Gangagen
Phage Research
In India, it is rare to come across companies that break the mould of
conventional research and get into challenging and relatively unknown fields.
Gangagen is one such.
Gangagen owes its existence to Dr J Ramachandran, a renowned
molecular biologist, who happened to watch a BBC documentary in 2000 on phages.
The programme discussed how phages (or bacteriophages), which are viruses that
kill bacteria, are used to treat bacterial infections with a huge degree of
success in Russia. Despite Dr Ramachandran's wide and varied experience in
research on antibiotics and bacterial infection, phages were totally new to him.
This set his mind racing on the possibilities for breakthrough research on
phages. Having dealt with bacterial infections in the pharma research industry,
he was suddenly hopeful that the solution lay in phages.
An Idea that Paid Off
Enthused by the bright prospects, Dr Ramachandran acted swiftly by starting a
company called Gangagen Biotechnologies Pvt Ltd. He floated the idea to
Bangalore-based ICF Ventures, which pooled an initial investment of $2 million.
He roped in molecular biologists Dr Sriram Padmanabhan and Bharati Sriram, who
left their lucrative jobs to answer the calling of innovative research. The
company kicked off operations in September 2000 by renting 800 sq. ft space,
infrastructure and people at Bangalore Genei. Their first job was to create a
comprehensive "library" of infectious bacterial samples and phages
from hospitals in Bangalore, Vellore and Hyderabad.
According to Dr Ramachandran, phages are easy to find and the
best samples can be obtained in the unlikeliest of places, from river waters to
temple ponds to even sewage.
Globally, there are a handful of phage research companies,
scattered across countries like the US, Canada, Russia, Georgia and Israel. To
make headway and create a niche for the company, Dr Ramachandran went for an
out-of-the box approach. It was a known fact that once a phage attacks a
bacterial cell it synthesizes its own proteins, multiplies prolifically, kills
the host and bursts out of the host cell in a process called lysis. Although the
bacterial cell would be destroyed in the process, there is a potential harm from
the release of dangerous endotoxins and the body's own immune system, which
could respond by producing antibodies.
This, Dr Ramachandran thought could be prevented if the
phages could somehow be contained within the host cell after killing the
bacterium. He filed a patent for this concept and Dr Padmanabhan and his team
started work to bring about this process.
The team succeeded. Phages encoded two proteins-holins and
endolysin, for causing cell lysis. What the Gangagen scientists did was to
introduce a recombinant gene that was deficient in endolysin protein. The
result: the genetically modified phage gets rid of the bacteria and at the same
time is restricted within the host cell. The body in turn eliminates the
bacteria harmlessly. " We are the only company in the world to hold IP on
this technology and it has given us a competitive edge that cannot be bettered
by others," said Dr Padmanabhan, who heads the molecular biology division.
Dr Ramachandran filed the full patent application in August 2002. Another patent
followed for whole cell vaccines that contain phage-filled cells.
"Experiments on animals have shown that these phages have countered
infection effectively," said Dr Goda Krishna, business and operations
manager, Gangagen, Bangalore.
"We Need a Novel
Alternative to Antibiotic Drugs."
-Dr J Ramachandran, founder and president of Gangagen Inc.
 Dr
J Ramachandran is a veteran from the biotechnology and pharmaceutical
industry, who has served earlier as head, R&D, Astra Zeneca, Bangalore.
He was also president of Astra Biochemicals Pvt Ltd and of the merged
entity AstraZeneca India. He is credited with discovering and developing
new therapies for tackling tuberculosis and antibiotic resistant
infection. He has also been associated with leading US biotech companies
like Neurex and Genentech in California.
With such a formidable research record, it seems only natural that he
made the natural progression to a new path-breaking area-phage therapy. He
shares his thoughts on the exciting research opportunity that phage
research offers.
How do you think phage research has evolved
over the years and where does Gangagen figure on the map?
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. What Gangagen is
doing is developing technology to improve the quality of phage therapy. We
are the only company to develop IP in this area. We have several top-notch
researchers and phage biologists on our board. Some of them include Dr
Ryland Young, an expert on molecular biology of phage lysis, Dr Sankar
Adhya, a renowned scientist who's done considerable work on model phage
lambda and Dr Carl Merill, a scientist at the National Institute of
Health.
At what stage of development is the company
right now?
