SAN DIEGO, May 15, 2015 /PRNewswire/ -- Angionetics Inc., a
majority-owned operating unit of Taxus Cardium Pharmaceuticals
Group (Symbol: CRXM), today announced a presentation at the
18th Annual American Society of Gene & Cell Therapy
Conference on the Phase 3 Generx® angiogenic gene therapy
program. The presentation was given at the scientific
symposium entitled "Frontiers of Cardiovascular Gene and Cell
Therapy" which was held in New Orleans,
Louisiana.
The review and clinical update, entitled "Optimization of Generx
[Ad5FGF-4] Clinical Trial Design for Refractory Angina: Interim
Results of the ASPIRE Phase 3 Clinical Study" was presented by the
Company's Chief Scientific Officer, Gabor M. Rubanyi, M.D., Ph.D.
Dr. Rubanyi outlined the current scientific knowledge about
the mechanistic basis of adaptive coronary collateral growth, the
biological processes that are targeted by therapeutic angiogenesis,
recent discoveries based on Company-sponsored pre-clinical and
clinical research, and provided an update on the Generx angiogenic
gene therapy Phase 3 international clinical study.
Dr. Rubanyi reported that only about 20%-30% of patients with
coronary artery disease have a well-developed coronary collateral
network, and that independent clinical studies have confirmed that
a well-established coronary collateral network is associated with
reduced myocardial ischemia, infarct size following a heart attack,
and cardiovascular mortality. Dr. Rubanyi further noted that
the Company has identified several patient groups with cardiac
conditions and syndromes, experiencing persistent angina due to
cardiac microvascular insufficiency, who may also benefit from the
Generx angiogenic gene therapy product candidate. The presentation
is available for viewing at
http://phx.corporate-ir.net/phoenix.zhtml?c=77949&p=irol-presentations
Generx Product Candidate
The Generx®, alferminogene tadenovec [Ad5FGF-4] Phase 3
product candidate, is a first in class, single-dose, disease
altering therapeutic, specifically targeted for the cardiac
micro-vasculature, that is designed to leverage cardiac plasticity
to stimulate and augment the formation of new coronary structures
in patients with cardiac microvascular insufficiency (CMI) and
coronary artery disease. This process is believed to increase the
level of micro-vascularity, to enhance cardiac perfusion, and
improve cardiac performance, as measured by exercise tolerance and
the occurrence and severity of myocardial ischemia-driven
angina. The Generx microvascular therapy is designed to
easily fit within the current practice of medicine, as a
single-dose treatment, which is administered by an interventional
cardiologist using standard cardiac catheters during an
approximately one-hour, out-patient, angiogram-like procedure,
which is conducted in a hospital or medical center. The
Company's proprietary Generx angiogenic gene therapy technology
platform is being developed for treatment of specific subgroup
patient populations with coronary artery disease, as well as for
patients with orphan medical indications, all of which have
myocardial ischemia due to CMI and experience persistent
symptomatic angina pectoris despite maximum doses of currently
available medications, and who are not optimal candidates for
surgical and percutaneous interventions. These subgroups
include patients who have been diagnosed with (1) progressive
coronary artery disease and who have reached clinically defined
stages in their disease cycle; (2) "female pattern" angina; (3)
Cardiac Syndrome X; and (4) certain orphan medical indications
including variant anginas like Prinzmetal's angina.
The Science & Biology of Ad5FGF-4
The Generx [Ad5FGF-4] angiogenic gene therapy product candidates
are comprised of three key elements that include (1) a myocardial
delivery vector; (2) a therapeutic transgene and (3) proprietary
methods of gene therapy. The Generx [Ad5FGF-4] product candidate is
a gene therapy construct that utilizes an adenovirus serotype 5
delivery vector that is replication-deficient, non-integrating and
drives short-term transient expression of the Fibroblast Growth
Factor-4 (FGF-4) transgene. Generx is designed to stimulate
the body's natural healing response to ischemic coronary artery
disease by promoting microvascular angiogenesis and arteriogenesis,
and enhancing cardiac perfusion. Adenovirus is the most
studied and well-characterized, gene therapy delivery vector, and
has cGMP manufacturing and testing standards established by the
FDA. When administered by an interventional cardiologist into the
coronary arteries under transient ischemic conditions through the
use of a standard balloon catheter, Generx distributes into the
heart's microvascular pathways and transfects heart cells by
binding to cell surface coxsackievirus-adenovirus receptors (CAR).
CAR receptors are found throughout the heart, and the binding of
Generx to CAR receptors is enhanced by the induction of transient
ischemia and the use of agents like nitroglycerin to boost
endothelial cell permeability during administration.
