Previous Investigations

Most work in phage therapy focuses on the application of lytic bacteriophages since these bring about destruction of the target bacterium. However, lytic phages are sometimes difficult to isolate and may have other disadvantages. For clinical therapeutic applications Novolytics also uses obligately lytic phages in final formulations. However it may start with lysogenic phages where naturally occurring lytic phages are difficult to isolate.

MRSA – The Initial Target

Novolytics seeks to combat infectious disease caused by antibiotic resistant bacteria. The first target organism is Methicillin-Resistant Staphylococcus aureus (MRSA) and the first application is nasal decolonisation of MRSA. From a clinical perspective MRSA is primarily one of hospital cross-infection rather than the repeated evolution of resistance. The spread of MRSA is increased where patients are moved from ward to ward, or between hospitals and nursing homes. Patients who have suppressed immune systems are at greater risk of contracting this infection, which can result in increased hospitalisation stay, increased morbidity and mortality and increased cost to the community at large. Effective treatment is heavily dependent upon the identification and treatment of carriers. Novolytics has developed a gel containing a cocktail of phages targeted at MRSA to treat nasal carriage of MRSA, thus significantly reducing the incidence of MRSA transmission.

Future Product applications

Humans

Novolytics' first phage product is formulated as a gel and in this guise lends itself to direct topical application. The most obvious applications after nasal decolonisation are treatment of wounds/ulcers and treatment of patients subject to therapeutic regimes where catheters or other in-dwelling devices are used frequently. Renal dialysis patients are an example. Theoretically the MRSA phage cocktail could be used to treat pneumonia where the offending bacterium is MRSA, or bacteraemias again caused by systemic infection with MRSA. However it is clear that some applications will be easier to achieve than others either from a delivery aspect or from an ethical perspective. Commercially the Company believes preference should be given to those applications that are least risky from a delivery perspective. The most attractive additional therapeutic applications for the MRSA cocktail are:

1. Complicated Skin and Skin Structure Infections - formulation would be a gel
2. Catheters and other In dwelling devices - formulation would be a gel

Thereafter

1. Infectious endocarditis - formulation could be a gel but might be a modified spray
2. Infected Burns - formulation could be a gel but might be a modified spray

Infectious endocarditis can arise as a result of infection following dental treatment and it is conceivable that the gel might be applied to dental patients as a precaution in the same way as the Company is planning to apply its gel formulation to patients nasally colonised with MRSA.

Clostridium Difficile and other Bacterial Targets

The Company has a commercial collaboration with a leading UK University to help it design a new phage cocktail targeted at Clostridium difficile. It also plans to develop new cocktails targeted at the control of infectious diseases caused by bacteria for which there are few if any effective antibiotics. Examples include Extended Spectrum Beta Lactamase ("ESBL") enterics and enterococcals. ESBL enterics are bacterial infections caused by bacteria that have the ESBL enzyme, which mediates resistance to third generation cephalosporins (such as ceftazidime, cefotaxime, and ceftriaxone) and monobactams (eg. aztreonam). Such bacteria (typically E.coli and Klebsiella) usually live quite harmoniously in the bowel but can cause trouble if they end up where they should not be, such as in the urinary tract. This may happen if a patient has a urinary tract catheter inserted and there is poor hygiene. The commonest infections caused by enterococci are urinary tract infections and wound infections; they also frequently colonise open wounds and skin ulcers. Enterococci are amongst the most antibiotic resistant bacteria isolated from humans. Minor infections can usually be treated by antibiotics such as penicillins, macrolides or tetracyclines, taken by mouth. However serious infections often need prolonged treatment, usually with several antibiotics administered together by injection.

Animals

Novolytics is working with a European consortium (FP7 Concord) that seeks to understand the epidemiology of MRSA, particularly community acquired MRSA and Farm Associated MRSA. Novolytics is involved in the development of an effective treatment for MRSA in the farmyard setting starting with pigs as an exemplar species. If effectiveness can be demonstrated the Company may seek to address bovine mastitis which is frequently associated with Stapylococcus aureus infections and which has considerable economic implications for farmers as a result of reduced milk sales.