South Rampart Pharma Announces New Study in Neurobiology of Pain Demonstrating How SRP-001 Delivers Central, Non-Toxic Pain Relief

• Study highlights novel epigenomic modulation in the central nervous system as a key mechanism for SRP-001's analgesic effects
   
• Data further supports SRP-001's unique positioning as a safer, non-opioid, non-toxic analgesic
   
• Initiation of Phase 2 clinical trials with SRP-001 for acute pain remains on track for 2025

NEW ORLEANS, July 28, 2025 /PRNewswire/ -- South Rampart Pharma, Inc., a clinical-stage biopharmaceutical company focused on innovative non-opioid pain therapies, today announced the publication of new research in the journal Neurobiology of Pain. The paper, titled "A non-toxic analgesic elicits cell-specific genomic and epigenomic modulation by targeting the PAG brain region¹," describes distinctive epigenomic mechanisms within the central nervous system through which SRP-001 alleviates pain without common toxicities associated with current analgesics. The full paper is accessible online via Neurobiology of Pain [https://www.sciencedirect.com/science/article/pii/S2452073X25000145?via%3Dihub].

The study demonstrates that SRP-001 modulates specific genomic and epigenomic pathways exclusively within the periaqueductal gray (PAG) region of the midbrain, a critical center for pain modulation. The research highlights SRP-001's unique effects on transcription factor activities and neuron-neuron interactions disrupted by inflammatory pain via the Neurexin-Neuroligin signaling pathway.

"This body of work provides new insights into SRP-001's unique analgesic properties by elucidating its epigenomic modulation within the periaqueductal gray (PAG), a key brain region for pain control," said Dr. Hernan Bazan, co-founder and CEO of South Rampart Pharma. "SRP-001 generates the metabolite AM404, which potently activates TRPV1 receptors within the PAG, triggering a well-characterized central analgesic cascade involving CB1 receptors. This central mechanism effectively attenuates pain perception and restores neuronal interactions disrupted by inflammatory pain, highlighting SRP-001's potential to offer pain-relieving benefits and sustained neuronal health beyond conventional peripheral-only analgesics. Importantly, the rationale design of SRP-001 has not only improved safety but also conferred a faster onset of action and a longer duration of action – each a critically differentiating factor for the treatment of pain."

Key scientific findings from the paper include:

• SRP-001 induces the formation of AM404, a potent analgesic metabolite that activates the Transient Receptor Potential Vanilloid subtype 1 (TRPV1), commonly known as the capsaicin receptor, specifically within the PAG. The PAG is a crucial brain region that orchestrates descending pain modulation pathways.
   
• Epigenomic analysis identified distinct changes in transcription factor activities, notably restoring SOX family transcription factors in oligodendrocytes and SP/KLF family transcription factors in neurons, crucial for myelination and neural repair, both critical processes impaired in chronic and inflammatory pain states.
   
• SRP-001 suppresses AP-1 family and TFEB transcription factor activities, indicating potential anti-inflammatory and analgesic effects independent of changes in gene expression.
   
• SRP-001 effectively restores Neurexin-Neuroligin synaptic signaling disrupted by inflammatory pain, underscoring its potential to maintain synaptic integrity and neuronal protection

This study complements recent external research published in Proceedings of the National Academy of Sciences (PNAS) that demonstrated peripheral analgesic mechanisms of AM404 via direct inhibition of pain-specific sodium channels (NaV1.7 and NaV1.8)². Together, these findings underscore SRP-001's therapeutic potential through distinct central and peripheral actions to provide a much-needed pain management alternative for a wide range of conditions.

SRP-001 previously received FDA Fast Track designation, recognizing its potential as a safer alternative to opioids, acetaminophen, and NSAIDs, all of which pose risks of addiction and toxicity. Phase 2 clinical trials are planned to launch in the second half of 2025.

References

1. Bazan, H. A., Giles, B. L., Bhattacharjee, S., Edwards, S., & Bazan, N. G. (2025). A non-toxic analgesic elicits cell-specific genomic and epigenomic modulation by targeting the PAG brain region. Neurobiology of Pain, 18, 100192. https://www.sciencedirect.com/science/article/pii/S2452073X25000145?via%3Dihub
    
2. Maatuf, Y., Kushnir, Y., Nemirovski, A., Ghantous, M., Iskimov, A., Binshtok, A. M., & Priel, A. (2025). The analgesic paracetamol metabolite AM404 acts peripherally to directly inhibit sodium channels. Proceedings of the National Academy of Sciences of the United States of America, 122(23), e2413811122. https://doi.org/10.1073/pnas.2413811122

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 South Rampart Pharma 

South Rampart Pharma, Inc. is dedicated to advancing safe, effective, non-opioid treatments for acute, chronic, and neuropathic pain. The company's pipeline of first-in-class small molecules addresses critical gaps in pain management, reducing risks associated with current analgesics, such as abuse potential and organ toxicity. For more information, visit www.southrampartpharma.com.

The Company's lead program, SRP-001, uniquely targets the midbrain's PAG region, offering effective pain relief without opioid abuse potential, acetaminophen's liver toxicity, or NSAIDs' kidney toxicity. Completed Phase 1 randomized controlled trials demonstrated SRP-001's favorable safety and pharmacokinetic profile [ClinicalTrials.gov Identifier: NCT05484414], paving the way for Phase 2 studies in neuropathic and acute pain, as well as migraine headache, anticipated to commence in 2H 2025.

Investor Contact:
Josh Blacher, MBA
Chief Financial Officer
[email protected]

Media Contact:
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Russo Partners
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SOURCE South Rampart Pharma