3,591,532 shares of common stock issuable upon exercise of Series B common stock warrants, originally issued to the selling stockholders in a private
placement transaction in May 2024, as described in the prospectus.

This post-effective amendment No. 1 to Form S-1 on Form S-3 is being filed by the
Registrant to (i) convert the registration statement on Form S-1 into a registration statement on Form S-3, and (ii) update certain other information in the registration statement, including a reduction in the aggregate number of shares of common
stock being offered by the selling stockholders to an aggregate of 3,248,878 shares of common stock.

No additional securities are being registered under
this post-effective amendment. All applicable registration fees payable in connection with the registration of the shares of the common stock covered by the Form S-1 were previously paid by the Registrant at the time of the original filing of the
registration statement on Form S-1.

The information in this preliminary prospectus is not complete and may be changed. These securities may not be sold until the registration statement filed with the Securities and Exchange Commission is effective. This preliminary prospectus is not an offer to sell nor the solicitation of an offer to buy these securities in any jurisdiction where the offer or sale is not permitted.

SUBJECT TO COMPLETION DATED APRIL 11, 2025 PRELIMINARY PROSPECTUS Up to 3,248,878 Shares of Common Stock This prospectus relates to the offer and sale from time to time by selling stockholders named herein of up to an aggregate of 3,248,878 shares of common stock of Plus Therapeutics, Inc., a Delaware corporation (“Plus Therapeutics,” “Company,” “we,” “us” or “our”). The shares of common stock covered in this prospectus consist of:

| • |     | up to 108,685 shares of common stock; |

| • |     | up to 48,285 shares of common stock issuable upon exercise of Series A common stock warrants (“Series A                                                                              
 Common Stock Warrants”) beneficially owned by certain executive officers and directors who participated in the Initial Subscription (as defined below) (the “Company