Immuron targets the gut not the liver
NB: This article by Juliet Preston was originally published on MedCity News: medcitynews.com
Surprise, surprise; fatty liver disease is associated with a poor Western diet.
That’s not a revelation, but Immuron has an interesting take on exactly how a high fat and high sugar diet help drive the inflammation behind NASH.
Approximately five percent (15.9 million) of Americans are believed to have non-alcoholic steatohepatitis (NASH), but that’s just the tip of the iceberg. It comes as a progression of non-alcoholic fatty liver disease (NAFLD), which affects an estimated 75-100 million Americans. With such solid
With such solid blockbuster potential, startups and Big Pharma are pouring into the field.
Immuron is taking a somewhat radical approach. Its investigational NASH drug called IMM-124E targets bacteria as a key driver of liver inflammation. The formulation is manufactured from bovine colostrum, explained CEO Thomas Liquard in a recent phone interview.
“We’re basically able to engineer colostrum to produce a specific set of antibodies that we can use to target just about any bacteria in the gut, without affecting the rest of the microbiota,” he said.
Headquartered in Melbourne, Australia, Immuron’s proof-of-concept is an over-the-counter product called Travelan, available in the United States, Canada, and a handful of other countries. Based on a small placebo-controlled trial, Travelan prevented new cases of travelers’ diarrhea with 90 percent efficacy, Liquard said. It does this by targeting E. coli, the bacteria responsible for a majority of cases.
The company moved on to two clinical applications: Clostridium difficile (c. diff) infections and NASH, which is now in Phase 2 trials.
IMM-124E is an interesting take on NASH. It accepts that a major contributing factor is the poor quality of the Western diet — but it’s not the long-term build-up of fat that does the damage.
“The high levels of sugar and fat in our diet, especially glucose, creates an overgrowth of Gram-negative bacteria in the gut,” Liquard explained.
Not all Gram-negative bacteria are bad, he noted. They do, however, all share a common feature known as a lipopolysaccharide (LPS) receptor. According to Liquard, when the bacteria dies or sheds, pro-inflammatory byproducts of LPS enter the bloodstream.
“LPS is not the pathway per se, it’s a trigger of inflammation,” he said. It causes injury, which leads to the development of NASH.
Because the liver is right next to the intestines and stomach, it takes the biggest hit when the gut bacteria shed LPS into the bloodstream. By targeting certain Gram-negative bacteria, IMM-124E is designed to prevent the overflow of LPS into the liver.
“We’re not an antibiotic, so we don’t kill the bacteria,” Liquard explained. “We block that overgrowth of bacteria in the gut without destroying the rest of the microbiota.”
There are a number of benefits to this approach. With its novel mechanism, IMM-124E would likely pair well with any future NASH therapies — or drugs for the many comorbidities found in this patient population, such as heart disease and metabolic syndrome. Targeting the Gram-negative gut bacteria could also cut down on LPS-driven inflammation and damage in other organs such as the pancreas, which Liquard said was demonstrated in the Phase 1 trial.
There also seems to be some sort of feed-forward effect beyond the LPS suppression as the body gets a handle on the inflammation.
“Because you decrease the levels of LPS within the gut, you see an anti-inflammatory response from patients,” Liquard said. “In all of our studies, you see the cytokines going down, you see regulatory T-cells – which are the T-cells that regulate inflammation – go down. The type of regulatory T-cells that decreases inflammation goes up.”
A microbiota approach also has the ability to treat a wide range of patients. That differs from any other companies, he said, which target specific pathways that may only apply to a subset of patients. With a lack of biomarkers, it’s hard to know who to treat.
The challenge of treating a sick population is also front of mind for the FDA. Any potential therapies need to be suitable for chronic use in patients with obesity-related comorbidities. An investigational NASH drug from Intercept Pharmaceuticals, for example, appears to increase LDL-cholesterol levels, a major concern in this patient population.
For Immuron, the broad applicability of IMM-124E may pose a novel hurdle. Where to start?
“We need to be very strategic in terms of how we bite that NASH apple,” Liquard said. “To make sure we don’t bite off more than we can chew.”
Editor’s note: Immuron (ASX:IMC) represents a speculative investment and those considering this stock for their portfolio should seek professional financial advice before making a decision.
S3 Consortium Pty Ltd (CAR No.433913) is a corporate authorised representative of Longhou Capital Markets Pty Ltd (AFSL No. 292464). The information contained in this article is general information only. Any advice is general advice only. Neither your personal objectives, financial situation nor needs have been taken into consideration. Accordingly you should consider how appropriate the advice (if any) is to those objectives, financial situation and needs, before acting on the advice.
Conflict of Interest Notice
S3 Consortium Pty Ltd does and seeks to do business with companies featured in its articles. As a result, investors should be aware that the Firm may have a conflict of interest that could affect the objectivity of this article. Investors should consider this article as only a single factor in making any investment decision. The publishers of this article also wish to disclose that they may hold this stock in their portfolios and that any decision to purchase this stock should be done so after the purchaser has made their own inquires as to the validity of any information in this article.
The information contained in this article is current at the finalised date. The information contained in this article is based on sources reasonably considered to be reliable by S3 Consortium Pty Ltd, and available in the public domain. No “insider information” is ever sourced, disclosed or used by S3 Consortium.