South Rampart Street in New Orleans is within a section of the city known as the “Birthplace of Jazz” for the legendary musicians who shaped the genre a century ago, from Jelly Roll Morton to especially Louis Armstrong.
Today, a vascular surgeon who grew up in New Orleans and developed an affinity for “Satchmo” aspires to be a standout in a whole different field, as the head of a drug development startup named for the historic thoroughfare.
South Rampart Pharma is working to develop an oral small molecule non-opioid pain treatment which has generated early positive clinical data as a therapy for acute and chronic pain, as well as preclinical studies in diabetic and chemotherapy neuropathy.
“We’re giving homage to jazz, where jazz was born, and all of that stuff being from New Orleans,” Hernan A. Bazan, MD, South Rampart Pharma’s CEO, told GEN. Bazan co-founded the company with his son Nicolas G. Bazan, MD, PhD, professor and director of LSU’s Neuroscience Center of Excellence.
A spinout from Louisiana State University (LSU) Health New Orleans School of Medicine, from which it licenses technology, South Rampart is developing non-opioid analgesics led by an oral form of its sole pipeline candidate SRP-001. The Phase II-ready non-NSAID (non-steroidal anti-inflammatory drug) is an AM404 agonist designed to target the endocannabinoid (CB1) pain receptors in the brain.
SRP-001 is designed to eliminate the hepatotoxicity associated with acetaminophen (ApAP), as well as avoid kidney and gastrointestinal dose-limiting effects since it is not an NSAID. And with its non-opioid profile, South Rampart asserts, SRP-001 enjoys a lower potential for abuse than opioids. South Rampart developed SRP-001 as a new chemical entity in collaboration with Julio Alvarez-Builla, PhD, an emeritus professor at University of Alcalá in Spain.
Toxicity-free mechanism
In July, a team of researchers led by Bazan and his son published a paper detailing how SRP-001 alleviated pain without common toxicities associated with current analgesics. The study showed SRP-001 to modulate specific genomic and epigenomic pathways exclusively within a key center for pain modulation, the periaqueductal gray (PAG) region of the midbrain.
Specifically, SRP-001 was shown to work by generating AM404, a metabolite that potently activates the capsaicin receptor or Transient Receptor Potential Vanilloid subtype 1 (TRPV1) within the PAG, triggering a well-characterized central analgesic cascade involving CB1 receptors.
According to Bazan, his son, and colleagues, that central mechanism effectively attenuates pain perception and restores neuronal interactions disrupted by inflammatory pain, results that they say highlight SRP-001’s potential to offer pain relieving benefits and sustained neuronal health beyond conventional peripheral-only analgesics.
“In place of the hepatotoxic ApAP, nephrotoxic NSAIDs, and addictive opioids, we have developed a safe, non-hepatotoxic and non-addictive alternative by eliminating the formation of the damaging secondary metabolite NAPQI [N-Acetyl-p-Benzoquinone Imine],” the Bazans and their colleagues reported.
Their research also associated SRP-001 with:
Restoring SOX family transcription factors in oligodendrocytes and SP/KLF family transcription factors in neurons, crucial for myelination and neural repair.
Suppressing AP-1 family and TFEB transcription factor activities, which according to the company indicates potential anti-inflammatory and analgesic effects independent of changes in gene expression.
Effectively restores neurexin-veuroligin synaptic signaling disrupted by inflammatory pain, underscoring its potential to maintain synaptic integrity and neuronal protection
“Pretty, pretty sobering”
South Rampart is among numerous drug developers working on non-opioid pain treatments designed to avoid the serious—and worse—side effects associated with opioid drugs, from addiction to death.
Among such treatments in development until this summer had been Vertex Pharmaceuticals’ VX-993. In August, Vertex halted development of VX993, shelving plans for pivotal trials of the selective NaV1.8 inhibitor after it failed a Phase II trial (NCT06619860).
The randomized, double-blind, placebo-controlled dose-ranging study showed that patients treated with VX-993 did not achieve statistically significant improvement on the trial’s primary endpoint, the time-weighted Sum of the Pain Intensity Difference from 0 to 48 hours (SPID48), compared to placebo.
“The fact that that didn’t meet a primary endpoint in a Phase II, I think, is pretty, pretty sobering,” Bazan said, cautioning that he had not seen detailed data and thus could not comment specifically on the study’s findings.
Because SRP-001 is based on the metabolite AM404, Bazan said, it has the advantage of a clinically validated mechanism as used by the drug known as acetaminophen in the U.S. and paracetamol in the U.K., the active ingredient in brand name drugs such as Tylenol® and Panadol®.
“I think the post-VX993 world needs a differentiated solution. And again, it speaks to the need for multiple modalities, multiple mechanisms. That’s why, having something that isn’t just a follow-on, me-too is important, so that patients can benefit, and so that the pain space can keep on moving forward.”
