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Xencor/XmAb7195/XmAb7195/1 Ea

XmAb7195

CompletedaPhase1aclinicaltrialinhealthysubjectsandatopicsubjectswithhighIgElevels;EnteredPhase1trialforsubcutaneousformulationin2016.

XmAb7195targetsIgEwithitsvariabledomain,andusestheXmAbimmuneinhibitorFcdomaintotargetFcγRIIb,resultinginthreedistinctmechanismofactionforreducingIgElevels.Bycomparison,theonlymarketedantibodytocontrolIgEinsevereasthma,omalizumab,hasonlyonemechanismofaction:blockingIgEreceptorbinding.ItdoesnotclearIgEfromthecirculationorpreventIgEproduction.

ThreeDistinctMechanismsofAction

1

SequestersfreeIgEtoblockIgEsignaling.

2

SuppressesB-celldifferentiationintoIgE-secretingplasmacells.

3

RapidclearanceofIgEfromcirculationviahighFcγRIIbbindingandbreakdownintheliver.

Asdemonstratedbyomalizumab,IgEinhibitionisavalidatedstrategyforreducingasthmasymptomsanddisABIlity.However,omalizumabreachesonlyafractionofitsmarketpotentialduetosuboptimalpotency.OptimizedwiththeXmAbimmuneinhibitorFcdomain,XmAb7195hasachievedprofoundlylowlevelsofserumIgEininhumanclinicaltesting,eveninsubjectswithIgElevelstoohightotreatwithomalizumab. XmAb7195offersthepotentialforsuperiorIgEcontrolandsuperiorclinicalefficacy.

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