Company: SCLXW
Filing Date: 2025-07-23
Form Type: 424B3
Source: 0001193125-25-163077
Chunk: 3

Company: Scilex Holding Co
Filing Date: 2025-07-23
Form: 424B3
Chunk 3
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 Common Stock at a ratio of 1-for-35 (the “Reverse Stock Split”). Unless otherwise noted, the share and per share information in the
Prospectus and this prospectus supplement reflects the effect of the Reverse Stock Split. The Company’s historical financial statements included in the Prospectus and this prospectus supplement do not reflect the Reverse Stock Split.

This prospectus supplement updates and supplements the information in the Prospectus and is not complete without, and may not be delivered or
utilized except in combination with, the Prospectus, including any amendments or supplements thereto. This prospectus supplement should be read in conjunction with the Prospectus and if there is any inconsistency between the information in the
Prospectus and this prospectus supplement, you should rely on the information in this prospectus supplement.

See the section titled “Risk Factors” beginning on page 23 of the Prospectus as well as risks and uncertainties described under similar headings in any amendments or supplements to the Prospectus to read about factors you should consider before buying our securities.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or passed upon the accuracy or adequacy of this prospectus supplement or the Prospectus. Any representation to the contrary is a criminal offense.

The date of this prospectus supplement is July 23, 2025

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 Date of Report (Date of earliest event reported): July 22, 2025 SCILEX HOLDING COMPANY (Exact name of registrant as specified in its charter)

| Delaware                     |     | 001-39852   |     | 92-1062542         |
| (State or other jurisdiction 
 of incorporation)            |     | -Commission 
 File Number |     | -IRS Employer      
 Identification No. |

960 San Antonio Road, Palo Alto, California, 94303 (Address of principal executive offices, including zip code) Registrant’s telephone number, including area code: (650) 516-4310 N/A (Former name or former address, if changed since last report) Check the appropriate box below if the Form 8-Kfiling is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

| ☐ | Written communications pursuant to Rule 425 under