Dr Heather Fairhead founded Phico Therapeutics with seed funding from Cambridge Research and Innovation Limited (CRIL). The company has since raised over £9 million, including UK government grants of £350,000 and investment from institutional investors and Business Angels. Phase I and Phase II clinical trials with Phico’s first product, SASPject™ PT1.2 are funded by a Strategic Translation Award of over £1 million from The Wellcome Trust.
Phico Therapeutics has given oral and poster presentations at major conferences around the world including ICAAC 2007/8/9 and ECCMID 2008/9.
Phico Therapeutics is based at the Babraham Bioincubator near Cambridge and employs a team of 14, including nine full-time, post-doctoral scientists.
Phico Therapeutics’ technology, known as SASPject™, is a new concept in antibacterial therapy and could potentially form the basis of a new generation of antibiotics. SASPject™ combines broad-spectrum antibacterial proteins called SASP, or small, acid-soluble spore protein(s), with delivery vectors that can each be programmed to target selected bacteria. SASPject™ works by injecting a gene that encodes SASP, directly into targeted bacteria. The targeted bacteria then produce SASP, which bind to the bacterial DNA and inactivate it. Functional DNA is crucial to cell survival. SASP ‘turn off’ DNA so the targeted bacterial cell cannot metabolise or reproduce. The immune system can then remove the bacteria from the body.
Crucially, SASP bind to all bacterial DNA, irrespective of the sequence of that DNA. Spontaneous mutations in DNA, or the import of new DNA that gives new characteristics to the bacterial cell, are key ways in which bacteria develop resistance to antibiotics. Neither of these strategies affects the ability of SASP to bind to and inactivate bacterial DNA.
Because SASP can bind to and inactivate all of the DNA inside bacteria, including plasmid DNA, which is a common source of antibiotic resistance genes, it could actively help to prevent the spread of antibiotic resistance and toxin genes.
This approach has the potential to provide a number of significant advantages over traditional antibiotics:
•The unique mode of action of SASP makes it unlikely that bacteria will be able to develop resistance to this antibacterial protein.
•SASPject™ technology can be used to target any selected bacteria, individual or multiple bacterial species or genera, including those that are multi-antibiotic resistant.
•Unlike conventional antibiotics, SASPject™ has no effect on any bacteria other than those at which it is targeted. Normal skin and gut bacteria ("good bacteria") are unharmed.
•SASPject™ target selectivity prevents the release of toxins and other inflammatory cell components from non-target bacteria thus potentially minimising associated side effects.
The role of Phico's SASPject™ delivery vectors is simply to inject SASP genes into selected target bacteria. For this purpose, Phico modifies a single, fully characterised bacterial virus (bacteriophage) for each type of target bacterium. SASPject™ vectors target only bacterial cells and no other cell type.
SASPject™ can potentially be targeted at any bacteria but initial products in development are focused on multi-drug resistant bacteria, or “superbugs”.
SASPject™ PT1.2 is aimed at Staphylococcus aureus, including MRSA. MRSA infections were first detected in the late 1990s but are now a global problem in hospitals. Thousands of fatalities have been recorded as a direct result of MRSA infection and infection control is vital to many national health systems. SASPject™ PT1.2 will be used for the intra-nasal decolonisation of S. aureus, including MRSA. A Phase I clinical trial has been successfully completed and a Phase II trial will commence in Q1, 2011.
SASPject™ PT2.X, aimed at Clostridium difficile is the most common cause of serious diarrhoea in hospitals and is one of the major causes of healthcare-associated infections. Symptoms can be as serious as intestinal perforation or death. There are an estimated 500,000 cases of C. difficile infection (CDI) in the US each year and more than 50,000 in the UK in 2007. Mortality rates almost quadrupled between 1999 and 2005. SASPject™ PT2.X will be an oral therapy against CDI. The selectivity of SASPject™ PT2.X is suited to the treatment of CDI because the normal bacterial flora of the gut are left unharmed, making it more difficult for C. difficile to re-establish an infection.
SASPject™ PT3.X is being developed against antibiotic resistant Gram negative bacteria including E. coli, K. pneumoniae and P. aeruginosa. These bacteria can cause serious infections and their resistance to conventional antibiotics is spreading.
SASPject™ PT4.X is being developed from SASPject™ PT1.2 for use against systemic staphylococcal infections.