To fund its planned upcoming Phase II trials focused on acute pain, South Rampart is raising an $8 million Series A round led by the regional angel investment network Gulf South Angels and Ochsner Ventures.
At first glance, $8 million doesn’t sound like a lot of capital in a field where startups typically raise tens if not hundreds of millions of dollars. So far this year, the top two venture capital awards have been both $600 million financings (obesity drug developer Kaleira Therapeutics and Isomorphic Labs, a London-based AI drug company spinout of Google DeepMind).
Bazan says the $8 million that South Rampart is raising will enable it to fund its planned Phase II trial in acute pain. South Rampart would need more capital, however, if it wanted to run in parallel additional trials assessing SRP-001 in chronic pain and neuropathic pain.
Hourly wages, no salary
The company keeps a tight enough lid on expenses that it pays its employees hourly wages rather than an annual salary plus perks. “Both of us co-founders, we don’t take salary. Obviously we have equity, so we want this to be successful and we’re working towards it,” the elder Bazan said.
Other than its regulatory and toxicology executives, he added, South Rampart has been able to keep its staff in place through strong relationships—though the company has partnered with Outcome Capital, a Boston-based life sciences advisory and investment banking firm, to hold conversations with potential pharma and investor partners in order to secure strategic pharmaceutical partnerships or licensing agreements.
Paul Mieyal, PhD, CFA, a former managing director with Outcome Capital who became South Rampart’s chief business officer last month told GEN he first learned about the company while meeting Bazan a few years back during the annual J.P. Morgan healthcare conference in San Francisco.
“It was clear that, in the backdrop of the non-opioid pain space, both politically, legislatively, and clinically, there were a lot of drivers and a receptive market for new modalities, and what South Rampart had developed was very different than what other people were working on,” Mieyal said, days before joining the company.
“It was a very significant advancement and material advancement versus many of the other approaches that have been tried over basically the last 20 years, in terms of opioid sparing, combining existing drugs—acetaminophen plus opioids, ibuprofen plus acetaminophen—every other combination of pain drugs you can think of,” Mieyal added. “But there’s been very few truly novel drugs which have come out in the last quarter century.”
Ochsner Ventures is the venture arm of Ochsner Health System, which along with the NIH has helped fund South Rampart’s R&D. Hernan Bazan is a physician and professor of surgery at Ochsner Health System, while the NIH has awarded the company a pair of grants in recent years.
In 2023, South Rampart was awarded a $399,539 Commercial Readiness Project (CRP) grant (2SB1NS119103-04) from the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), designed to propel the company toward market readiness. The grant was awarded toward South Rampart hiring a part-time or “50% effort” chief financial officer to pursue an aggressive partner engagement plan to secure a partnership to support Phase III trials and commercialization.
Business knowhow
“The NIH has been working the last several years to be very pro-business in terms of giving business knowhow with market reports and [advising], consider doing this from a financial point of view. Consider doing this from a strategy point of view. Some market overviews, and so on. And it helps,” Bazan said. “With those funds we’ve been able to then bring in a CFO part-time from New York that has also helped with a lot of this outreach and engagement.”
In addition to the CRP grant, between 2020 and 2023 South Rampart received a three-year $1.9 million Fast-Track Small Business Technology Transfer (STTR) Commercialization Grant (1R42NS119103), also administered through NINDS. That grant was designed to fund late-stage preclinical development of SRP-001 in collaboration with the Louisiana State University Health Sciences Center (LSUHSC) Neuroscience Center of Excellence.
“That allowed us to do a lot of the pre-IND work and some mechanistic work,” Bazan said. “We were fortunate we were able to be very competitive.”
Last year, the NIH awarded Bazan its 2024 NIH Helping to End Addiction Long-term® (NIH HEAL) Initiative® Director’s Trailblazer Award. The award recognizes HEAL-funded researchers in the early or middle stages of their careers who are expanding research into addressing the pain and opioid crises in new directions.
“I was very humbled to receive this recognition from the leadership of the NIH, as HEAL is helping to end addiction long term,” Bazan said.
Bazan was one of five NIH HEAL award winners last year, and the only one who received the award for a drug development effort.
They’re a great group of people,” Bazan said. “My sense from speaking with them is they’re very good people, very devoted to their work. For many of them, it’s like a calling.
That work is continuing, he added, despite cuts to the agency’s funding and staff this past year.
“I think behind the noise that we see and we hear in the news, the work is starting to get done again. And it has to get done because we’re losing the race for AI [development], and the race [to develop] rare earth minerals to China. And we can’t lose biotech and life science to China and Europe,” Bazan asserted.
“Postdocs and very savvy young PIs have been going to Europe or Canada, because they have better landings,” professionally speaking, he continued. “The RoI [return on investment] is clear on life science and biotech in the U.S. I think we have to keep that in mind.”
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