It will take a while before we bring out our product. R&D
takes a long time. We will be conducting clinical trials in two phases,
which will take another three-four years. After that, our product has to
be approved by regulatory authorities. I cannot hazard a guess about how
long that could take.
We will file the product in the US first. Six months
after that, we will also file it internationally. We would like to license
our product to interested pharmaceutical and biotechnology companies. Our
phage product will cover around 80 percent of pathogens and will be for
topical use.
What prompted you to start work in this new
field? How would you explain the different research areas of Gangagen in
India and Canada?
Over the years, there has been an overuse and misuse of
antibiotics. Since many bacteria are getting resistant to antibiotics,
there is a dire need for some novel drug. The therapeutic values of phages
have been neglected for some time. It is a very exciting area.
We have a diffused approach at Gangagen, which helps us
to concentrate on specific areas of research. In India, our focus is on
human uses of phages. We believe that a developing country like ours is in
the greatest need of such therapy since most deaths here are from
bacterial infections than say heart disease. Also, since phages were
discovered more than 100 years ago in the Ganges, we thought it was apt to
focus on human applications.
The company's Canadian counterpart, Gangagen Life
Sciences, does research on the veterinary and environmental applications.
Canada is a country where they are proactive on environmental policies.
They faced a lot of problems due to the pathogen E coli0157, which spreads
from animal manure to humans. By using phages, we are trying to eliminate
the pathogen in animals, plants and the environment.
How expensive is phage research?
Phage research involves more of microbiology and molecular
biology and not expensive chemistry. We estimate a two- to three-fold cost
savings compared to the R&D of antibiotic drugs.
What is the investment that has gone into the
company?
Initially, ICF, which is based in Bangalore, pitched in with a
seed fund of in $2 million in 2000. We had a second round of funding from
angel investors who ploughed in another $2 million in 2002. Right now, we
are in talks with VCs who can fund around $3-5 million to help with our
expansion plans in Bangalore. |
Modus Operandi
Gangagen Inc. is US-based and has two subsidiaries. Gangagen Biotechnologies Pvt
Ltd (GBPL), based in Bangalore, focuses on human applications, while Gangagen
Life Sciences Inc. (GLSI), based out of Ottawa, Canada, works on veterinary and
environmental applications of phages.
GLSI is headed by Michel Cretien, a renowned medical
scientist. This division works on developing phages to get rid of bacterial
infection in animals, plants and the environment.
The bacterial contamination of manure that causes ground
water pollution is a serious issue in Canada. The problem assumed serious
proportions in 2000 when several people died after drinking contaminated water
in Canada. Treating meat infected with bacteria is another issue. Several
countries may make it mandatory for meat manufacturers to ensure that that their
product is free from contamination. GLSI is trying to introduce phages that
could be given to cattle before slaughter to pre-empt any possible dangerous
infection in meat thereafter.
The Indian division is currently looking at human topical
applications. However, it will take around four years before the product would
see the light of day. The first phase of clinical trials on the product will get
underway by the end of the year. This will be followed by more trials, safety
and efficacy tests in humans and getting the product approved by regulatory
authorities. "Some researchers tell us that it is unethical to make them
wait for so long to get a good product like this," quips Dr Goda Krishna.
Future Direction
GBPL's research threw up a very useful by-product, a diagnostic kit to detect
bacterial infection. While the regular kits available in the market fail to
detect contamination soon enough, Gangagen's kit could detect the bacterial
load based on phage activity immediately. This is faster and more
cost-effective, according to Bharati Sriram, who heads the diagnostics group.
The company, which is yet to file a patent on the kit, thinks that this could
find application in medical diagnostics, food processing and soft drink
manufacturing companies.
The company has mapped out the sequence of research to follow
from here on. Next in line are phage research to treat oral infections, urinary
tract infections and ultimately tuberculosis and cholera. "We believe that
phages can also attack dormant Mycobacterium tuberculosis bacteria. So the
possibilities are enormous." Around six more patents are in the offing.
To strengthen its research activities, the company is in
talks with VCs to raise more funds to expand the Bangalore base, especially the
pharmacology and fermentation divisions.
Dr Padmanabhan best describes the Gangagen experience. " We look forward
to come to work everyday. This concept is a gold mine."
Priya Sreenivas, CyberMedia New
spriyas@cmil.com
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