Company: SCLXW
Filing Date: 2025-11-24
Form Type: 424B3
Source: 0001193125-25-293873
Chunk: 6

Company: Scilex Holding Co
Filing Date: 2025-11-24
Form: 424B3
Chunk 6
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 Cover Page Interactive Data File, formatted in Inline Extensible Business Reporting Language (iXBRL).                          |

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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, Ph.D.                 |
| Name:                  |     | Henry Ji, Ph.D.                     |
| Title:                 |     | Chief Executive Officer & President |

Date: November 24, 2025 4

Exhibit 10.1 SCILEX HOLDING COMPANY November 23, 2025 Holder of Warrants Issued in April 2024 and December 2024

| Re: | Inducement Offer to Exercise Warrants Issued in April 2024 and December 2024 |

Dear Holder: Scilex Holding Company (the “ Company”) is pleased to offer to you (“ Holder”, “ you” or similar terminology) the opportunity to receive (i) new warrants to purchase shares of the Company’s common stock, par value $0.0001 per share (the “ Common Stock”) and (ii) a reduction in exercise price of the Existing Warrants (as defined below) in consideration for exercising for cash the Company’s Common Stock Purchase Warrants to purchase an aggregate of (a) 428,572shares of Common Stock issued to you on April 25, 2024, with an exercise price of $38.50 per share and (b) 475,824 shares of Common Stockissued to you on December 13, 2024, with an exercise price of $22.72 per share (collectively, the “ Existing Warrants”), as set forth on the signature page hereto. The issuance of the shares of Common Stock underlying the Existing Warrants (the “ Warrant Shares”) were initially registered pursuant to the registration statement on Form S-3(File No. 333-276245),as amended by that certain Post-Effective Amendment No. 1 to Form S-3on Form S-1Registration Statement (File No. 333-280882)(the “ Registration Statement”). The Registration Statement is currently effective and, upon exercise of the Existing Warrants pursuant to this letter agreement, will be effective for the issuance of the Warrant Shares. Capitalized terms not otherwise defined herein shall have the meanings set