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Inotek Pharmaceuticals Announces Presentation of Phase 2 Clinical Data for
INO-1001 at ACC Demonstrating PARP Inhibition and Anti-inflammatory Activity
in Plasma of Patients Undergoing Primary Percutaneous Coronary Intervention
BEVERLY, Mass
March 27, 2007
Inotek Pharmaceuticals Corporation announced today
the presentation of positive Phase 2 clinical data demonstrating
the safety of INO-1001 as well as the potential for INO-1001 as
a preventative agent for cardiac reperfusion injury. The study was
conducted in subjects with acute ST-elevated myocardial infarction
(STEMI) undergoing primary percutaneous coronary intervention. The
presentation was made in a poster session at the American College
of Cardiology (ACC) 56th Annual Scientific Session in New Orleans,
Louisiana. INO-1001 is an inhibitor of poly(ADP-Ribose) polymerase
(PARP), a nuclear enzyme that directs the repair of damaged DNA
via the activation and recruitment of DNA repair enzymes and is
being studied as a treatment for certain acute cardiovascular conditions
and cancer. Additionally, PARP inhibition shows promise in inflammatory
disorders. PARP’s role in the inflammatory response may result
from its ability to potentiate the activity of key inflammatory
transcription factors (NF-kappaB and AP-1).
“Whereas advances in pharmacologic and mechanical reperfusion
therapy have improved the outcomes of patients with STEMI, reperfusion
injury, which is associated with severe damage to the cardiac tissue,
is a significant complication that has no current safe and effective
treatment options,” commented Dr. Andrew Salzman, Inotek’s
President and CEO. “These Phase 2 data provide further support
for our PARP inhibitor program in cardiovascular disease. These
results combined with existing preclinical data suggest that INO-1001
produces significant PARP inhibition and has the potential to protect
cardiac tissue from damage.”
Researchers from the Brigham and Women’s
TIMI Study Group and Inotek Pharmaceuticals reported that plasma
from patients treated
with INO-1001 suppressed ex vivo PARP activation. This effect was
observed up to 24 hours following drug administration. Furthermore,
INO-1001 treatment was associated with a trend towards reduced levels
of select inflammatory proteins, including C-reactive protein and
interleukin-6. No-drug related serious adverse events were observed
in the 30 patients receiving drug during the study period.
The Phase
2 trial was a prospective, single-blind, multi-center, dose-escalation
study of a single dose of intravenous INO-1001 (200
mg, 400 mg, or 800 mg) administered in adults presenting with
acute STEMI who were to be treated with primary PCI. The study enrolled
40 patients between the ages of 48 and 63. The primary endpoint
of the study was to evaluate the safety, tolerability and pharmacokinetic
profile of INO-1001. The secondary objectives of the study were
to characterize the pharmacodynamic profile of INO-1001 and to
evaluate
various biomarkers of necrosis and inflammation.
About PARP Inhibitors
Poly (ADP-ribose) polymerase (PARP) is an abundant nuclear enzyme
that mediates the repair of DNA single strand breaks through the
activation and recruitment of DNA repair enzymes. PARP’s
role in the inflammatory response may result from its ability
to potentiate
the activity of key inflammatory transcription factors (NF-kappaB
and AP-1). PARP inhibitors have shown promise in a variety of
inflammatory and ischemia/reperfusion diseases, including those
related to acute
cardiovascular conditions. PARP inhibitors may also have potential
application in cancer, and are being studied to ascertain their
ability to block one of the key defense mechanisms that cancer
cells rely upon to resist standard chemotherapy. By blocking tumor
defenses,
PARP therapy may increase the susceptibility of tumors to standard
chemotherapy or even reverse tumor resistance.
About INO-1001
INO-1001 represents Inotek’s lead candidate in a series of
novel PARP inhibitors discovered by Inotek. In July 2006, Inotek
and Genentech, Inc. entered into an exclusive global collaboration
to discover, develop, manufacture and commercialize PARP inhibitors,
including INO-1001, for the potential treatment of cancer. Additionally,
Genentech has retained an option to develop and commercialize Inotek’s
PARP inhibitors to prevent cell death and complications associated
with various acute cardiovascular conditions and procedures. Inotek
has retained all rights to develop and commercialize PARP inhibitors
outside of cancer and the specific acute cardiovascular diseases
included in Genentech’s option. A number of oral and intravenous
next generation PARP inhibitors are in development for various
disease states, including cancer.
About Inotek Pharmaceuticals
Inotek Pharmaceuticals Corporation (www.inotekcorp.com) is a Phase
2, drug-development company with a deep pipeline of small molecule
compounds targeting the key biological processes involved in
cell survival and tissue injury. Inotek’s three platform
programs have resulted in six novel molecules in various stages
of preclinical
and clinical development that target: 1) PARP, a nuclear enzyme
that is fundamental to DNA repair and inflammation; 2) peroxynitrite,
a highly toxic oxidative and nitrosative species produced by
cells in response to injury; and 3) the purinergic receptor
family,
with a specific focus on adenosine receptors.
Inotek was founded
in 1996 and currently has 140 employees, located in its corporate
headquarters and main research laboratories in
Beverly, Massachusetts and its clinical operations and GMP production
facilities in Israel. Inotek has developed integrated capabilities
from early discovery through Phase 2 clinical development.
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