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Why is malaria an important disease in the 21st century?

Malaria is important because aggressive, coordinated efforts to control the disease have had a direct impact on health and economic indicators in the world's poorest countries. In 2015 there were approximately 212 million cases of malaria worldwide in the 91 countries with ongoing transmission of this mosquito-borne disease. While significant progress has been made over the last fifteen years in reducing malaria cases by around 60%, and reducing mortality by around 40%, this disease remains one of the major health problems in the developing world. With an estimated 429,000 deaths in 2015 from malaria, and a child dying every two minutes from the disease, the world's poorest countries are effectively being robbed of the next generation.

The progress that has been made is the result of using insecticide-treated bed nets, vector control (mosquito elimination), and drugs designed to prevent or cure the disease, yet overuse—and often misuse—of these interventions has contributed to growing drug resistance. As a result, there is an urgent need to develop new drugs that are active against resistant parasites, as well as new insecticides to address the same problem of resistance with insecticide-treated bed nets.

You mentioned drug resistance as a persisting challenge. Please share more about the opportunity for new drugs in this area.

The challenge of drug resistance is one that we face across many different areas of healthcare, with antibiotics, antivirals, and anti-malarial drugs. Often this is associated with overuse or misuse of drugs, and we have a legacy issue with malaria in that many of the drugs that we have today were first used as monotherapy. The drugs used on their own, and not in combination, don't have a partner drug to protect them, making them particularly vulnerable to resistance.

One of the other issues is that there have often been substandard drugs produced, or even counterfeit drugs, that may contain far less than the required amount of drug that is needed to really suppress the parasite in the blood, and as a result of this there has been emerging resistance that has rendered our drugs ineffective, one after the other. But we need to stay ahead of the parasite, and in order to do that we need to attack it in different ways.

Since MMV and its partners began working in the malaria space, the number of targets or different ways we can attack the parasite has increased from 5 targets in 1999 to around 26 targets today. This is unprecedented in terms of biological gains against any organism, and it gives us an enormous opportunity to battle the parasite in new ways, get ahead of the threat of resistance, and ensure we have the drugs that we will need tomorrow.

You mentioned that MMV and its partner have created six new drugs for malaria. What do you see as the role and value of partnership in malaria drug innovation?

The question of why partnerships are so important is one that's really central to the DNA, if you like, of MMV. I often say that we are nothing without our partners, and that is absolutely true.

We try and assemble various groups, be they from academia or from industry. What we are looking for is true excellence in different areas, as well as key assets such as drug libraries, chemical libraries that can be brought forward. Each partner in our value chain has a unique role and plays to their strengths. It's only by bringing the best of the best together and assembling that value chain that we can rapidly develop new anti-malarial drugs and deliver them in a timely manner, and in a way that makes them both accessible and affordable.

How and when did MMV's collaboration with Japan begin?

MMV had been looking at partnering with Japanese companies since 2009, but without the contacts and a real understanding of the Japanese pharmaceutical industry it was very hard for us to make inroads and to really form the connections that we needed. We were interested in Japanese companies because of the excellence that Japan has in pharmaceutical drug development. Japan has some of the giants of the pharmaceutical industry; it also has a wealth of diversity in its compound collections. So Japan really was a logical choice, but was difficult to approach as an outsider. That all changed with GHIT’s establishment.

We had very early contact with BT Slingsby (GHIT’s CEO) when he was at Eisai, as well as with Tachi Yamada in some of the support that he was providing around GHIT’s inception. It really seemed like the perfect solution for bringing other entities in and partnering with the Japanese pharmaceutical powerhouse to make progress. In doing this, we were able to form strategic alliances with groups like Takeda, Eisai, Sumitomo, and the other companies that we are now forging relationships with.

More broadly, how is Japan helping transform what is possible in the malaria field?

Japan is doing this in a number of different ways. The first is the very formation of GHIT, which brings together all of the ingredients necessary for success. Through GHIT, you are bringing together academia and that innovation from within Japan. You're bringing together the Japanese pharmaceutical industry, its core expertise in drug development, its libraries, and its distribution reach globally. You're bringing together the product development partnerships like MMV, which have the disease-area understanding and can complement Japanese companies, most of which haven't worked in the malaria field before.

And then there's the extraordinary commitment by the Japanese government, which is really throwing its weight and its resources behind this to provide the funding that can drive the whole enterprise forward. That's very unique.

Please describe MMV’s partnership with Takeda on DSM265 (funded by GHIT). Why is this work innovative?

DSM265 is the first of a novel mechanism of action, meaning that it attacks the parasite in a totally different way. It's what's called a DHODH inhibitor. It attacks a specific enzyme in the parasite, and has interesting characteristics.

First, because DSM265 has a new mechanism of action it will be active against drug-resistant parasites, which is absolutely essential. Second, because it's very, very potent we can see that this drug, even on its own, can kill the majority of parasites in the blood. The next step in development is to look for an appropriate partner drug, so that is can be part of a drug combination. It's too valuable to lose to future resistance.

Another characteristic of DSM265 is that when administered orally it persists in the blood stream for a good length of time. This means that it has the potential to be used as a single-dose treatment, because it can remain in the blood long enough to kill all the parasites. That is a real breakthrough. It means that after just one dose given by a doctor or a healthcare worker, patients can go on their way knowing that they are cured. This overcomes a key challenge in some of the environments where we work, where patients often don't complete the full course of treatment. Often this is because the patient’s family wants to save the remaining doses in case another child in the family gets sick, and as a result the first child doesn't get cured properly, which increases the threat of resistance.