Cardium Therapeutics Generx Presentation January 2013
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Cardium Therapeutics Generx Presentation January 2013



Cardium Therapeutics' (NYSE MKT: CXM) Generx® product candidate (alferminogene tadenovec, Ad5FGF-4) is a DNA-based angiogenic growth factor therapeutic being developed for the potential treatment of ...

Cardium Therapeutics' (NYSE MKT: CXM) Generx® product candidate (alferminogene tadenovec, Ad5FGF-4) is a DNA-based angiogenic growth factor therapeutic being developed for the potential treatment of patients with advanced coronary artery disease. Generx is designed to stimulate the growth of supplemental collateral blood vessels in the heart in order to enhance myocardial blood flow in patients who have insufficient blood flow due to atherosclerotic plaque restricting flow in the coronary arteries that supply the heart. Generx has progressed through four randomized, placebo-controlled clinical studies at over 100 medical centers in the United States and Western Europe that have enrolled over 650 patients.

Generx is designed as a disease-modifying regenerative medicine therapeutic that can elicit structural and physiologic changes in the heart (the growth of new collateral blood vessels) following a one-time intracoronary administration from a standard cardiac infusion catheter. In contrast, traditional drug therapies such as nitrates and beta blockers provide transient symptomatic relief of anginal chest pain without changing the underlying disease. In the United States, anti-anginal drugs have traditionally been registered by the FDA based on improvements in exercise treadmill tolerance testing (ETT), which can confirm short-term symptomatic relief of angina. Based on the disease-modifying nature of Generx, Cardium believes that a more objective and appropriate measure to assess the effectiveness of angiogenic therapy is cardiac perfusion, the actual blood flow in the heart under stress using SPECT imaging (single photon emission computed tomography) or another advanced imaging technique. Cardiac perfusion directly shows and quantifies improvements in the underlying physiologic condition, i.e. insufficient blood flow under stress. Generx is currently being developed for international markets outside United States as a treatment alternative for patients who may not have access to or may not be candidates for costly and invasive surgical revascularization procedures, such as coronary artery bypass surgery and angioplasty/stents.

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Cardium Therapeutics Generx Presentation January 2013 Cardium Therapeutics Generx Presentation January 2013 Presentation Transcript

  • 15-Jan-13 Product & Technology Overview 2013 Cardium Therapeutics, Inc. Generx ® Angiogenic Therapy Regenerative Medicine for Interventional Cardiology DNA-Based Non-Surgical 1 Angiogenic Therapy
  • Forward Looking Statements This presentation may contain forward-looking statements, including comments concerning clinical trials and product development programs, evaluation of potential opportunities, the level of corporate expenditures, the assessment of Cardium’s technology by potential corporate partners, capital market conditions, timing of events, cash consumption and other subjects. Actual results could differ materially from these forward-looking statements for many reasons, including the risks described under "Risk Factors" in the Company’s Annual Report on Form 10-K and Quarterly Reports on Form 10-Q as filed with the Securities and Exchange Commission. No guarantee about future results, performance or achievements can be made. Neither Cardium nor its agents intend to 2013 Cardium Therapeutics, Inc. update any of the forward-looking statements after the date of this presentation to conform them to actual results or to changes in expectations. 2
