KAF156

KAF/lumefantrine

KAF156 is the first compound to progress into clinical development from the novel imidazolopiperazine class of antimalarial molecules. A key strength of the drug is its potential to both treat and prevent malaria, including resistant strains. Phase IIa studies have demonstrated that KAF156 rapidly kills both P. vivax and P. falciparum malaria parasites.
 

KAF156 plus lumefantrine

KAF156 belongs to a novel class of antimalarial molecules, the imidazolopiperazines, and in phase IIa trials was able to rapidly clear both P. falciparum and P. vivax parasites. On this basis, in 2017, KAF1561 will enter phase IIb combination studies with the antimalarial lumefantrine.

KAF156 enters phase IIb combination studies

KAF156, a promising compound in MMV’s portfolio, has entered phase IIb patient trials in combination with an improved new formulation of the existing antimalarial lumefantrine. KAF156 is the first compound from a novel class of antimalarials, the imidazolopiperazines, and has the potential to be a game-changer in malaria elimination, rapidly curing malaria infections including resistant strains and blocking transmission of the parasite.

MMV and Novartis expand partnership

MMV and Novartis announced today that it will further expand their long-standing partnership. Novartis will lead the development of antimalarial compound KAF156 with scientific and financial support from MMV in collaboration with the Bill & Melinda Gates Foundation. This agreement sets out the terms and conditions for the development of KAF156 and its future availability to patients.

Ganaplacide-lumefantrine

Novartis

Product vision
  • Uncomplicated malaria treatment and resistance management
MoA
  • Recent ganaplacide data suggest effect on parasite internal protein secretory pathway. Target not yet fully determined. Decreased susceptibility to ganaplacide is associated with mutations in three P. falciparum genes, CARL (cyclic amine resistance locus), UDP-galactose and Acetyl-CoA transporters
  • Lumefantrine inhibits the parasite conversion of toxic heme to non-toxic hemozoin
Key features

Ganaplacide

  • Novel mechanism of action – activity against parasites that are resistant to current drugs

  • Rapid killing of parasites (parasite clearance time <48 hours)
  • Effective against P. falciparum and P. vivax species
  • Transmission-blocking activity in a Standard Membrane Feeding Assay
  • Potential for causal prophylaxis by blocking early liver stage of parasite

Lumefantrine

  • Used in combination with artemether since 1998 in over 1 billion patients
  • New lumefantrine formulation with improved release profile bioavailability
Status
  • Phase IIb combination studies completed
  • Phase IIb study in paediatric population (KALUMI) ongoing
Next milestone

  • Completion of Phase IIb KALUMI studies

  • Phase III study decision
Previously
  • KAF156, GNF156. Novartis in discovery partnership with MMV, Wellcome Trust, and the Swiss Tropical and Public Health Institute
MMV Project Director
  • Dr Gonzalo Acuña
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