Drug Discovery Projects
MMV welcomes proposals in the following areas:
1. Compounds having activity against Plasmodium falciparum blood stages and ideally an inability to select resistant mutants in vitro for use in treatment (TCP1) or chemoprevention (TCP1-TPP2)
Novel chemical series with asexual blood stage EC50<500nM and which have one or more of the following key features:
- A known, novel mechanism of action without cross resistance to clinical or marketed antimalarials. Priority will be given to mechanisms that are not represented in the MMV portfolio.
- An inability to select resistant mutants in vitro after at least 60 days’ incubation with compound
- Potency on early stage gametocytes similar to that for asexual blood stages
- Potency on stage V gametocytes (TCP5) similar to that for asexual blood stages and evidence of transmission blocking to the mosquito
- Potency on P. falciparum liver stages (TCP4) similar to that for asexual blood stages
- A long half-life (ideally >4h in rodents) and confirmed in vivo efficacy. Compound series with very long rodent half-lives (>10h) are of particular interest.
For advanced series, we are seeking novel compounds with, ideally, a predicted human half-life >100h and a predicted oral single human dose <500mg.
2. Compounds addressing the key priorities of the malaria eradication agenda (TCP3 and TCP6)
Novel families of molecules in the hit-to-lead or lead optimization stages, without G6PD deficiency liabilities that either:
- kill or reactivate hypnozoites for use as part of a P. vivax radical cure;
- have oral endectocide activity suggesting human single monthly dose <100mgs
In each of the above, where possible, example compounds in the series should have measured in vitro physical property and metabolism data, e.g. solubility, LogD, microsomal intrinsic clearance (Clint). The MMVSola tool can be used to predict a human half-life and dose.
Please complete the 3-page Letter of Interest (LOI). Proposals involving a biological target should also complete and submit the target information template. See further instructions on how to complete the LOI.
Compounds for Target Identification
MMV also welcomes requests for support to investigate the mechanism of action of compounds:
MMV is a founder member of the Malaria Drug Accelerator (MalDA). MalDA, a consortium funded by the Bill and Melinda Gates Foundation and led by Prof. Elizabeth Winzeler (UCSD), is working on a project to identify mechanisms of action of antimalarial compounds having phenotypic activity. Compounds can be considered for such target identification activities provided that the following criteria are met:
- Plasmodium whole cell EC50 <1uM and the chemical structure can be shared
- At least 10mgs of compound can be provided to the consortium
- The provider completes the one page Excel template
The Call for African proposals will be launched in the coming months. Subscribe to our newsletter to stay informed.
All applications for any of the above must use the specified templates and should be sent electronically to proposals [at] mmv.org by 12 noon CET, March 25th, 2022.