  • Scientific Overview and Therapeutic Rationale DNA-Based Cardiovascular Therapeutics  New regenerative  Ischemia (coronary heart medicine biological disease) is an important tools for interventional precursor for effective cardiology growth factor DNA-based therapy  Leverages the healing power of  Designed to stimulate cardiac plasticity microvascular cardiac angiogenesis  Proprietary, catheter- based intracoronary  Driven by upstream delivery approach regulatory gene (FGF-4) during an angiographic that stimulates a cascade procedure of other important growth factors  One-time non-surgical 2013 Cardium Therapeutics, Inc. treatment  First DNA-based biologic to advance to U.S. FDA  DNA transgene Phase 3 (with fast track delivery and CAR status) and Registration / receptor-based Generx [Ad5FGF-4] Phase 3 Study in Russia preferential cardiac uptake 3
  • Generx® Highlights  Generx [Ad5FGF-4] (CardioNovo® trade name in Russia) represents a new therapeutic class of regenerative medicine DNA-based biologics for interventional cardiology that is designed to stimulate the natural growth of microvascular circulation for a condition termed cardiac microvascular insufficiency (CMI) for patients with myocardial ischemia and symptomatic angina pectoris due to advanced coronary disease. Generx is administered one-time, using a standard balloon cardiac catheter.  Generx is initially being currently developed, in markets outside the U.S., as treatment alternative for patients who may not have access to costly and invasive advanced mechanical revascularization procedures, including coronary artery bypass surgery and angioplasty/stents, or may no longer be optimal candidates for these procedures.  Ad5FGF-4 has been evaluated in four clinical studies in North America and Western Europe at over 100 medical centers with over 650 patients participating in these studies. Data from the clinical studies have been published in leading peer reviewed medical journals.  The product appears safe and capable of improving microvascular circulation in certain patients, as measured by SPECT imaging, and improvements using standard ETT assessments. 2013 Cardium Therapeutics, Inc.  An independent 10-year clinical study (n=845) by Swiss researchers, published in the American Heart Association’s journal Circulation, have reported that patients with high levels of collateral circulation in the heart have a statistically significant mortality advantage when compared to patients with low collateral flow.  Generx was cleared by the FDA to initiate the AWARE Phase 3 clinical study (with Fast Track status) by the FDA, for certain refractory patients. Ad5FGF-4 is the only DNA-based cardiovascular biologic to be cleared for Phase 3 clinical study by the FDA. 4
  • Generx® Highlights  The AWARE clinical trial was inactivated by Cardium based on economic considerations due to the patient recruitment challenges for a small targeted population group in the U.S. where by-pass surgery and angioplasty are commonly available to patients of all ages.  Generx is now being evaluated in a Phase 3 / registration study (the Aspire Study) for 100 patients with advanced coronary artery disease at up to six major medical centers in the Russian Federation in connection with a commercialization plan covering the marketing and sale of Generx in Russia. Ad5FGF-4 will be marketed and sold in Russia under the trade name “Cardionovo.”  Recent discoveries from Cardium-sponsored preclinical studies at Emory University showed that induced transient ischemia (i.e. balloon catheter-based occlusion/ reperfusion as in an ordinary angioplasty, but at lower pressure) substantially increases Generx’s DNA vector’s transfection efficiency to heart muscle cells. These new findings offer the opportunity to further enhance angiogenic response and lower response variability in patients.  