Company: SMNR
Filing Date: 2025-06-11
Form Type: S-4/A
Source: 0001193125-25-139124
Chunk: 499

Company: Semnur Pharmaceuticals, Inc.
Filing Date: 2025-06-11
Form: S-4/A
Chunk 499
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inf of 0.916 µg*h/mL (observed with SP-102)compared to 0.943 µg*h/mL (observed with intravenously administered dexamethasone). Notably, there was a 16-foldincrease in the Tmax following epidural injection of SP-102.The median Tmax was 4.00 hours for SP-102compared to 0.25 hours for the comparison group. All 12 subjects with sciatica showed continuous reduction in back and leg pain during the one-monthobservation period following a single epidural injection of SP-102. This study demonstrated that at an equivalent initial dose of dexamethasone, the systemic exposure to dexamethasone following epidural injection of SP-102did not exceed the exposure following intravenous injection of the RLD. The PD effects, measured as white blood cell count, cortisol levels and glucose levels, as well as the tolerability profile, were similar between the two treatments. SP-102injections were generally well tolerated and did not result in new unexpected side effects. We believe this trial supports a 505(b)(2) NDA, utilizing the known systemic safety of the FDA-approvedRLD dose. Toxicology Studies — Study Nos. 1014-1512 and 1014-2847 We conducted PK and toxicology studies in two non-rodentanimal species to assess SP-102administered via epidural and intrathecal routes with single and multiple dose regimens. Pharmacokinetically, a prolonged 304

increase in the active dexamethasone metabolite was consistent with the extended residence time of the viscous gel formulation of SP-102 at the site of injection. There were no new unexpected toxicology findings apart from well-characterized toxicity findings commonly observed with administration of dexamethasone sodium phosphate. Based on these studies, we selected the 10mg dexamethasone in 2mL volume dose for our further clinical studies. This selection was endorsed by the FDA during our pre-IND meeting.

Preclinical Toxicology Study — UPD003-IS21

We conducted a preclinical toxicology study designed to simulate the accidental introduction of epidural steroids into arterial blood vessels providing blood supply to the spinal cord, which is a major cause of neurological complications associated with current administration of suspension steroids containing particulates. A 2 mL (10 mg of dexamethasone) injection of SP-102 was injected over one to two minutes into the verte