Company: SCLXW
Filing Date: 2025-12-29
Form Type: 424B3
Source: 0001193125-25-335429
Chunk: 24

Company: Scilex Holding Co
Filing Date: 2025-12-29
Form: 424B3
Chunk 24
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 that could result in significant negative                              
 consequences, and our product candidates may cause undesirable side effects that could delay or prevent their regulatory approval. |

Risks Related to our Business and Operations

| • |     | If we are unable to retain our key executives, it may delay our development efforts and harm our business, 
 financial condition and results of operations.                                                             |

| • |     | Any disruption in our research and development facilities could adversely affect our business, financial 
 condition and results of operations.                                                                     |

Risks Related to our Intellectual Property

| • |     | We are substantially dependent on the intellectual property we in-license                                                                                                                                                                             
 from Oishi and Itochu, and if we lose the right to license such intellectual property or if the Product Development Agreement is terminated for any reason, our ability to commercialize ZTlido and develop and commercialize SP-103 would be harmed. |

| • |     | We are party to the Romeg License Agreement for the in-licensing of                                                                                                                                                                              
 certain intellectual property rights from Romeg with respect to the commercialization of GLOPERBA, 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 |

15

| 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 Ownership of our Common Stock

| • |     | If our operations and performance do not meet the expectations of investors or