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Immunomedics, Inc. Constructs New Bispecific Antibodies Using The Dock And Lock (DNL) Technology

Published: Jun 05, 2006

ATLANTA, June 5 /PRNewswire-FirstCall/ -- Immunomedics, Inc. , a biopharmaceutical company focused on developing monoclonal antibodies, and its wholly owned subsidiary, IBC Pharmaceuticals, Inc., today reported the construction of two new bispecific antibodies that bind to both CD20 and CD22 antigens on B lymphocytes. A poster describing the design, characterization and in vitro activity in lymphoma cell lines of the CD20/CD22 bispecific antibodies was presented at the 42nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Atlanta, Georgia.

Designated as TF3 and TF5, the new bispecific constructs were created using the Dock and Lock (DNL) method recently published in the Proceedings of the National Academy of Sciences (please refer to http://www.immunomedics.com/news_pdf/2006_PDF/PR04252006.pdf), and was developed by a team of scientists at Immunomedics and IBC Pharmaceuticals. Both constructs were fully humanized, comprised of Immunomedics' humanized anti-CD20 (hA20) antibody and humanized anti-CD22 antibody, epratuzumab. TF3 is made up of two anti-CD20 antibody fragments linked to one anti-CD22 antibody fragment, whereas TF5 was constructed by fusing two anti-CD22 antibody fragments to one anti-CD20 fragment.

TF3 and TF5 were shown to be stable in both human and mouse sera. Both bispecific antibodies inhibited the growth of human lymphoma cell lines in vitro. Under the same experimental conditions, TF3 showed a 1000-fold higher potency as compared to the parent antibody, hA20, which also reflects a higher cytotoxicity over rituximab, since hA20 was shown to be similar in activity to rituximab in an article published by Stein and coworkers in the April 15, 2004, issue of Clinical Cancer Research. The anti-proliferative activity of TF3 and TF5 is attributed to the ability of the two bispecific antibodies to cross-link CD20 and CD22. These encouraging studies are now being expanded to compare these bispecific antibodies to epratuzumab, hA20, and rituximab in animal models of human lymphoma, with the intention of bringing the best construct into clinical testing.

"This research confirms our conviction and expanding patent portfolio involving the development and use of bispecific antibodies for improved cancer therapy, which we believe introduces a new paradigm in the immunotherapy of cancer," commented Cynthia L. Sullivan, President and Chief Executive Officer of Immunomedics. "It also validates our recently described DNL platform technology for making stable fusion proteins, in this case comprising bispecific or bifunctional antibodies for use in cancer therapy," she added.

Recently, the anti-CD22 humanized antibody, epratuzumab, has also shown activity in NHL, particularly when combined with rituximab, as well as a monotherapy in patients with lupus or primary Sjogren's syndrome. It is believed that epratuzumab's mechanism of action differs from that of rituximab by showing less B-cell depletion and more B-cell modulation. Given that these antibodies are directed against different B-cell targets and appear to function differently, it was hypothesized that a bispecific antibody targeting both B-cell antigens might show improved activity as compared to each parent antibody by itself.

About the Dock and Lock (DNL) Method

The DNL method is a platform technology that utilizes the natural interaction between two proteins, cyclic AMP-dependent protein kinase (PKA) and A-kinase anchoring proteins (AKAPs). The region that is involved in such interaction for PKA is called the dimerization and docking domain (DDD), which always appears in pairs. Its binding partner in AKAPs is the anchoring domain (AD). When mixed together, DDD and AD will bind with each other spontaneously to form a binary complex, a process termed docking. Once "docked," certain amino acid residues incorporated into DDD and AD will react with each other to "lock" them into a stably tethered structure. The outcome of the DNL method is the exclusive generation of a stable complex, in a quantitative manner that retains the full biological activities of its individual components. Diverse proteins, peptides, and nucleic acids are among suitable components that can be linked to either DDD or AD. Since DDD always appears in pairs, any component that is linked to DDD will have two copies present in the final products.

About IBC Pharmaceuticals

IBC is a development-stage biopharmaceutical company focused on the development and commercialization of proprietary pretargeting agents for the detection and treatment of various cancers and other serious diseases. These products are based on IBC's patented technology platform referred to as the "Affinity Enhancement System," or AES. The Company currently has several product candidates in pre-clinical and clinical development, and is extending its pretargeting technology to include bispecific antibodies made by the "dock and lock" method.

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. Our lead product candidate, epratuzumab, which development, manufacture and commercialization rights we have licensed to UCB, S.A. for the treatment of all autoimmune indications worldwide, is currently in two pivotal Phase III trials for the treatment of patients with moderate and severe lupus (ALLEVIATE A and B). 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 90 patents issued in the United States, and more than 250 other issued patents worldwide, protects our product candidates and technologies. Visit our web site at http://www.immunomedics.com. We also have a majority ownership in IBC Pharmaceuticals, Inc., which is developing a novel dock and lock platform technology, 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.

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 ccheng@immunomedics.com

Immunomedics, Inc.

CONTACT: Dr. Chau Cheng, Associate Director, Investor Relations & BusinessAnalysis, +1-973-605-8200, extension 123, ccheng@immunomedics.com

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