2. Safe Harbor
This presentation may contain certain ‘forward-looking statements’. All statements,
other than statements of historical fact, that address activities, events or
developments that we intend, expect, project, believe or anticipate will or may
occur in the future are forward-looking statements. Such statements are based upon
certain assumptions and assessments made by our management in light of their
experience and their perception of historical trends, current conditions, expected
future developments and other factors they believe to be appropriate.
The forward-looking statements included in this presentation are also subject to a
number of material risks and uncertainties. We caution investors not to place undue
reliance on the forward-looking statements contained in this presentation.
We would advise reading our annual report filed with the United States Securities
and Exchange Commission on Form 10-K for a more detailed description of these
risks.
Cell Therapy
3. Our Company Mission
To improve the quality and length of life
by providing innovative cell therapy for patients
CYTORI - The Leader in Cell Therapy.
Cell Therapy
5. Pathway to Market Access
Clinical Data / Trials
Indications for Use
Reimbursement
Translational Studies
Growing Data on Fistulas
> 100 wound pts treated CE Mark Claims for
High success rate fistula - 2010
Most difficult cases Healthcare economic
Expansion of claims for evaluation in process
wounds in process Innovation funding
Specific DRGs over time
Cell Therapy
6. Pioneers: Translational Medicine
North Tees & Hartlepool NHS Foundation Trust
is looking for scientific appreciation through peer
review and has not yet confirmed a significant
benefit in a study that Involved sufficient
numbers of patients
Dr. Borowski
North Tees, UK
7. ~ 4,000 Patients Treated
Cardiovascular
Soft Tissue
F O C U S
Cell Therapy
9. Chronic Myocardial Ischemia
Change in Max Volume of Oxygen (MV02) from Baseline to 6 & 18 months
The Precise Trial
20.0
19.0
P<0.05 P<0.05
18.0
17.2 17.1
16.0 16.6
15.5 15.3
14.0 Transplant List
Baseline 6 Mos 18 Mos
ADRC’s
Standard of Care
Cell Therapy
10. Chronic Myocardial Ischemia
MVO2:significant change at 18 months
• MVO2 correlates to improved survival
• MVO2 ≤ 14 = 47% 1 yr survival rate
METS: significant change at 18 months
Infarct size: 8.2% change at 6 months
Cytori procedure safe and feasible through
18-months
Lower cardiac mortality rate:
• At avg. follow up of 28 months:
- 2/6 placebo
- 1/21 treated
Next Steps:
Applying for European Approval
* On-site Review completed in May
Initiating US IDE Clinical Trial: ATHENA
* Successful pre-IDE meeting with
FDA
Cell Therapy
11. Chronic Heart Failure
What Really Matters For Patients
Improved Reduced
Improved
Heart Mortality
Activity
Condition
Cell Therapy
12. “No Option” Heart Failure
Estimated Market Size for No Option Patients in Europe
Region # of Patients (Incidence) # of Patients (10-Yr
Prevalence)
United Kingdom 40,000 400,000
Italy 40,000 400,000
Germany 55,000 550,000
France 40,000 400,000
Spain 30,000 300,000
Total G5 205,000 2,050,000
* Estimated price per treatment: $ 10,000
G5 Market
$ 20 Billion*
Cell Therapy
13. Acute Heart Attack
APOLLO TRIAL
• Prospective European Multicenter Trial
• Randomized (3:1)
• Double Blind
• Placebo controlled
• Blinded independent core labs
• Safety & Feasibility Trial
• n = 14 (4 placebo, 10 treated)
Eric Duckers, MD, PhD
Rotterdam, The Netherlands
Cell Therapy
14. The APOLLO trial
6 & 18 month follow-up
Percent of Left Ventricle Infarcted:
Infarct size normalized to ventricle size (%LVI) improved more in ADRC patients
compared to placebo control patients (late enhancement cMRI): +5,1% abs. and +59%
rel. improvement compared to placebo control, PTE)
change in rel.infarct size (I/LV) (matched pairs)
all pts baseline 6 mo
control
Tx
24,7% 24,7%
ADRC
Tx
31,6% 15,4%
all patients
p=NS matched pairs
Slides & Data provided by:
All MRI images were assessed by an independent, blinded core lab (CCL, Boston, MA) Eric Duckers, MD, PhD
15. The APOLLO trial
6 & 18 month follow-up
Perfusion defect: Reduction in perfusion defect in patients treated with ADRC
compared to placebo control patients (3,5-fold improvement)
as analyzed by MIBI SPECT (visual rest scores, PTE)
MIBI SPECT TSS change (matched pairs)
+253% +87%
improvement improvement
p=NS Slides & Data provided by
All SPECT images were assessed by an independent, blinded core lab (CCL, Boston, MA)
Eric Duckers, MD, PhD
16. The APOLLO trial
6 & 18 month follow-up
Perfusion defect in LAD territory:
Reduction in perfusion defect in patients treated with ADRC
compared to placebo patients (9,7-fold improvement in LAD perfusion
territory) as analyzed by MIBI SPECT (TSS scores)
