As the GHIT Fund Closes Out First Five Years of R&D for Lifesaving Medical Breakthroughs, It Launches Next Phase, Focusing on Access and Delivery, Bringing Total Investment to 13.2 Billion Yen (US$123 Million)

TOKYO, March 28, 2018 /PRNewswire-USNewswire/ -- The Global Health Innovative Technology (GHIT) Fund today announced a total of 1.6 billion yen (US$15.5 million) and 10 partnerships to support product development of new lifesaving drugs, vaccines and diagnostics for malaria, tuberculosis and neglected tropical diseases such as Chagas disease, schistosomiasis and leishmaniasis.

The announcement comes as GHIT prepares to enter its second five-year investment cycle. Its first phase of funding generated compelling progress on a host of potentially transformative tools. GHIT is now well positioned to support new partnerships that will focus on moving these tools out of its product pipeline and into the hands of those who need them most. With the additional capital secured through its replenishment announced last June, GHIT will continue to invest in promising global collaborations at each stage of product development—from discovery to clinical trials—with the goal of advancing two products through regulatory approvals by the end of 2022.

Since it was launched in 2013, GHIT has invested approximately 13.2 billion yen (US$123 million) in 74 global product development partnerships that leverage Japanese science and capabilities in pharmaceutical research and development. Currently, 28 discovery projects, 14 preclinical projects, and seven clinical trials are under way in low- and middle-income countries; three projects have achieved proofs-of-concept (Phase II trials); and one project will begin a Phase III trial this year.

"We are immensely proud of the robust portfolio of potential lifesaving products we have created with our network of partners in Japan and around the world," said BT Slingsby, MD, PhD, MPH, the CEO of GHIT. "This highlights that our business model, as a catalyst and investor of product development, is working, but the true measure of success is getting effective, affordable, tools into the hands of every single person who needs them. Now is when the really important work starts, and we're ready for it."

Investment in NTDs
Tackling Some of the World's Most Neglected Diseases: Leishmaniasis and Chagas Disease

GHIT will continue to invest in a number of promising projects in its product pipeline that tackle both leishmaniasis and Chagas disease. According to the World Health Organization (WHO), there are an estimated 50,000 to 90,000 new cases of visceral leishmaniasis (VL) reported annually. VL is a fatal disease which, if left untreated, in over 95 percent of cases, causes fever, weight loss, enlargement of the spleen and anemia. Over 90 percent of all VL cases are found in seven countries in South Asia, Africa and Latin America: Brazil, Ethiopia, India, Kenya, Somalia, South Sudan and Sudan.

At the same time, Chagas disease kills more people in Latin America than any other parasitic disease. Caused by the parasite Trypanosoma cruzi, which is spread by the triatomine bug (also known as the "kissing bug"), Chagas disease infects about 8 million people a year, often without causing any immediate symptoms. But over time, Chagas disease can eventually lead to severe heart damage and intestinal problems—the greatest cause of death—as well as physical disability. The Centers for Disease Control and Prevention estimate that more than 300,000 people in the United States are infected with Chagas disease during their travels in endemic areas.

GHIT's largest investment this round is approximately 600 million yen (US$5.6 million) for an ongoing collaboration between Takeda Pharmaceutical Company Limited (Takeda) and Switzerland's Drugs for Neglected Diseases initiative (DNDi) to advance an anti-parasitic treatment for VL. New and better treatments for VL are urgently needed as existing treatments are toxic, costly, and usually require painful injections and intravenous infusions. These treatments are also ineffective against drug-resistant parasites and in patients co-infected with HIV.

Takeda and DNDi are working to develop a safer, more effective and shorter-course treatment that could be both delivered orally and in the field, as well as to patients co-infected with HIV. Scientists have already identified several selected lead compounds during the previous study. With the continued investment from GHIT announced today, the partners will create formulations suitable for preclinical studies and first-in-human studies (Phase I) in the future, and complete preclinical toxicology and safety studies.

