Company: SCLXW
Filing Date: 2025-05-07
Form Type: POS AM
Source: 0001193125-25-115054
Chunk: 2

Company: Scilex Holding Co
Filing Date: 2025-05-07
Form: POS AM
Chunk 2
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 22, 2022, which registration statement was initially declared effective by the SEC on January 11, 2024 (the “Shelf Registration Statement”). The Shelf Registration Statement registered up to $500,000,000 in aggregate principal amount of common stock, preferred stock, warrants, debt securities, rights and units. The Company also filed a registration statement on Form S-3(No. 333-280882)with the SEC on July 18, 2024, which registration statement was declared effective by the SEC on July 25, 2024 (the “Resale Registration Statement” and, together with the Shelf Registration Statement, the “Original Registration Statements”). The Company is not currently eligible to use the Original Registration Statements as a result of its failure to timely file its Quarterly Report on Form 10-Qfor the period ended September 30, 2024. Accordingly, the Company is filing this Post-Effective Amendment No. 1 to Form S-3on Form S-1(this “Post-Effective Amendment No. 1”) (i) pursuant to Rule 429 under the Securities Act of 1933, as amended (the “Securities Act”), to combine the prospectuses included in the Original Registration Statements, (ii) to convert each of the Original Registration Statements into a Registration Statement on Form S-1,(iii) to update the section entitled “Selling Securityholder” contained in the accompanying prospectus to reflect, among other things, earlier sales or dispositions of securities made by the Selling Securityholder, and (iv) to serve as a Section 10(a)(3) update to each of the Original Registration Statements and to make certain other updates to the prospectus that forms a part of this Post-Effective Amendment No. 1. No additional securities are being registered under this Post-Effective Amendment. The Company completed a l-for-35reverse stock split on April 15, 2025. Unless indicated otherwise, all share and per share information presented in the prospectus forming a part of this Post-Effective Amendment No. 1 reflects the completion of the reverse stock split. The Company’s historical financial statements included in this prospectus do not reflect the reverse stock split. The Shelf Registration Statement initially registered the following securities:

| • |     | (i) 168,068 shares of the Company’s common stock, par value $0.0001 per share (the “Common Stock”), (ii) common warrants to purchase up to 168,068 shares of