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Principal Investigator: quaisar Ali
Organization: ANGION BIOMEDICA CORPORATION
Fiscal Year: 2019
Award: $220,731
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
Project Abstract
The blossoming diabetes, obesity and metabolic syndrome epidemics have taken a toll on the North
American liver. The incidence and prevalence of non-alcoholic fatty liver disease (NAFLD), whose
genesis is in simple steatosis, and non-alcoholic steatohepatitis (NASH), are staggering. Left
untreated, NASH can progress to NASH with increasing levels of fibrosis, cirrhosis and hepatocellular
carcinoma (HCC). This disease continues to present a challenge to the gastroenterologist who has
few, if any, combat-ready tools at his/her disposal. While a number of promising agents are in clinical
trials in NASH, none has met approval. Liver disease is a chronic indication that will necessitate a
long course of therapy, which brings with it the attendant risk of drug related side effects. The
proposed program seeks to advance a highly targeted therapeutic, that is both, potentially effective,
and potentially safe, for the treatment of NASH. This program is based on new information on the
biology governing liver fibrosis, viz. the Rho-associated coiled-coil kinase (ROCK)2-hepatic stellate
cell (HSC)-fibrosis (ROCK2-HSC-fibrosis) axis and the synthesis of ANG4201, a proprietary, orally
bioavailable, small molecule inhibitor that can potentially interrupt this cascade. Under the aegis of
this SBIR Phase I application, we will first obtain a profile of ANG4201 pharmacokinetics (PK), and its
exposure-IC50 relationship (Specific Aim # 1). In Specific Aim # 2, we will use these data to evaluate
the efficacy of ANG4201 in two etiologically distinct models of liver disease. Unlike the first generation
of dual ROCK (1 &2) inhibitors, it is anticipated that a selective ROCK2 inhibitor will not only prove
efficacious in mitigating fibrosis but will also carry a lower risk of any side effects associated with
chronic dosing.
Terms: <21+ years old><Adjuvant><Adult><Adult Human><American><Anti-inflammatory><Assay><Bioassay><Bioavailability><Bioavailable><Biochemical><Biologic Assays><Biologic Availability><Biological Assay><Biological Availability><Biology><Blood Plasma><Blossoms><Calponin Phosphatase><Causality><Chronic><Cirrhosis><Clinical Trials><Collagen><Data><Deposit><Deposition><Diabetes Mellitus><Diet><Disease><Disorder><Dose><Drug Administration Schedule><Drug Exposure><Drug Kinetics><Drug effect disorder><Drugs><Epidemic><Ethanethioamide><Etiology><Evaluation><Exposure to><Female><Fibrosis><Flowers><Gastroenterologist><Generations><Hepatic Disorder><Hepatic Stellate Cell><Hepatocarcinoma><Hepatocellular Carcinoma><Hepatocellular cancer><Hepatoma><Incidence><Interruption><Ito Cell><Kinases><Lead><Left><Legal patent><Libraries><Liver><Liver Cells Carcinoma><Liver Fibrosis><Liver diseases><Medication><Metabolic syndrome><Mice><Mice Mammals><Modeling><Murine><Mus><Myosin-Light-Chain Phosphatase><NAFLD><NASH><Obesity><Oral><Patents><Pb element><Pharmaceutic Preparations><Pharmaceutical Preparations><Pharmacokinetics><Pharmacological Study><Pharmacology Study><Phase><Phosphorylation><Phosphotransferase Gene><Phosphotransferases><Physiologic Availability><Plant Blooms><Plasma><Plasma Serum><Position><Positioning Attribute><Prevalence><Primary carcinoma of the liver cells><Program Development><Protein Phosphorylation><Proteins><Reticuloendothelial System, Serum, Plasma><Risk><SBIR><Safety><Schedule><Sirius Red F3B><Small Business Innovation Research><Small Business Innovation Research Grant><Staining method><Stains><Therapeutic><Thioacetamide><Time><Toxic effect><Toxicities><Transphosphorylases><adiposity><adulthood><antiinflammatory><appropriate dose><base><causation><cirrhotic><combat><convenience food><corpulence><corpulency><corpulentia><diabetes><dietary><disease causation><drug action><drug candidate><drug development><drug discovery><drug/agent><fast food><fibrotic liver><heavy metal Pb><heavy metal lead><hepatic body system><hepatic disease><hepatic fibrosis><hepatic organ system><hepatopathy><in vivo><inhibitor><inhibitor/antagonist><liver carcinoma><liver disorder><male><membrane-organizing extension spike protein><moesin><myosin phosphatase><non-alcohol fatty liver disease><non-alcohol induced steatohepatitis><non-alcoholic fatty liver disease><non-alcoholic liver disease><non-alcoholic steato-hepatitis><non-alcoholic steatohepatitis><nonalcoholic fatty liver disease><nonalcoholic steato-hepatitis><nonalcoholic steatohepatitis><obese><obese people><obese person><obese population><off-patent><optimal drug dosage><optimal drug dose><pharmacodynamic biomarker><pharmacodynamic marker><picrosirius red><programs><rho><safety study><side effect><sirius red F 3B><small molecule inhibitor><standard of care><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><tool>