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.
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.
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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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