Company: SCLXW
Filing Date: 2025-05-14
Form Type: 424B3
Source: 0001193125-25-119822
Chunk: 117

Company: Scilex Holding Co
Filing Date: 2025-05-14
Form: 424B3
Chunk 117
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 may not meet the level of statistical significance 
 required for approval by the FDA;                                                                         |

| • |     | it may disagree with our interpretation of data from preclinical studies or clinical trials; |

| • |     | it may not agree that the data collected from clinical trials of our product candidates are acceptable or                                                                                                                     
 sufficient to support the submission of an NDA or other submission or to obtain regulatory approval in the United States, and such authorities may impose requirements for additional preclinical studies or clinical trials; |

| • |     | it may disagree regarding the formulation, labeling and/or the specifications of our product candidates; |

| • |     | such authorities may decline to approve the manufacturing processes or facilities of third-party manufacturers 
 with which we contract for clinical and commercial supplies; and                                               |

| • |     | the approval policies or regulations of the FDA or comparable non-U.S.                                             
 regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval. |

Of the large number of drugs in development, only a small percentage successfully complete the regulatory approval processes and are commercialized. This lengthy approval process, as well as the unpredictability of 73

future clinical trial results, may result in our failing to obtain regulatory approval to market our product candidates, which would significantly harm our business, financial condition and
results of operations. In addition, regulatory authorities may approve any of our product candidates for fewer or more limited indications than we request, may not approve the price we intend to charge for our product candidates, may grant approval
contingent on the performance of costly post-marketing clinical trials, or may approve a product candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that product candidate.
Any of the foregoing scenarios could materially harm the commercial prospects for our product candidates.

We have limited experience
submitting applications for marketing authorization to the FDA, and we cannot be certain that any of our product candidates will be successful in clinical trials or receive regulatory approval. Further, our product candidates may not receive
regulatory approval even if our clinical trials are successful. With the change in presidential administrations in 2025, there is substantial uncertainty as to how, if at all, the new administration will seek to modify or revise the requirements and
policies of the FDA and other regulatory agencies with jurisdiction over our product candidates. The impending uncertainty could present new challenges or potential opportunities as we navigate the clinical development and approval process for our
product candidates. Furthermore, the U.S.