Francisco F. Aviles, MD, PhD Hospital General Universitario (PI)Gregorio Marañon Madrid, Spain Emerson C. Perin, MD, PhDTexas Heart Institute (Co-PI)Houston, TX, USA Francisco F. Aviles, MD, PhD Hospital General Universitario (PI)Gregorio Marañon Madrid, Spain Emerson C. Perin, MD, PhDTexas Heart Institute (Co-PI)Houston, TX, USA The Precise Trial 6 Month Preliminary Results The Precise Trial 6 Month Preliminary Results Sponsor: Cytori Therapeutics

Study Sites and Investigators Madrid, Spain (22) Francisco Fernandez Aviles, MD, PhD Pedro Luis Sanchez, MD, PhD Ricardo Sanz, MD Rotterdam, Netherlands (3) H.J. (Eric) Duckers, MD, PhD Copenhagen, Denmark (1) Jens Kastrup, MD Utrecht, Netherlands(1) Steven Chameleau, MD, PhD Madrid, Spain (22) Francisco Fernandez Aviles, MD, PhD Pedro Luis Sanchez, MD, PhD Ricardo Sanz, MD Rotterdam, Netherlands (3) H.J. (Eric) Duckers, MD, PhD Copenhagen, Denmark (1) Jens Kastrup, MD Utrecht, Netherlands(1) Steven Chameleau, MD, PhD

27 pts 3:1 randomization Double blind 27 pts 3:1 randomization Double blind LVA/ NOGA Cell Injection/ Placebo Injection LVA/ NOGA Cell Injection/ Placebo Injection 6 Month Assessment - CCS - SPECT - NHYA - Echo - MRI - MVO 2 6 Month Assessment - CCS - SPECT - NHYA - Echo - MRI - MVO 2 Early Assessments Control Group Placebo 6 pts Control Group Placebo 6 pts Liposuction 300ml 2 hrs cell processing Liposuction 300ml 2 hrs cell processing Study Design 12 Month Assessment 18 Month Assessment Long term follow up to 36 mo. Core lab analysis: - Echo - SPECT - MRI - Holter - NOGA Core lab analysis: - Echo - SPECT - MRI - Holter - NOGA

Inclusion Criteria CCS II-IV and/or NYHA II-III LVEF  45% (Echo) Presence of reversibility by SPECT CAD not amenable to surgical or percutaneous revascularization Hemodynamic stability Ability to walk on a treadmill Ability to undergo liposuction Signed informed consent CCS II-IV and/or NYHA II-III LVEF  45% (Echo) Presence of reversibility by SPECT CAD not amenable to surgical or percutaneous revascularization Hemodynamic stability Ability to walk on a treadmill Ability to undergo liposuction Signed informed consent

Exclusion Criteria Age 75 years Presence of Atrial Fibrillation Presence of LV thrombus Presence of severe valvular heart disease Bleeding diathesis History of malignancy in the last 5 years Age 75 years Presence of Atrial Fibrillation Presence of LV thrombus Presence of severe valvular heart disease Bleeding diathesis History of malignancy in the last 5 years

Exclusion Criteria Presence of ACS or MI in the past 30 days LV wall thickness <8 mm at the target area for cell injection History of sudden cardiac death or sustained VT and/or VF unless (1) within 24 hrs of an acute MI; or, (2) the Subject has an AICD Presence of ACS or MI in the past 30 days LV wall thickness <8 mm at the target area for cell injection History of sudden cardiac death or sustained VT and/or VF unless (1) within 24 hrs of an acute MI; or, (2) the Subject has an AICD

Targeting the Area for Stem Cell Injection Anatomical( angiogram) Perfusion (SPECT) Perfusion (SPECT) Viability/ hibernation (EMM) Viability/ hibernation (EMM)

Transendocardial Injections Total of 15 injections Volume of 0.2 cc Targeted to ischemic myocardium Injection Criteria:  Unipolar voltage  6.9mV  Loop Stability  4  PVC upon needle insertion Total of 15 injections Volume of 0.2 cc Targeted to ischemic myocardium Injection Criteria:  Unipolar voltage  6.9mV  Loop Stability  4  PVC upon needle insertion UniV LLS

Demographics and Baseline Characteristics Control (n=6) Treatment (n=21) Age55.7± ±6.3 Male4 (66.7%)17 (81%) Female2 (33.3%)4 (19%) Body Mass Index (kg/m 2 )30.8 ± ±4.8 Diabetes5 (83.3%)12 (57.1%) HTN5 (83.3%)17 (81.0%) Smoking3 (50.0%)9 (42.9%) Prior MI4 (66.7%)19 (90.5%) Prior PCI5 (83.3%)21 (100.0%)

