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World first | Human clinical study shows synthetic CBD formula eradicates Staphylococcus Aureus

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Philadelphia PA and Sydney Australia, 3 February 2021: Clinical stage synthetic cannabinoid company Botanix Pharmaceuticals Limited has today published positive data from a world first human clinical study, examining the safety, tolerability and efficacy of its BTX 1801 antimicrobial product for the eradication of Staphylococcus Aureus (Staph).

Staph, also called golden staph, is a common bacterium that lives on the skin or in the nose. In most situations it is harmless; however, if it enters the body through a cut in the skin, it can cause a range of mild to severe infections, or even death. As part of this study, Botanix was working to minimise the risk of infection by removing or decolonising bacteria from the nose – a primary site for spreading infection to other parts of the body (the nose is frequently touched, usually more than 40 times a day).

The BTX 1801 Phase 2a nasal decolonisation proof of concept study showed that two different BTX 1801 synthetic CBD formulations (ointment and gel) were safe, well tolerated and successful at eradicating Staph bacteria from the nose of healthy volunteers nasally colonised[1] with Staph.

Eradication rates as high as 76.2% were obtained at Day 7 post treatment, with eradication effects extending through to Day 28 of the study to 23.8%, despite no further treatment after Day 5. Botanix met the endpoints of its BTX 1801 Phase 2a study.

“We are very pleased to announce this top-line data that demonstrates synthetic cannabidiol (“CBD”) is a safe and effective nasal decolonisation agent.  Moreover, this is the first time that synthetic CBD has been shown to have clinical utility as an antimicrobial agent in humans,” said Botanix President and Executive Chairman, Vince Ippolito.

“These results support continued development of BTX 1801 for the treatment of a variety of infections, in addition to the prevention of post-surgical infections.”

Antibiotic resistance is a significant global challenge in the context of public health, with the UN forecasting drug resistant diseases could cause 10 million deaths each year by 2050 and result in an annual economic loss of US$100 trillion if new solutions are not found.[2]     

Staph and methicillin-resistant Staph (MRSA) are the leading cause of Surgical Site Infections[3] (SSIs) and approximately 80% of SSIs are caused by the patient infecting themselves from their own nose. Antibiotics used for nasal decolonisation (e.g. BactrobanTM also known as mupirocin) have seen a significant increase in the development of resistance, with some hospitals recording resistance rates as high as 95% restricting its use.

“BTX 1801’s observed upfront eradication rates and sustained eradication effect, following the treatment period, is very encouraging.  Data from the BTX 1801 study represents a significant milestone and enhances the potential of better infection prevention measures in surgical settings to combat the growing global development of antibiotic resistance,” said Murdoch University’s Chair of Public Health, Professor Geoffrey Coombs.

Botanix is now actively exploring opportunities for its synthetic cannabidiol and broader cannabinoid analog assets in other secondary infections, and across different of routes of administration.

Summary of 1801 Study design and endpoints

The 1801 Study was a randomised, vehicle-controlled, double-blind, Phase 2a study conducted at a single site due to constraints associated with COVID-19. The primary objectives focused on evaluating safety and tolerability, as well as evaluating the effectiveness of two different candidate formulations of BTX 1801 (ointment or gel containing synthetic cannabidiol), compared to their respective vehicle or placebo formulations (the ointment or gel without synthetic cannabidiol). Each formulation was applied twice daily for 5 consecutive days to the anterior nares (the inner surface of the nose) of healthy participants intranasally colonised with Staph.  Male and female healthy volunteers aged 18-65 were eligible to enrol in the 1801 Study.

Safety and tolerability were evaluated at prespecified timepoints during treatment (Days 1 to 5) and following treatment at Day 7 (2 days after the end of treatment), Day 12 (7 days following the end of treatment) and at Day 28 (23 days after the end of treatment).  Efficacy was evaluated at Day 7, Day 12 and Day 28.  No prospective calculations of statistical power were made for this exploratory study. 

Summary of 1801 Study results

Results of the BTX 1801 Study show the two formulations of BTX 1801 met the Study endpoints. Firstly, BTX 1801 was safe and well tolerated, with all 66 enrolled participants successfully completing the 1801 Study with each group (ointment, gel and vehicle) consisting of 22 participants. The incidence of adverse events was low, mild in severity and occurred at similar rates across the different treatment groups with no severe events reported.  Secondly, efficacy of both ointment and gel formulations at the primary endpoint of Day 12 was demonstrated. 

At Day 7, one of the secondary endpoints (2 days after the end of the treatment period), Staph eradication was demonstrated in 76.2% and 68.8% of the participants in the BTX 1801 ointment and gel groups respectively, compared with 27.8% of participants in the combined vehicle groups. At Day 12 (7 days after the end of the treatment period), the primary endpoint, BTX 1801 demonstrated Staph eradication in 38.1% of participants in the ointment group and 25.0% in the gel group, compared to 16.7% for the combined vehicle groups.

Despite no treatment since Day 5 of the study, by Day 28, the other secondary endpoint, (23 days after the end of the treatment period), Staph eradication rates of both formulations of BTX 1801 only declined slightly from Day 12, to 23.8% and 18.8% for the BTX 1801 ointment and gel groups respectively, compared with 12.5% for participants in the combined vehicle groups.

