Company: SCLXW
Filing Date: 2025-05-14
Form Type: 424B3
Source: 0001193125-25-119846
Chunk: 32

Company: Scilex Holding Co
Filing Date: 2025-05-14
Form: 424B3
Chunk 32
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BA, and if we lose the right to license such intellectual property or if the Romeg License Agreement is terminated for any reason, our ability to 
 commercialize GLOPERBA would be harmed.                                                                                                                                                                                                          |

| • |     | If we are unable to maintain patent protection for ZTlido, GLOPERBA, ELYXYB and our product candidates, or if the            
 scope of the patent protection obtained is not sufficiently broad, we may not be able to compete effectively in our markets. |

Risks Related to Government Regulations

| • |     | The regulatory approval processes of the FDA and comparable non-U.S.                                                       
 regulatory authorities are lengthy, time-consuming and inherently unpredictable, and if we are ultimately unable to obtain |

18

| regulatory approval for our product candidates, our business, financial condition and results of operations will be substantially harmed. Moreover, gaining approval for a product candidate in one       
 country or jurisdiction does not guarantee that we will be able to obtain approval for or commercialize it in any other jurisdiction, which would limit our ability to realize our full market potential. |

| • |     | Any approved product candidate will be subject to ongoing and continued regulatory requirements, which may result 
 in significant expense and limit our ability to commercialize such products.                                      |

Risks Related to our Relationship with Sorrento

| • |     | Sorrento previously supported many of our important corporate functions. Accordingly, our historical consolidated                                                                                                                                         
 financial statements may not necessarily be indicative of the conditions that would have existed or our results of operations if we had been operated as an unaffiliated company of Sorrento, and we have and will continue to incur incremental costs as 
 a stand-alone public company.                                                                                                                                                                                                                             |

Risks Related to Ownership of our Common Stock

| • |     | If our operations and performance do not meet the expectations of investors or securities analysts, the market 
 price of our securities may decline.                                                                           |

| • |     | We are an emerging growth company, and we cannot be certain if the reduced reporting requirements applicable to 
 emerging growth companies will make our Common Stock less attractive to investors.                              |

| • |     | The securities being offered in this prospectus represent a significant percentage of our outstanding Common                                                                                                                                             
 Stock. The Selling Securityholders purchased the securities covered by this prospectus at different prices, some significantly below the current trading price of such securities, and some Selling Securityholders received such securities without any 
 consideration, and may therefore make substantial profits upon resales.