GHIT will seek to further accelerate drug discovery for both Chagas disease and leishmaniasis through continued support for the Neglected Tropical Diseases Drug Discovery Booster. That effort, led by the nonprofit R&D organization DNDi, was launched in 2015 with four pharmaceutical companies, including Eisai Co., Ltd., Shionogi & Co., Ltd., Takeda, and AstraZeneca plc. AbbVie Inc., Celgene Corporation, and Merck KGaA joined the initiative later. This groundbreaking initiative involving global pharmaceutical partners could potentially cut cost by bringing in-kind contributions and speed up the process of identifying promising compounds. The pharmaceutical companies involved in the collaboration allow DNDi to hunt for new "treatment leads" by simultaneously searching millions of unique compounds maintained in each company's extensive compound libraries. As of today, the booster project had identified and launched further work on 17 different seed compounds, while eight "hit" series were expanded and moved into further studies. In addition, from this round, Astellas Pharma Inc. will join the initiative, bringing more compounds to probe as potential candidates for new treatments. GHIT will provide approximately 150 million yen (US$1.4 million) in continued investments to this initiative.

A budget of approximately 88 million yen (US$0.8 million) will be invested by GHIT for a new partnership that will bring together Japan's Nagasaki University (NEKKEN), National Institute of Advanced Industrial Science and Technology (AIST), and High Energy Accelerator Research Organization (KEK) with the United Kingdom's London School of Hygiene and Tropical Medicine (LSHTM). Together, they will work at the frontiers of biomedical research to use the CRISPR/Cas9 genome-editing tool to analyze the essentiality of 1,000 genes in Trypanosoma cruzi parasites and to identify potential drug targets for development of new chemotherapeutic agents to combat Chagas disease.

Finally, Daiichi-Sankyo RD Novare will receive approximately 12 million yen (US$0.1 million) to screen its natural product library for potential leishmaniasis and Chagas disease drugs in partnership with DNDi.

Investment in Schistosomiasis
Stamping Out "Snail Fever"

Schistosomiasis is an infection caused by exposure to parasitic blood fluke worms that develop and multiply in freshwater snails, which is why it is sometimes called "snail fever." Some 90 percent of infections occur in Africa, where safe water is often scarce. While rarely fatal, left untreated, the disease can cause anemia, stunted growth, learning impairments and chronic inflammation of the liver and spleen. According to the WHO, more than 206 million people required treatment for schistosomiasis in 2016—usually with praziquantel, the gold standard treatment. However, in order to successfully fight and ultimately eliminate schistosomiasis, it is also essential to monitor and detect new and reoccurring cases. That piece of the puzzle is impaired by a lack of affordable, sensitive, user-friendly field tests, as existing diagnostics do a poor job of detecting low levels of the disease.

GHIT is investing approximately 76 million yen (US$0.7 million) in a partnership involving Japan's Institute of Tropical Medicine, Nagasaki University (NEKKEN) and the Netherlands-based Lygature and Leiden University Medical Center (LUMC) to develop a fast, simple, antibody test capable of diagnosing schistosomiasis for control and elimination programs. The project is known as DTECT-Schisto, which stands for Diagnostic Tools for Elimination and Control programs Targeting Schistosomiasis. GHIT's funding will support what is known as a "proof-of-concept" study that will seek to select and validate specific parasitic antigens for assessment of schistosome-directed antibodies in patient blood or urine. At the end of this two-year concept development study, researchers will provide a shortlist of validated protein and/or glycan antigens with diagnostic performance in serum and urine. This will be the starting point for technical feasibility studies.

Investment in Malaria
Preventing Malaria Parasites from Weaponizing the Human Immune System

GHIT's new investment of approximately 88 million yen (US$0.8 million) includes a partnership between Japan's Nagasaki University Institute of Tropical Medicine (NUITM), Pennsylvania State University (PSU) and Antigen Discovery, Inc (ADI)., both of the United States, to develop a vaccine candidate that is designed to block the malaria parasite from using the human body's immune system to power its invasion of red blood cells.

Human malaria cases rose in 2016 to 200 million, and the Plasmodium falciparum form of the disease continues to kill more than 400,000 people every year. Most of those killed are children under 5 years old in sub-Saharan Africa. While anti-malaria drugs, bed nets, indoor spraying and other interventions have produced progress against malaria, a highly effective vaccine could be a game-changer for malaria eradication in the future.

Researchers from NUITM, PSU and ADI will study whether an aspect of the immune system known as the "complement system," which should be helping the body fight the illness, is unwittingly collaborating with the enemy and helping malaria parasites intensify their attack. Recent data suggests that P. falciparum can subvert the complement system and trigger it to attack the immune system and protect the parasite. By studying this unusual shifting of biological alliances, the scientists hope to develop antibodies that could be used in a vaccine formulation that would block the parasite from corrupting the complement system.

