Company: SCLXW
Filing Date: 2025-11-24
Form Type: 424B3
Source: 0001193125-25-293882
Chunk: 0

Company: Scilex Holding Co
Filing Date: 2025-11-24
Form: 424B3
Chunk 0
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|                                    |     | Filed Pursuant to Rule 424(b)(3) |
| PROSPECTUS SUPPLEMENT NO. 12       
 (to Prospectus dated May 13, 2025) |     | Registration No. 333-268603      |
| PROSPECTUS SUPPLEMENT NO. 12       
 (to Prospectus dated May 13, 2025) |     | Registration No. 333-280882      |
| PROSPECTUS SUPPLEMENT NO. 12       
 (to Prospectus dated May 13, 2025) |     | Registration No. 333-275117      |

SCILEX HOLDING COMPANY Up to 1,594,207 Shares of Common Stock Up to 198,810 Shares of Common Stock Issuable Upon the Exercise of Warrants Up to 1,402,955 Warrants Up to 3,593,288 Shares of Common Stock Up to 3,250,000 Shares of Common Stock offered by the Selling Securityholder Up to 6,685,714 Shares of Common Stock This prospectus supplement updates and supplements: (i) the prospectus dated May 13, 2025, which forms a part of our registration statement on Form S-1(No. 333-268603)for which Post-Effective Amendment No. 3 was filed with the Securities and Exchange Commission (the “SEC”) on May 7, 2025 and declared effective by the SEC on May 13, 2025 (the “Post-deSPAC Prospectus”); (ii) the prospectus dated May 13, 2025, which forms a part of our registration statement on Form S-1(No. 333-280882)for which Post-Effective Amendment No. 1 was filed with the SEC on May 7, 2025 and declared effective by the SEC on May 13, 2025 (the “Conversion Prospectus”); and (iii) the prospectus dated May 13, 2025, which forms a part of our registration statement on Form S-1(No. 333-275117)for which Post-Effective Amendment No. 2 was filed with the SEC on May 7, 2025 and declared effective by the SEC on May 13, 2025 (the “Oramed Resale Prospectus” and together with the Post-deSPAC Prospectus and the Conversion Prospectus, the “Prospectuses”). This prospectus