Back in October 2013 Medicines for Malaria Venture (MMV) selected a compound designed and developed at the Drug Discovery Unit (DDU), University of Dundee to enter preclinical development. In June 2015, the discovery, properties and mode of action of the compound DDD107498 were published in the journal Nature.
At the time Professor Ian Gilbert, Head of Chemistry at the DDU and co-leader of the team who developed the compound said “The publication describes the discovery and profiling of this exciting new compound. It reveals that DDD107498 has the potential to treat malaria with a single dose, prevent the spread of malaria from infected people, and protect a person from developing the disease in the first place.
“There is still some way to go before the compound can be given to patients. However, we are very excited by the progress that we have made.”
Professor Kevin Read, joint leader of the project, also based at the Drug Discovery Unit at Dundee, said, “New drugs are urgently needed to treat malaria, as resistance to the current gold-standard antimalarial drug is now considered a real threat. The compound we have discovered works in a different way to all other antimalarial medicines on the market or in clinical development, which means that it has great potential to work against current drug-resistant parasites. It targets part of the machinery that makes proteins within the parasite that causes malaria.”
In 2015, MMV partnered with Merck KGaA for the development of DDD107498 (now called M5717) and it entered the first stages of human clinical trials in 2017 (https://clinicaltrials.gov/ct2/show/NCT03261401). M5717 was well tolerated, behaving in healthy human volunteers as predicted and was hoped for from the extensive preclinical testing. Furthermore, in a human challenge model, where healthy human volunteers are infected with a small number of the parasites that cause malaria under tightly controlled conditions, M5717 was fully effective at treating these individuals with a single oral dose. Planning is underway for the second stage of clinical trials, entering clinical development of M5717 in combination with another partner drug.
The DDU and MMV have worked together since 2009 to identify potential new treatments for malaria. Speaking in 2015 Prof. Ian Gilbert acknowledged the critical part the partnership with MMV plays in the success of the DDU anti-malaria drug discovery, “Dr Paul Willis at MMV and Sir Simon Campbell, a mentor from MMV’s Expert Scientific Advisory Committee, gave invaluable input to the project. We have extensively profiled the compound, investigating its properties to understand how it works; this could not have been done without MMV’s scientific input and support of its network of partners around the world.”
The DDU malaria team have twice won MMV Project of the year. The first time for DDD107498 and the second time in 2018 for their work on developing further potential anti-malaria medicines against the target lysyl-tRNA synthetase. This is an enzyme which the malaria parasites need to make the proteins it needs to survive.
The current malaria team is led by Dr Beatriz Baragaña, Prof. Ian Gilbert and Prof. Kevin Read. The team includes members across all the disciplines in the DDU.