These findings have now been integrated into the Russian-based ASPIRE clinical study protocol.  A senior group of current Cardium physicians and business executives have worked on the 2013 Cardium Therapeutics, Inc. Generx research and development effort from the initial development (1996) to the present.  During the Generx development cycle, over $250 million has been invested in the product formulation, manufacturing and clinical study by Collateral, Schering and Cardium.  As a DNA-based bio-reactor manufactured product, Generx is projected to have favorable gross margins and offers the potential to generate substantial revenue in large markets with coronary artery disease. 5
  • Generx®: Historical Perspective Collateral Schering AG Cardium Commercial Therapeutics As Strategic Partner Therapeutics International (NASDAQ) with Collateral Formed to Development Therapeutics Acquire Activities University of Technology from Schering Acquires California Schering / Bayer Collateral in 2002 Russia San Diego FDA Phase 3 Clearance for $160 Million with Fast Track Status Brazil Discovery, Licensing & Phase 3 Clearance India Phase 1/2 to and Initial for Registration Study Phase 2b/3 in Russia Preclinical Studies 2013 Cardium Therapeutics, Inc. 1996 1997 - 2005 2005 - Present Current Status 6
  • Developing new and innovative, cost-effective advanced care for coronary heart disease patients in international markets 2013 Cardium Therapeutics, Inc. Generx Cardio Chant 7
  • Generx® [Ad5FGF-4] Clinical & Commercial Development Activities Cardium Innovations • Expanded target coronary artery disease patient population AGENT 1–4 • Established new quantitative ASPIRE primary efficacy endpoint using Phases 1 & 2/3 SPECT imaging Phase 3 Clinical Studies Clinical Study • New balloon catheter-based delivery techniques to leverage Treatment: Stable Cardium’s transient ischemia Condition: Cardiac discoveries to boost cell Microvascular Insufficiency Angina for Patients with transfection for Patients with Myocardial “Refractory” Coronary Ischemia Due to Coronary • Developed new “bio-assay” Artery Disease production batch release assay Artery Disease that measures angiogenic 2013 Cardium Therapeutics, Inc. Primary Endpoint: response to Generx Primary Endpoint: ETT Improvement • Five-year real-time product RPDS Improvement as stability (at -70°C) confirmed Measured by SPECT 650 Patients at • Simplified and standardized 100 Medical Centers new cath lab product 100 Patients preparation techniques 8
  • Generx® [Ad5FGF-4] Product Focus for Russian Federation Generx is being developed to promote the growth of microvascular circulation in the heart. It is administered by a cardiologist through a cardiac catheter during an outpatient procedure. The product is a new treatment option for a condition termed Cardiac Microvascular Insufficiency (CMI) in patients with myocardial ischemia and symptomatic angina pectoris due to coronary artery disease, for such patients that have limited access to advanced medical care including coronary angioplasty and stents as well as coronary artery by-pass surgery, and patients who are not optimal candidates for those procedures. A long-term study (n = 845) has shown that patients with a higher collateral blood flow index may have an improved mortality benefit when compared to patients with a relatively lower collateral blood flow index. Selected Health Statistics Benchmarks United Russian 2013 Cardium Therapeutics, Inc. Demographic Metrics States Federation Average Life Expectancy - Males 76 64 Cardiovascular Death Rates per 100,000 80 297 9