GHIT will continue to invest in a malaria vaccine project spearheaded originally by the University of Florida in the United States in close partnership with Japan's CellFree Sciences, Co. Ltd. The partnership has grown to include Japan's Hamamatsu Pharma Research Inc. (HPR); Cameroon's Centre Pasteur du Cameroon (CPC); and, from the United States, Ology Bioservices Inc., and the Infectious Disease Research Institute (IDRI). These partners continue to develop a "transmission-blocking vaccine" (TBV) that is designed to disrupt malaria transmission by mosquitoes—the vector that transmits malaria parasites to the community. Among vaccines under development, this particular TBV is the only candidate that could potentially block both P. falciparum and P. vivax parasites, the most common causes of malaria. The continued investment of approximately 348 million yen (US$3.2 million) will allow the preclinical development of a formulation to move the vaccine forward into first-in-human studies (Phase I).

GHIT will also invest approximately 45 million yen (US$0.4 million) in a continued partnership between Japan's Sumitomo Dainippon Pharma Co., Ltd. and Switzerland's Medicines for Malaria Venture (MMV) to develop better drug compounds to fight the disease. This round of funding will allow researchers to further refine hit compounds and move them into what is known as the "lead optimization phase," which can include non-clinical safety evaluations.

A partnership with MMV, Takeda and the University of Melbourne's Bio21 Molecular Science and Biotechnology Institute will also receive approximately 46 million yen (US$0.4 million) in additional funding to undertake an innovative new path of malaria research based on anticancer agents known as proteasome inhibitors to fight drug-resistant malaria parasites. The parasite's proteasome works as a protein "shredder" that allows it to clear cells of damaged components as a critical part of its complex and vicious life cycle, underpinning its ability to cause illness and death. A previous GHIT investment allowed the researchers to identify promising compounds that are capable of inhibiting the parasite's proteasome mechanism. With this new investment, the partners hope to use these compounds as part of an early lead generation effort to put scientists closer to developing new weapons against drug-resistant malaria.

Investment in Tuberculosis
Countering the Rise of Drug-resistant Tuberculosis

GHIT will continue to invest in the development of a new medicine to combat tuberculosis. While the common form is treatable, infectious disease experts worry that a growing number of infections with multidrug-resistant and extensively drug-resistant strains of tuberculosis could lead to a major global health crisis. Drug-resistant infections are steadily weakening, and at times completely overwhelming, medications that have been used for decades to control the disease. Researchers are now in a race against time to develop new tuberculosis drugs that can counter the rise of resistant strains. 

With that in mind, GHIT is directing approximately 200 million yen (US$1.9 million) to an innovative project, aiming to discover a tuberculosis treatment with a new mechanism of action, between Japan's Eisai Co. Ltd. and partners from the United States: the Broad Institute, the Mycobacteria Research Laboratories at Colorado State University and the University of Chicago. TB Alliance will be an advisor on the project. The funding will be used to advance a new antimicrobial series discovered from Broad's Diversity-Oriented Synthesis library to help in the global fight against tuberculosis. Working by a completely new mechanism, these new antibiotics kill the causative pathogen, Mycobacterium tuberculosis, by starving it of an essential metabolic building block. The team now seeks to develop newer derivatives with improved activity and properties for preclinical development.

The first of its kind in Japan, the GHIT Fund is an international public-private partnership between the Government of Japan, multiple pharmaceutical companies, the Bill & Melinda Gates Foundation, the Wellcome Trust, and the United Nations Development Programme (UNDP). The GHIT Fund invests and manages a portfolio of development partnerships aimed at neglected diseases, such as HIV/AIDS, malaria, tuberculosis and neglected tropical diseases that afflict the world's poorest people. The GHIT Fund mobilizes Japanese pharmaceutical companies, academic and research organizations to engage in the effort to create new drugs, vaccines, and diagnostics. For more information, please visit https://www.ghitfund.org.

*All amounts are listed at the exchange rate of USD1 = JPY107.3, the approximate exchange rate on February 28, 2018.

*All amounts are listed at the exchange rate of USD1 = JPY107.3, the approximate exchange rate on February 28, 2018.

SOURCE Global Health Innovative Technology Fund (GHIT Fund)

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https://www.ghitfund.org/