The Global Health Innovative Technology (GHIT) Fund, a pioneering initiative involving the government of Japan, the Bill & Melinda Gates Foundation and five Japanese pharmaceutical companies, has announced funding of more than US$12 million to accelerate development of novel tools and drugs to combat tuberculosis and other neglected diseases.

The public-private partnership, set up last year with an initial five-year commitment of over US$100 million, has awarded three grants totalling US$6.8 million to facilitate discovery and development of new drugs and formulations addressing schistosomiasis, Chagas disease and Wolbachia bacteria.

A second round of funding, worth US$5.65 million, will support a novel vaccine candidate for tuberculosis.

The GHIT Fund also announced a new programme, the Hit-to-Lead Platform, aimed at converting drug ‘hits’ from the anti-infective libraries of Japanese pharmaceutical companies into “lead compounds”. A budget of US$2.2 million over two years has been allocated for the Platform.

Chagas combination

The first of the three grants, worth US$3.84 million, goes to the Drugs for Neglected Diseases initiative (DNDi) and Japan’s Eisai. These partners will investigate a new approach to Chagas disease, combining benznidazole with the experimental triazole compound E1224.

Under the leadership of DNDi’s Dr Isabela Ribeiro, the collaborators will over the next two years conduct a Phase II proof-of-concept study evaluating the efficacy and safety of the benznidazole/E1224 combination. Data from this trial will be used to help design a Phase III multi-country study.

The partners will also work towards registration of E1224, including a number of requisite chemistry, manufacturing and controls activities and non-clinical tests.

Currently available drug therapy for Chagas disease – benznidazole and nifurtimox – is poorly tolerated in adults, difficult to use and often fails to cure chronic infections, which can lead to cardiovascular disorders such as enlarged heart, heart failure, severely altered heart rhythm and heart attack, GHIT notes.

Paediatric praziquante

A US$1.86 million grant for the development and registration of a paediatric formulation of praziquantel, the gold-standard treatment for schistosomiasis, has gone to a partnership  between Top Institute Pharma, Merck KGaA, Astellas Pharma and Switzerland’s Tropical and Public Health Institute.

Praziquantel is currently recommended only for adults and children over the age of six years. Effective treatment of younger children with schistosomiasis is hampered by a lack of relevant clinical data and difficulty swallowing praziquantel tablets due to their size and bitter taste.

The partnership has produced test batches of two new formulations, called racemate praziquantel and levo-praziquantel. Both of these will be tested first in adults, with taste tests in children to follow. 

Anti-Wolbachia therapy

The third grant, for US$1.09 million, has been awarded to the Liverpool School of Tropical Medicine in the UK and the University of Liverpool’s collaboration with Eisai to investigate new drug compounds against Wolbachia bacteria.

Anti-Wolbachia therapy with the antibiotic doxycycline has proved safer and more effective than existing antifilarial drugs in field trials conducted over recent years, GHIT points out.

However, the doxycycline course requires four to six weeks of daily treatment, which is potentially harmful for young children and pregnant women.

To date, screening of more than 10,000 potential anti-Wolbachia compounds has generated about 50 potential targets, leading to identification of some six molecule types with anti-infective potential.

The Liverpool/Eisai Researchers will focus on two of these proposed chemical groups. They plan to conduct a 12-month, head-to-head comparison study of the two leading chemical types, with the goal of identifying a single candidate for potential drug development within one to two years.

Novel vaccine

Funding of US$5.65 million will support work on a novel vaccine candidate to combat tuberculosis under co-development by the National Institute of Biomedical Innovation, Japan’s Create Vaccine and Aeras, an international non-profit biotechnology concern based in the US.

GHIT awarded the partnership an initial grant of US$700,000 for these efforts in November, 2013. The additional funding will allow for further preclinical development to advance the vaccine candidate to Phase I safety and immunogenicity testing.  

In mice, the vaccine candidate boosted the level of protection conferred alone by BCG (Bacillus Calmette–Guérin), the current vaccine against tuberculosis, GHIT said. Invented nearly 90 years ago, BCG provides insufficient protection to teenagers and adults, the group with the highest TB burden, it added.

Hit-to-Lead Platform

The Hit-to-Lead Platform is designed to provide a bridge between early drug discovery and GHIT’s typical grant phase, which begins with the optimisation of lead compounds. GHIT will issue a request for proposals for the new platform later this year.

“Japanese pharmaceutical companies and research institutes have considerable resources, including compound libraries that have yet to be screened to see what they might have to offer for infectious diseases like malaria, tuberculosis and neglected diseases,” commented  Dr. Kiyoshi Kurokawa, board chair for the GHIT Fund.

“The Hit-to-Lead Platform will expand the drug pipeline for these diseases by bringing forward compounds that have not been previously screened or that are known to target mechanisms of action in a new and more effective way.”

The pharmaceutical consortium members of the GHIT Fund are Astellas Pharma, Daiichi Sankyo, Shionogi and Takeda Pharmaceutical.