PRE-CLINICAL DEVELOPMENT: Corgentin
Corgentin
(Ad5IGF-l), a pre-clinical product candidate, is a next-generation
DNA-based therapeutic using the insulin-like growth factor-I
gene carried by an adenovector that is being designed as
a one-time treatment to promote the repair and restoration
of damaged cardiomyocytes and enhance cardiac function following
a heart attack (acute myocardial infarction) through the
beneficial cardiac effects of prolonged IGF-I protein expression.
We believe that Corgentin offers the potential to improve
post-infarct cardiac healing through DNA-based, targeted
myocardial cell delivery and the resulting sustained cardiac-restorative
bioactivity. Corgentin will be delivered using the Company's
proprietary technology covering methods of intracoronary
cardiac administration. The biological properties of
IGF-I, including inhibition of apoptosis, adaptive cardiomyocyte
hypertrophy, recruitment of cardiac progenitor cells,
as well as the induction of angiogenesis and enhancement
of cardiac function, provide the rationale for the development
of a therapy directed at myocardial repair and restoration.
This biology predicts Corgentin's potential to improve
functional recovery and prevent ventricular dysfunction
and the associated progression to congestive heart failure
following myocardial infarction and reperfusion.
The safety of systemic IGF-I protein therapy has been confirmed in multiple human clinical studies for a number of medical indications. While there is abundant published scientific literature validating the multiple beneficial cardiac effects of IGF-I, systemic IGF-I protein delivery generally lacks the ability to target cardiomyocytes for effective therapy. We believe that by targeting the heart with intracoronary, DNA-coded, myocardial-directed delivery, using the proprietary methods pioneered for the Generx development program, Corgentin has the potential to induce a positive biologic response. The targeted cardiomyocytes are expected to produce sustained therapeutic protein levels in the myocardium where it is needed. We estimate that over 1,000 patients have been treated with various dose levels of IGF-I protein, and 450 patients have received Generx (Ad5FGF-4, a DNA-based angiogenic growth factor) via intracoronary administration. We believe the safety and preliminary efficacy from these studies provide further support for the clinical potential of Corgentin.
In vitro pre-clinical development studies have
confirmed published data supporting the myocardial benefits
of IGF-I in cell-based assays by protecting cardiomyocytes
against apoptosis, inducing adaptive cardiomyocyte hypertrophy
and inducing proliferation of human coronary artery endothelial
cells. Cardium's in vivo proof-of-concept pilot study
in pigs, based on its coronary occlusion/reperfusion
myocardial infarct model, tested intracoronary administration
of Corgentin to promote myocardial repair following a
significant heart attack (myocardial infarction). This
double-blind, randomized, placebo-controlled study was designed
to simulate the clinical approach in which Corgentin would
be administered after emergency reperfusion therapy to
a heart attack patient. Following infarction in the pre-clinical
animal model, echocardiographic analysis documented recovery
and restoration of ventricular function and reversal
of early left ventricular remodeling in the Corgentin-treated
group, compared to placebo. Post-mortem analysis of the
hearts provided convincing histological evidence of the potential
for post-infarct myocardial protection with this therapy.
Corgentin Therapeutic Approach for Heart
Attack
The Company will seek to advance the current
standard of care for patients with Acute Coronary Syndrome
through the development of Corgentin to enhance myocardial
healing in and around the infarct zone when used as an
adjunct to existing vascular-directed pharmacologic and
interventional therapies. As
currently envisioned, Corgentin will be developed as
a treatment to be administered to heart attack patients
immediately following percutaneous coronary intervention
to open the blocked blood vessel and restore blood flow.
The objective of this treatment approach is focused on enhancing
myocardial repair and restoration for heart cells that have
been injured as a result of the heart attack. Today's
current standard of care is vascular-directed, focusing on
restoring blood flow, while Corgentin will seek to broaden
treatment to include a cardiomyocyte-directed therapy to
repair cells that have been injured as a result of a heart
attack (see figure).
It should be noted that even with the
best of care and successful early intervention such as
tPA or emergency angioplasty, about 30% of heart attack patients
will eventually go on to decompensation through left
ventricular remodeling and progressive congestive heart failure.
This explains in large part why heart failure remains an
epidemic health problem despite improved treatments for acute
cardiac events. A
therapeutic approach such as Corgentin has the potential
to change the clinical outcome for heart attack patients
by slowing or preventing remodeling, decompensation,
and congestive heart failure.
To further confirm the utility of the Corgentin approach
and establish its commercialization potential, the Company
plans to develop additional pre-clinical information through
sponsored studies. If confirmatory, the Company may then
consider initiating clinical studies, on its own or with
a corporate development partner.
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