Incannex announces in vitro results from sepsis-associated acute respiratory disease drug studies

Clinical-stage cannabinoid development company Incannex Healthcare (ASX: IHL) has announced positive preliminary results on the anti-inflammatory activity of lead drug IHL-675A against sepsis-associated acute respiratory distress syndrome (SAARDS), which is the leading cause of mortality of COVID-19.

In an in vitro assay involving drug constituents cannabidiol (CBD) and hydroxychloroquine (HCQ), Incannex has identified the range of effective concentrations to completely inhibit the inflammation biomarkers, called Cytokines, in human cells.

They’re now awaiting results on the assessment of the two drugs in a combination product whereby lower doses of the two drugs combined is theorised to achieve the same level of efficacy, minimising the potential for unwanted side effects and the delineation of the defined IHL-675A product.

Assay method

The assay saw human peripheral blood mononuclear cells (PBMCs) isolated from three different donors and treated with CBD or HCQ at a range of concentrations prior to the induction of an inflammatory response using bacterial lipopolysaccharide (LPS). An untreated control where only LPS was added was also included in the experiment.

After a 24-hour incubation period in the presence of each study drug and LPS, the culture medium was analysed for levels of key inflammatory cytokines using a Luminex-based assay.

According to Incannex, CBD and HCQ displayed “linear anti-inflammatory dose response curves” – in other words, with increasing concentrations of drug, the PBMCs produced less cytokines in response to stimulation with LPS.

Cytokines are cell-signalling molecules which aid cell-to-cell communication in immune responses and stimulate the movement of cells towards sites of inflammation, infection, and trauma.

Elevated levels of those cells secrete more cytokines and this “cytokine storm” recruits even more immune cells, fueling a cascading cycle which eventually damages host tissues and organs.

This can lead to “wet lung”, damaging the patient’s lung tissue and can ultimately lead to death, as has been seeing in some hospitalised COVID-19 patients.

The highest concentrations of CBD and HCQ tested by IHL were found to completely inhibit cytokine production by PBMCs in response to bacterial LPS after 24 hours.

Preliminary results

Incannex chief scientific officer Dr Mark Bleackley said the assay’s preliminary results bode well for the drug’s development.

“The potent anti-inflammatory activity of both CBD and HCQ is encouraging for the development of IHL-675A in prevention and treatment of sepsis associated ARDS”, he said.

“Identifying the optimal combination of CBD and HCQ will contribute to the design of an IHL-675A fixed dose combination product whereby lower doses of drugs can achieve the same level of efficacy”.

The next steps for the program include the receipt and assessment of in vitro combination assays, followed by a Stage 2 in vivo study that will assess the optimal fixed dose combination in an animal setting.

SAARDS infection

Sepsis occurs when a patient’s immune system overreacts to an infection, producing excessive levels of inflammatory cytokines which attract immune cells.

When the lungs are damaged by the cytokine storm hyper-inflammatory response, SAARDS is said to be occurring.

SAARDS is characterised by widespread inflammation of the lungs (often referred to as ‘wet lung’ or pneumonia) inhibiting a patient’s ability to oxygenate blood.

It is believed to be a leading cause of lung, urinary tract, stomach and skin infections as well as COVID-19 infection.

For many decades, the treatment of SAARDS has been limited to the use of oxygen ventilators to treat symptoms of acute respiratory disease but not the underlying inflammation “feedback loop” caused by the infection.

There is currently no registered pharmacotherapy (drug) treatment for SAARDS.