02624nas a2200577   4500000000100000008004100001653003900042653003000081653001900111653001900130653002000149653001900169100001200188700001500200700001300215700001100228700001600239700001200255700001400267700001100281700001000292700001500302700001700317700001500334700001800349700001300367700001300380700001300393700001500406700001700421700001300438700001400451700001400465700001500479700001700494700001100511700001300522700001300535700001000548700001200558700001500570700001600585700001300601700001300614700001100627700001500638245009700653856007500750520120700825022001402032       2019                            d10aNeglected tropical diseases (NTDs)10aLymphatic filariasis (LF)10aAnti-Wolbachia10aDrug Discovery10amacrofilaricide10aonchocerciasis1 aHong DW1 aBenayoud F1 aNixon GL1 aFord L1 aJohnston KL1 aClare R1 aCassidy A1 aCook D1 aSiu A1 aShiotani M1 aWebborn PJ H1 aKavanagh S1 aAljayyoussi G1 aMurphy E1 aSteven A1 aArcher J1 aStruever D1 aFrohberger S1 aEhrens A1 aHübner M1 aHoerauf A1 aRoberts AP1 aHubbard AT M1 aTate E1 aSerwa RA1 aLeung SC1 aQie L1 aBerry N1 aGusovsky F1 aHemingway J1 aTurner J1 aTaylor M1 aWard S1 aO'Neill PM00aAWZ1066S, a highly specific anti- drug candidate for a short-course treatment of filariasis.  uhttps://www.pnas.org/content/pnas/early/2019/01/02/1816585116.full.pdf3 a<p>Onchocerciasis and lymphatic filariasis are two neglected tropical diseases that together affect ∼157 million people and inflict severe disability. Both diseases are caused by parasitic filarial nematodes with elimination efforts constrained by the lack of a safe drug that can kill the adult filaria (macrofilaricide). Previous proof-of-concept human trials have demonstrated that depleting &gt;90% of the essential nematode endosymbiont bacterium, , using antibiotics, can lead to permanent sterilization of adult female parasites and a safe macrofilaricidal outcome. AWZ1066S is a highly specific anti- candidate selected through a lead optimization program focused on balancing efficacy, safety and drug metabolism/pharmacokinetic (DMPK) features of a thienopyrimidine/quinazoline scaffold derived from phenotypic screening. AWZ1066S shows superior efficacy to existing anti- therapies in validated preclinical models of infection and has DMPK characteristics that are compatible with a short therapeutic regimen of 7 days or less. This candidate molecule is well-positioned for onward development and has the potential to make a significant impact on communities affected by filariasis.</p>
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