Company: SCLXW
Filing Date: 2025-05-14
Form Type: 424B3
Source: 0001193125-25-119831
Chunk: 2

Company: Scilex Holding Co
Filing Date: 2025-05-14
Form: 424B3
Chunk 2
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 the registration of the shares of our Common Stock hereunder. The Selling Stockholder will bear all commissions and discounts, if any, attributable to its sales of the Resale Shares.

Our Common Stock is listed on the Nasdaq Capital Market under the symbol “SCLX”. On May 13, 2025, the last reported sales price
per share of our Common Stock was $4.19.

On April 15, 2025, we effected a reverse stock split of our Common Stock at a ratio of 1-for-35 (the “Reverse Stock Split”). Unless otherwise noted, the share and per share information in this prospectus reflects the effect of the Reverse Stock Split.
The Company’s historical financial statements included in this prospectus do not reflect the Reverse Stock Split.

We are an
“emerging growth company” as that term is used in the Jumpstart Our Business Startups Act of 2012 (the “JOBS Act”) and, as such, we have elected to comply with certain reduced public company reporting requirements for this
prospectus and future filings with the Securities and Exchange Commission.

We may amend or supplement this prospectus from time to time
by filing amendments or supplements as required. You should read this prospectus, together with additional information described under the heading “Where You Can Find More Information”, and any amendments or supplements carefully before
you invest in any of our securities.

INVESTING IN OUR COMMON STOCK INVOLVES SUBSTANTIAL RISKS. YOU SHOULD REVIEW CAREFULLY THE RISKS AND UNCERTAINTIES DESCRIBED UNDER THE HEADING “RISK FACTORS” BEGINNING ON PAGE 23 OF THIS PROSPECTUS.

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. Any representation to the contrary is a criminal offense.

The date of this prospectus is May 13, 2025.

TABLE OF CONTENTS

|                                                                         |     | Page |     |
| ABOUT THIS PROSPECTUS                                                   |     |      |   1 |
| CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS                    |     |      |   3 |
| CERTAIN DEFINED TERMS                                                   |     |      |   5 |
| PROSPECTUS SUMMARY                                                      |     |      |  10 |
| THE OFFERING                                                            |     |      |  21 |
| RISK FACTORS