As a global debate rages on the future of antibiotics due to the presence of yet another “superbug,” NDM-1 resisting all known antibiotic treatments, the health community is seriously looking at alternate options. One of the most promising alterna­tives appears to be the use of bacterio­phages, the viruses that kill bacteria, which was used extensively in many parts of the world prior to the discov­ery of the wonder antibiotic Penicillin in the 1920s. The super convenience of Penicillin and other antibiotics relegated phages to the background. In this gloomy scenario, there is hope. GangaGen Biotechnologies, founded by a renowned molecular biologist from AstraZeneca 10 years ago to relentlessly pursue phage research, is close to getting the world’s first phage-based product ready to tame the deadly bacteria strains stalking patients around the world. Ganga­gen is ready to start the human trials of the world’s first “superbug” killer, StaphTAME, a genetically-modified protein developed from phages. In an interview to Narayanan Suresh and Jahanara Parveen of Technology Review India, Gangagen’s founder, J. Ramachandran, talks about his breakthrough product, his passion­ate search to find a “superbug” killer, and the help he needs from the global society to complete his dream of a “harmful bacteria-free” world.

J. Ramachandran
Credit: Courtesy of Gangagen Biotechnologies

TR: How do you think phage research has evolved over the years and where does Gangagen figure on the map?

Ramachandran: In the 1960s scientists looked at phages only as a model and didn’t concentrate on the therapeutic aspects. The phage DNA model was the hottest topic of research. This faded in the 1970s and 1980s. In the last decade, there has been a revival in phages because of the problem of antibiotic resistance.

Phage therapy is almost 100 years old. Gangagen is developing a tech­nology to improve the quality of phage therapy. We are probably the only company to develop intellectual property in this area. We have had several top researchers and phage biologists on our board since the inception. Some of them include Ryland Young, an expert on molecular biology of phage lysis, Sankar Adhya, a renowned scientist who has done considerable work on model phage lambda, and Carl Merill, a scientist at the National Institute of Health, U.S.

What are the current areas of research at Gangagen?

Gangagen has developed a highly proprietary product called Staph­TAME (also known as P128) for the control of the superbug MRSA (Methicillin Resistant Staphylococcus Aureus) which is currently the most serious hospital-acquired infection. All preclinical development of Staph­TAME has been completed and a suc­cessful pre-investigational new drug meeting with the U.S. Food and Drug Administration has been concluded. Gangagen is preparing to conduct clinical trials of StaphTAME later this year both in the U.S. and in India. StaphTAME is a recombinant protein that kills MRSA and all Staph bac­teria rapidly (in minutes) by a novel mechanism.

Pseudomonas aeruginosa is the most antibiotic-resistant patho­gen after MRSA and is the source of major infection in burns and wounds. Gangagen is developing a proprietary product for the control of Pseudo­monas aeruginosa that is currently undergoing preclinical development. Gangagen hopes to advance this product into clinical trials next year.

Our research team is also engaged in the discovery and development of phage-based products for the control of other pathogens including Clos­tridium difficile, which often emerges as a secondary infection following antibiotic treatment and is rivaling MRSA as a hospital-acquired infec­tion in the UK.

Is there enough innovation/research happening in the area of phage therapy globally? Which are the other compa­nies working in this area?

Gangagen is a pioneer in develop­ing innovative products based on phages. Many of the phage compa­nies around the world did not pursue innovation but rather focused on the production of natural phages which have some limitations. Release of endotoxins from the pathogens killed by phages, immune response to the phage, and potential for acquir­ing toxic genes from a pathogen and transferring it to the beneficial bacte­ria present in the patient are some of the problems in the use of naturally occurring whole phages. Gangagen developed the proprietary “Lysis-deficient Phages” to circumvent these problems through genetic engineer­ing of the natural phages. Lysis-defi­cient Phages kill the pathogens as effectively as the natural phages but due to the deletion of the “endoly­sin” gene, they do not release phage or endotoxins and therefore do not have the opportunity to transfer toxic genes. Two patents on the Lysis-defi­cient Phages were issued to Ganga­gen by the U.S. Patent Office in 2005. This accomplishment of Gangagen was described in an article in Bio­Spectrum in July 2004. Phage Thera­peutics in Seattle, Washington, in the U.S. started in 1997 to develop natural phage against MRSA but closed down in 2003. Exponential Therapies, the oldest phage company, started in 1994 but closed the phage program in 2005. There are several small companies developing natural phage for agricul­tural use and animal health in various stages of development.