Aerpio Therapeutics LLC — Department of Health and Human Services SBIR Phase I: NEI

Description

Abstract Diabetic macular edemaDMEis the leading cause of vision loss in the working age population whichconsidering the worldwide epidemic of diabetesrepresents a growing socioeconomic challengeDME is characterized by the destabilization of retinal blood vessels resulting in the accumulation of fluid in the maculathe area of the retina responsible for central visionThe current standard of care for DME is anti VEGFvascular endothelial growth factortherapy but many patients do not respond adequatelyprompting an intensive effort to discover targets for development of adjunctive therapiesThe Tiepathway is a widely recognized central regulator of vascular stabilityand Tiereceptor activation has become a prime target for the development of novel therapies for retinal vasculopathiesincluding DMEWith deep knowledge of the TiepathwayAerpio is developing first in class therapies based on activating Tieby targeting VE PTPvascular endothelial protein tyrosine phosphatasea key negative regulator of Tiereceptor activationTowards this endAerpioandapos s lead small molecule VE PTP inhibitorAKBprovided the first clinical proof of conceptPoCfor Tieactivation in a Phasea study in DMEdemonstrating improved resolution of macular edema when administered with ranibizumaban FDA approved anti VEGF agentBased on this clinical PoCAerpio has advanced a therapeutic antibody program targeting the VE PTP extracellular domainECDthrough preclinical PoC and early development of a clinical candidateARPThe overall objective of this fast track proposal is to advance ARPthrough IND enabling studies required to support the first clinical trial in patients with DMEThe Phasespecific aims are directed towards completing key tasks required to enable the GLP toxicology programAimAssess binding of ARPin healthy and diseased human tissuesComparison of binding of the monoclonal antibody ARPto target epitopeon targetor at potential cross reactive sitesoff targetin healthy and diseased human tissue may provide important data regarding regulation of VE PTP expression in diseased tissueAimDevelop bioanalyticalBAassays to support nonclinical pharmacokineticPKand Tox studiesBA assays for detection of ARPin biological matrices and dose formulation are crucial for the Tox studies proposed in PhaseUpon meeting the Phasemilestonesthe Phasespecific aims are directed towards production of drug supply for and implementation of the IND enabling NC Tox studiesAimManufacture ARPto enable the PK and GLP toxicology studiesAimConduct IND enabling NCTox studiesUpon meeting the PhasemilestonesAerpio will be well positioned to implement the firstin human clinical trialputting ARPanother step closer to providing the first highly effective adjunctive therapy for the substantial number of patients with DME and other sight threatening retinopathies who do not adequately respond to VEGF antagonists Narrative Diabetic macular edemaDMEthe leading cause of vision loss in the working age populationstems from destabilization of blood vessels in the back of the eye leading to leakage of fluid and swelling of the maculathe part of the retina responsible for sharp central visionWhile FDAapproved VEGF antagonists can reduce the fluid and have revolutionized the treatment of DMEaboutof patients fail to respond adequately to these agents leading to an intensive search for new therapiesThis proposal will advance the early phase development of ARPa novel therapeutic agent that targets a pathway critical for stabilizing blood vessels in the back of the eye and has the potential to provide sight saving therapy for a substantial number of patients with DME who fail to respond current therapies