The Drugs for Neglected Diseases initiative (DNDi) welcomes renewed support from Japan’s Global Health Innovative Technology Fund (GHIT Fund) for its drug discovery and early-stage development programmes pursuing new drug candidates for the treatment of leishmaniasis and Chagas disease.
A major contributor to DNDi’s not-for-profit research and development (R&D) programmes since 2013, GHIT Fund will provide a total of JPY 955 million (EUR 7.4 million) in additional funding for four projects over the 2021-2023 period, each underpinned by vital collaborations between DNDi and its Japanese R&D partners.
‘These four new investments are a further testament to the critical, long-term support provided by the GHIT Fund, which enables DNDi and our Japanese partners from the pharmaceutical industry, research institutes, and academic institutions to discover and develop innovative new treatments for neglected patients,’ said Charles Mowbray, DNDi Discovery Director. ‘The world-leading R&D capabilities of our partners coupled with the GHIT Fund’s support for early-stage research are incredibly important, creating a special and unique environment for scientific innovation for global health. We believe that these newly supported projects will play a crucial part in the effort to develop new treatments for patients suffering from Chagas disease and leishmaniasis.’
Safer, simpler, more effective treatments for leishmaniasis and Chagas disease are urgently needed. Existing treatments for leishmaniasis can be painful, toxic, lengthy, and costly, and poorly adapted for use in the most affected communities. Treating leishmaniasis is also difficult because it depends on several factors, including the form of the disease, other co-existing infections, the parasite species, and different patient populations – as treatment responses differ by region. There are only two drugs available to treat Chagas disease, both discovered half a century ago. While effective for some patients, existing treatments last eight weeks and sometimes have serious side effects.
Projects in focus
Hit-to-lead development for visceral leishmaniasis and Chagas disease – with Mitsubishi Tanabe Pharma Corporation
A continuation of DNDi’s compound screening collaboration with Mitsubishi-Tanabe that succeeded in identifying promising T. cruzi and/or Leishmania active series, this project aims to identify at least one compound series that meets DNDi’s target candidate profiles for new chemical entities for leishmaniasis and Chagas disease. Efforts will focus on strengthening the early-stage R&D pipeline for the two diseases by providing new promising series that bolster the prospects for successful development of all-new treatments.
S07 lead optimization for visceral leishmaniasis – with Takeda Pharmaceutical Company Limited
This project originated from DNDi’s successful GHIT-funded NTD Drug Discovery Booster programme which, following further development in collaboration with Takeda, identified and advanced novel compounds against visceral leishmaniasis, resulting in the S07 lead chemical series of compounds that show promising efficacy and safety profiles. The collaboration will now support medicinal chemistry optimization for the S07 leads it has identified, with the aim of progressing at least one optimized lead to deliver a pre-clinical candidate compound for visceral leishmaniasis.
DNDI-6174 pre-clinical development for leishmaniasis – with Eisai Co., Ltd.
Emerging from the leishmaniasis L205 lead optimization series, DNDI-6174 presents a new mode of action to the leishmania portfolio as well as a low human dose prediction and a very promising safety margin. It was nominated as a pre-clinical candidate, and through this two-year project, DNDi and Eisai will collaborate to prepare the way for future Phase I clinical development in healthy human volunteers.
Screening for visceral leishmaniasis – with The University of Tokyo
The objective of this new collaboration is to screen the chemical library of the University of Tokyo’s Drug Discovery Initiative (DDI) against Leishmania donovani to identify hit series for progression as candidates for hit-to-lead optimization – the first GHIT-supported project screening a Japanese academic chemical library of this size and complexity. The project also aims to provide new information on antileishmanial modes of action and on the biology of Leishmania parasites while fostering collaboration and expertise in anti-leishmanial screening and validation in Japan. DNDi’s contribution to this project will be provided fully on an in-kind basis.
Leishmaniasis is a neglected tropical disease that threatens an estimated one billion people worldwide. It is a complex disease that presents in several forms – visceral, cutaneous, mucocutaneous, and post-kala-azar dermal leishmaniasis – and is caused by 20 different Leishmania parasite species. An estimated 700,000 to 1 million new cases of leishmaniasis occur annually, with 20,000 to 30,000 deaths.
About Chagas disease
Caused by the protozoan Trypanosoma cruzi and transmitted by biting insects known as ‘kissing bugs’, Chagas disease is endemic in 21 countries in the Americas and is also present in Europe, Japan, and Australia. Chagas affects approximately 6-7 million people, with 30,000 new cases and 14,000 deaths per year. As people typically show no symptoms for many years, most are unaware they have the disease. Up to a third of people with Chagas will eventually suffer heart damage that can lead to progressive heart failure or sudden death. Chagas kills more people in Latin America each year than any other parasitic disease, including malaria.
About the Drugs for Neglected Diseases initiative (DNDi)
A not-for-profit research and development organization, DNDi works to deliver new treatments for neglected patients, those living with Chagas disease, sleeping sickness (human African trypanosomiasis), leishmaniasis, filarial infections, mycetoma, paediatric HIV, and hepatitis C. DNDi is also coordinating a clinical trial to find treatments for mild-to-moderate COVID-19 cases in Africa. Since its inception in 2003, DNDi has delivered eight new treatments to date, including new drug combinations for visceral leishmaniasis (kala-azar), two fixed-dose antimalarials, and DNDi’s first successfully developed new chemical entity, fexinidazole, approved in 2018 for the treatment of both stages of sleeping sickness. dndi.org
Phone: +41 79 431 6216
Photo credit: Vinicius Berger-DNDi