  • CardioNovo®: Russian Federation Phase 3 Registration Study International Markets Elements (Initially Russian Federation) (ASPIRE) CardioNovo [Ad5FGF-4] Product (alferminogene tadenovec) RHA Cleared Phase 3 / Clinical Status Registration Study 100 Men & Women Multi-Center, Randomized, Clinical Study Population Controlled Parallel-Group Patient Population Myocardial Ischemia as a Treatment Option for Patients Medical Indication Considering Angioplasty / 2013 Cardium Therapeutics, Inc. Stents & Bypass Surgery Improvement in Reversible Clinical Endpoint Perfusion Deficit Based on SPECT Imaging Clinical Study Status Initiated 2012 10
  • Generx ® [Ad5FGF-4] DNA-Based Angiogenic Therapy Interventional cardiology-focused product candidate that is being developed for a medical condition termed Cardiac Microvascular Insufficiency (CMI) in patients with myocardial ischemia and symptomatic chronic stable angina pectoris due to coronary artery disease. 2013 Cardium Therapeutics, Inc. Patients with CMI have had an insufficient angiogenic response to their current disease state and may benefit from a therapy to biologically enhance cardiac perfusion through the facilitation of collateral vessel formulation. This condition is diagnosed by SPECT imaging, and other catheter-based diagnostic techniques. 11
  • Generx® Pioneering DNA-Based Regenerative Medicine DNA-based therapy is designed to enable a patient’s own cells to produce a therapeutic protein directly where it is needed in the body. The 2013 Cardium Therapeutics, Inc. Generx product candidate is designed to induce localized angiogenic growth factor production following its one- time delivery to stimulate the growth of microvascular circulation. 12
  •  2013 Cardium Therapeutics, Inc.13 Cardiovascular Angiogenesis
  • Coronary Artery Disease Natural Disease-Induced Angiogenic Vascularization 2013 Cardium Therapeutics, Inc. OFF ON 14
  • Beneficial Effects of a Disease-Induced Angiogenic Vascularization Summary Research “A well-functioning coronary collateral circulation saves lives in patients with chronic stable coronary artery disease.” 2013 Cardium Therapeutics, Inc. From Meier et al. Circulation 2007; 116:975-83. 15
  • Generx® Late-Stage Clinical Development 2013 Cardium Therapeutics, Inc. 16
  • Generx® Revolutionary Alternative Therapy for Heart Disease Coronary Artery Non-Surgical Bypass Graft Cardiovascular Surgery Gene Therapy Objective 2013 Cardium Therapeutics, Inc. 17
  • Generx® Leveraging the Power of Biology This illustration utilizes computer models of DNA-based on data generated by x-ray crystallography, a technique for determining the structure 2013 Cardium Therapeutics, Inc. of a molecular sample, together with a portion of the DNA sequence of Generx (Ad5FGF-4), Cardium’s lead clinical product candidate. Digital illustration of DNA. 18
  • Technology Platform: Non-Surgical DNA-Based Angiogenic Therapy Methods of Intracoronary DNA-Based Angiogenic Therapy X Adenovirus DNA-Based Manufacturing Delivery (Ad5) Know-How & Expertise Angiogenic Growth Factor (FGF-4) 2013 Cardium Therapeutics, Inc. Generx® [Ad5FGF-4] (alferminogene tadenovec) 19
  • Generx® (alferminogene tadenovec) DNA-Based Adenovector Cassette  Demonstrated CV Safety Database with FDA  Established FDA Manufacturing Standards  High Cardiac Transfection Levels due to a Binding Affinity with CAR Receptors and Enhanced by Ischemia  Transient Expression - - Does Not Integrate into Adenovector construct Host Genome Carries the FGF-4 Gene for Cardiac Delivery  Manufacturing in High Titer 2013 Cardium Therapeutics, Inc.  Easily Manipulated Research Studies: Coronary Intracoronary Administration Extraction Rate  Relatively Low Cytotoxity Pre-Clinical Porcine Study  Mutagenesis Improbable 98% (mean) Giordano et al. Nat Med 1996;2:(5):534  Very Favorable Phase 1/2 Clinical Study – AGENT Trial Manufacturing Cost 87% (median) Grines et al. Circulation 2002;105:1291 20