MIBI SPECT TSS change (matched pairs)
+867% +800%
improvement improvement
p=NS
Slides & Data provided by:
All SPECT images were assessed by an independent, blinded core lab (CCL, Boston, MA) Duckers, MD, PhD
Eric
17. The APOLLO trial
6 & 18 month follow-up
Change in ESV
ESV was markedly reduced in ADRC patients as compared to placebo control patients
(as measured by 2D TTE, cMRI and SPECT, PTE)
change in ESV (cc, 2D TTE)
24,4 cc
improvement
(-72,2%)
Slides & Data provided by:
All TTE images were assessed by an independent, blinded core lab (CCL, Boston, MA) Eric Duckers, MD, PhD
18. The APOLLO trial
6 & 18 month follow-up
Change in EDV i.c.c. post-AMI adverse remodeling
EDV was significantly reduced in ADRC patients compared to placebo-control patients
(as measured by 2D TTE, cMRI and SPECT, PTE),
indicating a significant reduction of adverse post-AMI adverse cardiac remodeling
change in EDV (cc, 2D TTE)
39,1 cc
improvement
(-56,9%)
Slides & Data provided by:
All TTE images were assessed by an independent, blinded core lab (CCL, Boston, MA) Eric Duckers, MD, PhD
19. The APOLLO trial
Ventricular Tachyarrhythmias and Ventricular Extra Systoles
as manifestations of developing post-AMI Cardiomyopathy up to 18 mo
Placebo ADRC
P-value
(n=4) (n=9)
Ventricular TachyArrhythmia
patients w documented VT 2 / 4 (50%) 3 / 10 (30%) NS
total episodes of VT 11 5 < 0.05
average episodes/ patient 2.8 0.5 < 0.05
Placebo ADRC
P-value
(n=4) (n=9)
Premature Contractions (PVC)
patients w > 10 PVC/ hr 3 / 4 (75%) 0 / 10 (0%) < 0.05
total PVC / patient at 18 mo FU 1607 284 < 0.001
average PVC / 24 hr / patient 146 24 < 0.05
Continuous telemetric/ holter registration in first 6 days post AMI
48 hr holter registrations weekly in first month
24 hr holter registrations monthly in first 6 months
Analysis by Student-t- tests Slides & Data provided by:
All Holter registrations were assessed by an independent, blinded core lab
Post hoc analysis by Thoraxcenter/ MCL Eric Duckers, MD, PhD
20. The APOLLO trial
Ventricular ectopy in post-AMI patients
as manifestations of developing cardiomyopathy
cum. ventricular ectopy per 24 hr registration
P < 0.001
Weeks after AMI
Analysis by Student-t-test
All Holter registrations were assessed by an independent, blinded core lab Slides & Data provided by:
Post hoc analysis by Thoraxcenter/ MCL
Eric Duckers, MD, PhD
21. APOLLO: Summary
ADRCs are safe in the treatment of STEMI
No safety concerns
No new Major Adverse Cardiac Events
No Deaths
Efficacy
Concordant improvement in infarct and ischemia:
Mean reduction in Infarct Size is maintained to 18 months
Improvement in cardiac perfusion is maintained to 18 months
Long-term data indicates slowing progression toward heart failure
Positive impact on arrhythmia in cell-treatment patents
Cell Therapy
22. Acute Heart Attack
“We show if you protect the
muscle in the acute phase of MI
you will indeed have
sustained improvement”
Eric Duckers, MD, PhD
Rotterdam, The Netherlands
Cell Therapy
23. Acute Heart Attack
ADVANCE TRIAL
• European Pivotal Trial
• Prospective
• Randomized (2:2:1)
• Double Blind
• Placebo controlled
• Blinded independent core labs
• Up to 370 patients for STEMI
• Currently enrolling & treating
Eric Duckers, MD, PhD
Rotterdam, The Netherlands
Cell Therapy
24. Acute Myocardial Infarction
Estimated Market Size for AMI Patients in Europe
Annual Heart Attack Incidence (EU) 1.9 million
% STEMI (large heart attacks) 38%
Target Addressable Procedures 720,000
Estimated Price per Treatment $ 10,000
EU AMI Market
$ 7.2 Billion
Cell Therapy
25. Lumpectomy Reconstruction
RESTORE II TRIAL
• Prospective European Multicenter Trial
• ‚No Option‛ Partial Mastectomy patients
• 1 year primary follow up
• Blinded independent core labs
• 71 Patients treated
Eva Weiler-Mithoff, MD
Glasglow, United Kingdom
Cell Therapy
26. Lumpectomy Reconstruction
Clinical:
• Safe & Persistent Therapy
• 85% Investigator Satisfaction
• 75% Patient Satisfaction
• 36% (24/66) patients underwent 2nd procedure
MRI – independent core laboratory:
• High rate of improvement in breast shape
• High rate of improvement in defect shape
Eva Weiler-Mithoff, MD
Glasglow, United Kingdom
Cell Therapy
28. Lumpectomy Reconstruction
“The use of lipomodelling for reconstruction after breast cancer surgery has become a
common technique. However, in the radiation injured patient, repeat procedures are
often required. Cytori's Celution System supplements a fat graft with a patient's
own adipose-derived regenerative cells to improve graft take and help regenerate
damaged tissue. This minimally invasive treatment approach could reduce or
eliminate the practice of repeat procedures, leading to significant cost savings for the
NHS.”
