Company: SMNR
Filing Date: 2025-08-12
Form Type: S-4/A
Source: 0001193125-25-178821
Chunk: 498

Company: Semnur Pharmaceuticals, Inc.
Filing Date: 2025-08-12
Form: S-4/A
Chunk 498
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 evaluated in a number of preclinical studies and clinical trials as a potential treatment for sciatica. Key findings from the preclinical studies and clinical trials include:

| • |     | The introduction of SP-102 into blood vessels did not result in neurological complications in the UPD003-IS21 preclinical toxicology study; |

| • |     | SP-102 showed an extended residence time and tolerability in the 1014-1512 and the 1014-2847 preclinical studies; |

| • |     | Repeat injections of SP-102 showed continued pain reduction with no unexpected adverse events based on preliminary results from the SP-102-03 study; and |

| • |     | SP-102 showed an extended local activity with epidural administration in the ES-1504 study. |

Study Details Phase 3 Pivotal Clinical Trial — CLEAR We have completed a pivotal, randomized, double-blind, placebo-controlled Phase 3 trial, CLEAR, that enrolled 401 patients with sciatica at over 40 sites across the United States. The study included an open-label extension where subjects were followed for up to 24 weeks after treatment to evaluate the tolerability of administering SP-102in a larger patient population. After week four, subjects who met certain pain criteria received open-label SP-102to investigate the tolerability of repeat injections and the duration of pain relief following injection. This well-controlled, double-blind, randomized trial was designed to demonstrate evidence of the analgesic effect and tolerability of SP-102.The schematic of this Phase 3 trial is demonstrated in the flowchart below. The primary objective of this study was to evaluate the analgesic effect of SP-102on average leg pain, measured using the NPRS following a single transforaminal injection. These results were compared to an intra-muscular injection of placebo over a four-week period. The secondary objectives of this study include (i) evaluation of the degree of disability over time as measured by the ODI; (ii) characterization of the change of the subject’s radiculopathy symptoms and overall condition, using a combination of PainDETECT, modified Brief Pain Inventory, Clinical Global Impression of Change (“CGIC”), and Patient Global Impression of Change (“PGIC”) and (iii) evaluation of the tolerability of a single and repeat SP-102injection. 299

Schematic of CLEAR - SP-102 (SEMDEXA) Phase 3 Pivotal Trial Results of CLEAR - SP-102Phase 3