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[1] Nasal colonisation or carriage of S. aureus was confirmed on 3 separate occasions over a period of up to 43 days prior to the subject receiving treatment.

[2] No Time to Wait: Securing the future from drug-resistant infections. Report to the Secretary-General of the United Nations (2019) available at https://www.who.int/antimicrobial-resistance/interagency-coordination-group/IACG_final_report_EN.pdf?ua=1

[3] Decolonization to Reduce Post discharge Infection Risk among MRSA Carriers, Huan et al Feb 14 2019, N Engl J Med 2019; 380:638-650

UQ media release | Research establishes antibiotic potential for cannabis molecule

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Synthetic cannabidiol, better known as CBD, has been shown for the first time to kill the bacteria responsible for gonorrhoea, meningitis and legionnaires disease.

The research collaboration between The University of Queensland and Botanix Pharmaceuticals Limited could lead to the first new class of antibiotics for resistant bacteria in 60 years.

The UQ Institute for Molecular Bioscience’s Associate Professor Mark Blaskovich said CBD – the main nonpsychoactive component of cannabis – can penetrate and kill a wide range of bacteria including Neisseria gonorrhoeae, which causes gonorrhoea.

“This is the first time CBD has been shown to kill some types of Gram-negative bacteria. These bacteria have an extra outer membrane, an additional line of defence that makes it harder for antibiotics to penetrate,” Dr Blaskovich said.

In Australia, gonorrhoea is the second most common sexually-transmitted infection and there is no longer a single reliable antibiotic to treat it because the bacteria is particularly good at developing resistance.

The study also showed that CBD was widely effective against a much larger number of Gram-positive bacteria than previously known, including antibiotic-resistant pathogens such as MRSA (methicillin-resistant Staphylococcus aureus) or ‘golden staph’.

Dr Blaskovich said cannabidiol was particularly good at breaking down biofilms—the slimy build-up of bacteria, such as dental plaque on the surface of teeth—which help bacteria such as MRSA survive antibiotic treatments.

Dr Blaskovich’s team at the Centre for Superbug Solutions mimicked a two-week patient treatment in laboratory models to see how fast the bacteria mutated to try to outwit CBD’s killing power.

“Cannabidiol showed a low tendency to cause resistance in bacteria even when we sped up potential development by increasing concentrations of the antibiotic during ‘treatment’.”

“We think that cannabidiol kills bacteria by bursting their outer cell membranes, but we don’t know yet exactly how it does that, and need to do further research.

The research team also discovered that chemical analogs – created by slightly changing CBD’s molecular structure—were also active against the bacteria.

“This is particularly exciting because there have been no new molecular classes of antibiotics for Gram-negative infections discovered and approved since the 1960s, and we can now consider designing new analogs of CBD within improved properties.”

Vince Ippolito, the President and Executive Chairman of Botanix, said the research showed vast potential for the development of effective treatments to fight the growing global threat of antibiotic resistance.

“Congratulations to Dr Blaskovich and his team for producing this significant body of research—the published data clearly establishes the potential of synthetic cannabinoids as antimicrobials,” Mr Ippolito said.

“Our Company is now primed to commercialise viable antimicrobial treatments which we hope will reach more patients in the near future. This is a major breakthrough that the world needs now.”

Dr Blaskovich said collaborating with Botanix has sped up the research, with Botanix contributing formulation expertise that has led to the discovery that how cannabidiol is delivered makes a huge difference in its effectiveness at killing bacteria.

The collaboration has enabled Botanix to progress a topical CBD formulation into clinical trials for decolonisation of MRSA before surgery.

“Those Phase 2a clinical results are expected early this year and we hope that this will pave the way forward for treatments for gonorrhoea, meningitis and legionnaires disease.

“Now we have established that cannabidiol is effective against these Gram-negative bacteria, we are looking at its mode of action, improving its activity and finding other similar molecules to open up the way for a new class of antibiotics.”

JOURNAL ARTICLE:

This research has been published in Communications Biology. See journal article HERE.

VIDEO:

Video news release and b-roll package is available HERE.

MEDIA:

H^CK Director, haley@hck.digital, +61 423 139 163 | Dr Mark Blaskovich, m.blaskovich@imb.uq.edu.au, +61 (0) 414 955380 | IMB Communications, communications@imb.uq.edu.au, +61 (0) 405 661856;

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The PASTEUR Act

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Two US lawmakers have introduced a bipartisan bill to create a new payment model to encourage drug developers to develop new classes of antibiotics.

It’s called the PASTEUR Act, which will facilitate upfront payments to companies in exchange for unlimited access to their antibiotics. In turn, drug makers can recover their costs and turn a profit, before selling large volumes of product. 

Relevant extracts include:

  • An antimicrobial drug developer can apply to receive a ‘critical need antimicrobial’ designation
  • Contracts will range from $750 million to $3 billion and will be paid out over a period of up to 10 years or through the length of patent exclusivity

Botanix Pharmaceuticals wholeheartedly welcomes this news. As we enter a critical period of R&D for our BTX 1801 antimicrobial resistance (AMR) platform, this is a significant endorsement of the immediate need for novel antibiotics and further evidence of the world’s most powerful pharmaceutical influencers prioritising expedited and significant expenditure in this space.

Read a summary of the bill here.