South Rampart Pharma's pursuit of novel non-opioid pain treatments

SRP-001, a promising new pain medication developed by South Rampart Pharma Inc., has shown significant safety and efficacy in its phase 1 clinical trial. The study, led by Dr. Hernan Bazan, co-founder and CEO of South Rampart, was titled “Transcriptomic signature, bioactivity and safety of a non-hepatotoxic analgesic generating AM404 in the midbrain PAG region.” The findings reveal that SRP-001 induces higher levels of N-arachidonoylphenolamine (AM404) in the midbrain's periaqueductal grey (PAG) region than acetaminophen, a metabolite crucial for pain relief.

SRP-001 stands out as a safer alternative to current pain medications, eliminating the risks of abuse, liver toxicity, and kidney damage often associated with existing treatments. Preclinical evaluations and a completed phase 1 randomized controlled trial (RCT) involving 56 human subjects highlighted SRP-001's safety, tolerability, and effective pharmacokinetics. Notably, these evaluations did not report any adverse effects on the liver, kidneys, or other critical organs, marking SRP-001 as a significant advancement in pain management.

Dr. Bazan highlighted the urgent need for innovative pain treatments, noting that acute, chronic, and neuropathic pain affect up to 27% of adults worldwide, including over 51 million in the U.S. Current treatments such as opioids, acetaminophen, and NSAIDs carry significant risks of addiction and toxicity with overuse. With its known mechanisms for pain relief and compelling phase 1 trial data, the company plans to advance SRP-001 into phase 2 randomized and controlled studies for acute and neuropathic pain in the latter half of 2024.

SRP-001 has been shown to facilitate the production of AM404, a strong activator of TRPV1 in the PAG region, a critical area in the brain's pain response. Furthermore, single-cell transcriptomics of the PAG region indicated that SRP-001 modulates pain-related gene expression and cell signaling networks, including endocannabinoid signaling and genes linked to mechanical nociception and fatty acid amide hydrolase (FAAH).

The study also emphasizes that SRP-001 avoids liver toxicity due to the lack of NAPQI formation and maintains hepatic tight junction integrity, unlike NSAIDs, which can cause significant kidney and gastrointestinal damage with overuse. Comprehensive genotoxicity, safety pharmacology, and non-clinical toxicology evaluations, including ICH-compliant studies and GLP toxicity studies in two animal species, confirmed SRP-001's non-genotoxic nature and its lack of adverse effects on pulmonary or cardiac functions.

The phase 1 RCT concluded that SRP-001 is safe and well-tolerated, with a half-life extending up to 10.1 hours. The FDA granted SRP-001 Fast Track designation for acute pain in October 2023, and South Rampart Pharma is preparing to launch a phase 2 trial in acute pain in the second half of 2024, targeting neuropathic pain, acute and chronic pain, and acute migraine headaches.

South Rampart Pharma, Inc. is a clinical-stage biopharmaceutical company dedicated to developing effective and safe pain treatments. Their focus is on creating new small molecule therapeutics that mitigate the prevalent risks of current pain medications, such as addiction and organ damage. The company’s pipeline includes novel compounds that have demonstrated efficacy in reducing pain and fever in pre-clinical studies without the associated toxicities of existing treatments.