Company: PSTV
Filing Date: 2025-06-18
Form Type: S-1
Source: 0001193125-25-142215
Chunk: 1

Company: PLUS THERAPEUTICS, INC.
Filing Date: 2025-06-18
Form: S-1
Chunk 1
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 non-acceleratedfiler, 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-2of the Exchange Act.

| Large accelerated filer |     | ☐ |     | Accelerated filer         |     | ☐ |
| Non-accelerated filer   |     | ☒ |     | Smaller reporting company |     | ☒ |
|                         |     |   |     | Emerging growth company   |     | ☐ |

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 June 17, 2025)

17,000,000 Shares of Common Stock

This prospectus relates to the offer and sale of up to 17,000,000 shares of our common stock, par value $0.001 per share, by Lincoln Park
Capital Fund, LLC, which we refer to in this prospectus as Lincoln Park or the selling stockholder.

The shares of common stock to which
this prospectus relates have been and may be issued by us to Lincoln Park pursuant to a purchase agreement, dated as of June 17, 2025 we entered into with Lincoln Park, which we refer to in this prospectus as the Purchase Agreement. We are not
selling any securities under this prospectus and will not receive any of the proceeds from the sale of