Company: SMNR
Filing Date: 2025-08-12
Form Type: S-4/A
Source: 0001193125-25-178821
Chunk: 486

Company: Semnur Pharmaceuticals, Inc.
Filing Date: 2025-08-12
Form: S-4/A
Chunk 486
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 including expectations for the size of the safety database and specific safety monitoring requirements. Specifically, the FDA requested that the confirmatory CLEAR-2 trial include a larger safety database to further validate the safety and efficacy of SP-102. Based on such guidance, we designed an open-label multi-center safety and efficacy trial, which we had expected to commence in the first half of 2024 and in which we would seek to enroll approximately 700 patients with moderate-to-severe LRP requiring an epidural steroid injection. In that trial, we expected to administer SP-102 in up to three injections during a six-month observation period. In February 2024, we had a Type D meeting with the FDA to preview the design of such trial with the FDA, in order to reduce the potential need for any other additional confirmatory trials prior to a 505(b)(2) NDA filing. During the Type D meeting, the FDA provided further guidance with respect to the requirements needed to help best position us to be able to satisfy the requirements for a 505(b)(2) pathway approval. Specifically, the FDA reaffirmed the need for a larger sample size and further requested confirmatory evidence of efficacy through a repeat injection. Based on this feedback, we have instead designed a Phase 3 CLEAR-2 trial, which is expected to be a randomized, active comparator and placebo-controlled, multi-center, safety and efficacy study of SP-102 in subjects with moderate to severe LRP enrolling approximately 700 patients to receive an open-label initial injection, and randomizing approximately 200 subjects to the second phase of repeat injection. The primary and key secondary endpoints of the CLEAR-2 trial are consistent with those used in the CLEAR-1 trial, including (i) average daily NPRS pain in the affected leg over four weeks following the initial injection of SP-102 and (ii) Oswestry Disability Index at four weeks following injection of SP-102 or placebo. We have also optimized certain secondary endpoints to capture additional potential clinical benefits of SP-102. We are currently manufacturing the clinical materials necessary to perform the additional Phase 3 CLEAR-2 study and expect to commence such trial in the second half of 2025. Given our experience from conducting the Phase 3 CLEAR-1 study, we expect to be able to complete the trial by mid-2026 and submit our 505(b)(2) NDA to the FDA for approval. If approved, and given SP-102’s fast-track designation, this would position us to achieve our targeted commercial