Research Project
9334641
ABSTRACT: This application is seeking funding specifically for Chemistry, Manufacturing, and Control (CMC) of scale-up production of long acting atrial natriuretic peptide (dANP) and its protected graft co-polymer (PGC) excipient for use in heart failure (HF) treatment. The extrinsic merit of this project will be the availability of cGMP grade PGC for use in prolonging the half-life of various peptide drugs that are in preclinical development by other companies. Our product goal at the end of this project is cGMP grade PGC-dANP. Additional funding for Toxicology and Phase 1 Clinical Trials from a private investor will be made available at delivery of cGMP grade PGC-dANP. ANP has a long history of efficacy in HF patients and those treated by 2-3day continuous infusion have shown smaller infarct size and lower incidence of readmission to hospital than controls. However, sustained ANP infusion for 2-3 days in hospital setting has a very high health care cost and longer treatment is impractical. PGC-dANP is a product that can be administered subcutaneously at home and can be continued for several months to further reduce future cardiac events, improve long term outcomes, and reduce overall health care costs. At this stage we can consistently produce 35g batch of PGC in our laboratory and we want to scale it up to 500g in a cGMP facility. We already developed the analytical requirements needed for lot release and stability testing but we need to define the widest range that will provide no significant difference in PK/PD profile. This is important to reduce risk of unnecessary cost of lot rejection especially for big batches worth several $100K. The Aims are: to establish the widest acceptable range of values that measure Quality, Integrity, Purity, Potency and Sterility (QIPPS) as lot release indicators required by the FDA and transfer the analytical methods to the appropriate GLP facilities; to scale up PGCs synthesis from our 35g process to 500g and produce 500g cGMP grade PGC; and to formulate PGC-dANP in a cGMP manner, with stability testing using QIPPS analysis in a GLP facility. PharmaIN Corp. Confidential
