Novel Small Molecules For Acute Liver Failure

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$254,257.00
Award Year:
2007
Program:
SBIR
Phase:
Phase I
Contract:
1R43AA016457-01A1
Award Id:
85211
Agency Tracking Number:
AA016457
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
ANGION BIOMEDICA CORP, 1050 Stewart Ave., Garden City, NY, 11530
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
053129065
Principal Investigator:
PRAKASH NARAYAN
(516) 326-1200
PNARAYAN@ANGION.COM
Business Contact:
ITXHAK GOLDBERG
() -
igoldberg@angion.com
Research Institution:
n/a
Abstract
DESCRIPTION (provided by applicant): Acute liver failure (ALF) constitutes a challenge to clinicians and scientists alike. Commonly associated with the alcohol-acetaminophen syndrome, its clinical course is unpredictable and polarizing, with death as the o utcome in a large percentage of cases. Given the lack of specific therapy, organ transplantation is the only clinically effective strategy. Consequently, the field is ripe for translational studies that identify and develop new therapeutic strategies that attenuate hepatocyte death, promote hepatic regeneration and improve outcome. In a best-case scenario, such therapeutics will accelerate spontaneous regeneration of the liver and preclude the need for transplantation; in the most severe cases, they will se rve as a hepatic bridge until transplantation. Significant evidence suggests that scatter factor / hepatocyte growth factor, exerts direct hepatoprotective effects and can potentially be used as a therapeutic in ALF. However, the feasibility of using thi s growth factor in the form of gene or protein therapy is compounded by numerous logistical issues. Low molecular weight compounds that mimic the activity of SF/HGF could overcome these logistical difficulties and provide effective therapy. Using a product discovery engine comprising phage display, 3-dimensional molecular modeling, protein chemistry and preclinical biology, we have identified Ang 1170, an organic small molecule SF/HGF mimetic. Our studies indicate that Ang 1170 activates the SF/HGF/c-Met pa thway and exerts organoprotective effects. Importantly, in a rodent model of ALF, Ang 1170 reduces mortality, and attenuates hepatic injury. We have since constructed a structural library around Ang 1170 comprising 21 compounds with potential SF/HGF-like a ctivity. The goal of this Phase I application is to couple targeted proteomics to in vivo efficacy studies in order to identify a lead candidate (Ang 1170 or one of its analogs) within this library for the treatment of ALF. The lead candidate emerging from this study will be submitted to in- depth, preclinical SBIR Phase II studies (oral and delayed efficacy, preclinical models of ALF combining co- morbid conditions, pharmacokinetics and safety studies) with the ultimate objective of using a small molecule SF/HGF-mimetic for therapeutic use in ALF. Acute liver failure remains a significant cause of morbidity and mortality. A small molecule hepatocyte growth factor mimetic that is hepatoprotective is of tremendous clinical benefit.

* information listed above is at the time of submission.

Agency Micro-sites


SBA logo

Department of Agriculture logo

Department of Commerce logo

Department of Defense logo

Department of Education logo

Department of Energy logo

Department of Health and Human Services logo

Department of Homeland Security logo

Department of Transportation logo

Enviromental Protection Agency logo

National Aeronautics and Space Administration logo

National Science Foundation logo
US Flag An Official Website of the United States Government