The transfected heart cells then express and release FGF-4
protein, which promotes the growth of new blood vessels that
increase blood flow to ischemic heart tissue. In addition,
the Generx FGF-4 transgene has been modified to include a signal
peptide, which allows its effective secretion from cells that
express the protein (such as cardiac myocytes). The Company's
preclinical studies showed that therapeutic efficacy is
significantly increased by the presence of such a signal sequence
in the growth factor DNA construct. This finding is explained by
the fact that FGF-4 acts in a paracrine manner (i.e. it is released
from target cells and acts on neighboring cells to stimulate new
vessel formation in the heart).
Company-sponsored pre-clinical research has demonstrated
localized FGF-4 protein expression in the heart following Generx
administration, and shown that pre-existing antibodies to the
adenovector have no significant impact on treatment effect. Recent
Company-sponsored research studies have also shown that FGF is a
key angiogenic regulatory protein that stimulates the release and
action of other angiogenic factors, including vascular endothelial
growth factors (VEGF), platelet-derived growth factors (PDGF), and
hepatocyte growth factor (HGF), to orchestrate and promote the
growth of cardiac microvasculature (a functional collateral
network) in ischemic cardiac tissue. Research further indicates
that the Generx angiogenic gene therapy product candidate has the
capacity to enlarge pre-existing collateral arterioles
(arteriogenesis) and to stimulate the formation of new capillary
vessels (angiogenesis) when driven by cardiac
hemodynamic-impairment and ischemic stimulus.
Generx® ASPIRE Phase 3 Clinical Update
The ASPIRE study is a 100-patient, randomized and controlled
multi-center study enrolling patients at leading international
cardiology centers. The ASPIRE study is designed to further
evaluate the safety and effectiveness of Cardium's Generx DNA-based
angiogenic product candidate, which has already been tested in
clinical studies involving 650 patients at more than one hundred
medical centers in the U.S., Europe and elsewhere. The efficacy of
Generx is being quantitatively assessed using rest and stress SPECT
(Single-Photon Emission Computed Tomography) myocardial imaging to
measure improvements in microvascular cardiac perfusion following a
one-time, non-surgical, catheter-based administration of
Generx. The Cedars-Sinai Medical Center Nuclear Cardiology
Core Laboratory in Los Angeles,
California, is the central core lab for the study and is
responsible for the analysis of SPECT myocardial imaging data
electronically transmitted from the international medical centers
participating in the ASPIRE study.
In June 2014, the Company
announced data from an interim analysis from the current
International Clinical Study. The interim analysis from the ASPIRE
study showed that the Generx product candidate, together with
Cardium's new catheter-based delivery protocol, appears to be safe
and well tolerated. In addition, statistically significant
improvement in myocardial perfusion was identified by the efficacy
endpoint of SPECT imaging. At eight weeks, Generx treatment
resulted in a 24% improvement in Reversible Perfusion Defect Size
(RPDS), a statistically significant response compared to the
control group (p=0.01, n=11). The observed improvement in RPDS with
Generx in the ASPIRE trial is consistent with RPDS improvement
previously reported in the Generx AGENT Phase 2 clinical study
(n=52) [Grines et al., J Am Coll Cardiol. 2003; 42:1339-47].
Improvement in RPDS was observed in 77% of patients in the AGENT-2
study, and 86% of the patients from the interim ASPIRE data
analysis, giving a pooled response rate of 79%. Furthermore, the
improvements in RPDS reported in both the ASPIRE and AGENT clinical
studies are similar in magnitude to large vessel revascularization
procedures, either bypass surgery or angioplasty (PCI), involving
the right coronary artery (RCA), the left anterior descending
artery (LAD) and the left circumflex artery (LCx), as reported in
patients undergoing these procedures [Berman et al., J Nucl
Cardiol. 2001; 8:428-37].
In addition, since the International Clinical Study and the
U.S.-based FDA-cleared AGENT-2 perfusion studies were intentionally
designed using the same primary quantitative functional efficacy
endpoint of RPDS at the same 8 week interval after a single Generx
administration, and both studies were independently statistically
significant, Cardium has conducted a pooled analysis of the SPECT
results. This additional data analysis of the interim ASPIRE data
with the AGENT Phase 2 study data shows that patients treated with
Generx have a 25% improvement in RPDS that is also statistically
significant compared to the pooled control groups (p=0.005,
n=63).
About Angionetics Inc.
