Novel targeted therapy for pancreatic cancer

ABTELUM BIOMEDICALINCaims to advance a humanized anti DEspR neutralizing antibodyABTwith a stabilized IgGkappa frameworkas a potential first in class therapy for pancreatic adenoductal carcinomaPDACwith the worst prognosis among all cancersTo advance IND enabling experiments for ABTthis SBIR Phase I tests the therapeutic hypothesis that ABTwill inhibit metastatic progression and increase overall survivalrelevant to Stage IV PDAC patients and resected PDAC patientsWe propose testing ABTin the biological context of pancreatic peritoneal metastasisPPMin order to stringently test efficacy and gain insight into its safety in the biological context of the worst of PDAC metastasesand in the presence of its debilitating co morbiditiesWe project that this preclinical approach will be more predictive of clinical trial efficacyDEspR is a clinically relevant target with a unique multi pronged mechanism of actionDEspR is induced inof PDAC patient tumors testednin primary and metastatic tumorsin all stages and both sexesABTtargets and inhibits key metastasis driversacancer stem like cellsCSCsresulting in decreased CSC survivalanoikis resistance and self renewal required for metastatic dissemination and seedingbangiogenic endothelial cellsangECsresulting in inhibition of angiogenesis required for metastatic tumor outgrowth beyondmmand maintenance of CSC niche integrityand in cactivated neutrophilsactPMNsresulting in decreased survival thus eliminating actPMN roles in tumor cell invasiveness and immune evasionMoreoveras DEspR is minimally present in normal tissuesABThas an inherent mechanism for safetywith no chemotherapy like toxicities or adverse eventsThese advantages are supported by experimental evidence and multiple patent applicationswith US PatentissuedABTour lead amongother candidatesexhibits improved binding and functional activity compared to its murine precursor mAbTo advance INDenabling experimentswe propose the following aimsAimTowards IND filingwe will test Awhether ABTdose dependently increases overall survival better than the standard of care gemcitabine and placebo controlsand Bwhether DEspR mechanism based biomarkers correlate with treatment responseto facilitate translation to the clinicSurvival efficacy studies will be done in two CSC derived xenograftCDXPPM nude rat models in both sexesAimTowards IND filingwe will study anti DEspR ABTmechanism of action in vivo by Aelucidating its target engagement on tumor cellsmicrovesselsand neutrophils in advanced stage primary PDAC PPM tumorsand Bby determining the tumor bioeffects on induction of apoptosis in invasive and bulk tumor cells as expected from ABTandapos s mechanism of actionin contrast to isotype controlImpactCompletion of aims will attain IND enabling experiments to advance ABTas a novel therapy for PDAC with no chemotherapy like toxicities and for other cancers as well This research aims to advance the translation to the clinic of a potential first in class fully humanized antiDEspR antibodyABTas novel cancer therapy with a three pronged mechanism of action which inhibits key players in metastasiscancer stem cellsCSCtumor blood vessel formationand activated neutrophils which promote tumor cell invasiveness and immune evasionWe propose to rigorously test ABTin a CSC derived xenograft tumor model pancreatic peritoneal metastasiswhich has no curativeintent therapyCompletion of this SBIR Phase I will attain key milestones towards IND filing for ABTin order to advance translation to the clinic for PDACand in futuretherapy for other metastatic cancers