Scilex Holding Co美股招股说明书(2025-11-24版)

Filed Pursuant to Rule 424(b)(3)RegistrationNo.333-268603RegistrationNo.333-280882RegistrationNo.333-275117 PROSPECTUS SUPPLEMENT NO. 12(to Prospectus dated May13, 2025)PROSPECTUS SUPPLEMENT NO. 12(to Prospectus dated May13, 2025)PROSPECTUS SUPPLEMENT NO. 12(to Prospectus dated May13, 2025) SCILEX HOLDING COMPANY Up to 1,594,207 Shares of Common StockUp to 198,810 Shares of Common Stock Issuable Upon the Exercise of Warrants Up to 3,593,288 Shares of Common StockUp 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 May13, 2025, which forms a part of our registration statement onFormS-1(No.333-268603)for which Post-Effective Amendment No.3 was filed with the Securities and Exchange Commission (the “SEC”) on May7,2025 and declared effective by the SEC on May13, 2025 (the “Post-deSPAC Prospectus”); (ii) the prospectus dated May13, 2025, which forms a partof our registration statement on FormS-1(No.333-280882)for which Post-Effective Amendment No.1 was filed with the SEC on May7, 2025 anddeclared effective by the SEC on May13, 2025 (the “Conversion Prospectus”); and (iii)the prospectus dated May13, 2025, which forms a part of ourregistration statement on FormS-1(No.333-275117)for which Post-Effective Amendment No.2 was filed with the SEC on May7, 2025 and declaredeffective by the SEC on May13, 2025 (the “Oramed Resale Prospectus” and together with the Post-deSPAC Prospectus and the Conversion Prospectus,the “Prospectuses”). This prospectus supplement is being filed to update and supplement the information in the Prospectuses with the informationcontained in our Current Report on Form8-K,filed with the SEC on November24, 2025 (the “Current Report”). Accordingly, we have attached the Our Common Stock is listed on the Nasdaq Capital Market under the symbol “SCLX”. On November24, 2025, the last reported sales price pershare of our Common Stock was $22.00. Our Public Warrants are listed on the Nasdaq Capital Market under the symbol “SCLXW.” On November13, On April15, 2025, we effected a reverse stock split of our Common Stock at a ratio of1-for-35(the “Reverse Stock Split”). Unless otherwisenoted, the share and per share information in the Prospectuses and this prospectus supplement reflects the effect of the Reverse Stock Split. This prospectus supplement updates and supplements the information in the Prospectuses and is not complete without, and may not be deliveredor utilized except in combination with, the Prospectuses, including any amendments or supplements thereto. This prospectus supplement should be readin conjunction with the Prospectuses and if there is any inconsistency between the information in the Prospectuses and this prospectus supplement, you See the section titled “Risk Factors” beginning on page 23 of the Post-deSPAC Prospectus, page 23 of the Conversion Prospectus, andpage 23 of the Oramed Resale Prospectus, as well as risks and uncertainties described under similar headings in any amendments orsupplements to the Prospectuses to read about factors you should consider before buying our securities. UNITED STATESSECURITIES AND EXCHANGE COMMISSION SCILEX HOLDING COMPANY (Exact name of registrant as specified in its charter) 92-1062542(IRS EmployerIdentification No.) Check the appropriate box below if the Form8-Kfiling is intended to simultaneously satisfy the filing obligation of the registrant under any of thefollowing provisions: ☐Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)☐Soliciting material pursuant to Rule14a-12under the Exchange Act (17 CFR240.14a-12)☐Pre-commencementcommunications pursuant to Rule14d-2(b)under the Exchange Act (17 CFR240.14d-2(b))☐Pre-commencementcommunications pursuant to Rule13e-4(c)under the Exchange Act (17 CFR240.13e-4(c)) Securities registered pursuant to Section12(b) of the Act Item 1.01.Entry into a Material Definitive Agreement. Warrant Inducement Agreement On November23, 2025, Scilex Holding Company, (the “Company”) entered into a warrant inducement agreement (the “Warrant InducementAgreement”) with a certain institutional investor (the “Investor”), pursuant to which the Investor agreed to exercise (the “Exercise”) (i) a warrant topurchase shares of common stock, par value $0.0001 per share, of the Company (“Common Stock”) issued to the Investor on April25, 2024, which iscurrently exercisable for 428,572 shares and has an exercise price of $38.50 per share (the “Existing April 2024 Warrants”) and (ii)a warrant to purchaseshares of Common Stock issued to the Investor on December13, 2024, which is currently exercisable for 475,824 shares and has an exercise price of$22.72 per share (together with the Existing April 2024 Warrants, the “Existing Warrants”). As consideration for the Exercise, the Company agreed to(i)reduce the exercise price of the Existing Warrants to $22.