Phico Therapeutics, a Cambridge-based company developing unique antibiotic technology to address one the most urgent challenges facing medicine today, has achieved a major milestone in the development of agents to eradicate multidrug resistant bacteria including Escherichia coli (E. coli) and the “Indian superbug”, NDM-1 Klebsiella pneumoniae which carries the NDM-1 gene and enzyme.

Phico Therapeutics CEO Dr Heather Fairhead gave two lectures and present two posters at ICAAC, the premier conference on antimicrobial agents and infectious diseases, which showcases the latest-breaking science and lectures from top researchers from around the world.

Dr Fairhead presented F-2066 - SASP: Efficacy against Pseudomonas aeruginosa in a Murine Pneumonia Model demonstrating that Phico Therapeutics’ SASPject PT3.1 shows promising in vitro and in vivo activity against P. aeruginosa, a prominent ICU pathogen with high levels of antibiotic resistance, as is increasingly seen in other bacteria such as MRSA, E. coli and K. pneumoniae. In this study, PT3.1 was shown to be effective in treating P. aeruginosa lung infection.

“It is an honour for me to have been invited to present this poster at ICAAC 2012 highlighting the progress we have made in the development of this revolutionary technology” explains Dr Heather Fairhead CEO, Phico Therapeutics. “We are creating a new class of antibacterial that we can use to more effectively treat patients with multidrug resistant strains of Gram-negative bacteria including E. coli and K. pneumoniae.”

Phico continue to develop products in their antibiotic platform technology, SASPject, which is specifically designed to combat the problem of antibiotic resistance.

The successful completion of a £1.03m Wellcome Trust Strategic Translation Award supported a phase I trial which showed that Phico’s first product, SASPject PT1.2, to treat nasal infections of the bacterium Staphylococcus aureus, including the superbug MRSA, is safe and well tolerated in healthy human volunteers. Phico is developing PT3 products to broaden the range of activity in drug resistant Gram negative bacteria.

SASPject PT3 products are intravenous treatments for infections of Gram-negative bacteria such as P. aeruginosa, K. pneumoniae and E. coli, which may carry the NDM-1 enzyme. Metallo-beta-lactamase-1 (NDM-1) is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics which are a mainstay for the treatment of antibiotic-resistant infections.

Because the NDM-1 gene is carried on plasmids, the gene can be readily transferred between different strains of bacteria by horizontal gene transfer. The resulting bacteria are resistant to multiple classes of antibiotics, including beta-lactam antibiotics, fluoroquinolones, and aminoglycosides, but most were still susceptible to colistin, although at least one death has been reported in a patient after treatment with colistin. Since being identified in Sweden in 2009 in a Swedish national of Indian origin, NDM-1 has spread throughout the world with cases appearing in Canada, the UK, Japan, the USA and India. Other genetic elements conferring high levels of antibiotic resistance, such as “VIM”, are also spreading at an alarming rate. This demonstrates the crucial need for new technologies that fight bacterial infection. SASPject PT3 has been shown to be unaffected by all these antibiotic resistances.

SASPject is a novel antibiotic therapy that can be targeted to any bacteria including multi-drug resistant bugs. The active agent is an antibiotic protein called SASP which is coupled to delivery vectors that can be narrow spectrum to target selected individual bacterial species, or broad spectrum to target multiple species or genera of bacteria.

SASP works by binding to bacterial DNA and inactivating it. It switches off all primary functions in the bacterial cell and stops it from reproducing, thereby halting the spread of infection. Crucially, SASP can bind anywhere on the DNA so the development of resistance by bacteria is considered unlikely. The SASP gene is delivered to selected bacterial species using targeted nano-devliery vehicles (NDVs). The bacteria synthesise the anti-bacterial SASP after gene delivery, which leads to rapid cell death.

Phico’s SASPject products deactivate the bacteria and prevent the release of toxins and other inflammatory cell components from both target and non-target bacteria thus potentially minimising toxicity. 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 potentially minimising the gastrointestinal side effects common to traditional antibiotics.

SASPject PT3 products are being developed against antibiotic resistant Gram-negative bacteria including P. aeruginosa, E. coli and K. pneumoniae. These bacteria can cause serious infections and their resistance to conventional antibiotics is spreading.