Products in the pipeline

Tuberculosis

There is a need for new anti-TB drugs as current anti-TB therapy is very long, six months for drug sensitive TB and more than two years for drug resistant TB and the numbers of MDR and XDT TB cases are increasing all over the world.

Thus, drugs which have potential to reduce the duration of treatment and/or effective against resistant strains of M. Tuberculosis will have immense value in TB control programs.

We have developed from a bacteriophage, a recombinant protein that specifically and rapidly kills mycobacterium by disrupting the mycolic acids in the bacterial cell wall. This protein is effective against growing as well as resting cells of M. smegmatis, M. bovis BCG, and M. tuberculosis H37RV and has synergistic activity with anti-TB drugs viz., Rifampicin, Isoniazid and Ethambutol. In-vivo efficacy of this protein against tuberculosis is in progress. We are also evaluating this protein against M. ulcerans, the causative agent of Buruli ulcer also.

Gram negative infections

Gram-negative bacteria can cause many types of infections. Certain types of Gram-negative bacteria are highly resistant to available antibiotics and some strains are now resistant to most or all available antibiotics resulting in increased morbidity, mortality and contributing to escalating healthcare costs. Strains of pathogenic bacteria such as E.coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumanii are highly problematic because of multi-drug resistance. GangaGen is utilizing the Tail Associated Muralytic Enzymes (TAMEs) technology to discover and develop phage-based proteins to kill these pathogenic multi-drug resistant Gram-negative bacteria. We aim to develop anti-Gram negative proteins which in combination with standard antibiotics will be highly useful to combat these pathogenic bacteria.

Phages that kill without release of bacterial toxic contents

In the eastern European countries, Phage therapy is routinely practiced to treat infections in people. In the west however, regulators are reluctant to allow use of bacteriophages in humans. Various factors constitute considerable challenges to be overcome before Phage therapy gets the nod.

At GangaGen, using modern genetic engineering approaches, we are addressing the issues that limit the use of phages for human therapy. We recognized the major disadvantages to be (i) immune response to phage in patients, (ii) acute release of toxins that can lead to sepsis, (iii) lack of linear dosing due to exponential replication and release of phages in vivo and (iv) transfer of toxic genes to innocuous beneficial bacteria in vivo and in the external environment. We have developed strategies to generate modified bacteriophages that can effect killing of the bacteria without culminating in lysis of the cell. This overcomes the deficiencies of the natural phage whereby, progeny phages are not released in a large bolus; there is minimal release of bacterial toxins; there is reduced potential for immune response; and the approach affords dose-definition.

GangaGen’s Lysis-defective phage technology can be used to develop proprietary phage products for C.difficile infection and in generation of whole cell vaccines for E.coli.

C.difficile

This bacterium causes infectious diarrhea in hospitalized patients. As the bacteria overgrow they release toxins that attack the lining of the intestines.With the current increase in severity and recurrence of infection coupled with incidence in individuals lacking the traditional risk factors, this is assuming high clinical importance.Gangagen’s proprietary technology of lys-minus phage is a suitable approach to control this pathogen in the gut whereby C.difficile is specifically killed without overt release of toxins. This is in early discovery phase and the Company is looking to develop a phage product for C. difficile in collaboration with interested parties

E.coli

E.coli (Escherichia coli) are normal residents in the human gut and most of them are harmless. There are however strains of E.coli that can cause severe infections. While some cause treatable diarrhea, others, such as the strain O157:H7, may also cause bloody diarrhea, anemia or kidney failure, which can lead to death. There are also specific strains of E. coli that cause recurrent urinary tract infections, in situations where the normal defences fail. E.coli typically enters the urinary tract through the urethra and begins to multiply in the bladder. They adhere to the cells lining the urinary bladder and grow into a full-blown infection. Gangagen’s proprietary technology of phage-incapacitated whole cell vaccine, is a suitable approach to prevent such infections. This is also in early discovery phase and amenable to collaboration for development of a vaccine product.