Company: SCLXW
Filing Date: 2025-09-29
Form Type: 424B3
Source: 0001193125-25-221022
Chunk: 20

Company: Scilex Holding Co
Filing Date: 2025-09-29
Form: 424B3
Chunk 20
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 of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

|                          |     | SCILEX HOLDING COMPANY |     |                                       |
|                          |     | By:                    |     | /s/ Henry Ji                          |
|                          |     | Name:                  |     | Henry Ji                              |
| Date: September 26, 2025 |     | Title:                 |     | Chief Executive Officer and President |

4

Exhibit 10.1

SECURITIES PURCHASE AGREEMENT

SECURITIES PURCHASE AGREEMENT (this “Agreement”), dated as of September 23, 2025, by and among
Scilex Holding Company, a Delaware corporation, with headquarters located at 960 San Antonio Road, Palo Alto, CA 94303 (“SHC”), Scilex, Inc., a Delaware corporation and wholly owned subsidiary of SHC (“Scilex, Inc.” and together with SHC, each a “Seller” and jointly, the “Sellers”) the purchasers listed on the Schedule of Buyers attached hereto (individually, a “Buyer” and collectively,
the “Buyers”) and, solely with respect to Sections 4, 5 and 10 (the “Specified Sections”), Semnur Pharmaceuticals, Inc., a Delaware corporation (“Semnur”).

RECITALS

1. Each Seller and each Buyer is executing and delivering this Agreement in reliance upon the exemption from securities
registration afforded by the Securities Act of 1933, as amended (the “1933 Act”), and the rules and regulations thereunder as promulgated by the United States Securities and Exchange Commission (the “SEC”).

2. Each Seller currently holds shares of common stock, par value $0.0001 per share, of Semnur (“Semnur Common Stock”).

3. Each Buyer wishes to purchase from the Sellers, and the Sellers wish to sell such Buyer, upon the
terms and conditions stated in this Agreement, such aggregate number of shares of Semnur Common Stock set forth opposite such Buyer’s name in column (3) on the Schedule of Buyers attached hereto (which aggregate amount for all Buyers
together shall be 12,500,000 shares of Semnur Common Stock, consisting of an aggregate of 554,849 shares of Semnur Common Stock currently held by SHC and 11,945,151 shares