In 2015 not only was the team at the University of Dundee selected to win MMV’s Project of the Year 2014 for its discovery and the details of the compound published in Nature1, but MMV also signed a contract with Merck KGaA, Darmstadt, Germany, to continue its future development. Dr Beatrice Greco of Merck S.A. explains what's exciting about the molecule as well as the next steps.
1. What is exciting about DDD498?
DDD498 has a novel mechanism of action: in preclinical models, it has shown activity against parasites resistant to currently available antimalarials, and indications of high potency. Owing to these attributes, it has potential to become a highly efficacious compound and to play an important part in the treatment of uncomplicated malaria in the future.
Due to its predicted long half-life, it might have potential to protect against malaria in endemic countries (chemoprotection), and as it inhibits gametocyte formation, it might also block transmission, which would be essential for eliminating malaria. All of this is a promising premise for further investigations.
2. What are the next steps for the project?
In February 2016, based on the high quality of the molecule and the data on its biological activity, the decision was taken to progress the compound into the regulatory preclinical phase of drug development.
The team is currently completing the essential preclinical and regulatory activities required to determine if DDD498 can then enter into first-inhuman trials potentially in 2017. This includes pivotal toxicology studies as well as in vitro and in vivo studies of drug metabolism and pharmacokinetics. The data generated will enable us to determine if future clinical development is possible and what a safe starting dose and regimen would be, as well as the predicted therapeutic range for the clinical trial.
We look forward to continuing the excellent collaboration with the very committed and supportive team at MMV.
1 Baragaña B et al. A novel multiple-stage antimalarial agent that inhibits protein synthesis. Nature. 522(7556):315-20 (2015).