Case Study

→Malaria kills over 600,000 people annually, the majority children under five.

→A phase 1b human clinical study of single oral doses of M5717 demonstrated single dose cure and was recently published in

The Lancet →Merck KGaA licensed DDD107498, renamed M5717, as their flagship anti-malarial for pre-clinical and clinical development.

DDU compound DDD107498 can cure malaria with a single dose costing less than $1

Malaria is a debilitating parasitic disease posing a risk to nearly half the world’s population. The predominant malaria parasite, Plasmodium falciparum, has developed resistance to current treatments and new drugs are therefore urgently needed to effectively treat and eventually eradicate malaria. New anti-malarials must meet several requirements: (a) novel modes of action with no cross-resistance to current drugs; (b) single-dose treatments with activity against bloodstage disease; (c) activity against liver stages that can prevent disease (chemoprotection or prophylaxis); (d) compounds active against the sexual stages (gametocytes) to block transmission of malaria.

The DDU has been working closely with Medicines for Malaria Venture (MMV), a not-for-profit public-private research and development (R&D) partnership, since 2009 to identify new treatments for malaria. Working with collaborators in Columbia University, USA, and the Wellcome Sanger Institute we delivered DDD107498, a compound that acts through inhibition of protein synthesis, with parasite translation elongation factor eEF2 as its target. After treatment with DDD107498 the parasites cannot make essential proteins and die.

The completely novel mode of action of DDD107498 make it a very attractive prospect for further development. Crucially, it is effective against parasites resistant to current drugs at a cost of goods within MMV’s goal of $1 per treatment. In 2014, MMV formally declared DDD107498 as a candidate for preclinical development. The discovery won MMV’s Project of the Year 2014. At the time MMV said:

“This molecule has caused a stir… DDD498 has potent activity against multiple stages of the malaria parasite’s lifecycle, giving it the potential to cure and stop the spread of the disease as well as protect people, all in a single-exposure”.

Thanks to the attractive properties of DDD107498, MMV was able to successfully partner the compound with Merck KGaA where it was licensed as their flagship anti-malarial for pre-clinical and clinical development and renamed M5717. The compound successfully completed human safety clinical trials (phase 1a) in 2018 and, remarkably, demonstrated single-dose cure in a human volunteer infection model of malaria, in a second human 1b trial, This has just been published in the Lancet (doi.org/10.1016/ S1473-3099(21)00252-8) . Together, these studies demonstrate that M5717 supports the potential for single-dose administration and suggests that future combination therapies of M5717 with a partner-drug are warranted to mitigate the risk of resistance.

The Head of Merck Global Health Institute explains the impact on the company:

“The DDU’s work to identify DDD107498 and characterise it and its safety profile meant that Merck were provided with a highly effective drug candidate ready for clinical trial. The DDU de-risked the process and provided the incentive for us to proceed to clinical development in 2017 with a new drug for malaria that we would have been very unlikely to develop independently. This also allowed Merck to develop our malaria portfolio”.