Immunotherapeutics to prevent HCV reinfection

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$600,000.00
Award Year:
2013
Program:
STTR
Phase:
Phase I
Contract:
1R41AI108024-01
Award Id:
n/a
Agency Tracking Number:
R41AI108024
Solicitation Year:
2013
Solicitation Topic Code:
NIAID
Solicitation Number:
PA10-124
Small Business Information
Gaithersburg, MD, -
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
601000750
Principal Investigator:
KELLYWARFIELD
(240) 454-8936
kelly@integratedbiotherapeutics.com
Business Contact:
MAHTABHEKMAT
(240) 454-8935
mahtab@integratedbiotherapeutics.co
Research Institute:
STANFORD UNIVERISTY

STANFORD UNIVERSITY
3160 PORTER DRIVE, SUITE 100
STANFORD, CA, 94305-6203
() -

Abstract
DESCRIPTION (provided by applicant): Up to 170 million people worldwide are chronically infected with HCV Hepatitis C virus (HCV) putting the infected individuals at significant risk for cirrhosis, liver failure and liver cancer. End- stage liver diseasecaused by HCV is the leading indication of liver transplantation (LT) in the United States. However, reinfection with HCV occurs universally and allograft failure because of reinfection is the most common cause for retransplantation and death among HCV-infected LT recipients. Shortly after LT, HCV reinfection is universal and poorly controlled by current antiviral treatments. While there is new optimism in the treatment of chronic HCV infection with two recent FDA approved direct acting antivirals DAA, telaprevir and boceprevir, they are not recommended for treating HCV in the transplant setting due to likely adverse drug-drug interaction. Cumulative evidence indicates a protective role for virus neutralizing (Vn) antibodies for HCV, which could be used as an alternative approach to prevent HCV reinfection in liver transplant recipients. The goal of this project is to develop a highly effective immunotherapeutic to prevent HCV reinfection in liver transplant patients based on antibodies that limit the abilityof the virus to escape via mutations In Specific Aim 1, broadly neutralizing human monoclonal antibodies (HMAb) to HCV envelope glycoprotein will be produced via affinity maturation that are not associated with viral escape. A yeast display system will beused to affinity mature HMAbs for improved binding and neutralization authentic cell culture infectious HCV virion (HCVcc) of different genotypes. The lead antibodies will be assessed for the ability to limit viral escape with multiple infectious HCVcc. The antibody with the highest potencies and an acceptable stability profile against different HCVcc genotypes along with its wt clone will be selected for testing using the uPA/SCID model. In Specific Aim 2, the affinity matured HCV HMAb having greatest neutralizing potencies against diverse genotype HCVcc, and not associated with viral escape, will be evaluated in the uPA/SCID chimeric human liver mouse model of acute HCV infection. Subsequent and future work will further evaluate the lead candidate(s) leading to a final candidate product, conduct the crucial, additional efficacy studies in a HCV human-mouse liver chimeric animal model, establish the required assays for clinical development, and develop the required cell banks and a scalable manufacturing process for production of a clinical lot for testing in a phase 1 safety and immunogenicity human clinical trial. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Up to 170 million people worldwide are chronically infected with HCV Hepatitis C virus (HCV) putting the infected individuals at significant risk for cirrhosis liver failure and liver cancer. End- stage liver disease caused by HCV is the leading indication of liver transplantation in the United States. However, reinfection with HCV occurs universally and allograft failure because of reinfection is the most common cause for retransplantation and death among HCV-infected LT recipients. The goal of this project is to develop a highly effective immunotherapeutic to prevent HCV reinfection in liver transplant patients based on antibodies that limit the ability of the virus to escape via mutations.

* information listed above is at the time of submission.

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