Scientific Journal Gene Therapy Reports That Cardium's Gene Activated Matrix Technology Accelerates Periodontal Tissue Regenerat
15 September 2009 - 12:00AM
PR Newswire (US)
SAN DIEGO, Sept. 14 /PRNewswire-FirstCall/ -- Cardium Therapeutics
(NYSE Amex: CXM) today reported on preclinical findings published
in the scientific journal, Gene Therapy, demonstrating that
Cardium's Gene Activated Matrix(TM) or GAM(TM) technology
accelerates periodontal tissue regeneration of oral
implant-supporting wounds. The PDGF-B gene therapy accelerates bone
engineering and oral implant osseointegration study (Chang, et al.,
Gene Therapy; 10 September 2009; doi: 10.1038/gt.2009.117)
conducted by researchers at the University of Michigan is available
online at nature.com/doifinder/10.1038/gt.2009.117, and reports on
the use of AdPDGF-B/collagen (the key component of the Company's
Excellarate(TM) product candidate) to promote oral implant
osseointegration. The study's findings demonstrate that
AdPDGF-B/collagen is safe, accelerates and enhances oral implant
osseointegration, and leads to significantly higher bone-implant
contact, defect fill, bone area and tissue mineral density than
placebo. (Logo:
http://www.newscom.com/cgi-bin/prnh/20051018/CARDIUMLOGO) Oral
implants are widely accepted in dental medicine as a reconstructive
treatment for tooth replacement due to disease, injury or
congenital defects. Growth factor application has been advocated to
improve osteogenesis and osseointegration, however, as a result of
the transient action and short half-life of proteins, the sustained
bioavailability associated with growth factor gene delivery has
been proposed as an effective alternative for the delivery of
growth factor proteins. The preclinical study demonstrated that the
initial response to a bolus administration of rhPDGF-BB protein was
strong, but the short half-life of the protein results in rapid
degradation with a decrease in the mitogenic response. In contrast,
PDGF-B gene delivery using Cardium's Gene Activated Matrix
technology resulted in sustained protein expression that lasted for
approximately 14 days. The benefits of this prolonged availability
are expected to be even more evident in planned large animal
critical size defect models. The study also reported that there was
no dissemination of the AdPDGF-B vector away from the treatment
site, and no alteration of hematological and clinical chemistry
parameters associated with the AdPDGF-B/collagen treatments. The
authors conclude that, "This approach shows the ability of
Ad-PDGF-B to accelerate oral implant osseointegration. The data
support the concept that Ad-PDGF-B gene delivery may be an
effective and safe mode of therapy comparable with PDGF-BB
application to promote dental implant osseointegration and oral
bone repair." "The results of this preclinical study demonstrate
the potential benefits of our GAM technology for bone engineering
and oral implant osseointegration and further support our decision
to expand the focus of the Company's regenerative medicine
technologies to include orthobiologics," reported Christopher J.
Reinhard, Chairman and Chief Executive Officer of Cardium
Therapeutics and Tissue Repair Company. "Cardium's Gene Activated
Matrix technology and protein-producing gene portfolio are
important building blocks as we expand our product development
programs from wound healing biologics into the emerging new high
growth market segment of orthobiologics." Orthobiologics Product
Platform The Company recently announced plans to develop a
DNA-based orthobiologics product portfolio based on research and
development by Cardium's Tissue Repair Company that will initially
focus on non-union bone fractures for medically-compromised
patients, and spinal fusion for patients with degenerative disc
disease. Orthobiologics is a rapidly growing segment of the
orthopedics market and represents biologically-active products
designed to enhance musculo-skeletal repair and regeneration.