Angionetics Inc., a majority-owned subsidiary of Taxus Cardium
Pharmaceuticals Group, is focused on the development and
commercialization of novel DNA-based therapeutics designed to
promote the heart's innate natural capacity to modulate the
formation and growth of cardiac microvascular circulation to
enhance blood flow (perfusion) in patients with a variety of
ischemia-driven disease conditions and refractory angina and
myocardial ischemia due to cardiac microvascular insufficiency
(CMI), and other cardiovascular disease conditions. For more
information, visit www.angionetics.com
On April 13, 2015, Angionetics
reported that it entered into an agreement to sell a 15% stock
equity interest for an aggregate purchase price of $3,000,000, payable in three tranches to be
completed by May 30, 2015. The
agreement contemplates that this initial funding is a bridge equity
investment to a separate larger financing to be conducted by
Angionetics Inc. including a potential registration and public
offering of securities. The proceeds from this Angionetics
equity investment will be used to advance the international and
United States Phase 3 clinical studies of Generx, for working
capital, and transactional expenses to facilitate current plans to
advance Angionetics forward as an independent company with direct
access to capital markets and strategic partnerships.
In addition, on April 7, 2015,
Taxus Cardium and Angionetics announced an exclusive territorial
license agreement with Dr. Reddy's Laboratories covering the
co-development, marketing and sales of Generx in certain
international markets including the Russian Federation and the Commonwealth of
Independent States. Positive safety and efficacy findings from the
Company's Generx international Phase 3, Russia-based ASPIRE study were announced at
the Annual 2014 Biotechnology Industry Organization Conference
following completion of a protocol-specified interim data
analysis. Dr. Reddy's Laboratories operates across the
globe. Major markets include the
United States, India and
Russia.
Taxus Cardium Pharmaceuticals Group
Taxus Cardium Pharmaceuticals Group Inc. is a holding company
that manages and operates the following investments: (1)
Angionetics, a majority-owned business unit focused on the clinical
development and commercialization of Generx®, an
interventional cardiology, angiogenic gene therapy Phase 3 product
candidate designed for the potential treatment of patients with
cardiac microvascular insufficiency and myocardial ischemia due to
advanced coronary artery disease (www.angionetics.com); (2)
Activation Therapeutics, a business unit focused on the
commercialization of Excellagen®, an FDA-cleared
flowable dermal matrix designed as a professional-use advanced
wound care product for the treatment of chronic non-healing
diabetic foot, venous and pressure ulcers, which also has
additional potential tissue regeneration applications based on stem
cells and other biologics (www.excellagen.com); (3) LifeAgain, an
advanced medical data analytics (ADAPT®)technology platform focused
on developing new and innovative products for the life insurance
and healthcare sectors (www.lifeagain.com); and (4) Healthy Brands
Collective, a functional food and nutraceutical company which
acquired Taxus Cardium's To Go Brands® business
(www.healthybrandsco.com). For more information about Taxus
Cardium, visit the Company's website www.cardiumthx.com.
Forward-Looking Statements
Except for statements of historical fact, the matters discussed
in this press release are forward looking and reflect numerous
assumptions and involve a variety of risks and uncertainties, many
of which are beyond our control and may cause actual results to
differ materially from expectations. For example, there can be no
assurance that results or trends observed in one clinical study or
procedure will be reproduced in subsequent studies or in actual
use; that new clinical studies will be successful or will lead to
approvals or clearances from health regulatory authorities, or that
approvals in one jurisdiction will help to support studies or
approvals elsewhere; that the company can attract suitable
commercialization partners for our products or that we or partners
can successfully commercialize them; that our product or product
candidates will not be unfavorably compared to competitive products
that may be regarded as safer, more effective, easier to use or
less expensive or blocked by third party proprietary rights or
other means; that the products and product candidates referred to
in this report or in our other reports will be successfully
commercialized and their use reimbursed, or will enhance our market
value; that new product opportunities or commercialization efforts
will be successfully established; that third parties on whom we
depend will perform as anticipated; that we can raise sufficient
capital from partnering, monetization or other fundraising
transactions to maintain our stock exchange listing or adequately
fund ongoing operations; or that we will not be adversely affected
by these or other risks and uncertainties that could impact our
operations, business or other matters, as described in more detail
in our filings with the Securities and Exchange Commission. We
undertake no obligation to release publicly the results of any
revisions to these forward-looking statements to reflect events or
circumstances arising after the date hereof.
Copyright 2015 Taxus Cardium Pharmaceuticals
Group Inc. All rights reserved.
For Terms of Use Privacy Policy, please visit
www.cardiumthx.com.
Cardium Therapeutics®,
Generx®, Cardionovo®, Tissue Repair™,
Excellagen®, Excellarate™, Genedexa™, and LifeAgain™,
are trademarks of Cardium Therapeutics, Inc., Tissue Repair Company
or LifeAgain Insurance Solutions Inc. Other trademarks belong to
their respective owners.
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SOURCE Taxus Cardium (CRXM)