  • Generx® FGF-4 Gene  Regulates angiogenesis  Signal peptide – secreted FGF protein  Binds to extracellular matrix proteins  Abundant FGF-4 receptors found in cardiac tissue  Upstream growth factor that can recruit and stimulate responses in downstream target cells 2013 Cardium Therapeutics, Inc.  Appears to require ischemia induced co-factors to augment the angiogenesis process 21
  • Generx Dose Response Bioactivity Assay Visualization of the Angiogenic Process by Endothelial Tube Formation 1ng/mL 2ng/mL 4ng/mL 8ng/mL Representative Images (T=13.5 days) of rhFGF-4 stimulation of angiogenic networks in the Essen BioScience HUVEC Tube Formation Assay. E, 1ng/mL rhFGF-4 induced HUVEC clustering as well as a small amount of tube formation. F, 2ng/mL rhFGF-4 induced clusters and tube formation. G, 4ng/mL rhFGF-4 initiated HUVEC differentiation into longer tubes and more complex networks, as observed by the increase in branching. H, 8ng/mL rhFGF-4 stimulate significant tube and network formation. 2013 Cardium Therapeutics, Inc. 22
  • Generx® Understanding the Beauty of Cardiac Physiology Microvascular Pathways When infused into the coronary arteries using a non-surgical cardiac catheter, the 2013 Cardium Therapeutics, Inc. Generx product candidate travels through the coronary microvascular circulation into the small caliber capillaries where it is believed to be taken up by the myocardium. Colored magnification: x3000 at 6x7cm size. 23
  • Generx [Ad5FGF-4] Proprietary Intracoronary Administration of DNA-Based Cardiovascular Growth Factor Therapeutic  Non-surgical delivery by intracoronary administration by interventional cardiologist during an angiogram procedure 2013 Cardium Therapeutics, Inc.  Utilizes standard balloon catheter which can be easily integrated into diagnostic angiogram procedures or with other percutaneous coronary interventions  New induced transient ischemia / reperfusion techniques are designed to enhance DNA uptake and expression in the heart  40% administered to right coronary circulation and 60% to left coronary circulation 24
  • Generx® [Ad5FGF-4] Catheter-Based Enhanced Angiogenic Intracoronary Delivery Microvascular Circulation 2013 Cardium Therapeutics, Inc. 25
  • The Therapeutic Process of Cardiac Microvascular Angiogenesis Generx has been evaluated in studies of over 650 patients (including 450 Generx-treated patients) in four multi-center, double-blind, placebo-controlled SPECT Imaging clinical studies at 100 medical centers. Generx is the most clinically advanced DNA-based cardiovascular angiogenic growth factor therapeutic in the world. One-Time Treatment DNA-Based Delivery 2013 Cardium Therapeutics, Inc. Generx [Ad5FGF-4] (alferminogene tadenovec) Angiogenic Response AGENT-2 - Representative Generx-treated patient: 77% improvement in cardiac perfusion at 8 weeks equivalent to bypass surgery and PCI (angioplasty/stenting) at one year. 26
  • AGENT 2: Primary Endpoint SPECT Imaging Angiogenic Mechanism of Action Study Change in Reversible Perfusion Defect 8 Weeks Mean Reduction in RPDS (%) 6 5 4 3 2 p=0.14 1 p<0.05* 2013 Cardium Therapeutics, Inc. 0 Placebo 10e10 vp n=17/16 n=35 * Excludes one extreme placebo outlier 27
  • Generx® [Ad5FGF-4] Clinical Studies Clinical Number Region / Patient Clinical Year Study Name Study Patients County Status Endpoint Phase Recruited Phase 1/2 Class 2 – 3 Exercise 1999 AGENT-1 U.S. Dose finding 79 Angina Treadmill Time & safety Phase 2a 9% Reversible AGENT-2 Mechanism SPECT 2001 North America Reperfusion 52 of Action Imaging Defect Study AGENT-3 Class 2 – 4 Exercise 2004 North America Phase 2b/3 300 Angina Treadmill Time Western Class 2 – 4 Exercise 2004 AGENT-4 Europe & Phase 2b/3 252 Angina Treadmill Time South America Exercise Class 3 – 4 Treadmill Time 2013 Cardium Therapeutics, Inc. U.S. Beta 2008 AWARE U.S. Phase 3 Angina (Time to ST Tested Segment Depression) Phase 3 Russian 9% Reversible SPECT 2011 ASPIRE Registration 100 Federation Perfusion Defect Imaging Study TOTAL 783 28
