2-Dose Cp Model

An enabling aspect of our Phase 2 effort will be use of two improved models, including our novel 2-dose CP model in mice developed in Phase 1 that for the 1st time, reproduces the AKI and CKD pattern in humans treated with CP. Given the potential advantages a peptide agonist vs. RNLS protein, including reduced potential for cardiovascular side effects and immunogenicity; ease of manufacturing and stronger intellectual property, we will confirm and extend that a peptide agonist is equal or better than RNLS, and select the best clinical development candidate. Successful results will advance the understanding of CP-induced kidney injury and set the stage and define the lead drug for IND enabling studies and clinical development for a RNLS agonist to significantly enhance use of CP therapy.
Select lead agonist. Renal CP toxicity reduction will be a major driver for lead selection (50% or greater protective effects on CP renal toxicity using serum creatinine, inulin based GFR, and CP-AKI injury score) selecting a peptide if it is equal or better than rRNLS. Milestone (M1): Use the improved models including ours, to compare the ED50 dose of rRNLS and 2 RNLS peptides for ability to prevent CP caused AKI and limit progression to CKD; M2: Compare rRNLS and 2 RNLS peptides in multiple dosing studies to decrease CP toxicity in our improved model and assess serum chemistries, hematology, clinical signs, body and organ weights, behavioral/physiological observations (Irwin tests), acoustic startle response, and gross autopsy observations. M3: Determine pharmacokinetics on effective agonists with longer T1/2 and greater AUC desirable. M4: Select