BioWorld International Correspondent

LONDON - Phico Therapeutics Ltd. raised £750,000 (US$1.4 million) from business angels in a second-round funding, which should enable it to progress its bacteriophage antibiotic platform technology and get the lead product into Phase I trials.

Heather Fairhead, CEO, told BioWorld International the decision to raise a relatively modest amount was made in the interest of existing investors.

"We are still relatively early stage and felt we could push forward with private money," she said. "The amount raised will get us to Phase I, where we will have a significant uplift in value."

Reaching Phase I with the lead product, against hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) infection, will take until the third quarter of 2005. Fairhead then intends to do a venture capital funding round to pay for clinical trials.

Cambridge-based Phico has developed SASPject, a technology platform for developing antibiotics that can be used against all bacteria, but can also be targeted against specific infections. The technology uses bacteriophages for delivering the lethal small-acid-soluble protein (SASP) gene to pathogenic bacteria. The gene targets a fundamental mechanism, common to most bacteria, that inactivates DNA. Fairhead said that would make it difficult for bacteria to develop resistance to antibiotics based on SASPject.

"Spontaneous mutations in DNA, or the import of new DNA, giving new characteristics to the bacterial cell are key ways in which bacteria develop resistance to antibiotics, and neither of these strategies will affect the ability of SASP to bind to and inactivate bacterial DNA," she said.

Furthermore, SASP binds to all bacterial DNA, including plasmid DNA, which is a common source of antibiotic-resistance genes, and therefore actively helps to prevent the spread of resistance.

In laboratory studies, the SASP gene causes a 99 percent fall in the viability of E. coli. Bacteriophages can infect only bacteria, so there is no risk of delivering the gene to a patient's cells. Also, the approach should limit side effects, as loss of bacterial viability is not accompanied by bacterial cell lysis and the release of toxins and other inflammatory cell components.

The possibility of using bacteriophages to combat infection was first recognized more than 90 years ago. Phages bind to bacterial cells, injecting their genetic material, which instructs the cell to produce more phages. The cell wall of the bacterium then disintegrates, releasing the new phages to invade more bacterial cells. However, the bacteriophages themselves die once the bacteria are eliminated.

The potential of bacteriophages largely was overlooked following the development of penicillin, but interest has been rekindled by the development of antibiotic-resistant bacteria.

Each species of bacteria has specific bacteriophages, opening the way for Phico to develop products against specific infections. But Fairhead said SASPject also could be used to develop broad-spectrum antibiotics by modifying a phage so that it infects more than one bacteria.

"The strength of our approach is that we are using the same gene in each case, with the specificity coming from the bacteriophage," she said. "At the same time, we know how to modify phages to broaden the spectrum of effect."

By the time Phico has completed the preclinical development of the MRSA product, Fairhead said the SASPject platform would be mature enough to be licensed. The company is developing a product against Clostridium difficile infections also, and intends to progress a broader-spectrum product.

"C. difficile is a very good example of the advantage of being able to target an antibiotic against a particular infection," Fairhead said. "Giving broad-spectrum antibiotics makes this condition worse because it destroys the [intestinal] flora. It's a great case for targeted treatment."

Fairhead was a molecular microbiologist working mainly in pathogens when she came up with the idea of using bacteriophages as a vehicle. She founded Phico in September 2000 with seed funding from Cambridge Research and Innovation Ltd. and raised £450,000 in a first round in June 2002.

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