Brian Winn
Head of Technology & Product Innovation
NHS National Innovation Centre
www.nic.nhs.uk
Cell Therapy
29. Breast Reconstruction
Estimated Market Size for Breast Reconstruction in Europe
Annual Breast Cancer Incidence - Europe 332,000
% Lumpectomy eligible ~70%
Target Addressable Market (Incidence) 230,000
Target Addressable Market (Prevalence) > 1,000,000
EU Lumpectomy Reconstruction Market: $ 3.7 Billion
* Estimated price per treatment: $ 3,000 (USD)
Cell Therapy
30. Progress Toward Market Access (EU)
Clinical Data / Trials
Indications for Use
Reimbursement
Soft Tissue / Breast Reconstruction
Chronic Heart Disease
Acute Heart
Cell Therapy
31. Market Access Today
Pre-Clinical /
Clinical Data
Indications for Use
Private Pay / Grants
Current Opportunities
• Aesthetics Market
• Translational Research Market
• StemSource Cell Banks
Cell Therapy
32. Market Access Today
• Revenue growth yr / yr
• Quarters remain lumpy
• Steady growth of Celution
installed base
• No annuity sales growth
• Shifting sales focus:
Soft Tissue Reconstruction
Current Opportunities
• Aesthetics Market
• Translational Research Market
• StemSource Cell Banks
Cell Therapy
33. Driving Toward Market Inflection Point
Clinical Data / Trials
Indications for Use
Reimbursement
REGENERATIVE MEDICINE MARKET
Market Inflection Point
Drive Consumable
Utilization
Efficiency of Sales & Service
Cell Therapy
34. EU Regulatory
STRATEGY
PART I: Tool Claims
PART II: Therapeutic Claims
CE Mark Process
Foundational Device: Approved 2007
Claims Expansion: Approved 2010
Breast Reconstruction
Breast Augmentation
Crohn’s Fistula
Claims Expansion: In Process
Chronic “No Option” Myocardial Ischemia
Pivotal Clinical Trial: In Process
ADVANCE: Acute Myocardial Infarction Cell Therapy
35. Japan Regulatory
STRATEGY
PART I: Tool Claims
PART II: Therapeutic Claims
Japan MHLW / PMDA
Application for Device Approval in process
Application for Breast Reconstruction in process
- based on Restore I & Restore II data
Various investigator led translational studies* including:
Radiation wounds
Incontinence
Fistula /wounds
* Translational studies in Japan require MHLW approval Cell Therapy
37. US Regulatory
US FDA in Process
MOST IMPORTANT PROCESS WITH FDA
US IDE Trial for Cardiovascular: ATHENA
Chronic Ischemia
pre-IDE meeting successful
File IDE in Fall ’11
Plan to begin enrollment in mid-2012
Ultimately FDA’s IDE – PMA process:
provides clinical trial data
specific indications for use
supports applications for reimbursement
Cell Therapy
38. US Regulatory
US FDA in Process
US HUD: Perry Rombergs Disease
Step 1: Humanitarian Use Designation
Currently Negotiating HUD with FDA
Step 2: Humanitarian Device Exemption
Small trial, reimbursement usually available
Clinical label in a soft tissue indication
Restricted indications for use / market
Orphan Indication
Cell Therapy
39. US Regulatory
US FDA in Process
• Multiple 510(k) apps pending / in process of submission
• These include various predicates / indications
• FDA status quo remains negative on 510(k) pathway
• We believe the pathway is appropriate
• 2 applications are currently under appeal
• Potential to utilize Circuit Courts
• Cost effective, efficient, independent
