Gentium Spa (AMEX:GNT)
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Gentium S.p.A. (AMEX:GNT) (the "Company") today reported
that on February 7, 2006, Guenther Eisser, Chief of Biology Research
for Gentium, will present a poster entitled, "Defibrotide, an
endothelium stabilizing drug, has anti-angiogenic properties in vitro
and in vivo," at the Angiogenesis in Cancer and Vascular Disease
Congress being held in Miami, Fla. from February 4-8, 2006.
The anti-angiogenic potential of Defibrotide was tested in-vitro
using the sprouting of cells from the rat aortic ring in Matrigel(TM)
and a kit with human microvascular endothelial cells forming
vessel-like structures across a layer of dermal fibroblasts
(AngioKit(TM)). The in-vivo testing of Debrotide was performed in mice
injected with human gastric cancer.
The results show that daily application of Defibrotide almost
quantitatively blocks sprouting in the aortic ring assay at
concentrations corresponding to pharmacologic Defibrotide blood
levels. Similarly, the second in-vitro assay (AngioKit(TM))
demonstrates that Defibrotide reduces vessel formation of human
microvascular endothelial cells across a barrier of dermal
fibroblasts. In-vivo tumor angiogenesis in a human gastric cancer
grown in nude mice was attenuated on day 5 by Defibrotide. Initial
Western blotting results show that Defibrotide reduces
phosphorylation-activation of p70S6 kinase, which is a key target in
the P13K/Akt/mTOR signaling pathway linked to endothelial cell and
pericyte proliferation and activation.
Dr. Eisser concluded, "Our data suggest that while Defibrotide is
known for its endothelium-protecting function, it also inhibits tumor
blood vessel formation and thus should be considered for further
testing as an anti-cancer agent, either alone or in combination with
other drugs."
Commenting on the presentation of this data, Dr. Laura Ferro,
chairman and chief executive officer of Gentium, stated, "We are
pleased to present the work of Dr. Eisser and his colleagues as it
expands our knowledge of Defibrotide's possible pharmacodynamic
actions, thereby elucidating the potential therapeutic benefits that
might be tested in a variety of cancer and vascular indications.
"These findings expand our understanding of the possible utility
of Defibrotide as an anti-tumor agent. Earlier preclinical studies
conducted at the Jerome Lipper Multiple Myeloma Center at Harvard
University's Dana Farber Cancer Institute which were very promising
and suggested that Defibrotide sensitizes Multiple Myeloma (MM) cells
to anti-MM agents in the bone marrow by preventing the molecular
cascade of events triggered by MM-bone marrow stromal cells contact.
This pre-clinical study provided the framework for an independent,
multi-center Phase I/II clinical trial of Defibrotide in the treatment
of Multiple Myeloma that is currently underway in Italy."
Defibrotide to Treat Severe VOD
The Company is awaiting Institutional Review Board approval for
its pivotal U.S. Phase III trial of Defibrotide to treat Severe VOD
and expects to initiate that trial in the coming weeks.
Defibrotide to Prevent VOD
The Company recently initiated a Phase II/III trial with
Defibrotide to prevent VOD in pediatric patients. The randomized study
will include 270 pediatric patients undergoing SCT at 30 clinical
sites in Europe and Israel and will evaluate the ability of
Defibrotide to prevent VOD.
The Company plans to initiate a Phase II/III trial with
Defibrotide to prevent VOD in adult patients in Europe during the
second quarter of 2006 and in the U.S. by early 2007.
Defibrotide to Treat Multiple Myeloma
Defibrotide is the subject of an independent Phase I/II study to
treat Multiple Myeloma (MM) in combination with Melphalan, Prednisone,
and Thalidomide (MPT) that is underway at ten centers in Italy. This
Phase I/II dose-escalating, multi-center, non-comparative, open label
study is designed to assess the safety and the efficacy of Defibrotide
with MPT regimen as a salvage treatment in advanced refractory MM
patients. The Company intends to evaluate the results of this trial
with its scientific advisors to determine what its clinical
development plans are for this indication.
About Defibrotide
Defibrotide is a single-stranded DNA that protects the vascular
endothelial cells, particularly those of small vessels, from damage
and activation. After binding to endothelial cells, Defibrotide
decreases cell adhesion and pro-coagulant activity of activated
endothelial cells and increases the fibrinolytic potential of
endothelial cells. Defibrotide's effects are predominately local
within the vascular bed, and there is no significant effect on
systemic coagulation. Its beneficial pharmacological effects are due
to its anti-thrombotic, anti-inflammatory and anti-ischemic
properties.
About VOD
VOD is a potentially life-threatening condition. The International
Bone Marrow Transplant Registry estimated that approximately 45,000
people received blood and bone marrow transplants in 2002. Certain
high dose chemotherapy and radiation therapies and stem cell
transplantation (SCT) can damage cells of the blood vessels and result
in VOD, a blockage of the small veins of the liver which can lead to
liver failure and the failure of other organs (Severe VOD). SCT is a
frequently used treatment following high dose chemotherapy and
radiation therapy. Based on the Company's review of more than 200
published papers it is estimated that approximately 20% of patients
who receive SCT contract VOD. Approximately 80% of patients who
contract Severe VOD die within 100 days of SCT. VOD is considered one
of the most important and challenging complications of SCT. There
currently are no approved therapies to treat or prevent VOD in the
U.S. or the E.U.
About Gentium
Gentium S.p.A. is a biopharmaceutical company located in Villa
Guardia (Como), Italy that is focused on the research, discovery and
development of drugs derived from DNA extracted from natural sources,
and drugs that are synthetic derivatives, to treat and prevent a
variety of vascular diseases and conditions related to cancer and
cancer treatments. Defibrotide, the Company's lead product candidate
in the U.S., is an investigational drug that has been granted Orphan
Drug status by the U.S. FDA to treat VOD, Fast Track designation by
the U.S. FDA for the treatment of Severe VOD in recipients of stem
cell transplants and Orphan Drug designation by European Union
regulators to treat and prevent VOD.
Cautionary Note Regarding Forward-Looking Statements
This press release contains "forward-looking statements." In some
cases, you can identify these statements by forward-looking words such
as "may," "might," "will," "should," "expect," "plan," "anticipate,"
"believe," "estimate," "predict," "potential" or "continue," the
negative of these terms and other comparable terminology. These
statements are not historical facts but instead represent the
Company's belief regarding future results, many of which, by their
nature, are inherently uncertain and outside the Company's control. It
is possible that actual results may differ, possibly materially, from
those anticipated in these forward-looking statements. For a
discussion of some of the risks and important factors that could
affect future results, see the discussion in our Prospectus filed with
the Securities and Exchange Commission under Rule 424(b)(5) under the
caption "Risk Factors."