Following on results observed with Tissue Repair's Excellarate(TM)
product candidate, which is targeted to the repair of soft tissues
(particularly diabetic ulcers), the Company's orthobiologics
initiative will build on and extend the underlying technology that
has been developed by the Tissue Repair Company to hard tissue
applications such as bone, including: (1) proprietary Gene
Activated Matrix(TM) or GAM(TM) delivery and ligand targeting; (2)
use of GAM to locally produce proteins capable of stimulating bone
and other tissue growth; and (3) a substantial body of pre-clinical
research and development supporting the use of GAM to deliver bone
growth factors. Cardium believes that future DNA-based products
offer the potential to provide patients and healthcare systems with
more cost-effective alternatives to current and planned
protein-based therapeutics. Cardium's initial orthobiologics focus
will be on the development of Osteorate(TM), a DNA-based
non-surgical injectable bone graft gel to repair bone fractures and
regenerate tissue in certain medically-compromised patient
populations. Osteorate will be based on a reformulation of
Cardium's DNA-based Excellarate wound healing product candidate,
now in late-stage clinical development, which is designed to
stimulate localized and sustained cellular production of
platelet-derived growth factor-B (PDGF-B) protein as a treatment
for patients with non-healing diabetic foot ulcers. The Gene
Activated Matrix technology allows for a broad spectrum of
formulations which would include, but not be limited to, collagen,
demineralized bone matrices, allograft and synthetic graft
materials. Based on recently announced formulation advances,
Osteorate would be developed as a pre-mixed ready-to-use-syringe
that would be stored in a physician's office at a temperature of
about 4 degrees Celsius. PDGF-B protein is a well known bone growth
mediator and is already used in several FDA approved products and
medical devices for soft and hard tissue healing. The Gene
Activated Matrix technology platform is expected to be further
expanded with the use of other genes capable of promoting bone
repair, in order to biologically enhance surgical spinal fusion
procedures in patients with degenerative disc disease. Exemplary
genes include a chimeric variant of BMP-4 (chBMP4), which offers
the potential for the localized and sustained cellular expression
and release of Bone Morphogenetic Protein-4 (BMP-4) to potentially
enhance spinal fusions. A pre-clinical research study, conducted by
Cardium's Tissue Repair Company, entitled Bone Induction by
AdBMP-2/Collagen Implants, (Schreiber, et al., J Bone Joint Surg,
2005, May; 87(5): 1059-1068) demonstrated that local delivery of an
adenovector encoding BMP-2 (AdBMP-2) in a collagen matrix rapidly
induced new bone formation compared to controls. The chBMP4 variant
is believed to be even more effective for orthobiologics
applications such as bone repair. Cardium plans to explore
potential collaborations with other companies in the orthopedics
space, including orthopedic device manufacturers and others having
an interest in developing novel approaches designed to improve the
healing and regeneration of bone following traumatic bone injuries,
which are affecting a substantial and increasing proportion of the
human population as patients survive to older ages along with
general improvements in medicine and healthcare. Gene Activated
Matrix Technology Platform Cardium's proprietary Gene Activated
Matrix technology platform is designed to provide a therapeutic
level of protein synthesis at a specific site in the body and can
be used in soft tissue such as skin, ligament, tendons and
cartilage, as well as in hard tissue such as bone. The technology
is distinctive in that it is immobilized gene delivery that allows
for localized control of gene uptake. The Gene Activated Matrix
comprises any biocompatible matrix containing a gene or DNA vector
encoding for a growth factor or any therapeutic protein. The Gene
Activated Matrix technology allows for a broad spectrum of
formulations and the use of any biocompatible matrix, natural or
synthetic, which would include, but not be limited to, collagen,
demineralized bone, allograft and other synthetic graft materials.
The Company's studies have shown that proliferative cells migrate
into the Gene Activated Matrix and then take up the immobilized
gene resulting in localized and sustained production of micro
quantities of growth factor proteins or other therapeutic proteins
based on the protein-producing DNA of choice. Compared with current
protein therapy, which may be limited due to the inherent short
half-life of a protein once administered into the human body, the
Company believes that the localized and sustained production of
micro-quantities of DNA-driven proteins at the injury site within a
Gene Activated Matrix offers the opportunity to significantly
enhance the availability of therapeutic proteins to the cells
performing tissue repair and lower the overall level of protein
required. Cardium's Orthobiologics Research Significant
pre-clinical research has been conducted and published by
researchers and collaborators at Cardium's Tissue Repair Company
and the University of Michigan demonstrating the safety and
benefits of adenovector-mediated platelet-derived growth factor
gene expression in the areas of periodontal tissue engineering and
bone-grafting applications. Published data for periodontal tissue
engineering include: (1) Platelet-Derived Growth Factor Gene
Delivery Stimulates ex Vivo Gingival Repair, (Anusaksathien, et
al., Tissue Eng. 2003 August; 9(4): 745-756); (2) Engineering of
Tooth-Supporting Structures by Delivery of PDGF Gene Therapy
Vectors, (Jin, et al., Mol Ther, 2004 April; 9(4): 519-526); (3)
Platelet-derived Growth Factor-B Gene Delivery Sustains Gingival
Fibroblast Signal Transduction, (Lin, et al., J Periodont Res,
2008; 43: 440-449); and (4) Adenovirus Encoding Human
Platelet-Derived Growth Factor-B Delivered to Alveolar Bone Defects
Exhibits Safety and Biodistribution Profiles Favorable for Clinical
Use, (Chang, et al., Human Gene Therapy, 2009 May; 20: 486-496).
