Company: SCLXW
Filing Date: 2025-05-07
Form Type: POS AM
Source: 0001193125-25-115054
Chunk: 1

Company: Scilex Holding Co
Filing Date: 2025-05-07
Form: POS AM
Chunk 1
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 by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-acceleratedfiler, smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company” and “emerging growth company” in Rule 12b-2of the Exchange Act.

| Large accelerated filer |     | ☐ |     | Accelerated filer         |     | ☐ |
|                         |     | ☒ |     | Smaller reporting company |     | ☒ |
|                         |     |   |     | Emerging growth company   |     | ☒ |

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ☒ Pursuant to Rule 429 under the Securities Act of 1933, as amended, and as further described below under the heading “ Explanatory Note”, the prospectus contained in this Post-Effective Amendment No. 1 to Form S-3on Form S-1,which constitutes a post-effective amendment to the registrant’s Registration Statement on Form S-3(File No. 333-280882)originally declared effective on July 25, 2024, will be used as a combined prospectus in connection with the registrant’s earlier Registration Statement on Form S-1(File No. 333-276245)originally declared effective on January 11, 2024. Accordingly, upon effectiveness, this Post-Effective Amendment No. 1 to Form S-3on Form S-1will also constitute a post-effective amendment to such earlier registration statement. The registrant hereby amends this registration statement on such date or dates as may be necessary to delay its effective date until the registrant shall file a further amendment which specifically states that this registration statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act of 1933, as amended, or until the registration statement shall become effective on such date as the Securities and Exchange Commission, acting pursuant to said Section 8(a), may determine.

EXPLANATORY NOTE Scilex Holding Company (the “Company”) filed a shelf registration statement on Form S-3(No. 333-276245) with the Securities and Exchange Commission (the “SEC”) on December