Pharmacology & human Phase 1 safety & dose escalation studies using anti-GP88 in aggressive breast cancer

Innew cases of breast cancerBCandrelated deaths are expected in the USof these are patients with aggressive triple negative BCTNBCor anti estrogen aromatase inhibitor resistantAE AIBC that do not have targeted therapy and rely on radiotherapy and aggressive chemotherapyA new approach that benefits these patients and provides increased life expectancy needs to be developedWe have identified GPa glycoprotein that is produced by cancer cells and stimulates their growth and survival leading to formation of more aggressive tumorsGPis found in BC but not in normal breast tissueThere is compelling biological and clinical evidence to suggest that GPcan be used to develop novel targeted therapy with companion diagnostics that could impact treatment and improve survival of TNBC and AE AI BC patientsWe have developed a tissue test to identify patients with tumors expressing GPand an anti GPAGto block the action of GPon tumor tissues to ainhibit tumor growth and bincrease the efficacy of current BC drugsWe have safety and efficacy data in animals and will in our Phasedevelop a dosing strategy in mice before moving into human studies as part of the PhaseAdditionallya blood test has been developed to monitor patients while on treatmentUsing AGas the therapy with two companion diagnostic testswe will carry out a phase IA B clinical trial in humans to determine safety of AGmanufactured under GMP in the Phaseand will collect tumor tissue and blood on all patients to evaluate for GPexpressiontissueand concentrationbloodSignificanceOfcases of breast cancerBCdiagnosed in the US incases will be estrogen receptor positive andHeroverexpressing for whom targeted therapies are available as well as biomarker tests to identify those who may benefit from such drugsHoweverthere aremajor at risk BC groups who have limited treatment choicesanti estrogenaromatase inhibitor resistant populationAE AIand triple negative BC populationTNBCThe PI s discovery of a theranostic target that is a driver of tumorigenesis and has therapeutic and companion diagnostics applicationswill address both BC populationsHypothesisWe identified GPankDa glycoprotein autocrine growthsurvival factor involved in deregulated growth leading to aggressive tumor formationThe PI demonstrated GPs critical role in the process of cancer tumorigenesis andampsurvivalits overexpression in BC tumors but not in normal breast tissue andampits secretion into biological fluids at increased levels in BC patients compared to healthy individualsUsing a tissue test to identify patients with GPpositive tumors and treating such patients with an antibody that neutralizes GPand blocks its autocrine effect on cancer cells will inhibit tumor growth and increase efficacy of current BC drugsEvidencePathological studies established GPtumor expression as a predictive marker for recurrenceClinical studies showed BC patients with progressive BC have elevated GPserum levels compared to healthy individualsIn Vivo studies demonstrated AGa recombinant anti GPcan reduce growth of human BC xenografts in mice and potentiate the effect of SOC drugsGMP manufacturing of AGhas been developedlots of AGhave been produced and formulated as injectableRepeat dose toxicology study in non human primates established AGsafetyStrategy andampApproach of Fast Track SBIRPhasespecific aims will collect pharmacology data in mice to link our efficacy andampsafety data to identify a dose and schedule for AGin human studiesPhasewill focus on a phase IA B clinical trial to determine safety of AGin humansTumor tissue collection and serial blood sampling will evaluate GPtissue expression and blood concentration in enrolled TNBC and AE AI BC patients demonstrated to express GPcorrelated with outcomeThe IHC test measures GPexpression in tumor tissue to identify GPpositive patientsThe serum GPEIA provides real time monitoring of disease statusThe PhaseSpecific Aimmanufacturegms of GMP AGfor Phase IA B clinical studiesSpecific Aimperform a Phase IA B clinical study inapatients with solid tumors to determine maximum tolerated doseoptimum biological dose andbexpansion cohorts with TNBC and AE AI BC patients with GPpositive tumorsOverall ImpactBlocking action of GPin aggressive cancer using a first in class neutralizing antibody willinhibit tumor growthpotentiate SOC drugsThere is compelling biological and clinical evidence to suggest GPis a therapeutic target with companion diagnostics for BC that could impact treatment and improve survival of patients with TNBC and AE AI BC