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Ex Vivo Gene Therapy for Hemophilia A

Award Information

Department of Health and Human Services
Award ID:
Program Year/Program:
2009 / STTR
Agency Tracking Number:
Solicitation Year:
Solicitation Topic Code:
Solicitation Number:
Small Business Information
1860 Montreal Road Tucker, GA 30084-
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Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
Phase 2
Fiscal Year: 2009
Title: Ex Vivo Gene Therapy for Hemophilia A
Agency: HHS
Contract: 2R42HL083531-02
Award Amount: $1,126,694.00


DESCRIPTION (provided by applicant): Hemophilia A is a congenital bleeding disorder caused by genetic mutations affecting a plasma protein, termed factor VIII (fVIII), whose function is to facilitate blood clotting. State of the art treatment of hemophilia A consists of frequent intravenous infusion of fVIII containing products. The current limitations to treating hemophilia are 1) morbidity due to joint disease resulting from repeated bleeding into individual joints, 2) the cost of fVIII products, 3) the d evelopment of immune responses against fVIII that hinder treatment efficacy and 4) access to fVIII products. Owing to these limitations approximately 30% of hemophilia A patients are treated worldwide. Gene therapy has the potential to cure hemophilia A si nce only a limited amount of fVIII is needed to provide clinical benefit to the patient. However, three phase 1 clinical trials have been conducted and the outcome has been disappointing due to the extremely low, non-therapeutic levels of fVIII produced by each gene therapy strategy. The mission of Expression Therapeutics is to develop products that will improve the standard treatment of individuals with hemophilia A by incorporating our technology, which is based on proprietary methods that result in drama tic increases in fVIII biosynthesis and secretion from genetically- engineered cells. Our Phase I STTR preclinical studies demonstrated proof-of-concept that Expression Therapeutics' high expression fVIII technology facilitates very high-level fVIII produc tion in a mouse model of hemophilia A following ex vivo retroviral modification and transplantation of hematopoietic stem cells. These studies lead us to the identification of a lead fVIII transgene, designated ET-801, that is the focus of this proposal. E T-801 contains gt90% human sequence and lt 10% of sequences that confer the high-expression properties required to overcome the hurdle of low-level expression seen in previous clinical trials. The goal of the proposed studies in the current Phase II STTR a pplication is to complete the preclinical manufacturing, efficacy and toxicology studies necessary for IND approval and initiation of a human clinical trial. We propose to manufacture and characterize cGMP grade ET-801 lentiviral vector in vitro and in viv o in order to evaluate the effectiveness of our proposed gene therapy strategy in small (mouse) and large (canine) animal models. Completion of these studies will constitute the framework for which a phase 1 clinical trial will be developed and conducted. PUBLIC HEALTH RELEVANCE: Current treatment for hemophilia A, which is a bleeding disorder caused by genetic mutations affecting a blood protein, termed factor VIII (fVIII), relies on infusion of plasma-derived or recombinant fVIII to restore circulating fV III activity. This therapy is extremely expensive and difficult to maintain, and is, therefore, only offered to 30% of hemophilia A patients worldwide. Gene therapy can cure the disease and this proposal focuses on overcoming the obstacles that limit succe ssful gene therapy for hemophilia A.

Principal Investigator:

Christopher B. Doering

Business Contact:

Gabriela Denning
Small Business Information at Submission:

EXPRESSION THERAPEUTICS 1860 Montreal Road Tucker, GA 30084

EIN/Tax ID: 120382893
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
Research Institution Information:
ATLANTA, GA 30322 7406
RI Type: Nonprofit college or university