Immunomedics Develops T-Cell Redirecting Bispecific Antibodies as Potential
Therapeutics for Solid and Liquid Tumors
Mechanism of Action Study on Epratuzumab Also Reported
WASHINGTON, April 10, 2013 (GLOBE NEWSWIRE) -- Immunomedics, Inc.
(Nasdaq:IMMU), a biopharmaceutical company primarily focused on the
development of monoclonal antibody-based products for the targeted treatment
of cancer, autoimmune and other serious diseases, today announced the
development of novel T-cell redirecting agents made as DOCK-AND-LOCK™ (DNL™)
complexes by tethering a single-chain variable fragment (scFv) that binds to
CD3 on T cells to different antibody fragments that target tumor antigens. The
preclinical study was presented at the 2013 Annual Meeting of the American
Association for Cancer Research (AACR).
The use of bispecific antibodies to redirect T cells for the killing of
targeted tumor cells has shown considerable promise both preclinically and
clinically. The Company has previously reported the generation of (19)-3s, a
prototype bispecific antibody that binds to CD19 on B cells and CD3 on T
cells, using the Company's patented DNL^TM platform technology. (19)-3s has
demonstrated in vitro the ability to direct T cells to destroy CD19-expressing
B cells by linking them together. (For more information, please refer to the
Company's press release at
In the current study, (19)-3s was found to be highly effective in vivo. In an
animal model of human lymphoma, 6 of the 8 animals that were treated with 43
micrograms of the DNL^TM-derived bispecific antibody for five doses remained
alive, with 5 of 8 animals tumor-free at the end of the study.
Encouraged by these results, a panel of novel T-cell redirecting bispecific
antibodies were created by DNL^TM as potential therapeutics for solid
malignancies. Three DNL^TM complexes, designated (14)-3s, (E1)-3s, and
(M1)-3s, were prepared by linking anti-CD3 scFv to humanized antibody
fragments with specificity for CEACAM5, TROP-2, and PAM4-antigen,
respectively. All three biomarkers are expressed in many solid tumors. (14)-3s
and (E1)-3s both exhibited anti-tumor activity in animal models of human
colonic and pancreatic cancers, respectively.
"The modular nature of DNL^TM has allowed us to rapidly produce a large number
of complexes as T-cell redirecting agents for various malignancies," commented
Cynthia L. Sullivan, President and Chief Executive Officer. "We are currently
evaluating the in vitro and in vivo properties of these DNL^TM complexes in
cognate solid tumors," Ms. Sullivan added.
At the same AACR meeting, a study on the mechanism of action of epratuzumab
was also presented.
Epratuzumab is a humanized anti-CD22 antibody currently in clinical
development for B-cell lymphoma and systemic lupus erythematosus, an
autoimmune disease. Although epratuzumab is capable of depleting on average
35% of circulating B cells in patients, its in vivo mechanism of action,
especially its involvement in regulating B-cell antigen receptor (BCR)
signaling, remains poorly understood.
In this preclinical study, peripheral blood mononuclear cells from either
healthy donors or lupus patients with flares were incubated with epratuzumab,
and the relative surface levels of CD22 and selected BCR regulators, including
CD19, CD21, and CD79b, were analyzed.
Epratuzumab promptly induced the transfer of CD22 and the 3 BCR-associated
regulators from B cells to other white blood cells such as monocytes, natural
killer cells and granulocytes, a process known as trogocytosis. The transfer
is mediated through the interaction of the fragment crystalline (Fc) region of
CD22-bound epratuzumab and the Fc receptors on the effector cells.
"This study revealed a previously unknown, and potentially important,
mechanism of action of epratuzumab," remarked Cynthia L. Sullivan, President
and Chief Executive Officer. "Whether the observed trogocytosis could be
correlated with the depletion of malignant B cells in lymphoid tissues is
currently under investigation," added Ms. Sullivan.
Immunomedics is a New Jersey-based biopharmaceutical company primarily 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, cytokines 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 also have a majority
ownership in IBC Pharmaceuticals, Inc., which is developing a novel
DOCK-AND-LOCK™ (DNL™) method with us for making fusion proteins and
multifunctional antibodies, 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. We believe that our portfolio of intellectual property,
which includes approximately 220 active patents in the United States and more
than 400 foreign patents, protects our product candidates and technologies.
For additional information on us, please visit our website at
www.immunomedics.com. The information on our website does not, however, form a
part of this press release.
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), forecasts of future operating results, potential
collaborations, 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 any cash payment that the Company might
receive in connection with a sublicense involving a third party and UCB, which
is not within the Company's control, new product development (including
clinical trials outcome and regulatory requirements/actions), our dependence
on our licensing partners for the further development of epratuzumab and
veltuzumab for non-cancer indications, 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.
CONTACT: Dr. Chau Cheng
Senior Director, Investor Relations & Grant Management
(973) 605-8200, extension 123
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