Cell Therapy
40. Patents: 35 Issued, 100+ Pending
North America/Europe Asia Emerging Markets
US: Korea: Australia:
CELUTION DEVICE (‘484) CELUTION DEVICE (‘995) CELUTION DEVICE (‘135)
CELUTION PLUS ADDITIVES (‘420) STEMSOURCE DEVICE (‘812) STEMSOURCE DEVICE (‘901)
CELUTION FOR CRS (‘488) CELUTION DEVICE (‘139) CELUTION FOR CARDIOVASCULAR (‘858)
STEMSOURCE DEVICE (‘115) CELUTION DEVICE WITH CENTRIFUGE OR
CELUTION FUTURE GENERATIONS (‘075) Singapore: FILTER (‘937)
CELUTION PLUS SENSORS FOR CLINICALLY CELUTION DEVICE & FUTURE
SAFE OUTPUT (‘670)
South Africa:
GENERATIONS (‘683)
CELUTION FOR BONE (‘043) CELUTION FOR CARDIOVASCULAR (‘446)
CELUTION FOR CARDIOVASCULAR
CELUTION OR CELGRAFT FOR SOFT TISSUE (‘590)
DEFECTS (‘684)
Mexico:
BEDSIDE COMPREHENSIVE CELUTION FUTURE GENERATIONS (‘348)
China: CELUTION FOR CARDIOVASCULAR (‘775)
DEVICE (‘059) CELUTION DEVICE (‘689)
CELUTION OUTPUT PLUS PROSTHETIC CELUTION FOR
FOR BONE RELATED DISORDERS (‘716)
Russia:
CARDIOVASCULAR (‘104) CELUTION FOR CARDIOVASCULAR (‘924)
CELLS PLUS FAT PLUS ADDITIVES (‘795)
CELLS PLUS FAT (‘672)
Japan: India:
CELUTION DEVICE (‘952) CELUTION DEVICE (‘706)
Europe: DEVICES FOR CELLS PLUS FAT CELUTION FUTURE GENERATIONS (‘529)
CELUTION FOR ACUTE (‘041) CELUTION DEVICE FOR TREATING WOUND
TUBULAR NECROSIS (‘834) CLINICALLY SAFE (‘556) HEALING (‘580)
Israel:
CELUTION DEVICE WITH CENTRIFUGE OR
FILTER (‘800)
*PATENTS ISSUED IN 2011 IN RED
Cell Therapy
41. Financial Information
Cash (Q2, 2011) $ 33 million
Additional cash post Q2 6 million
Shares Outstanding 52 million
Warrants (average price $ 3.80) 12 million
Options (vested; average price $5) 5 million
GE Loan (maturity 2013) $ 17 million
Operating cash loss average ~ $7 million / quarter over last 6 quarters
Trended higher over the past 2 quarters
Expect operating cash loss to move back down toward average 2H ’11
Actively reducing costs, narrowing focus, improving efficiency, investing
in our future
Additional partnership is a near term corporate goal
Cell Therapy
42. Strong Partners Supporting Growth of Business
Olympus Corporation (Japan): Manufacturing Joint Venture (2004)
• Co-design & manufacture next-generation Celution® One
• Available for ADVANCE heart attack trial
• Manufacturing expertise & service infrastructure
• Committed Partner: invested $55+mm
Green Hospital Supply (2007)
• Co-selling StemSource® Cell Banks in Asia
GE Healthcare (2008)
• Co-distribute Celution & StemSource in select countries
Astellas Pharmaceuticals (2010)
• Equity investment ($10 mm)
• Received right-of-first refusal for liver disease partnership
Future Partnerships Opportunities
• 10 Individual processes ongoing
• 6 distinct therapeutic areas
Cell Therapy
43. Many Near Term Value Drivers
• Chronic myocardial ischemia indications-for-use in Europe
• Celution One - CE Mark approval
• PureGraft approval in Japan
• Revenue growth for the full year 2011
Report of 18-month outcome data from APOLLO acute heart attack
trial
• Publish and Present complete RESTORE 2 trial 12-month data
• US FDA clearance or trial approval
• Design and prepare to begin ATHENA
• Growth in targeted emerging markets
• Establish a meaningful corporate partnership
43
Cell Therapy
