South Rampart Pharma Publishes SRP-001's Unique Pain Relief Mechanism and Phase 1 Trial Results in Scientific Reports

· SRP-001 is a novel, non-opioid new chemical entity without abuse, liver, and kidney toxicities present in current pain medications

· Publication introduces SRP-001 as a safer alternative to existing pain medications

· SRP-001 triggers N-arachidonoylphenolamine (AM404) formation in the midbrain's periaqueductal grey (PAG) region, a potent activator of TRPV1 that plays a crucial role in the brain’s response to pain

· FDA awarded SRP-001 Fast Track designation for acute pain in October 2023

· Phase 1 trial shows SRP-001 is safe and well-tolerated with favorable pharmacokinetics making it Phase 2-ready for the treatment of neuropathic pain, acute/chronic pain, and patients with acute migraine headaches.

· A Phase 2 trial in acute pain will launch in the second half of 2024

NEW ORLEANS, May 16, 2024 (GLOBE NEWSWIRE) -- South Rampart Pharma, Inc., today announced the publication of a paper in Scientific Reports describing the manner in which SRP-001 works in the brain to alleviate pain and the results of a Phase 1 randomized controlled trial (RCT)^1. The study, by Bazan et al., is titled, "Transcriptomic signature, bioactivity and safety of a non-hepatotoxic analgesic generating AM404 in the midbrain PAG region."

The publication reveals SRP-001's unique mechanism of action, producing higher amounts of N-arachidonoylphenolamine (AM404) than acetaminophen, a metabolite crucial for inducing pain relief in the midbrain’s periaqueductal grey (PAG) region. This discovery is supported by comprehensive preclinical evaluations, including in vitro and in vivo assessments of liver, kidney, and other end-organ toxicities, pain-relieving effects in pre-clinical models, alongside a completed Phase 1 RCT in 56 human subjects showcasing the compound's safety, tolerability, and robust pharmacokinetics (PKs).

Key findings in the published paper include:

· SRP-001 treatment induces the formation of AM404 in the midbrain's PAG region, a potent activator of TRPV1 that has a crucial role in the brain and dorsal horn's response to pain.· Single-cell transcriptomics of the PAG region uncovered that SRP-001 regulates pain-related gene expression and cell signaling networks, including endocannabinoid signaling, genes pertaining to mechanical nociception, and fatty acid amide hydrolase (FAAH).· The mechanical nociception and FAAH networks regulate the expression of critical genes encoding FAAH, 2-arachidonoylglycerol (2-AG), cannabinoid receptor 1 (CNR1), CNR2, transient receptor potential vanilloid type 4 (TRPV4), and voltage-gated Ca^2+ channel.· SRP-001 lacks hepatotoxicity due to an absence of NAPQI formation and hepatic tight junctions’ integrity protection. As a non-NSAID, it lacks this class’s risks of 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, confirm SRP-001’s non-genotoxic nature, lack of adverse effects on pulmonary or cardiac functions and absent treatment-related adverse effects or mortality in dose-escalating studies.· A completed Phase 1 RCT involving 56 subjects with single and multiple ascending dosing demonstrates that SRP-001 is safe and well-tolerated, with a half-life of up to 10.1 hours.“The quest for innovative pain solutions is critical, driven by the extensive prevalence of acute, chronic, and neuropathic pain,” said Hernan Bazan, M.D., the study’s lead author, South Rampart’s co-founder and CEO, and the John Ochsner Endowed Professor of Cardiovascular Innovation at Ochsner Health. “These pain conditions affect up to 27% of adults worldwide, including over 51 million adults in the U.S. Existing treatments such as opioids, acetaminophen, and NSAIDs pose risks of addiction and toxicity with overuse. Armed with known mechanisms for pain relief in the brain and compelling Phase 1 randomized trial data, we look forward to advancing SRP-001 into Phase 2 randomized and controlled studies for acute and neuropathic pain in the second half of 2024.”

*About the Publication*
Bazan HA et al. Transcriptomic signature, bioactivity and safety of a non-hepatotoxic analgesic generating AM404 in the midbrain PAG region. Sci Rep *14*, 11103 (2024). DOI: 10.1038/s41598-024-61791-z

*About Acute, Chronic, and Neuropathic Pain*
Acute, chronic, and neuropathic pain constitute significant yet distinctly different health challenges. Acute pain is the body's immediate alert to injury, typically intense but temporary. In contrast, chronic pain persists beyond three months, affecting an estimated 51.6 million U.S. adults in 2021 and nearly one-third of the global population. Neuropathic pain, resulting from nerve damage, affects approximately 7-10% of people worldwide. Traditional treatments, such as opioids, acetaminophen/paracetamol, and NSAIDs, while common, often fall short in efficacy and carry risks like addiction and organ damage. The opioid epidemic, characterized by 8.7 million Americans misusing prescription opioids, underscores the urgent need for safer, more effective pain management solutions. These pain categories not only compromise individual well-being but also impose a substantial economic toll, highlighting the critical need for innovation in pain treatment strategies.

*About Migraine*
Migraine is a widespread and complex neurological condition, affecting nearly 40 million Americans and over 1 billion people globally. It ranks as the primary cause of disability among individuals under 50. Characterized by severe, throbbing headaches, migraine episodes can last from four hours to three days. These episodes often feature incapacitating symptoms such as intense pulsating pain, nausea, vomiting, and heightened sensitivity to light and sound, significantly impacting daily life.

*About SRP-001*
The Company’s lead program, SRP-001, is a best-in-class analgesic that garnered FDA Fast-Track Designation for acute pain in October 2023. It uniquely targets the midbrain’s PAG region, offering a potentially effective pain relief solution devoid of the abuse potential of opioids, liver toxicity associated with acetaminophen, and kidney toxicity from NSAIDs overuse. A completed Phase 1 randomized controlled clinical trial data demonstrates the safety and robust pharmacokinetics for SRP-001 [ClinicalTrials.gov Identifier: NCT05484414], setting the stage for simultaneous Phase-2 ready programs in neuropathic and acute pain in 2H 2024, as well as migraine headache.

*South Rampart Pharma, Inc.*
South Rampart Pharma, Inc. is a clinical-stage biopharmaceutical company at the forefront of advancing the effective and safe treatment of pain by developing first-in-class novel small molecule therapeutics. It aims to mitigate the prevalent risks of existing pain medications, such as addiction and organ damage. The Company’s pipeline of novel compounds has effectively reduced pain and fever in pre-clinical studies without the abuse of non-opioid analgesics and the liver and kidney toxicities of current pain medicines.

^1HA Bazan et al. Transcriptomic signature, bioactivity, and safety of a non-hepatotoxic analgesic generating AM404 in the midbrain PAG region. *Sci Rep*. DOI: 10.1038/s41598-024-61791-z (2024).

*Investors:*
Josh Blacher, MBA
Chief Financial Officer
jblacher@southrampartpharma.com

*Media:*
Michael Rubenstein
LifeSci Communications
mrubenstein@lifescicomms.com