Company: SCLXW
Filing Date: 2025-12-29
Form Type: 424B3
Source: 0001193125-25-335429
Chunk: 273

Company: Scilex Holding Co
Filing Date: 2025-12-29
Form: 424B3
Chunk 273
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:

| • |     | demonstrated bioequivalence to Lidoderm in study 
 SCI-LIDO-PK-002A;                                |

| • |     | showed greater than or equal to 90% adhesion in over 90% of the subjects at the end of the 12-hour administration period in study SCI-LIDO-ADH-001; |

| • |     | showed superior adhesion to Lidoderm and Mylan’s generic lidocaine patch in studies SCI-LIDO-AHD-002 and 
 SCI-LIDO-ADH-003;                                                                                        |

| • |     | was not meaningfully impacted by heat or exercise in study SCI-LIDO-HEX-001; |

| • |     | was able to be used under showering and bathing conditions in study SCI-LIDO-ADH-004; and |

| • |     | did not show clinically meaningful dermal irritation in study SCI-LIDO-DERM-001. |

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ZTlido Study Details

Pivotal Bioequivalence Study - SCI-LIDO-PK-002A

We conducted a comparative single-dose PK study between ZTlido and Lidoderm designed as a two-way
cross-over in 54 healthy subjects. In this trial design, each subject received a single dose of three ZTlido or three Lidoderm patches followed by a washout period and the administration of the other product. The purpose of this study was to
establish bioequivalence between the products, which was determined by the statistical comparability of Cmax and AUC as shown in the figure below.

This was considered the pivotal clinical trial for ZTlido, as it provided the pharmaceutical bridge between the two products and showed that
ZTlido had comparable safety and efficacy to Lidoderm. As a result of successfully establishing the pharmaceutical bridge, no stand-alone clinical efficacy studies were required by the FDA to determine ZTlido’s analgesic effects for
ZTlido’s approval.

Mean Lidocaine Plasma Concentration Time Profiles - Semilog Scale

Pivotal Adhesion Study - SCI-LIDO-ADH-001

We conducted an open-label, single-treatment, single-period,
single-application adhesion performance study in 54 healthy, human subjects to assess the adhesion performance of ZTlido over the 12-hour administration period of the product. The study also investigated
whether ZTlido met an FDA established adhesion performance benchmark of greater than or equal