Company: PSTV
Filing Date: 2025-08-22
Form Type: S-8
Source: 0001193125-25-186490
Chunk: 0

Company: PLUS THERAPEUTICS, INC.
Filing Date: 2025-08-22
Form: S-8
Chunk 0
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As filed with the Securities and Exchange Commission on August 22, 2025 Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-8 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 PLUS THERAPEUTICS, INC. (Exact name of registrant as specified in its charter)

| Delaware                                 |     |         33-0827593 |
| (State or other jurisdiction of          
 incorporation or organization)           |     |   -I.R.S. Employer 
 Identification No. |
| 2710 Reed Road, Suite 160                
 Houston, Texas                           |     |              77002 |
| (Address of Principal Executive Offices) |     |          -Zip Code |

Fifth Amended and Restated Plus Therapeutics, Inc. 2020 Stock Incentive Plan Plus Therapeutics, Inc. 2015 New Employee Incentive Plan (Full title of the Plans) Marc H. Hedrick, M.D. President and Chief Executive Officer Plus Therapeutics, Inc. 2710 Reed Road, Suite 160 Houston, Texas 77002 (737) 255-7194 (Name, address and telephone number of agent for service) With copies to: David E. Danovitch Aaron M. Schleicher Sullivan & Worcester LLP 1251 Avenue of the Americas New York, New York 10020 (212) 660-3060 Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a 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-2under 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.

EXPLANATORY NOTE This Registration Statement (the “