South Rampart Pharma Publishes SRP-001's Unique Pain Relief Mechanism and Phase 1 Trial Results in Scientific Reports
May 16 2024 - 6:00AM
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 Ca2+
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 PublicationBazan 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
PainAcute, 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 MigraineMigraine 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-001The 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, MBAChief Financial
Officerjblacher@southrampartpharma.com
Media:Michael RubensteinLifeSci
Communicationsmrubenstein@lifescicomms.com