Safety Data Control (n=6) Treatment (n=21) Liposuction related complications00 LV Mapping-induced VT00 Holter: Atrial arrhythmias00 Sustained VT00 Pericardial Effusion00 Cerebrovascular event: TIA01 CVA00 Angina Exacerbation12 Myocardial Infarction: STEMI00 NSTEMI01 Heart Failure Exacerbation01 Liposuction related complications00 LV Mapping-induced VT00 Holter: Atrial arrhythmias00 Sustained VT00 Pericardial Effusion00 Cerebrovascular event: TIA01 CVA00 Angina Exacerbation12 Myocardial Infarction: STEMI00 NSTEMI01 Heart Failure Exacerbation01

Safety Data Deaths Cardiac Deaths: < 30 d 0 0 > 30 d < 180 d 0 1 > 180 d 2 0 Cardiac Deaths: < 30 d 0 0 > 30 d < 180 d 0 1 > 180 d 2 0 ControlTreatment Non-Cardiac Deaths: < 30 d 0 0 > 30 d < 180 d 0 1 > 180 d 0 1 Non-Cardiac Deaths: < 30 d 0 0 > 30 d < 180 d 0 1 > 180 d 0 1 Total Deaths: 2 3

Symptoms NYHA and CCS Class

2D Echocardiography Data 6 Months Baseline6 monthsp WMSI Control1.3±0.11.3±0.2ns Treatment1.7±0.21.5±0.2ns EDV Control165.6± ±34.5ns Treatment148± ±11.5ns ESV Control100.6± ±23.3ns Treatment86.4± ±9.8ns EF Control42.8± ±5.5ns Treatment42.4± ±3.9ns

LV Ejection Fraction 2D Echo

Magnetic Resonance Imaging 6 Months LVEF Infarct Size

Magnetic Resonance Imaging Change in Infarct Size at 6 Months Delayed Hyperenhancement

SPECT 6 Months * No statistical significant difference between groups and within each group.

Injection 6 Months UnipolarVoltage (viable/sca r) LinearLocalShortening (mechanical dysfunction) LinearLocalShortening NOGA

Injection 6 Months UnipolarVoltage (viable/sca r) LinearLocalShortening (mechanical dysfunction) LinearLocalShortening NOGA

Metabolic Equivalents (METS) 6 Months

Clinical Application of VO 2 Max VO 2 Max reflects the degree of the impairment in: Ventricular function (pumping capacity), Vascular function (O 2 delivery), Skeletal muscle metabolic capacity (O 2 utilization). Pts with VO 2 Max ≤ 14 ml kg -1 min -1 had a 1 year survival rate of only 47%. VO 2 Max reflects the degree of the impairment in: Ventricular function (pumping capacity), Vascular function (O 2 delivery), Skeletal muscle metabolic capacity (O 2 utilization). Pts with VO 2 Max ≤ 14 ml kg -1 min -1 had a 1 year survival rate of only 47%. Mancini et al, Circulation 1991

Baseline peak VO2 of 18 ml/kg/min. Follow-up for 17 months Better survival in patients with improvement in MVO2. LVEF improvement did not predict prognosis. Baseline peak VO2 of 18 ml/kg/min. Follow-up for 17 months Better survival in patients with improvement in MVO2. LVEF improvement did not predict prognosis. Florea et al, Eur Heart J, 2000 Improvement in Peak VO 2 is Associated with Improved Prognosis Even in patients with moderate functional compromise MVO2 was a better prognostic marker

Peak Oxygen Consumption (VO 2 Max) 6 Months

VO 2 Max Preliminary 18 Month Data

Conclusions This is the first in man transendocardial injection of autologous adipose derived stem cells (ADRCs) in patients with chronic ischemic heart disease. Autologous ADRCs harvesting and injection was safe in these severely compromised patients. There were no peri- procedural complications and there was no evidence of cell therapy related adverse events (arrhythmia, MACCE). Improvement in functional capacity as demonstrated by METS and VO 2 Max and a decrease of Infarct size as measured by MRI in ADRCs treated patients suggest potential efficacy which should be explored in a larger trial. This is the first in man transendocardial injection of autologous adipose derived stem cells (ADRCs) in patients with chronic ischemic heart disease. Autologous ADRCs harvesting and injection was safe in these severely compromised patients. There were no peri- procedural complications and there was no evidence of cell therapy related adverse events (arrhythmia, MACCE). Improvement in functional capacity as demonstrated by METS and VO 2 Max and a decrease of Infarct size as measured by MRI in ADRCs treated patients suggest potential efficacy which should be explored in a larger trial.