Cardium reports positive results from Generx Ad5FGF-4 Phase 3 study for treatment of myocardial ischemia

Pioneering Angiogenic Gene Therapy for the Potential Treatment of Millions of Patients with Heart Disease Worldwide

Taxus Cardium Pharmaceuticals Group Inc. (Trading Symbol: CRXM) will report today at the Biotechnology Industry Organization’s 2014 BIO International Convention on a pre-specified interim analysis from its international ASPIRE Phase 3 registration clinical study of Generx^® Ad5FGF-4, Cardium Therapeutics’ angiogenic gene therapy product candidate for patients with myocardial ischemia due to coronary artery disease. The presentation at the 2014 BIO International Convention, now underway at the San Diego Convention Center, will be by Christopher Reinhard, Taxus Cardium’s Chief Executive Officer and Cardium Therapeutics’ co-founder, at 4:30 pm June 24 in the Mission Beach room.

Cardium will report on positive safety and statistically significant efficacy data from a randomized, multi-center, controlled study’s primary registration endpoint of improvement in cardiac perfusion (blood flow) with Generx compared to the control group. Myocardial perfusion was measured by single-photon emission computed tomography (SPECT), a standard way of measuring blood flow at rest and during stress. Blood flow under stress was inadequate in all patients entering the study, as it is in millions of patients with heart disease worldwide. Patients were then randomized to receive the Generx product candidate or standard medical treatment for myocardial ischemia. Eight weeks following administration, the group of patients who received Generx were found to have significant improvements in myocardial blood flow under stress, as compared to the control group – and the degree of improvement in Generx patients was of a magnitude that is similar to that observed following coronary interventions such as bypass surgery or angioplasty and stenting, as described further below.

The ASPIRE clinical study represents the fifth clinical study under the Generx gene therapy worldwide development program, which when completed will have evaluated over 780 patients at over 100 medical centers in the United States, Western Europe, South America, Canada and the Russian Federation, where the current ASPIRE study is being conducted. The Generx program is considered the largest angiogenic cardiac gene therapy registration dossier in the world. For more information about Taxus Cardium, visit the Company’s website www.cardiumthx.com, and for access to the Generx 2014 BIO International presentation visit http://phx.corporate-ir.net/phoenix.zhtml?c=77949&p=irol-presentations.

Generx is designed to be administered one-time, by an interventional cardiologist on an out-patient basis during a brief angiogram-like procedure using a standard balloon catheter. The Generx angiogenic gene therapy product candidate is designed to stimulate the body’s natural healing response to ischemic coronary artery disease by promoting the growth of microvascular circulation in the heart in order to enhance blood flow (cardiac perfusion). Generx is intended as a treatment for patients with myocardial ischemia and persistent angina pectoris (chest pain) due to coronary artery disease, despite optimal medical therapy and bypass surgery or percutaneous coronary intervention (PCI). In addition, this therapy could potentially benefit patients who are diagnosed with cardiac microvascular insufficiency, defined as myocardial ischemia without large vessel disease sufficient to cause ischemia. This group of patients, consisting of about 10-20% of patients with angina pectoris, are not helped by bypass surgery or PCI because these techniques are only applicable to identifiable and treatable lesions in large vessels, and not the growth of smaller vessels.

The primary efficacy endpoint in the ASPIRE clinical study is improvement in myocardial perfusion as measured by changes after eight weeks in the reversible perfusion defect size (RPDS), determined using rest/stress single-photon emission computed tomography (SPECT) imaging. The ASPIRE study’s interim analysis shows 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. The SPECT studies were evaluated by the Los Angeles-based Nuclear Cardiology Core Laboratory at Cedars-Sinai Medical Center, the study’s central analytical core lab. At eight weeks, Generx treatment resulted in a 24% improvement in 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]. 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 ASPIRE and AGENT perfusion studies were intentionally designed using the same primary quantitative functional efficacy endpoint of RPDS at the same 8 week interval after 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).

“The new data from the international Phase 3 ASPIRE clinical study further supports findings of safety and efficacy from the four prior and published Generx angiogenic gene therapy (AGENT) clinical studies that have been conducted at over 100 medical centers worldwide. This represents another important step forward in the development of an innovative biology-based microvascular gene therapy tool for the interventional cardiologist designed to broaden the cycle of care for a large number of patients worldwide with myocardial ischemia,” noted Timothy Henry, MD, FACC, who is now the Chief of Cardiology at the Cedars-Sinai Heart Institute. Dr. Henry was previously the Director of Research for the Minnesota Heart Institute, and was an investigator in the Generx AGENT-3 Phase 2b/3 clinical study and first author on the published AGENT-3,-4 study report [Henry et al., J Am Coll Cardiol. 2007; 50: 1038-46].

An independent ten-year prospective study (n=845) has also demonstrated the importance of collateral circulation beyond simply the symptomatic relief of angina. This longitudinal study included a determination of cumulative survival rates related to cardiac mortality in patients with coronary artery disease. The study showed statistically significant increased cardiac survival for patients with well-developed collateral circulation at 97% over the ten year study period, compared to ten-year cardiac survival of 88% for patients with poorly developed collateral vessels (p=0.0109) [Meier et al., Circulation 2007;116:975-83].

“Heart disease is a leading global medical concern and is expected to be so for generations to come. Here at Cardium, we are focused on developing an effective and universally affordable cardiovascular regenerative gene therapy for ease of use within the current practice of medicine that can potentially be accessible to the millions of patients with ischemic heart disease worldwide. Our Generx product candidate is the result of this strategic focus and product development strategy” stated Christopher Reinhard, Taxus Cardium's chief executive officer and co-founder of Cardium Therapeutics.

“Looking back on the significant innovations in the field of coronary revascularization for heart disease, about every ten years a significant innovation takes hold and is transformative. Diagnostic coronary angiography began in 1958, by-pass surgery became generally available ten years later in 1969, followed by the introduction of angioplasty in 1979, the general use of bare metal stents in 1994, followed by the advent of drug eluting stents in 2002. Working with health authorities, clinical researchers and patients from around the world, we are working to develop Generx microvascular gene therapy as the next big transformative innovation for the fields of gene therapy and interventional cardiology” Reinhard further noted.

An article entitled “Identifying and Overcoming Obstacles in Angiogenic Gene Therapy for Myocardial Ischemia,” by Gabor M. Rubanyi, M.D., Ph.D., Cardium’s Chief Scientific Officer, has just been accepted for publication in the Journal of Cardiovascular Pharmacology. The publication outlines advances in scientific and medical knowledge pioneered by Cardium and others in therapeutic angiogenesis for myocardial ischemia, including mechanistic and biological insights, optimization of clinical trial design, and selection of target patient populations and meaningful efficacy endpoints. The publication also reports, for the first time, the results of studies performed by Cardium researchers demonstrating a synergistic interaction between Generx-expressed fibroblast growth factor-4 (FGF-4) and vascular endothelial growth factor (VEGF) in the promotion of neovessel formation, with evidence that FGF controls angiogenesis upstream of VEGF.