SHARE PRICE ASX:IHL $

Clinical Trials IHL-675A | Sepsis Associated Acute Respiratory Distress Syndrome (‘SAARDS’) Cannabidiol and hydroxychloroquine combined for the treatment of sepsis associated Acute Respiratory Distress Syndrome

SAARDS is the leading cause of mortality in those with COVID-19

SAARDS is a medical emergency and a type of respiratory failure whereby there are currently no registered pharmaceutical agents for its treatment. It is typically treated with mechanical ventilation and oxygen supplementation in an intensive care unit. Mechanical ventilation is usually delivered through a rigid tube which enters the oral cavity and is secured in the airway (endotracheal intubation), or by tracheostomy when prolonged ventilation is necessary.

Survival rates for ARDS vary depending on age, the underlying cause of ARDS, associated illnesses, and other factors. Some studies estimate that the mortality rate for ARDS is 36% to 52%. High mortality and the current COVID-19 necessitate urgent treatment alternatives.

  • Severe sepsis or septic shock is characterized by an excessive inflammatory response to infectious pathogens.
  • Acute respiratory distress syndrome (ARDS) is a devastating complication of severe sepsis, from which patients have high mortality.
  • The incidence of ARDS in adult patients with sepsis has typically been about 6%–7% in Western countries, increasing markedly in 2020 due to COVID-19 pandemic
  • SAARDS is the leading cause of death in those with COVID-19 infection
  • Those who recover from SAARDS, you often develop long term medical problems resulting from pulmonary fibrosis, or scarring, of the lung tissue.

IHL-675A for Sepsis Associated Acute Respiratory Distress Syndrome (“SAARDS”)

Incannex is developing a novel small molecule therapeutic IHL-675A comprising hydroxychloroquine (‘HCQ’) and cannabidiol (‘CBD’) for the potential treatment of sepsis-associated Adult Respiratory Distress Syndrome (‘SAARDS’), a major unmet clinical need and a leading cause of mortality associated with COVID-19 and other infections.

Incannex lodged a provisional patent application over IHL-675A for SAARDS with the Australian Patent Office in April of 2020 and has engaged a specialist pharmaceutical research organisation Pharmacology Discovery Services, a Eurofins Discovery Partner Lab, (‘Eurofins’) to conduct animal pre-clinical testing.

Incannex received positive results from its pre-clinical animal study for the assessment of the key constituents of IHL-675A against SAARDS. IHL-675A is hypothesised to limit the progression of infections to sepsis hyperinflammation caused by the “cytokine storm” feedback loop.

The study was designed in this manner to:

  1. Demonstrate the ability of Cannabidiol (‘CBD’) and Hydroxychloroquine (‘HCQ’) to inhibit inflammatory cytokine production associated with Sepsis and Sepsis Associated ARDS; and,
  2. assess the dose responses of CBD and HCQ to the production of cytokine inflammatory markers in rodents after inducing sepsis to benefit the design of the fixed dose combination product.

Compared to baseline mice, CBD reduced 5 key inflammatory cytokine levels by 31-90%, relative to the vehicle. Compared to baseline mice, HCQ reduced 5 key inflammatory cytokine levels by 39-88%, relative to the vehicle. 80% of results were deemed statistically significant.

Incannex is currently undertaking an in vitro study to assess the formulated combinations of CBD and HCQ that provide an optimal inflammation dampening response ratio. Results are expected in approximately 2-4 weeks. The second animal study to test for the optimal fixed dose combination will immediately follow the in vitro study.

Subject to success in stage 2 of animal studies, it is the opinion of FDA consultants Camargo Pharmaceutical Services that IHL-675A will be a candidate for FDA Emergency Use Authorisation resulting from the COVID19 pandemic. Incannex will also endeavour to supply IHL-675A under the Australian Special Access Scheme whilst it progresses its FDA data package in the pursuit of eventual product registration.

SAARDS is caused by a hyper-inflammatory response and is the leading cause of mortality associated with severe infections, including the COVID-19 coronavirus infection. There is significant unmet need in the treatment of SAARDS and there are no registered pharmacotherapy (drug) treatments available for the condition.

Update: December 2020

  • HL-675A components, cannabidiol and hydroxychloroquine, act synergistically to inhibit production of key inflammatory cytokines in in vivo studies
  • IHL-675A outperformed CBD alone significantly as presented in Appendix 1, Table 1
  • IHL-675A outperformed the predicted cytokine inhibition based on the activity of each drug alone by 26% to 81% across the five analysed cytokines after 2 hours
  • Incannex and Camargo Pharmaceutical Services LLC will conduct a Pre-IND meeting with the FDA to explore the fastest pathway for registration of IHL-675A
  • Incannex anticipates to be granted an expedited Pre-IND meeting due to the Company’s intention to submit a FDA Emergency Use Authorisation request for patients with COVID-19
  • Incannex has expanded its provisional patent protection to cover the treatment of a range of other inflammatory diseases that represent broad potential market opportunities for the Company, which are currently being evaluated.

What is SAARDS?

What is Sepsis Associated Acute Respiratory Distress Syndrome (‘SAARDS’)?

Acute respiratory distress syndrome (ARDS) occurs when fluid builds up in the tiny, elastic air sacs (alveoli) in your lungs. The fluid keeps your lungs from filling with enough air, which means less oxygen reaches your bloodstream. This deprives your organs of the oxygen they need to function.

SAARDS denotes that the ARDS is caused by Sepsis, which is a widespread infection of the bloodstream. People who have severe COVID-19 infection may develop SAARDS.

Many people who develop SAARDS do not survive. The risk of death increases with age and severity of illness. Of the people who do survive ARDS, some recover completely while others experience lasting damage to their lungs resulting from Fibrosis (scarring).

Causes & Symptoms

What are the causes of SAARDS?

Anyone can get sepsis, but the risk is higher in:

  • People with weakened immune systems
  • Babies and very young children
  • Elderly people
  • People with chronic illnesses such as diabetes, AIDS, cancer and kidney or liver disease
  • Someone suffering from a severe burn or wound.

Common infections that lead to SAARDS are:

  • Lung infection (i.e. COVID-19)
  • A urinary tract or kidney infection
  • A gut infection
  • A skin infection

The signs and symptoms of ARDS can vary in intensity, depending on its cause and severity, as well as the presence of underlying heart or lung disease. They include:

  • Severe shortness of breath
  • Labored and unusually rapid breathing
  • Low blood pressure
  • Confusion and extreme tiredness

If you have ARDS, you can develop other medical problems while in the hospital. The most common problems are:

  • Scarring (pulmonary fibrosis)
  • Blood clots
  • Collapsed lung
  • Breathing problems
  • Tiredness and weakness
  • Problems with memory and thinking clearly.

Who It Affects & Current Treatment

Who is affected by SAARDS?

  • The incidence of ARDS in adult patients with sepsis has typically been about 6%–7% in Western countries, increasing markedly in 2020 due to COVID-19 pandemic
  • SAARDS is the leading cause of death in those with COVID-19 infection

SAARDS is a medical emergency and a type of respiratory failure whereby there are currently no registered pharmaceutical agents for its treatment.

SAARDS is the leading cause of death in those with COVID-19 infection

It is typically treated with mechanical ventilation and oxygen supplementation in an intensive care unit. Mechanical ventilation is usually delivered through a rigid tube which enters the oral cavity and is secured in the airway (endotracheal intubation), or by tracheostomy when prolonged ventilation is necessary.