  • Generx® Patient Pioneers Marilyn L. was a trial participant in the AGENT-3 clinical trial. She received a one-time treatment of 2013 Cardium Therapeutics, Inc. Generx, our DNA-based angiogenic product candidate for patients with recurrent angina due to coronary artery disease. 29
  • Generx® Key Peer-Reviewed Scientific & Medical Journals 2013 Cardium Therapeutics, Inc. Pre-Clinical AGENT-1 AGENT-2 Nature Circulation Journal of American Medicine (American Heart College of Cardiology Association Journal) 30
  • Generx® AGENT 3 & 4 Summary Research “We found a significant, gender- specific beneficial effect of Ad5FGF-4 on total ETT time, time to 1 mm ST-segment depression, time to angina and CCS Class in women. This is the first clinical report of a gender difference in response to cardiac angiogenic therapy.” “The potential importance of the observed gender-specific angiogenic response on the clinical treatment of refractory 2013 Cardium Therapeutics, Inc. angina is substantial and deserves further investigation.” JACC September 11, 2007 31
  • GENERX AGENT-2 PHASE 2A STUDY CLINICAL EFFICACY USING SPECT 77% Improvement AGENT-2 Journal of 2013 Cardium Therapeutics, Inc. American College of Cardiology Generx-Treated Patient Demonstrating Enhanced Cardiac Perfusion (n=52 / 88% men) 32
  • AGENT 2 - Comparison of SPECT Results to Revascularization and Medical Therapy Coronary Generx AGENT-2 Medical Parameter Revascular- Therapy ization Placebo 1x1010 vp Number 83 206 17 35 of Patients Age 66 11 68 10 57 9 59 8 Stress defect 18 11 16 10 20 8 20 9 extent (%) 2013 Cardium Therapeutics, Inc. Reduction of reversible -5 12 -0.8 7 -0.8 6 -4 6 defect (%) From Berman DS, et al. J of Nuclear Cardiol, 2001; 4:428-437 33
  • Generx AGENT 3 & 4 Clinical Studies Clinical Efficacy Using ETT Pooled-Analysis: Protocol-Specified Gender-Based Subgroup 12 weeks 6 months Women n=76 Placebo 109 vp 1010 vp Placebo 109 vp 1010 vp Exercise -4 60* 69* 7 75* 83* Duration (seconds percentage ) (-1%) (16%) (23%) (2%) (20%) (28%) 50 111 86 55 157* 94 Angina Onset (seconds percentage ) 2013 Cardium Therapeutics, Inc. (26%) (52%) (46%) (28%) (73%) (48%) Time to 1mm ST 13 50 63* 14 59* 86* Segment  (seconds percentage ) (4%) (16%) (27%) (5%) (19%) (36%) * < 0.05 34
  • AGENT 3/4 Clinical Studies: Concordance of Results from Prespecified Pooled Analysis of Gender-Based Subgroup Generx Ad5FGF-4 Women Time Point n=76 1x109 vp 1x1010 vp 12 Weeks p=0.032 p=0.002 ETT Duration 6 Months p=0.042 p=0.009 12 Weeks NS (0.216) p=0.031 Time to ECG Ischemia 6 Months p=0.036 p=0.011 12 Weeks NS (0.146) NS (0.125) Time to Angina 6 Months p=0.003 NS (0.094) 2013 Cardium Therapeutics, Inc. 12 Weeks NS (0.222) p=0.014 CCS Class Improvement 6 Months NS (0.341) p=0.042 12 Months p=0.038 p=0.006 NS=Not Significant 35
  • Effect of Chronic Angina Treatment with Ranexa and Single Intracoronary Administration of Generx (Ad5FGF-4) on ETT Duration at 12 Weeks (Difference from Placebo) 100 * ETT * P > 0.05 vs. placebo Mean change from Baseline (sec) 75 Generx 50 One Time Non-Surgical Angiogenic Therapy * 2013 Cardium Therapeutics, Inc. 25 Ranexa Chronic Anti-Anginal Drug 1000 mg Daily 0 Baseline ETT (sec): 300 Baseline ETT (sec): 470 % increase + 25% % increase + 5% (n = 30) (n = 255) 36
  • Beneficial Effects of Natural Disease-Induced Collateral Vessels 10-Year Follow-up in Patients with Coronary Heart Disease % CARDIAC DEATHS: Cumulative Survival Rate 10 year follow-up (n = 845) High Flow: 5 (2%) Deaths Low Flow: 37 (6%) Deaths (low collateral flow) 2013 Cardium Therapeutics, Inc. 67% ↓ (high collateral flow) Cardiac Deaths Time of Follow-up (months) From Meier et al. Circulation 2007; 116:975-83. 37