This body of research by the Tissue Repair Company and its
collaborators demonstrates the potential safety and benefits of
PDGF gene therapy for periodontal tissue repair and regeneration.
In addition, a pre-clinical research study, conducted by Cardium's
Tissue Repair Company, entitled Bone Induction by AdBMP-2/Collagen
Implants, (Schreiber, et al., J Bone Joint Surg, 2005, May; 87(5):
1059-1068) demonstrated that local delivery of an adenovector
encoding BMP-2 (AdBMP-2) in a collagen matrix rapidly induced new
bone formation compared to controls. Market Opportunity of Dental
Bone Graft Substitutes A new and rapidly growing market in
orthopedics is orthobiologics. According to one industry research
report, orthobiologics is the fastest growing segment in
orthopedics with an estimated growth rate of 17% and total
worldwide sales of $4.2 billion in 2007. The global market for such
products is projected to almost double from 2007 levels by 2012.
Worldwide dental implants are poised to achieve significant growth
as patients become aware of the health benefits achieved from
having viable teeth. With an estimated 69% of adults ages 35 to 44
having lost at least one permanent tooth to an accident, gum
disease, a failed root canal, or tooth decay, dental implants
represent a large market. By age 74, 26% of adults have lost all of
their permanent teeth and this population is growing as the number
of Americans over 55 is expected to increase by 60% in the next 20
years. In 2006, the combined U.S. market for dental bone graft
substitutes and other biomaterials was valued at slightly over $150
million. This market includes bone graft substitutes, tissue
engineering products, and dental membranes. The market is expected
to rapidly grow as the number of bone graft procedures associated
with dental implants increases. Market is expected to increase to
over $415 million by 2013. About Cardium Cardium is focused on the
acquisition and strategic development of new and innovative
bio-medical product opportunities and businesses that have the
potential to address significant unmet medical needs and definable
pathways to commercialization, partnering and other economic
monetizations. Cardium's investment portfolio includes the Tissue
Repair Company and Cardium Biologics, medical technology companies
primarily focused on the development of innovative therapeutic
products for tissue repair and cardiovascular indications. In May
2009, Cardium announced completion of the enrollment for the Matrix
Phase 2b clinical study to evaluate the Excellarate product
candidate as a treatment for patients with non-healing diabetic
ulcers. News from Cardium is located at http://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 stated
expectations. For example, there can be no assurance that an
orthobiologics product initiative can be initiated and successfully
developed, that results or trends observed in pre-clinical or
clinical studies or procedures will be reproduced in subsequent
studies or procedures, that the MATRIX study or other human
clinical trials can be conducted and completed in an efficient and
successful manner, that clinical studies even if successful will
lead to product advancement or partnering, that product formulation
enhancements will be successful or will effectively simplify or
expand the use of product candidates or technologies, that the GAM
technology can be successfully broadened or applied to additional
wound healing or tissue repair opportunities, that Excellarate,
Osteorate or our other product candidates will prove to be
sufficiently safe and effective, that our products 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, that FDA or other regulatory clearances or other
certifications, or other commercialization efforts will be
successful or will effectively enhance our businesses or their
market value, that our products or product candidates will prove to
be sufficiently safe and effective after introduction into a
broader patient population, or that third parties on whom we depend
will perform as anticipated. Actual results may also differ
substantially from those described in or contemplated by this press
release due to risks and uncertainties that exist in our operations
and business environment, including, without limitation, risks and
uncertainties that are inherent in the development of complex
biologics and in the conduct of human clinical trials, including
the timing, costs and outcomes of such trials, our ability to
obtain necessary funding, regulatory approvals and expected
qualifications, our dependence upon proprietary technology, our
history of operating losses and accumulated deficits, our reliance
on collaborative relationships and critical personnel, and current
and future competition, as well as other risks described from time
to time in filings we make 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 2009 Cardium Therapeutics, Inc. All rights reserved. For
Terms of Use Privacy Policy, please visit
http://www.cardiumthx.com/. Cardium Therapeutics(TM) and Generx are
trademarks of Cardium Therapeutics, Inc. Tissue Repair(TM), Gene
Activated Matrix(TM), GAM(TM), Excellarate(TM) and Osteorate(TM)
are trademarks of Tissue Repair Company. Other trademarks are the
property of their respective owners.
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CONTACT: Bonnie Ortega, Director, Investor/Public Relations,
Cardium Therapeutics, Inc., +1-858-436-1018, Web Site:
http://www.cardiumthx.com/
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