Results in: IMC’s lead drug reduces major factor in liver inflammation

Immuron Limited (ASX:IMC, NASDAQ:IMRN), a small-cap biotech company developing orally-delivered antibodies for the treatment of inflammatory-mediated and infectious diseases, today announced the topline results of its IMM-124E phase II Non-Alcoholic Steatohepatitis (NASH) clinical study.

A total of 133 NASH patients were enrolled in the study and treated with either IMM-124E or placebo for six months. In that time, IMM-124E was shown to result in a statistically significant reduction of serum Lipopolysaccharide (LPS) in patients with NASH.

IMM-124E is IMC’s flagship drug candidate, and is a first-in-class oral antibody therapy targeting the endotoxin LPS and other bacterial components.

The association between elevated serum LPS and the progression of NASH has been well-documented. As such, IMC believes the outcome of the trial is an important milestone, particularly as it looks to commercialise its IMM-124E candidate.

Results demonstrate excellent safety and tolerability; statistically significant reduction in serum endotoxin/liposaccharide (LPS) levels compared to placebo; statistically significant reduction in mean serum ALT in patients with elevated pre-treatment ALT; reduction of additional serum NASH biomarkers associated with liver damage – AST and CK-18; IMM-124E retained within the GI tract and not absorbed into the bloodstream, minimising side effects.

In addition, IMM-124E’s anti-LPS mechanism action may have wider therapeutic applications beyond NASH — an exciting prospect that the company intends to explore further.

Of course, it should be noted that Immuron is still a speculative stock and anything can happen. Investors should seek professional financial advice if considering this stock for their portfolio.

Professor of Gastroenterology and Hepatology from the Virginia Commonwealth University in Richmond and the study lead Principle Investigator, Arun Sanyal commented on the results: “This is truly a proof of concept for this first-in-class drug candidate. The IMM-124E drug candidate has been developed to target LPS in the gut and prevent it translocating into the portal circulation.

“The study results clearly demonstrate a statistically significant reduction of serum LPS levels in the treatment groups when compared to placebo and provides us with a proof of concept that metabolic endotoxemia can indeed be decreased using this drug candidate (IMM-124E) which targets the endotoxin LPS.

“We are encouraged that IMM-124E, a drug with an exceptional safety profile, can lower the LPS-associated inflammatory burden and improve liver enzymes. The potential clinical applications for this drug candidate are numerous and very exciting indeed.”

LPS reduction

During the trial, IMM-124E demonstrated a statistically significant reduction in serum LPS levels when compared to placebo. LPS is a bacterial endotoxin implicated in numerous peer review publications to drive liver inflammation, and to play a role in the progression of NASH.

In the study 63.3 per cent of patients treated with IMM-124E demonstrated a 15 per cent or greater decrease in serum LPS levels compared with only 35.5 per cent of patients showing a decrease for the placebo group, reaching statistical significance (p=0.0235). The opposite trend was observed in the placebo group with 54.8 per cent of patients demonstrating a statistical significant 15 per cent or greater increase in serum LPS levels by the end of the study, compared with only 26.7 per cent in drug treated patients (p=0.0193).

IMM-124E’s mechanism of action is consistent with the substantial peer review literature, in which LPS is thought to contribute to the progression of NASH.

ALT/AST reduction & reduction in CK-18

When comparing IMM-124E treated patients to placebo, significantly more treated patients demonstrated a decrease in mean serum ALT, by at least 30 per cent, than placebo in patients with elevated pre-treatment ALT (p=0.048). More than twice as many patients in the high dose reached this endpoint compared with placebo (36 per cent and 14 per cent for 1200mg vs. placebo respectively). IMM-124E also demonstrated a strong positive trend (p=0.0.098) in reducing ALT compared to the placebo group in all patients.

ALT was formerly known as serum glutamic-pyruvic transaminase (SGPT) and AST as serum glutamic-oxaloacetic transaminase (SGOT). Elevated levels of both liver enzymes signify some form of liver damage or injury.

IMM-124E also showed a statistical trend to reduce serum CK-18 levels compared to placebo. Serum CK-18 levels correlate with hepatocyte apoptosis (liver cell death) and liver damage — as such, reducing CK-18 levels in the context of NASH correlates with a reduction in liver damage.

Excellent safety profile confirmed

The trial results show that oral administration of IMM-124E is not absorbed into the blood stream, and therefore did not lead to increased levels of bovine immunoglobulin in the serum. This is more evidence of IMM-124E’s excellent safety profile, and also supports the potential use of the drug in combination with other medications.

In commenting on today’s major news, Dan Peres MD, Senior Vice President and Head of Medical at IMC said: “Immuron is pleased to report the first in-human clinical proof of IMM-124E decreasing serum LPS. We are excited to show this world First-In Class drug effect achieved in conjunction with a reduction in serum ALT, AST, and CK-18.

“The proof for IMM-124E’s non-absorbable nature and excellent safety profile as reported, will allow us to conduct further clinical research aimed at maximizing the effect with potentially higher doses and longer treatment times. Furthermore, these results support that IMM-124E offers potential as a standalone treatment or in combination with other classes of drugs.”

IMC Interim CEO Dr Jerry Kanellos added: “The Board of Immuron and Executive Management is very proud to have progressed our lead drug candidate IMM-124E to phase II proof of principle clinical trials. This has been a significant undertaking by the company and these results represent an opportunity for significant value creation for our loyal shareholders who have supported us over the journey.

“The Immuron team is extremely encouraged with these results, we have succeeded in demonstrating excellent safety and significant efficacy signals for our novel MoA in a relatively short treatment trial (24 weeks) and small numbers of patients (133 patients).

“Our results offer evidence of a therapeutic mechanism of action and a clear direction for further NASH studies. The growing literature implicating LPS in many diseases offers the potential for a much wider scope for LPS antagonism as a treatment modality. With IMM-124E being the world’s First Oral LPS Antagonist we are very confident, that when combined with its exceptional safety, there are substantial opportunities ahead across a broad range of diseases.”

Given the significance of these findings, the company will host a live investor conference call on Friday 9 March at 8:30am Australian EST to discuss the results.