ANGIOTENSIN THERAPEUTICS INC.
Angiotensin Therapeutics Inc is developing novel biologics primarily for treatment of kidney disease . Our main biologics are short variants of a natural enzyme called Angiotensin Converting Enzyme II (ACE2). The main therapeutic targets for these compounds are Acute kidney injury (AKI) which is a common complication of cardiac surgery and of decompensated heart failure and chronic kidney disease (CKD). Each year, acute kidney injury (AKI) is the cause of over 4 million hospitalizations in the United States. AKI is defined as a rapid (within hours or days) decline in kidney function and costs the United States healthcare system approximately 10 billion dollars per year. Each episode of AKI is associated with increased mortality and rehospitalization rate. Additionally, 41% of patients with AKI who survive, may not recover kidney function before hospital discharge. AKI is one of the major causes of hospitalizations and the incidence of AKI after Cardiac Surgery is up to 30 % of patients undergoing this frequent type of surgery. Proteinuria is defined as wastage of protein in urine and is a capital and frequent manifestation of kidney disease. Preventing or ameliorating the course of AKI and improving the existing therapies for the management of proteinuria and CKD are ultimately aimed to reduce the need of dialysis and associated mortality altogether.
Despite the clinical importance of AKI, there is currently no effective pharmacological intervention available to either prevent or treat AKI in the clinical setting. Proteinuria and progression of CKD to ESKD can be managed with existing therapies that, however, are only partially effective and there is a need of other therapies that are better than existing ones , such as ACE inhibitors and angiotensin II blockers, by offering differential features that increase the overall therapeutic and safety profile. Unlike the existing blockers of the renin angiotensin system the proposed compounds work like a natural enzyme, ACE2, that prevents the accumulation of Angiotensin II. The large molecular size of the native enzyme (~110kDa , however, renders it non-filterable by a normal glomerulus (the filtration unit of the kidneys).
We have bioengineered and tested three short variants of ACE2: AT-619, AT-605 and AT-618. Our research development has been primarily in murine models widely used to study AKI and CKD. In preclinical studies our compounds are amenable to kidney delivery via glomerular filtration and showed efficacy in a mouse model of AKI. These findings were presented at the November 2019 meeting of the American Society of Nephrology (ASN). The administration of our short ACE2 variants leads to more formation of Angiotensin 1-7 by the kidneys. Preventing undesirable angiotensin II accumulation and promoting formation of Angiotensin 1-7 is the likely mechanism that protects against the kidney damage seen in AKI and CKD. A notable finding is that with administration of our ACE2 based compounds blood pressure does not fall. This has clinical implications because the widely used RAS blockers (ACE inhibitors and Angiotensin receptor blockers) cause hypotension and hyperkalemia. Theoretical advantages as compared to existing RAS blockers are less risk of 1) Hypotension 2) Kidney hemodynamic alterations and 3) Less risk of hyperkalemia.
Business Strategy and the Ask
We are seeking funding for the pre-clinical studies and small batch that will advance the compound towards an Investigator initiated Research Investigational New Drug Application for the Food and Drug Administration. We are looking to raise $2.5M, to more rapidly expand the pace of the development of our compounds and to perform some of the necessary pharmacokinetics, toxicology, genotoxicity, safety pharmacology and efficacy studies in a larger animal models; perform the necessary GLP studies needed; as well as small scale production of IMP to produce data for an IND application to the FDA.
Dr. Dan Batlle: DBATLLE50@GMAIL .COM
Daniel Batlle MD, Founder/Owner Angiotensin Therapeutics Inc and Co-inventor of the ACE2 short variants
Cory Gutterman MPH, President, and CEO Angiotensin Therapeutics Inc
Jay Pandit MD, Advisory Board Member