Published:
Micromet Demonstrates That the Antibodies in Commercial Products Herceptin, Erbitux, Vectibix and Xolair Can Be Converted Into Highly Potent, T Cell- Engaging BiTE Antibodies
BETHESDA, Md., April 14 /PRNewswire-FirstCall/ -- Micromet, Inc.
(Nasdaq: MITI), a biopharmaceutical company developing novel, proprietary
antibodies for the treatment of cancer, inflammation and autoimmune diseases,
presented at the annual meeting of the American Association for Cancer
Research (AACR) inSan Diego, CA, data showing that commercial anti-cancer
antibodies trastuzumab (Herceptin(R); Genentech, Roche), cetuximab
(Erbitux(R); Bristol-Myers Squibb, Imclone, Merck Serono), and panitumumab
(Vectibix(R); Amgen) can be converted to highly potent BiTE(R) antibodies (1).
Likewise, the anti-IgE antibody omalizumab (Xolair(R); Genentech, Novartis)
for the treatment of asthma can also be successfully converted into a BiTE
antibody. BiTE antibodies are designed to direct the body's cytotoxic, or
cell-destroying, T cells against selected target cells, and represent a new
therapeutic approach to therapy of cancer and other diseases.
All four BiTE antibodies were constructed using Micromet's novel
proprietary BiTE platform that is fully human and cross-reactive with a wide
variety of non-human primates. The presentation at AACR shows that all BiTE
antibodies are active in eliminating cells expressing the respective target
antigens of human and macaque origin. The four BiTE antibodies with
specificity for EGFR, HER2/neu and IgE target antigens, all showed high
potency as demonstrated by redirected lysis of respective target cells at half
maximal concentrations below 1 ng/ml (18 picomolar).
"Our data show that commercially successful monoclonal antibody
therapeutics can be converted into the T cell-engaging BiTE antibody format
using our new BiTE platform," comments Patrick Baeuerle, chief scientific
officer of Micromet. "With the BiTE antibody platform, we can teach
conventional monoclonal antibodies how to recruit T cells for a very selective
and highly effective lysis of target cells. Proof of concept has been
established for the BiTE platform by MT103/MEDI-538, which has shown clinical
responses in relapsed and refractory non-Hodgkin's lymphoma patients."
Reference
(1) Lutterbuese, R. et al. Conversion of Cetuximab and Trastuzumab into
T Cell-engaging BiTE Antibodies Creates Novel Drug Candidates with
Superior Anti-tumor Activity. Annual Meeting of AACR, San Diego, 2008,
Abstract No. 2402.
About BiTE Antibodies
BiTE(R) antibodies are designed to direct the body's cytotoxic, or
cell- destroying, T cells against tumor cells, and represent a new therapeutic
approach to cancer therapy. BiTE antibodies have been shown to induce an
immunological synapse between a T cell and a tumor cell in the same manner as
observed during physiological T cell attacks. These cytolytic synapses enable
the delivery of cytotoxic proteins from T cells into tumor cells, ultimately
inducing a self-destruction process in the tumor cell referred to as
apoptosis, or programmed cell death. In the presence of BiTE antibodies, T
cells have been demonstrated to serially eliminate tumor cells, which explains
the activity of BiTE antibodies at very low concentrations and at very low
ratios of T cells to target cells. Through the process of killing cancer
cells, T cells proliferate, which leads to an increased number of T cells at
the site of attack.
Several antibodies in Micromet's product pipeline are BiTE antibodies and
have been generated based on Micromet's proprietary BiTE antibody platform.
The most advanced BiTE antibody is MT103 (MEDI-538), targeting CD19, and has
provided proof-of-concept in an ongoing phase 1 clinical study in patients
with advanced non-Hodgkin's lymphoma. MT110, which is targeting EpCAM (CD326)
and is the first BiTE antibody with potential applications in the treatment of
solid tumors, has completed preclinical development. Two additional BiTE
antibodies, targeting CEA and MCSP, are in preclinical development.
About Micromet, Inc. (www.micromet-inc.com)
Micromet, Inc. is a biopharmaceutical company developing novel,
proprietary antibodies for the treatment of cancer, inflammation and
autoimmune diseases. Three of its antibodies are currently in clinical trials,
while the remainder of the product pipeline is in preclinical development. The
BiTE(R) antibody MT103 is in a phase 2 clinical trial for the treatment of
patients with acute lymphoblastic leukemia and in a phase 1 clinical trial for
the treatment of patients with non-Hodgkin's lymphoma. BiTE antibodies
represent a new class of antibodies that activate a patient's own cytotoxic T
cells, considered the most powerful "killer cells" of the human immune system,
to eliminate cancer cells. Micromet is developing MT103 in collaboration with
MedImmune, Inc., a subsidiary of AstraZeneca plc. The second clinical stage
antibody is adecatumumab, also known as MT201, a human monoclonal antibody
which targets epithelial cell adhesion molecule (EpCAM)-expressing solid
tumors. Micromet is developing adecatumumab in collaboration with Merck Serono
in a phase 1b clinical trial evaluating adecatumumab in combination with
docetaxel for the treatment of patients with metastatic breast cancer. The
third clinical stage antibody, MT293 is licensed to TRACON Pharmaceuticals,
Inc. and is being developed in a phase 1 clinical trial for the treatment of
patients with cancer. In addition, Micromet has established a collaboration
with Nycomed for the development and commercialization of MT203, a human
antibody neutralizing the activity of granulocyte/macrophage colony
stimulating factor (GM-CSF), which has potential applications in the treatment
of various inflammatory and autoimmune diseases, such as rheumatoid arthritis,
psoriasis, or multiple sclerosis.
Forward-Looking Statements
This release contains certain forward-looking statements that involve
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additional information relating to the safety, efficacy or tolerability of our
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clinical trial data, the risk that we or our collaborators will not obtain
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statements, whether as a result of new information, future events or
otherwise.
SOURCE Micromet, Inc.
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