The Specific Aim of this direct to Phase II proposal is to carry out IND enabling work for our drug, Vastiras(r). Our first therapeutic target patient population is the ~400,000 people who suffer from acute decompensated heart failure (ADCHF or AHF) and present with renal compromise. These patients are hospitalized when diagnosed and become stable for a while; however, a high percentage relapse and are re-hospitalized. There is no cure for this patient population, but restoring both heart and kidney function are essential to prolonging life and improving quality of life. The current standard of care for ADCHF individuals is well known and primarily addresses symptoms (dyspnea, high blood pressure, water retention). While some patients respond well to conventional loop diuretics, diuretic resistance is common and the potential for renal damage with elevated dosing serious. To improve outcomes and reduce readmissions, better treatments are needed. To this end, we have developed Vastiras(r). Vastiras supports the kidney directly by augmenting the natural levels of proANP 31- 67 produced by the heart when overworked (stretched). In the clinic, synthetic proANP 31-67 does not show unwanted side effects. Vastiras increases glomerular filtration, improves excretion of salt and water with only moderate systemic vasodilation. Vastiras is expected to be used as a co-therapy to frontline cardiocentric therapy (beta-blockers, ionotropes) or other renally directed therapies (diuretics, ACE inhibitors, ARBs) to support heart function through improved hemodynamics and renal performance. Vastiras has desirable drug properties and is safe in humans, findings supported by Madeleine's limited clinical trial data with synthetic proANP 31-67. Our next step in translation to clinic is to conduct a Phase II clinical trial for safety and efficacy. To date, our clinical investigations used a peptide made frm a solid phase process, due to cost and convenience considerations for relatively small amounts of drug. However, Phase II and beyond will require large scale production. For affordable production at large scale, we have developed and validated a proprietary E. coli fermentation process. Since we are using a new manufacturing procedure, we must complete a set of chemistry, manufacturing, and control (CMC) studies and carry out animal toxicology work prior to running our Phase II trial, per the FDAs recommendation. To this end, we will carry out the following Tasks: Task 1: CMC - Chemistry, Manufacturing & Control (Requalification and Scale-up and QA/QC) Task 2: Preclinical Toxicology - Analysis in Rat and Non-Human Primate (NHP) Criteria for Success: CMC and preclinical toxicology studies must achieve parameters associates with FDA requirements of for clinical testing. Following success of our proposed studies, we will continue additional steps required to file an IND with the FDA in order to carry out our clinical studies.
About ~400,000 people suffer from acute decompensated heart failure (ADCHF or AHF) and present with renal compromise in the US. Current treatments are not very effective for this condition, resulting in a decreased quality of life and premature death. We are developing a drug to prolong life and improve quality of life for these patients.
