Company: SCLXW
Filing Date: 2025-09-29
Form Type: 424B3
Source: 0001193125-25-221020
Chunk: 4

Company: Scilex Holding Co
Filing Date: 2025-09-29
Form: 424B3
Chunk 4
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 2025.                                                       |
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| 104     |     | Cover Page Interactive Data File, formatted in Inline Extensible Business Reporting Language (iXBRL). |

| ^ | Certain identified information has been omitted pursuant to Item 601(b)(10) of Regulation S-K because such information is both (i) not material and (ii) information that the Registrant treats as private or confidential. The Registrant hereby undertakes to furnish supplemental 
 copies of the unredacted exhibit upon request by the SEC.                                                                                                                                                                                                                            |

2

SIGNATURES Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

| SCILEX HOLDING COMPANY |     |                                     |
| By:                    |     | /s/ Henry Ji                        |
| Name:                  |     | Henry Ji                            |
| Title:                 |     | Chief Executive Officer & President |

Date: September 26, 2025 3

***Certain identified information has been omitted from this exhibit because it is both (i) not material and (ii) information that the Registrant treats as private or confidential. Such omitted information is indicated by brackets (“[...***...]”) in this exhibit. ***

Exhibit 10.1

CONSULTING AGREEMENT

T HISC ONSULTINGA GREEMENT(this
“Agreement”), is dated as of September 22, 2025, by and betweenScilex Holding Company, a Delaware corporation, having a principal place of business at 960 San Antonio Road, Suite 100, Palo Alto, CA 94303
(“Scilex”) and Inform LLC, a California limited liability company (“Consultant”), with respect to the performance of services by Jaisim Shah (“Consultant Key Person”). Scilex and Consultant
may be referred to herein individually as a “party” or, collectively, as the “parties”.

W HEREAS,Scilex is in the business of developing, manufacturing and distributing pharmaceutical products; and

W HEREAS,in furtherance thereof, Scilex desires to retain Consultant to provide certain services and Consultant desires
to enter into this Agreement to provide such services on the terms and conditions set forth herein.

N OW, T HEREFORE,in consideration of the foregoing and the respective representations, warranties, covenants and agreements set forth in this Agreement, including the