IHL-675A Inflammatory Bowel Disease
About
IHL-675A is a novel cannabinoid combination product for treatment of inflammatory diseases including inflammatory bowel disease.
Program overview
IHL-675A is a cannabinoid-enhanced combination drug comprising hydroxychloroquine (‘HCQ’) and cannabidiol (‘CBD’). Incannex has demonstrated that IHL-675A components, HCQ and CBD act synergistically to inhibit production of inflammatory cytokines, both in vitro and in vivo, and reduce disease severity in three established inflammatory disease animal models.
The disease models that exhibited the greatest signals of efficacy relate to rheumatoid arthritis, inflammatory lung conditions and inflammatory bowel disease. The treatment of these indications has a combined global annual market size exceeding US$125B per annum.
Incannex has completed a phase 1 clinical trial to measure the safety, tolerability, and pharmacokinetic profiles of IHL-675A compared to the FDA reference listed drugs, Plaquenil (HCQ) and Epidiolex (CBD).
Incannex has completed a phase 1 clinical trial to measure the safety, tolerability, and pharmacokinetic profiles of IHL-675A compared to the FDA reference listed drugs, Plaquenil (HCQ) and Epidiolex (CBD).
Three cohorts of 12 participants (n=36) received either IHL-675A, CBD or HCQ and the clinical assessments were identical across the three arms of the trial. At the conclusion of the trial, Incannex observed IHL-675A to be well tolerated, with no adverse events of concern or serious adverse events.
Incannex has assessed the anti-inflammatory effect of IHL-675A on inflammatory bowel disease, using a mouse model of colitis. In this model, colitis is induced by intracolonic installation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in 50 % ethanol. The ethanol disrupts the intestinal barrier, permitting TNBS to interact with colon proteins.
Mice were treated with IHL-675A, CBD or HCQ for four consecutive days after administration of TNBS/ethanol to induce ulcerative colitis. A vehicle treated group and sham group were included in the study. Stool consistency was monitored over the course of the experiment. On Day 5 mice were sacrificed, blood collected for cytokine analysis and the colon removed for analysis.
Results IHL-675A outperformed both CBD and HCQ at reducing the colitis index, macroscopic damage score, stool consistency score, colon to body weight ratio and myeloperoxidase (MPO) levels. These results indicate that IHL-675A has a benefit in a mouse model of ulcerative colitis greater than that of CBD or HCQ alone. In turn, this indicates that IHL-675A has potential for treating inflammatory bowel disease in humans.
Addressable Market
- Inflammatory bowel disease treatment market is expected to reach USD $22.4 billion by 2026 (7)
Development
Incannex is currently planning a phase 2, blinded, placebo-controlled clinical trial to determine the safety and efficacy of IHL-675A cGMP soft gel capsules in patients with inflammatory bowel disease. The results of the trial will contribute to the combination rule assessment in a FDA505(b)2 new drug application dossier.
IHL-675A comprises a combination of HCQ, an expired patent registered pharmaceutical drug, and CBD. HCQ is a disease modifying anti-rheumatic drug that regulates the activity of the immune system, which may be overactive in some conditions. HCQ can modify the underlying disease process, rather than simply treating the symptoms.
Incannex has demonstrated that IHL-675A components, CBD and HCQ act synergistically to inhibit production of key inflammatory cytokines in an in vitro study of human cells and in four distinct successful in vivo experiments using established models of inflammation.
Incannex has evaluated the results of these experiments and believe IHL-675A to be a multi-use drug candidate suitable for the prevention and treatment of inflammation, with an initial focus on: rheumatoid arthritis, inflammatory bowel disease, and inflammatory lung conditions (acute respiratory distress syndrome, COPD, asthma, and bronchitis).
In a pre-IND meeting, the US FDA has agreed that marketing applications for IHL-675A should be 505(b)(2) applications. A 505(b)(2) New Drug Application (‘NDA’) contains full safety and effectiveness reports but allows some of the information required for NDA approval, such as safety and efficacy information on the active ingredients, to originate from historical studies not conducted by Incannex.
This will result in an accelerated and less-costly route to approval, compared with a traditional development path [505(b)(1)], whilst creating new and differentiated commercial products, subject to clinical success.