deCODE genetics
(Nasdaq: DCGN) today announced progress in the development of DG041, the
company's Phase II developmental compound for the prevention of arterial
thrombosis. The results of the Phase IIa and clinical pharmacology studies
presented today build upon previous findings demonstrating DG041's profile
as an anti-platelet compound that deCODE expects will make it possible to
block the formation of blood clots mediated through inflammation in
atherosclerotic plaques but without increasing bleeding risk. There is a
large unmet medical need for a drug with these characteristics, with
applicability to the prevention of heart attack, stroke and the progression
of peripheral artery disease (PAD). Drugs such as Plavix(TM) and aspirin,
the current mainstays of oral anti-platelet therapy, significantly increase
the risk of bleeding by broadly blocking platelet activity.
Recent advances in deCODE's therapeutic and diagnostics pipeline will
be discussed at the company's annual R&D event being held today in
Reykjavik. The presentations will be webcast live through the investors
page of the company's website at decode, starting at 9am
GMT/5am EDT, and will be archived on the site. Among the highlights to be
discussed are:
DG041 -- Arterial thrombosis.
DG041 is a novel, first in class antagonist of the EP3 receptor for
prostaglandins E2. deCODE initially identified EP3 as a target by isolating
variants in the gene encoding the EP3 receptor for prostaglandins E2 (PGE2)
that approximately double the risk of PAD, a common and debilitating
atherosclerotic condition in which the flow of blood to the legs is
progressively constricted. The mechanism through which EP3 modulates
platelet aggregation is distinct from those targeted by aspirin and
Plavix(TM). Following deCODE's gene discovery, work by leading
international scientists has demonstrated in mice that PGE2 is produced in
atherosclerotic plaques, promoting the formation of clots immediately at
the sites of plaque but not over normal blood vessels. The formation of
these thrombi is dependent on signaling through EP3. This pathway is left
largely unaffected by existing anti-platelet drugs such as aspirin and
Plavix(TM).
deCODE's medicinal chemistry group discovered DG041 as a means to
prevent arterial thrombosis by inhibiting the activity of EP3. In animal
studies and extensive Phase I clinical testing completed in mid-2006, DG041
was shown to effectively inhibit platelet aggregation through this pathway
without increasing bleeding time, and to be safe and well-tolerated at all
doses tested. Late last year, deCODE began a Phase IIa randomized,
placebo-controlled clinical trial of DG041 in 144 PAD patients, to examine
safety and tolerability of doses of 100mg twice a day and 400mg twice a day
and their effect on a range of biomarkers. Because a large proportion of
patients in this trial and subsequent trials would be taking other
anti-platelet compounds, the company simultaneously began work to identify
a sensitive biomarker of anti-platelet activity that could discriminate
between the effects of DG041 and these other agents. The
vasodilator-stimulated protein (VASP), which normally holds platelets in a
quiescent state when phosphorylated but causes platelets to bind when
dephosphorylated upon activation of EP3, was found to provide such a
biomarker. The company thus began a clinical pharmacology study to examine
DG041's effectiveness in blocking VASP-mediated platelet activation.
The results of these studies presented today provide a compelling
demonstration of DG041's potential as a next-generation oral anti-platelet
therapy -- an effective means of preventing arterial thrombosis
specifically at the sites of plaque lesions in the vasculature. In the
Phase IIa study, DG041 was found to reduce several markers of inflammation
-- c-reactive protein (CRP), monocyte chemotactic protein 1 (MCP1), and
soluble intracellular adhesion molecule (sICAM) -- in a dose-dependent
manner. Ankle- brachial index (ABI) measurements -- which gauge the
strength of blood flow to the legs and are a key measurement of the
severity of PAD - also showed improvement in both DG041 treatment groups.
There were no drug-related serious adverse events in the study and no
discernible difference in other adverse events between the DG041 and
matched placebo groups.
