ORLANDO, Fla., Dec. 10 /PRNewswire-FirstCall/ -- Immunomedics, Inc. , a biopharmaceutical company focused on developing monoclonal antibodies, today announced the development of new multivalent antibodies against the CD20 and CD22 antigens present on normal and malignant B- lymphocytes, which showed activities against B-cell lymphomas in tissue culture and in animal models. Results on these next-generation protein constructs were presented in two posters at the 48th Annual Meeting of ASH in Orlando, FL.
The first poster presentation described the characterization of a bispecific antibody (bsMAb) composed of an intact humanized anti-CD20 antibody, hA20, linked to two single-chain variable fragments (scFvs) of an anti-CD22 antibody, epratuzumab. Thus, this fusion protein is tetravalent with 4 binding sites, two for CD20 and two for CD22. This tetravalent bsMAb was found to have anti-lymphoma activity similar to either hA20 or epratuzumab in vitro. The studies further demonstrated that the CD20/CD22 bsMAb has a mode of action against B-lymphoma cells distinct from that of either hA20 or epratuzumab. More importantly, the tetravalent bsMAb was more effective in improving the survival of mice bearing human lymphomas, when compared with its parental antibodies, hA20 or epratuzumab.
In a second poster presentation, multiple hexavalent antibodies were constructed using the Company's proprietary protein engineering platform technology called the Dock-and-Lock methodology (DNL) by linking an intact hA20 or epratuzumab to two antigen binding antibody fragments (Fabs) of hA20 or epratuzumab. The resulting proteins: CD20/CD22 bsMAbs, hexavalent hA20, and hexavalent epratuzumab, each contain 6 binding arms. In cell cultures of human B-lymphoma cells, the hexavalent CD20/CD22 bispecific antibody constructs proved to be 100-times more potent in inhibiting growth than rituximab, while the hexavalent hA20 antibody was even more active. In contrast to rituximab or hA20, these new protein constructs lack constant region (Fc) functions, because no antibody-dependent or complement-mediated cellular cytotoxicities were observed, thus indicating that these new antibodies kill lymphoma cells exclusively by signal transduction mechanisms. Finally, studies with human lymphoma cells growing in mice showed that these new fusion proteins are very active in controlling tumor growth and increasing survival, even at very low doses (single injection of 4 micro gram).
In a statement by company President and CEO, Cynthia L. Sullivan: "These findings demonstrate that the DNL method can make multivalent fusion proteins that are stable for both in vitro and in vivo applications. More importantly, because multiple copies of binding sites are built into the final products, they are more potent than their parental proteins."
"While we have been focusing on using DNL to create more potent immunotherapy agents because of our expertise in monoclonal antibodies, the technology is versatile and also can be used to generate multifunctional binary complexes of proteins other than antibodies. This technology is particularly suitable for creating protein derivatives where conjugation or modification with non-protein groups are involved," she further commented.
About Immunomedics
Immunomedics is a New Jersey-based biopharmaceutical company focused on the development of monoclonal, antibody-based products for the targeted treatment of cancer, autoimmune and other serious diseases. We have developed a number of advanced proprietary technologies that allow us to create humanized antibodies that can be used either alone in unlabeled or "naked" form, or conjugated with radioactive isotopes, chemotherapeutics or toxins, in each case to create highly targeted agents. Using these technologies, we have built a pipeline of therapeutic product candidates that utilize several different mechanisms of action. We have recently licensed our lead product candidate, epratuzumab, to UCB, S.A. for the treatment of all autoimmune disease indications worldwide. We have retained the rights for epratuzumab in oncology indications for which UCB has been granted a buy-in option. UCB has development, manufacture and commercialization rights, and is responsible for all clinical trials evaluating epratuzumab for the treatment of patients with moderate and severe lupus. At present, there is no cure for lupus and no new lupus drug has been approved in the U.S. in the last 40 years. We believe that our portfolio of intellectual property, which includes approximately 108 patents issued in the United States, and more than 250 other issued patents worldwide, protects our product candidates and technologies. We also have a majority ownership in IBC Pharmaceuticals, Inc., which is developing a novel dock and lock methodology, and a new method of delivering imaging and therapeutic agents selectively to disease, especially different solid cancers (colorectal, lung, pancreas, etc.), by proprietary, antibody-based, pretargeting methods. Visit our web site at http://www.immunomedics.com/.
This release, in addition to historical information, may contain forward- looking statements made pursuant to the Private Securities Litigation Reform Act of 1995. Such statements, including statements regarding clinical trials, out-licensing arrangements (including the timing and amount of contingent payments), and capital raising activities, involve significant risks and uncertainties and actual results could differ materially from those expressed or implied herein. Factors that could cause such differences include, but are not limited to, risks associated with new product development (including clinical trials outcome and regulatory requirements/actions), competitive risks to marketed products and availability of required financing and other sources of funds on acceptable terms, if at all, as well as the risks discussed in the Company's filings with the Securities and Exchange Commission. The Company is not under any obligation, and the Company expressly disclaims any obligation, to update or alter any forward-looking statements, whether as a result of new information, future events or otherwise.
For More Information:
Dr. Chau Cheng
Associate Director, Investor Relations & Business Analysis
(973) 605-8200, extension 123
