Imaginab, Inc. — Department of Health and Human Services SBIR Phase II: 102

Description

DESCRIPTION provided by applicant A highly sensitive and specific clinical imaging agent to detect stage and monitor response to therapeutic intervention is urgently needed for prostate cancer patients To address this unmet need we initially generated a radiolabeled minibody Mb fragment Zr Df IAB M directed to Prostate Specific Membrane Antigen PSMA PSMA is significantly upregulated in the majority of human prostate cancers and its expression increases with increasing grade with the spread of metastatic disease and emergence of castration resistant phenotype making it one of the best validated markers and targets in prostate cancer In Phase IIa of the contract GMP grade Zr Df IAB M was manufactured enabling early Phase a clinical trials that are now complete The trials assessed safety dose ranges PK dosimetry biodistribution immunogenicity and initial signs of imaging efficacy Excellent data obtained in these early trials allowed us to advance Zr Df IAB M compound into Phase clinical trials in March During the transfer of the minibody manufacturing to another CMO to enable upcoming Phase clinical studies and commercialization ImaginAb introduced minor changes in the primary structure of the original IAB M to generate a more optimal Mb that is now called IAB M A These changes did not affect binding to PSMA but greatly improved stability manufacturability and homogeneity of the product candidate which will decrease manufacturing costs and potentially reduce immunogenicity Zr Df IAB M A has also demonstrated greater circulation stability in vivo in preclinical models with reduced renal clearance while maintaining excellent targeting to PSMA expressing tumors These results suggest that Zr Df IAB M A will retain similar targeting properties in patients while reducing the radioactive dose delivered to human kidneys a radiosensitive organ This improved Mb variant is currently in GMP manufacturing The overall goal of this SBIR Phase IIb contract proposal is to advance the clinical development of the Zr Df IAB M A compound towards BLA submission and commercialization In Phase IIb of the contract ImaginAb proposes to Complete the development and optimization of protein formulation s Df isothiocyanate conjugation process transfer to CMO and all product related characterization release assays for manufacturing of IAB M A Df IAB M A and Zr IAB M A Conduct preclinical characterization studies to compare the early Phase a clinical material and the new Zr Df IAB M A Perform bridging Phase studies with Zr IAB M A in patients to evaluate safety PK biodistribution and to compare to the original product candidate Achievement of these specific aims will enable proper design of future Phase study that will support potential of a subsequent BLA filing PUBLIC HEALTH RELEVANCE Prostate cancer remains a formidable disease with over men expected to be diagnosed and greater than expected to die in the U S in alone Importantly diagnostic imaging to detect stage and guide prostate cancer treatment remains a clear unmet clinical need The work proposed in this project will cover multiple activities required for the clinical development of Zr Df IAB M A as a commercially viable prostate cancer imaging agent The successful development of Zr Df IAB M A as an imaging reagent will provide a transformative asset in guiding therapy against this disease