Incannex Healthcare (ASX: IHL) has been buoyed by the potential of its candidate IHL-675A to become a multi-use medication after receiving positive results from another pre-clinical in vivo trial into the effect of the drug on inflammatory bowel disease.
Results from a mouse model of colitis indicate that IHL-675A – which combines cannabidiol (CBD) and hydroxychloroquine (HCQ) – has superior anti-inflammatory activity compared to CBD and HCQ used separately.
In the model, colitis was induced by intracolonic installation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in 50% ethanol, which disrupts the intestinal barrier and allows TNBS to interact with colon proteins.
Interaction of TNBS with high molecular weight proteins renders them immunogenic.
Administration of a single dose of TNBS in ethanol can lead to an immune response and Th1-mediated inflammation, which manifests in inconsistent stool formation and blood in the faeces.
Incannex managing director Joel Latham said the findings were a positive step in IHL-675A’s development.
“We know that CBD has been the focus of academic studies in relation to inflammation for some time,” he said.
“[We now believe] our proprietary IHL-675A combination-CBD-and-HCQ drug may have the potential to be clinically relevant to a large variety of conditions, including those for which CBD has previously been a research target molecule for their treatment,” he said.
The trial to assess the potential benefit of IHL-675A in the model of colitis used 11 groups of six mice, each treated with IHL-675A, CBD or HCQ for four days after administration of the TNBS/ethanol mix to induce ulcerative colitis.
A vehicle-treated group and sham group were also included.
Endpoint measures included stool consistency score (where a higher number is indicative of looser stools); colon weight; colon macroscopic damage score (which takes into account adhesions, strictures, ulcers or inflammations, and instances of wall thickening); colitis index; and myeloperoxidase (an enzyme abundantly expressed in neutrophil granulocytes which contributes to inflammatory damage in bowel disease).
The results from each endpoint were sham subtracted and the relative reduction calculated.
Mr Latham said IHL-675A outperformed CBD and HCQ at reducing all endpoint levels.
“The results indicate IHL-675A has a benefit in a mouse model of ulcerative colitis greater than that of CBD or HCQ alone,” he said.
“In turn, this indicates IHL-675A has potential for treating inflammatory bowel disease in humans.”
IHL-675A has now outperformed CBD for its ability to dampen inflammation in four separate pre-clinical models of evaluation relevant to various indications in humans, specifically sepsis-associated acute respiratory distress syndrome; chronic obstructive pulmonary disorder; asthma; bronchitis; and now inflammatory bowel disease.
The discovery that CBD and HCQ have synergistic anti-inflammatory activity has increased the potential for IHL-675A beyond these conditions and into other inflammatory indications.
Mr Latham said the company would continue to evaluate the drug’s potential for use in other inflammation-based conditions and specifically for those for which CBD has previously been a research target molecule for their treatment
“Incannex is evaluating relationships with major research organisations with global reach to continue a clinical and regulatory strategy and negotiations are ongoing,” he said.
Incannex plans to pursue patent protection in key global markets such as the US, Europe, Japan and Israel.
Inflammatory bowel disease is an umbrella term used to describe disorders which involve chronic inflammation of a person’s digestive tract, such as ulcerative colitis and Crohn’s disease.
Both conditions are usually characterised by diarrhea, rectal bleeding, abdominal pain, fatigue and weight loss.
While inflammatory bowel disease can be debilitating and may lead to life-threatening complications, the exact cause of it remains unknown.
One possibility is thought to be an immune system malfunction, which occurs when the human body tries to fight off an invading virus or bacterium but creates an abnormal immune response which causes the immune system to also attack cells in the digestive tract.