Pain relief without the risk: why SRP-001 could change everything

In the field of drug discovery, few areas face a more pressing need for innovation than pain management. For decades, opioids have dominated the space, but despite their effectiveness they are burdened by significant risks of dependence and misuse. As the limitations of current treatments become increasingly clear, researchers are exploring new, safer approaches. Among them is Dr Hernan Bazan, a vascular surgeon turned biotech chief executive, whose work on SRP-001 has the potential to reshape the way pain is treated.

As co-founder and chief executive of South Rampart Pharma, and a practicing academic vascular surgeon, Dr Bazan combines hands-on clinical experience with a strong track record in scientific research. With nine patents and over 50 peer-reviewed publications, he is firmly established in the field. His focus, however, is on addressing a critical gap in medicine: the lack of safe, non-addictive pain treatments – a challenge that has driven the development of SRP-001.

“As a practising surgeon, I recognise the critical need for non-addictive, toxicity-free analgesics,” Bazan said. “To address this unmet need, I co-founded South Rampart Pharma.”

The case for SRP-001

SRP-001 is not just another painkiller. Unlike opioids, it bypasses opioid receptors entirely, eliminating the risks of addiction and abuse. Instead, Bazan explains that the drug modulates genes involved in mechanical nociception – the body’s process of detecting harmful or painful stimuli such as pressure or injury – giving it a unique pain-relieving profile.

Preclinical studies show that SRP-001 is effective across several gold-standard pain models, including the Von Frey inflammatory test (used to measure sensitivity to touch), the Tail Flick assay (which assesses response to thermal pain) and the acetic acid-induced writhing test (used to evaluate visceral pain). What sets SRP-001 apart is its central mechanism of action, targeting the periaqueductal gray (PAG) – a key region in the brain responsible for regulating pain signals.

“SRP-001 functions via a centrally acting mechanism, offering a potentially broader analgesic profile and limiting off-target effects,” Bazan explains.

Unlike the newly approved NaV1.8 inhibitor, suzetrigine – which acts on peripheral sodium channels – SRP-001 leverages a brain-centric approach. Crucially, it is not associated with abuse potential. Still, Bazan says “Vertex’s work has been so important for the pain field – to get eyes on the large market size that matches the significant societal and clinical need for pain innovation.”

Pain management remains one of the most urgent frontiers in drug discovery. For decades, opioids have been the cornerstone of treatment, yet their effectiveness comes at a steep cost—widespread risks of dependence, misuse, and addiction.

How it works

A striking feature of SRP-001 is its ability to boost levels of AM404, a compound also produced by paracetamol in the brain, which plays a key role in reducing pain by acting on several important pathways. SRP-001 significantly increases AM404 levels in the PAG, which helps to disrupt pain signalling by stimulating TRPV1 (a receptor involved in detecting painful heat), influencing the expression of pain-related genes and engaging the CB1 cannabinoid receptor – known to reduce pain and inflammation.

Put simply, SRP-001 strengthens the brain’s natural ability to block pain, offering more effective relief than paracetamol without the harmful side effects.

“Our preclinical data demonstrate a superior pain relief profile over the current standard of care without toxic side effects,” says Bazan.

Liver-safe by design

One of the long-standing issues with paracetamol is its liver toxicity. It produces a harmful by-product, NAPQI, which can cause serious hepatic and renal damage. SRP-001 was designed to avoid this.

Using structure-based drug design, Bazan and his team have eliminated the formation of NAPQI while retaining and enhancing analgesic activity. Histological analysis confirms that SRP-001 does not damage liver cells or tight junctions. As a non-NSAID, it also avoids the gastrointestinal and renal side effects associated with drugs like ibuprofen.

“Our goal from the outset was to use a rational, structure-based drug design strategy to eliminate this toxic metabolite formation,” explains Bazan.

Addressing the opioid crisis

It is impossible to talk about pain relief today without acknowledging the opioid epidemic. This crisis has led to increased political, regulatory and scientific focus on non-opioid alternatives.

“Several converging regulatory and legislative factors create an optimal environment for novel non-opioid pain treatments,” Bazan notes.

With its favourable safety profile and broad potential for both acute and chronic pain, SRP-001 is well positioned for this moment. Bazan sees it as part of a broader shift towards combination therapies – an approach that will likely define the next generation of pain management.

From bench to bedside: what is next?

SRP-001 has already moved beyond the laboratory. South Rampart Pharma has completed its Phase 1 clinical trial, demonstrating strong safety, tolerability and pharmacokinetics. The next milestone is a Phase II trial, aiming to begin in 3Q2025, evaluating SRP-001 in acute pain following third molar extraction (wisdom tooth removal).

“This Phase II trial is strategically designed for a relatively short timeline, potentially allowing a full data readout by the end of the year,” Bazan says.

It is an ambitious path, but with an experienced team behind the programme, Bazan remains confident that SRP-001 could become one of the first in a new class of safe, effective pain treatments.

Final thoughts: changing the narrative

Dr Bazan is clear about the future direction of the field. Pain treatment, he says, will not be defined by a single breakthrough but by a diverse range of therapies that can be tailored to different patients and conditions.

“Indeed, future pain treatment will be multi-modality with effective and safe therapeutics,” he concludes.

SRP-001 may offer a glimpse of that future – a compound that combines the efficacy of existing drugs, the mechanism of paracetamol and a safety profile that addresses many of the limitations of current options. If it continues to deliver in clinical trials, SRP-001 has the potential to play a defining role in how pain is treated going forwards.