  • Generx®: Current Global Clinical Study Status International Markets U.S. Market Elements (Initially Russian Federation) (AWARE) (ASPIRE) Generx® [Ad5FGF-4] CardioNovo [Ad5FGF-4] Product (alferminogene tadenovec) (alferminogene tadenovec) FDA Clearance Phase 3 RHA Cleared Phase 3 / Clinical Status (with Fast Track Status) Registration Study 100 Men & Women 300 Women Multi-Center, Multi-Center, Randomized, Clinical Study Population Randomized, Placebo- Controlled Parallel-Group Controlled Patient Population Patient Population Anti-Angina for Refractory Myocardial Ischemia as a Patients who are not Optimal Treatment Option for Patients Proposed Medical Indication Candidates for Angioplasty / Considering Angioplasty / Stents & Bypass Surgery Stents & Bypass Surgery 2013 Cardium Therapeutics, Inc. Improvement in Reversible Improvement in Exercise Clinical Endpoint Time Based on Treadmill Perfusion Deficit Based on SPECT Imaging Pending Completion Clinical Study Status Initiated 2012 of International Studies 38
  • Clinical Efficacy Measures ETT SPECT 2013 Cardium Therapeutics, Inc. Exercise Treadmill Single Photon Emission Computed Stress Test Tomography Stress Test [United States Efficacy Measure] [Russian Federation Efficacy Measure] 39
  •  2013 Cardium Therapeutics, Inc.40 Therapeutic Comparison
  • Potential Therapeutic Positioning: Generx® / Cardionovo® (PTCA) Percutaneous Traditional Transluminal Drug Coronary Therapy Angioplasty & Stents Coronary Artery Disease Generx® (CABG) Non-Surgical 2013 Cardium Therapeutics, Inc. Coronary DNA-Based Artery Bypass Angiogenic Surgery Therapy 41
  • Potential Generx® [Ad5FGF-4] Medical Indications Based on Clinical Study Design  Patients with Cardiac Microvascular  Patients who have recurrent ischemic Insufficiency (CMI) with myocardial episodes under observation during or ischemia and stable angina pectoris after an acute myocardial infarction due to coronary artery disease  Patients with ischemic heart disease  Patients with stable angina pectoris who who desire or need revascularization have already had coronary bypass surgery but do not have access to coronary but have persistent angina bypass surgery or angioplasty  Patients who have had angioplasty  Patients who would benefit from or stenting but who continue to have revascularization (as above) but who symptoms of myocardial ischemia are at high risk for invasive procedures  Patients who are undergoing angioplasty or who do not want invasive procedures in whom revascularization is judged to be incomplete  Patients undergoing cardiac catheterization at a facility that does  Patients who are undergoing angioplasty not perform angioplasty who need with at risk myocardium downstream revascularization 2013 Cardium Therapeutics, Inc. from a coronary stenosis that can not be adequately dilated  Patients undergoing routine diagnostic cardiac catheterization for coronary artery  Patients who have evidence of silent disease who have any of the indications ischemia, as indicated by intermittent above. Generx may obviate the need for electrocardiographic changes during subsequent referral for bypass surgery or ambulatory monitoring, or ventricular for angioplasty contraction abnormalities during stress. Silent ischemia is a risk factor for subsequent major cardiac events 42
  • Generx® Potential Economic Opportunity Target Revenue per Dose Unit Volume Opportunity per Level I Level II Level III Economic Region $2,000 / dose $3,000 / dose $4,000 / dose 50,000 doses $100 Million $150 Million $200 Million 100,000 doses $200 Million $300 Million $400 Million 150,000 doses $300 Million $450 Million $600 Million 2013 Cardium Therapeutics, Inc. 200,000 doses $400 Million $600 Million $800 Million 43
  •  2013 Cardium Therapeutics, Inc.  2013 Cardium Therapeutics, Inc. 44