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Inhibition of Galectin-3 for Therapy of Remodeling After Myocardial Infarction

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R44AG054386-01A1
Agency Tracking Number: R44AG054386
Amount: $224,734.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NIA
Solicitation Number: PA15-269
Timeline
Solicitation Year: 2015
Award Year: 2016
Award Start Date (Proposal Award Date): 2016-08-15
Award End Date (Contract End Date): 2017-03-31
Small Business Information
665 3RD ST STE 250
San Francisco, CA 94107-1953
United States
DUNS: 031636660
HUBZone Owned: No
Woman Owned: Yes
Socially and Economically Disadvantaged: No
Principal Investigator
 CONSTANCE JOHN
 (415) 333-5570
 connie@mandalmed.com
Business Contact
 CONSTANCE JOHN
Phone: (415) 305-4888
Email: connie@mandalmed.com
Research Institution
N/A
Abstract

PROJECT SUMMARY ABSTRACT
The overall goal of this project is to develop a human protein that is an inhibitor of galectin as a biologic to
aid in the prevention and treatment of harmful remodeling after myocardial infarction MI heart attack and
thereby improve cardiac function and reduce mortality from subsequent heart failure MI is the most common
cause of cardiac morbidity and mortality in the Western world The incidence in the United States is
new attacks and recurrent attacks annually approximately one every seconds Fibrosis is triggered
by the physiological response to injury or infection and leads to the deposition of extracellular matrix and for
mation of new connective tissue Excessive or dysregulated fibrosis from insults can dramatically reduce the
functioning of the heart and other organs In the heart excessive interstitial fibrosis reduces contractility elas
ticity and distensibility exacerbating processes that lead to heart failure Although there are therapeutic agents
currently used after MI that are efficacious such as the mineralocorticoid receptor antagonists MRAs
angiotensin converting enzyme ACE inhibitors and angiotensin II receptor blockers ARBs and that have
shown anti fibrotic effects in animal studies the health burden from MI remains significant Fibrosis is regulated
by a number of inflammatory cytokines and growth factors and galectin has recently been implicated as a
major and novel mediator of organ fibrosis Increased serum levels of galectin have been approved in the
United States and the European Union as prognostic indicators of risk of death from progressive heart failure
supporting the hypothesis that galectin is a target for drug development Based on its mechanism of action
and structure the protein is a unique inhibitor of galectin with properties that convey therapeutic advantage
Our preliminary studies in a rat ischemia reperfusion I R injury model of MI showed very promising efficacy
The Specific Aims for this Fast Track Phase I II project are the following Phase I Aim is to determine
efficacy of Gal C therapy in animal models Determine antifibrotic potential of Gal C in the context of greater
injury caused by permanent ligation of the coronary artery and evaluate efficacy of Gal C therapy relative to
ARB and antifibrotic control drugs in a rat I R MI model Phase II Aim is to better understand efficacy of Gal
C therapy in animal models Determine efficacy and optimal dosage of Gal C in rat I R MI determine
efficacy of Gal C in comparison to a MRA and in combination with an ARB in rat I R MI model and determine
efficacy of Gal C in miniswine I R model of MI Aim is to develop GLP GMP production methods and a
formulation for Gal C Aim is to perform pharmacokinetic studies and acute subacute toxicology in rodents
Achievement of these aims is expected to position MandalMed to complete pre clinical development in the
near term and to subsequently file an Investigational New Drug IND application PROJECT NARRATIVE
The overall goal of this project is to develop a protein inhibitor of galectin termed galectin C as a
biologic to prevent and treat harmful remodeling after myocardial infarction and thereby improve cardiac
function and reduce mortality from subsequent heart failure Myocardial infarction is the most common cause of
cardiac morbidity and mortality in the western world The annual incidence in the United States is new
attacks and recurrent attacks Because current standard practice of minimizing time from onset of
myocardial infarction to re opening of the blocked artery has greatly reduced the incidence of death from acute
myocardial infarction heart failure subsequent to myocardial infarction has become the main mortality
associated with coronary events

* Information listed above is at the time of submission. *

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