A&G PHARMACEUTICAL, INC. — Department of Health and Human Services SBIR Phase II: 102

Description

SignificanceInnew cases of LC andrelated deaths are expected in the USOf new LC casesare non small cell lung cancerNSCLCandof these are diagnosed with metastaticlocally advancedinoperable LC with ayr survival of less thanA new approach is required to reduce the overall death rates in this devastating diseaseEfficacious therapies targeting EGFRALK and ROS translocations and vEGF are used in standard of careSoCHoweverthey are only effective in ltof the overall NSCLC populationFDA approved companion diagnostics are used to identify patients that may receive benefit from these drugsIn spite of these advancesno therapy is curative in advanced disease and median life expectancy for metastatic NSCLC remains atmthsHypothesisWe have identified GPankDa glycoprotein autocrine intimately involved in cellular deregulated growth leading to tumor formationThe PIdemonstrated GPs critical role in the biological process of cancer tumorigenesis and survivalits overexpression in LC tumors while it is not expressed in normal lung tissueits secretion into biological fluids at increased levels in LC patients compared to healthy individualsThus using a tissue test to identify tumors that express GPand then treating these patients with an antibody that neutralizes GPand therefore blocks its autocrine effect on cancer cells will ainhibit tumor growth and bincrease the efficacy of current LC drugsSupporting EvidencePathological studies established GPtumor expression as a predictive marker for recurrenceClinical studies showed LC patients with progressive disease have elevated GPserum levels compared to healthy individualsIn Vivo studies demonstrated that AGa recombinant anti GPcan reduce the growth of human LC xenografts in mice and potentiate the effect of SoC drugsStrategy and ApproachWe will carry out a phase I clinical trial using AGto determine safety and recommended phasedoseIn additionwe will require tissue collection and serial blood sampling on all patients to evaluate for GPexpressiontissueand concentrationbloodin enrolled patients and expansion cohorts of NSCLC and mesotheliomadiseases demonstrated to express GPcorrelated with outcomeThe IHC test measures GPexpression in tumor tissue to identify patients with tumors expressing GPThe serum GPEIA test can provide real time monitoring of disease status in the SoCSpecific aimManufacturegms of GMP AGfor the Phase I clinical studies Specific AimPerform a Phase I clinical study inapatients with solid tumors to determine maximum tolerated doseoptimum biological dose andbexpansion cohorts with LC and mesothelioma patientsOverall ImpactBlocking the action of GPin aggressive cancer such as LC using a neutralizing antibody willinhibit tumor growthpotentiate standard of care drugsThere is compelling biological and clinical evidence to suggest that GPis therapeutic target with companion diagnostics for NSCLC that could impact LC treatment and improve survival of patients with NSCLCLay outline Innew cases of LC andrelated deaths are expected in the USThe majority of these are non small cell lung cancerNSCLCthat are diagnosed with metastatic cancer and onlyof these will be alive atyrs post diagnosisDrugs that are effective in this disease are only useful in less thanof the NSCLC population and no curative therapies existA new approach that will benefit a larger population and provides increased life expectancy needs to be developedWe have identified GPa glycoprotein that is produced by cancer cells and stimulates growth and survival of the same cancer cells leading to tumor formationGPis found in LC but not normal lung tissueThere is compelling biological and clinical evidence to suggest that GPis therapeutic target with companion diagnostics for NSCLC that could impact treatment and improve survival of patients with NSCLCWe have developed a tissue test to identify which tumors express GPand an anti GPAGto block the action of GPon tumor tissues to ainhibit tumor growth and bincrease the efficacy of current LC drugsAdditionallya blood test has been developed to monitor patients while on treatmentUsing AGas the therapy with two companion diagnostic tests we will carry out a phase I clinical trial to determine safety of AGin humans and will collect tumor tissue and blood on all patients to evaluate for GPexpressiontissueand concentrationblood