Drug Discovery Projects
MMV welcomes proposals in the following three areas:
1. Compounds addressing the key priorities of the malaria eradication agenda
Novel families of molecules in the hit-to-lead or lead optimization stages are sought without G6PD deficiency liabilities that either:
- kill or reactivate hypnozoites for use as part of a P. vivax radical cure; or
- have activity against sexual stage V gametocytes and evidence of transmission blocking in SMFA.
2. Compounds having activity against asexual liver and/or blood stages
Novel chemical series with EC50<500nM and which have one or more of the following key features:
- A known, novel mechanism of action;
- An inability to select resistant mutants in vitro;
- Activity at more than one life-cycle stage;
- A long half-life (ideally >4h in rodents) and confirmed in vivo efficacy.
For advanced series, we are seeking novel compounds with, ideally, a predicted human half-life >100h and a predicted oral single human dose <500mg or an i.m. dose that can be administered in <1mL and sufficient for up to 3 months’ protection in humans.
3. Novel approaches for screening
To help identify new phenotypic and/ or target based hits, as well as confirm activity of MMV compounds on all human malaria asexual blood stages, new screening proposals are sought amongst the three categories below:
- Validated Plasmodium target-based assays, ideally with evidence of target essentiality beyond asexual blood stages. Biological validation should be supported by a biological target based screening assay suited for identification of novel chemical series.
- Novel whole cell phenotypic screening paradigms to potentially identify new relevant chemistry.
- Asexual blood stage assays for vivax and ovale malaria.
Please complete the 3-page Letter of Interest template. Proposals involving a biological target should also include 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:
- The Plasmodium whole cell EC50 <1uM and the chemical structure can be shared
- A minimum of 10mgs of compound can be provided to the consortium
A one page Excel template needs to be completed to submit a compound for target ID.
Call for African proposals
Finally, MMV welcomes proposals from endemic region African scientists focused in the following priority areas:
1. Compounds with confirmed activity on any antimalarial life-cycle stage
Novel families of molecules with confirmed activity (EC50 < 10uM) and a medicinal chemistry plan that tackles any known or anticipated liability. Priority will be given to proposals that maximize use of local natural products.
2. Assay development and screening
Assay development and screening to support discovery or development of novel antimalarials. Priority will be given to proposals that maximize use of local, field isolates.
Please complete the 2-page African Letter of Interest template. Proposals involving a biological target should also include the target information template. See further instructions on how to complete the African Letter of Interest.
Up to two African proposals of USD 20K each will be funded as part of this Call.