Micromet's BiTE® Antibodies Reveal Unique Mode of Action
Bethesda, MD, November 6, 2007 - Micromet, Inc. (Nasdaq: MITI), a
biopharmaceutical company developing novel, proprietary antibodies
for the treatment of cancer, inflammation and autoimmune diseases,
announced the publication of two new studies describing a unique mode
of action of Micromet's bispecific BiTE antibody therapeutics. The
studies were published in the Journal of Immunotherapy(1) and in
Cancer Immunology Immunotherapy(2), respectively.
BiTE antibodies are designed to transiently connect cytotoxic T cells
with cancer cells leading to a tightly controlled and serial
elimination of cancer cells. In this process, cytotoxic T cells are
activated, which causes them to proliferate, recharge their toxins
and increase their adhesiveness.
The two new studies have shown that BiTE antibodies activate T cells
only when cancer cells are present, but not when they are given to T
cells in the absence of cancer cells. The studies have also shown
that initial cytokine release by activated T cells is not required
for elimination of cancer cells, and that anti-inflammatory steroid
hormones can efficiently quench the initial cytokine release by
BiTE-activated T cells without reducing their capacity to kill cancer
cells.
"The highly conditional, target cell-dependent activation of killer T
cells by our BiTE antibodies is a very important safety feature in
patients," commented Patrick Baeuerle, Micromet's Chief Scientific
Officer. "Unlike other T cell-activating agents, BiTE antibodies
activate T cells in a highly controlled fashion that is intimately
linked to the desired therapeutic activity."
"We have observed depletion of circulating B lymphoma cells and have
confirmed partial and complete responses in the clinical trials with
MT103. At the same time, only very low systemic cytokine levels, if
any, were detected," commented Carsten Reinhardt, Micromet's Chief
Medical Officer. "The side effect profile of MT103 seen in the
ongoing phase 1 study is consistent with the conditional T cell
activation observed in the newly published studies."
References
1 Brischwein K, Parr L, Pflanz S et al. Strictly target
cell-dependent activation of T cells by bispecific single-chain
antibody constructs of the BiTE class. J Immunother. Vol. 30
(8):798-807, November/December 2007.
2 Brandl C, Hass C, d'Argouges S et al. The effect of dexamethasone
on polyclonal T cell activation and redirected target cell lysis as
induced by a CD19/CD3-bispecific single-chain antibody construct.
Cancer Immunol Immunother. Vol. 56:1551-1563 (2007).
About BiTE® Antibodies
BiTE® 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 product
development platform. The most advanced BiTE antibody is MT103
(MEDI-538), targeting CD19. Confirmed partial and complete responses
in an ongoing phase 1 clinical study with MT103 in advanced
non-Hodgkin's lymphoma patients have provided proof-of-concept that
BiTE antibodies can achieve clinically relevant results in patients.
Three other BiTE antibodies, targeting EpCAM (CD326), CEA and MCSP,
are in pre-clinical 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 in clinical
development. MT103 (MEDI-538), the first antibody developed utilizing
the BiTE® technology platform in Micromet's product pipeline, is
being evaluated in a phase 2 clinical trial for the treatment of
patients with acute lymphoblastic leukemia and 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 to eliminate cancer cells. Micromet
is developing MT103 in collaboration with MedImmune, a subsidiary of
AstraZeneca plc.
The second clinical stage antibody is adecatumumab (MT201), a human
monoclonal antibody targeting EpCAM expressing tumors. Adecatumumab
is being developed by Micromet in collaboration with Merck Serono in
a phase 1b clinical trial evaluating MT201 in combination with
docetaxel for the treatment of patients with metastatic breast
cancer. The third clinical stage antibody is MT293 (formerly D93),
also known as TRC093, a first-in-class humanized monoclonal antibody
that inhibits angiogenesis and tumor cell growth by binding cleaved
collagen. MT293, which is currently being tested in a phase 1
clinical trial, is licensed to TRACON Pharmaceuticals, Inc. and is
being developed for the treatment of patients with cancer and
age-related macular degeneration. In addition, Micromet has
established a collaboration with Nycomed for the development and
commercialization of MT203, Micromet's 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
risks and uncertainties that could cause actual results to be
materially different from historical results or from any future
results expressed or implied by such forward-looking statements.
Factors that may cause actual results to differ materially from any
future results expressed or implied by any forward-looking statements
include the risk that product candidates that appeared promising in
early research, preclinical studies or clinical trials do not
demonstrate safety and/or efficacy in subsequent clinical trials, the
risk that encouraging results from early research, preclinical
studies or clinical trials may not be confirmed upon further analysis
of the detailed results of such research, preclinical study or
clinical trial, the risk that additional information relating to the
safety, efficacy or tolerability of our product candidates may be
discovered upon further analysis of preclinical or clinical trial
data, the risk that we or our collaborators will not obtain approval
to market our product candidates, the risks associated with reliance
on outside financing to meet capital requirements, and the risks
associated with reliance on collaborators, including MedImmune, Merck
Serono, TRACON and Nycomed, for the funding or conduct of further
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of new information, future events or otherwise.
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Contact Information:
Company: Investors: Media:
Christopher Schnittker, SVP & CFO Susan Noonan Andrea tenBroek
(240) 752-1421 (212) 966-3650 (781) 684-0770
christopher.schnittker@micromet-inc.com susan@sanoonan.com micromet@schwartz-pr.com