The results of the placebo-controlled clinical pharmacology study also
announced today demonstrate that in a concentration-dependent manner DG041
dramatically inhibits platelet activation mediated through VASP as well as
platelet aggregation. DG041 also reduced levels of another indicator of
platelet activation, p-selectin. Moreover, the desired effect on VASP
appears to be achievable at doses lower than previously anticipated. deCODE
is thus very encouraged that in targeting EP3, the company is advancing a
potentially major new approach to anti-platelet therapy - one that acts
specifically to prevent arterial thrombi, targets a pathway not addressed
by existing drugs, with minimal impact on normal platelet function.
DG031 and DG051 - Heart attack
In its drug development programs targeting the leukotriene pathway for
the prevention of heart attack, deCODE is advancing the reformulation of
its FLAP inhibitor DG031 for re-entry into clinical trials. A lead
formulation has been identified and a 3-month accelerated stability study
completed. The company believes that a once-a-day dosing regimen may
provide even better pharmacodynamic effect than the previous twice-a-day
regimen. The company expects to be ready to restart Phase III testing near
year end. DG051, an inhibitor of leukotriene A4 hydrolase (LTA4H), has
successfully completed single- and multiple-dose Phase I testing. It has
demonstrated potent, dose-dependent lowering of the production of
leukotriene B4, the end product of the leukotriene pathway which deCODE's
genetics and biology work has pinpointed as a key means of modulating risk
of heart attack. DG051's pharmacokinetic profile supports its development
with once-a-day dosing, with a very satisfactory safety and tolerability
profile. The company plans to initiate Phase II clinical testing of DG051
later this year.
Diagnostics and gene discovery
In April deCODE launched deCODE T2(TM), the company's first DNA-based,
reference laboratory test for gauging individual risk of type 2 diabetes.
The company will provide an update on its marketing strategy for its
diagnostic tests and will discuss the upcoming launch of its deCODE AF(TM)
test, which detects a genetic variant that confers risk of atrial
fibrillation, the leading cause of cardiogenic stroke. The company is also
developing tests for sequence variants associated with risk of heart
attack, glaucoma and several other conditions in which deCODE has recently
isolated risk variants. Since the beginning of the year, deCODE has
dramatically accelerated its gene discovery work, publishing major new risk
variants for heart attack, breast cancer, prostate cancer, type 2 diabetes,
among others. The company expects to announce many additional discoveries
in the weeks and months ahead. deCODE is underscoring its position as the
global leader in the identification of genetic risk factors for common
diseases, building on this leadership by bringing together its human
genetics resources and capabilities with the power of genome-wide SNP
association chips.
About deCODE
deCODE is a biopharmaceutical company applying its discoveries in human
genetics to the development of drugs and diagnostics for common diseases.
deCODE is a global leader in gene discovery -- our population approach and
resources have enabled us to isolate key genes contributing to major public
health challenges from cardiovascular disease to cancer, genes that are
providing us with drug targets rooted in the basic biology of disease.
deCODE is also leveraging its expertise in human genetics and integrated
drug discovery and development capabilities to offer innovative products
and services in DNA-based diagnostics, bioinformatics, genotyping,
structural biology, drug discovery and clinical development. deCODE is
delivering on the promise of the new genetics(SM). Visit us on the web at
decode.
Any statements contained in this presentation that relate to future
plans, events or performance are forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995. These
forward-looking statements are subject to a number of risks and
uncertainties that could cause actual results to differ materially from
those described in the forward-looking statements. These risks and
uncertainties include, among others, those relating to technology and
product development, integration of acquired businesses, market acceptance,
government regulation and regulatory approval processes, intellectual
property rights and litigation, dependence on collaborative relationships,
ability to obtain financing, competitive products, industry trends and
other risks identified in deCODE's filings with the Securities and Exchange
Commission. deCODE undertakes no obligation to update or alter these
forward-looking statements as a result of new information, future events or
otherwise.
deCODE genetics
decode