An anti-CD74 MAb-drug conjugate for B-cell malignancies

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$802,014.00
Award Year:
2008
Program:
SBIR
Phase:
Phase II
Contract:
2R44CA108083-02A2
Award Id:
75517
Agency Tracking Number:
CA108083
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
300 AMERICAN ROAD, MORRIS PLAINS, NJ, 07950
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
115350605
Principal Investigator:
SERENGULAMGOVINDAN
(973) 605-8200
SGOVINDAN@IMMUNOMEDICS.COM
Business Contact:
() -
pparker@immunomedics.com
Research Institute:
n/a
Abstract
DESCRIPTION (provided by applicant): The goal of this work is to develop an antibody-doxorubicin conjugate for the targeted therapy of B-cell cancers that express the CD74 antigen. The Phase II project will focus on advancing this product for multiple myel oma, a common plasma cell malignancy that is incurable at this time. The average 5-year survival rate for these patients is only 30%, and there is thus a continued need for the development of newer therapies. The proposed product consists of a unique, huma nized, anti-CD74 monoclonal antibody linked covalently to multiple molecules of the chemotherapeutic, doxorubicin. This agent was shown previously to induce dramatic cures in immune-compromised mice carrying human tumor xenografts of the disease. The empha sis will be on cGMP manufacture and preclinical toxicology evaluation. Using the existing optimized procedure, a preliminary non-GMP preparation of the conjugate will be undertaken to test the scale-up process under controlled conditions, followed by a 5-g preparation and a 10-g preparation under cGMP conditions. Other aspects of the project will pertain to determinations of product stabilities to protracted storage, and validation of assays for various characterization and product-release criteria. Compara tive cardiotoxicity of the conjugated versus free form of the drug will be assayed in an in vitro experiment. Preclinical toxicology of the product will be evaluated in cynomolgus monkeys, non-human primate species expressing the CD74 antigen similar to hu mans. This experiment will build on a previous single-dose toxicity study, and determine acute toxicity, if any, engendered by repeat-administrations of the antibody-doxorubicin conjugate, at increasing dose levels, in the animal species that is most predi ctive of human toxicology. In addition, non-specific toxicity will also be evaluated in normal rats using doses of the conjugated form of doxorubicin that are one to two orders of magnitude greater than the anticipated starting dose in a Phase I clinical t rial. Finally, an Investigational New Drug application will be prepared and submitted to the FDA. Completion of these essential tasks should advance the product to the stage of clinical evaluation in multiple myeloma patients, expected to start in the SBIR Phase III period. PUBLC HEALTH RELEVENCE: Multiple myeloma (MM), a common plasma cell cancer, is incurable at the present time. The average 5-year survival rate is just 30%. The goal of the proposed project is to develop a safer and a more efficacious tar geted chemotherapy of MM using a unique tumor-selective antibody, which can complement or augment existing therapies.

* information listed above is at the time of submission.

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