Aberdeen 12th August 2015. In a study published this week in EBioMedicine, Aberdeen Royal Infirmary/University of Aberdeen’s Prof Graham Devereux and NovaBiotics demonstrate for the first time, the activity of NovaBiotics’ candidate cystic fibrosis (CF) therapy, Lynovex, within the complex physiological environment of CF sputum, including its ability to kill the emerging CF pathogen Mycobacterium abscessus.
23 adult CF patients from the CF clinic at Aberdeen Royal Infirmary participated in the study. The number of bacteria present in samples of their sputum was measured before, and 24 hours after exposure to Lynovex, with and without antibiotics frequently used to treat CF lung infections. The viscosity of the sputum samples following treatment with Lynovex in the laboratory was also measured.
The results obtained demonstrate Lynovex’s striking ability to reduce sputum bacterial levels within only a few hours of exposure. Lynovex outperformed tobramycin and ciprofloxacin (two antibiotics commonly used to treat CF lung infections) in its ability to kill the complex mix of sputum bacteria within these samples, but the combination of these antibiotics plus Lynovex was even more effective; an important finding as Lynovex is intended as an ‘add-on’ adjunct therapy to be used alongside existing CF antibiotics in order to make them more effective and to counteract/reverse drug resistance.
Some of the participating subjects in this study were infected with M. abscessus and these bacteria were isolated and their sensitivity to Lynovex assessed separately, with and without antibiotics currently used to treat M. abscessus. This allowed the team to determine, for the first time, whether Lynovex has a direct antimicrobial effect on M. abscessus as well as the other more common bacteria within CF sputum. The data generated show that the clinical isolates and one type strain of M abscessus tested were all sensitive to the antibiotic effects of Lynovex and that Lynovex also potentiated the antibacterial capacity of antibiotics commonly used to treat this pathogen. M. abscessus has been described as an emerging “monster” bacterium/complex of bacteria in CF that has rapidly taken hold as a clinically challenging infection, there are concerns about patient to patient spread and it is usually very resistant to antibiotics. M. abscessus is therefore very difficult to treat and consequently has a significant negative impact on clinical outcomes in those patients who are infected. Although only a very small number of M. abscessus were tested in this first study, the team have gained clear evidence on which to base larger tests of Lynovex as a potential candidate in the treatment regime against Mycobacterial infections in CF.
Prof Graham Devereux, lead clinical investigator, commented on the results of the study saying: “In this laboratory study, we investigated whether Lynovex is able to kill the bacteria living in their own environment, namely the sputum to which they are adapted to live in. The effects of Lynovex on sputum bacteria, sputum viscosity and Mycobacterium abscessus are very promising. Further work is required to see if Lynovex works when given to people with CF.”
Dr Deborah O’Neil, NovaBiotics CEO said: “This study’s findings are the next essential step in Lynovex’s journey towards being a new therapy option for CF. This exciting drug candidate simply will not work unless its pharmacologic effects – against bacteria and mucus - are retained within CF sputum. We have now confirmed this with the data reported in our EBioMedicine publication”. She goes on to say that: “The M. abscessus data are very encouraging and timely and we look forward to investigating this further as a matter of priority.”
Full text manuscript at: http://www.sciencedirect.com/science/article/pii/S2352396415301109.
About cystic fibrosis (CF)
CF is a chronic, life-limiting disease that affects the lungs, digestive tract and other organ systems. It is an inherited condition that affects around 70,000 individuals worldwide and is caused by any one of >1,500 mutations in a single gene (the CFTR gene). The effects of this mutation lead to symptoms in multiple internal organs with the lungs and the digestive system typically being the most significant tissues affected and where treatment is focused. The overproduction of mucus by the cells lining the airways and digestive tract lead to impaired lung function, recurrent or chronic respiratory infections and inflammation or degenerative lung damage and an impaired ability to digest food. The respiratory infections associated with CF have a deleterious impact on lung function, and the presence of particular bacterial or fungal pathogens can also rule out transplantation as an intervention option for CF patients. Antibiotic resistance to conventional or existing therapies is a major issue in CF because of the length of time and doses to which patients are exposed to these agents over the course of their life. Furthermore, a number of the emerging pathogens that are becoming more commonly associated with CF are inherently insensitive to conventional antibiotic therapies.
Lynovex® (NM001) has unique multi-modality as a potential novel CF therapy. It is antibacterial (rapidly bactericidal), an antibiofilm agent, mucoactive and it synergises with standard of care antibiotics to potentiate their effects on the bacterial pathogens associated with CF. With these properties, Lynovex® (NM001) has the potential to tackle the major clinical features responsible for progressive lung disease in CF; breaking down excessive, dehydrated mucus and killing the bacteria that infect and colonise the CF airways. In this respect, Lynovex® is not only active against drug resistant bacteria in CF but reverses antibiotic resistance in bacteria to conventional antibiotics when used as an adjunct/co-therapy.
NovaBiotics Ltd is a clinical-stage biotechnology company focused on the design and development of first-in-class anti-infectives for difficult-to-treat, medically unmet diseases. A leading innovator in the anti-infectives space, the Company’s robust pipeline includes clinical stage antimicrobials that have been derived from NovaBiotics’ proprietary anti-infective peptide platform and a “mini biologic” antibacterial-mucolytic compound (NM001/Lynovex®). NovaBiotics lead product, NP213 (Novexatin®) is being developed as a topical treatment for fungal nail infections (onychomycosis), a condition that affects more than 10% of the global population. NovaBiotics’ exciting pipeline of preclinical stage drug candidates is also demonstrating significant promise. These include Novamycin® (NP339, NP525), an antifungal peptide against Candida spp, Aspergillus spp and other clinically relevant yeasts and moulds as well as NP432 (Novarifyn®), a peptide antibacterial for difficult to treat multi-drug resistant Gram-negative and Gram-positive infections.