An Anti-CD-74 MAb-drug Conjugate for B-Cell Malignancies

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$134,285.00
Award Year:
2005
Program:
SBIR
Phase:
Phase I
Contract:
1R43CA108083-01A2
Agency Tracking Number:
CA108083
Solicitation Year:
2005
Solicitation Topic Code:
n/a
Solicitation Number:
PHS2005-2
Small Business Information
IMMUNOMEDICS, INC.
300 American Road, Morris Plains, NJ, 07950
Hubzone Owned:
N
Socially and Economically Disadvantaged:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
PUJA SAPRA
(973) 605-8200
PSAPRA@IMMUNOMEDICS.COM
Business Contact:
CYNTHIA SULLIVAN
(973) 605-8200
Research Institution:
n/a
Abstract
DESCRIPTION (provided by applicant): The objective of this work is to develop an antibody-drug conjugate that will be useful against B-cell malignancies that express the CD74 antigen. More specifically, the conjugate will be a doxorubicin derivative attached to the complementarity-determining region-grafted (humanized) monoclonal antibody termed hLL1. The agent in this project will be developed for the multiple myeloma indication, but the same agent would be expected to be useful against any CD-74-expressing malignancy, including non-Hodgkin's lymphoma (NHL). This SBIR Phase I application will continue to explore the efficacy of the doxorubicin-hLL1 conjugate in a preclinical animal model of human multiple myeloma, since a preliminary indication of efficacy has now already been demonstrated. We expect to see significant efficacy at low doses of administered conjugate, and, hopefully, cures of animals at higher and/or multiple doses. With continuing positive efficacy data, the production of the conjugate will be scaled up to multi-grams of material. In vitro cell binding studies will be done to show that drug conjugation has not impinged antibody-antigen binding characteristics. Studies of the biodistributions of doxorubicin and hLL1 from the conjugate will be carried out, using mass spectrometry and radiolabeled antibody, respectively, to show that localization is antibody specific and cellular antibody uptake can be correlated with cellular anthracycline uptake. In this Phase I SBIR work, feasibility will be shown by a quantifiable demonstration of in vivo efficacy, and the therapeutic index of dox-hlL1 will be determined at both single and multiple weekly doses. With Promising data, SBIR Phase II will support the efforts to transfer the MAb-drug conjugate to a Phase I or Phase I/II clinical trial in multiple myeloma or, in another B-cell malignnacy such as NHL. Positive results in such a Phase I or Phase I/II clinical trial will lead to pivotal studies directed toward securing an FDA-approved antibody-drug conjugate for the selected disease indication.

* information listed above is at the time of submission.

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