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Why do NTDs matter today?

NTDs are neglected tropical diseases that disproportionately affect the very poor. These diseases have been neglected for decades by pharmaceutical R&D because there is no return on investment to incentivize pharmaceuticals to find solutions for these patients. The term NTD covers a range of infectious diseases that affect patients living in Africa, Latin America, and Asia. These diseases debilitate, disfigure, blind or kill. The poorest of the poor – particularly women and children – are the hardest hit.

The burden of these diseases is significant in terms of morbidity, mortality, lost productivity and impaired economic growth, engendering a vicious cycle of poverty. The World Health Organization (WHO) has established a list of these NTDs to show the need for public commitment to find treatments or vaccines, eliminate the transmission, control and finally eliminate these diseases from the planet.

Why and how was DNDi established?

Founded in 2003 after MSF (Médecins Sans Frontières or Doctors Without Borders) received the Nobel Peace Prize, DNDi is a collaborative, patients’ needs-driven, not-for-profit drug R&D organization.

DNDi aims to develop drugs addressing the needs of patients suffering from the most neglected diseases. It was founded with research institutions from endemic countries where the patients live. MSF was one of the key founders, together with the KEMRI Institute in Kenya, the ICMR (Indian Council of Medical Research) in India, the Malaysian Ministry of Health, Pasteur Institute and the Oswaldo Cruz Foundation/Fiocruz (in Brazil). WHO is a permanent observer of DNDi.

The objective at the time was to limit the scope of the work on kinetoplastid diseases such as sleeping sickness, visceral leishmanaisis (VL) and Chagas disease in order to show that this model of publicprivate partnership could find alternative solutions that the standard pharmaceutical model could not provide because there is no return on investment from the pharmaceutical industry.

As said, DNDi was notably founded by MSF whose doctors had to face diseases in the field for which there were none or no adapted treatments. For instance, for African trypanosomiasis (sleeping sickness) patients were receiving melarsoprol, an arsenic derivative treatment, which killed 1 out of 20 of the patients to which it was given. For a doctor, it is devastating when your only options are interventions that will potentially kill a patient you're trying to save.

Being successful in the delivery of new treatments for sleeping sickness, VL and Chagas disease, DNDi expanded its activities in 2011 to other diseases such as paediatric HIV and filarial diseases. Also, its new Business Plan (2015- 2023) launched a new dynamic portfolio approach with the entry into its R&D portfolio of mycetoma and hepatitis C, two disease areas with significant unmet patient needs.

What other research gaps exist for NTDs?

We have very good models in some areas and much less predictive models in others. Of course, collaboration in building these models is key, because this is how you save time and money—not by investing in clinical trials, but investing more in pre-clinical trials, and then deciding based on preclinical results what you may see in humans. It is very important to have these big models.

When you move to clinical trials, then again there are questions. We think we know how to measure efficacy, but sometimes it takes a very long time, and the more time we spend on clinical development, the more time patients have to wait to access new treatments. We'd like to have clinical trials with earlier markers of efficacy—what we sometimes call surrogate markers—that are again themselves predictive of what you will see in patients. This is a science that has not yet matured very well.

DNDi has already successfully created new drugs for NTDs through cross-sector partnership. In what way have cross-sector partnerships been valuable?

First of all, it’s very clear that no one can do it alone. You need to have partners, but with DNDi we're talking of finding a solution for a shared objective as soon as possible, which requires the flexibility of having the right partner that is doing the right piece of work that needs to be done across a whole spectrum of activities. Each sector brings unique expertise to the table, and our role is to make everyone work together to reach a common goal.

The way we start a project offers a key example. We build a project with what we call a Target Product Profile (TPP). A TPP is defined by members who are part of platforms such as the LEAP Platform for leishmaniasis, the HAT Platform for sleeping sickness or the CCRP Platform for Chagas disease. The platforms bring together all the stakeholders, including those that will be using the product in the field: academics, physicians, national programs, ministries of health, NGOs, and the pharmaceutical industry. Everyone comes together and asks, "Okay, what would be the ideal profile of a drug or treatment for this specific disease? Also, what is acceptable? How far can we go to still accept this as bringing a solution?"

In your opinion, how is Japan helping to transform what is possible in vis-à-vis NTD product development?

Japan has a big history in global health. In 2000, it promoted the addition of infectious diseases to the G8 agenda and likewise was very active in promoting the Sustainable Development Goals (SDGs) in the last summit. This past August we were in Nairobi, where a TICAD (Tokyo International Conference on African Development) meeting was organized. It's very clear that Japan has a sustained commitment to global health.

If we look at our own portfolio of collaboration with Japan, there is a lot there. We've had collaboration early on with some research institutes. We also worked with Osaka University, the Tokyo University and Nagasaki University. We've had collaboration in Bangladesh to support a hospital funded by JICA. We have worked with many Japanese companies, including Astellas, Eisai, Takeda, and Shionogi. Additionally, we have collaboration on the immunomodulatorfor cutaneous leishmaniasis, again, with other Japanese companies and universities.

There's a long list of very regular collaborations since we opened our DNDi Japan office in Tokyo in 2004. We've continuously signed new agreements with different actors in Japan. So that in itself, when you look at DNDi's portfolio, it really shows how much Japan has been committed to work with us.

Paint a picture of this collaboration for us, using your partnership with Eisai on E1224 as a lens.

I think the Eisai example shows both the Japanese commitment and the leadership of Eisai's commitment to help the field of NTDs. In 2009, the agreement was signed very quickly to start a study and some work on Chagas disease. E1224 (fosravuconazole, a pro-dug of ravuconazole) is the compound that we've been testing in Chagas disease and also are now testing in Bolivia as a combination treatment.

We also have had some collaboration with Eisai for the NTD Drug Booster, and Eisai was one of the first companies to sign the sharing agreement, which is fantastic. Even more recently, in 2015 and 2016, we have a new collaboration with Eisai on fosravuconzaole to test it for the treatment of Mycetoma. Mycetoma is an absolutely devastating neglected disease. It is fantastic that Eisai has agreed for us to test it in Sudan.