C A R T-Cell

C O R P O R A T E
P R E S E N T A T I O N
The Cell Therapy Company
Clinical Stage Technology Platforms Targeting
Cardiovascular Diseases and Cancer
Leuven, March 21, 2015
Dr. Peter De Waele, VP R&D
N Y S E
C A R D
E U R O N E X T
B R U S S E L S
A N D
P A R I S :
IMPORTANT NOTICE
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from those in the forward-looking statements, including future revenues or performance; capital expenditure; financing needs; timely submission and approval of
anticipated regulatory filings; the successful initiation and completion of required Phase III studies; additional clinical results validating the use of adult autologous stem
cells to treat heart failure; satisfaction of regulatory and other requirements; and actions of regulatory bodies and other governmental authorities. As a result, of these
factors investors and prospective investors are cautioned not to rely on any forward-looking statements. Cardio3 disclaims any intention or obligation to update or review
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C3BS-CQR-1, C-Cure®, C-Cath, Cardio3 BioSciences and the Cardio3 BioSciences and C-Cath logos are trademarks or registered trademarks of Cardio3 BioSciences
SA, in Belgium, other countries, or both.
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CARDIO3 BIOSCIENCES PLATFORMS
Technology platforms supported by world-class
scientific research
•
•
Cardiopoiesis platform
CAR T-Cell platform
Invented at Mayo Clinic
A novel technology to treat heart failure
Invented at Dartmouth College
A unique approach to cancer
immunotherapy
Cardiovascular
Oncology
Congestive Ischemic Heart Failure
Congestive Non-Ischemic Heart
Failure
•
•
•
•
•
Acute Myeloblastic Lymphoma (AML)
Multiple Myeloma (MM)
Prostate
Ovarian
...
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CARDIO3 PIPELINE
CAR T-Cell
C-Cure®
Products
Indication
Preclinical
Phase I
Phase II
Phase III
Status / Milestones
Ischemic Heart Failure – CHART-1
• End of Enrolment; Mar 2015
• Futility analysis; Apr 2015
• Full data readout; Q2 2016
Ischemic Heart Failure – CHART-2
• Start of enrolment; Q3 2015
• End of enrolment; End 2016
• Full data readout; End 2017
Non-Ischemic Heart
Failure
AML & MM
• Start of enrolment; Q1 2015
• Interim data set; Q2-Q4 2015
• Full data readout; Mid-2016
Other liquid
tumors
• Target identification 2015
• Start Phase IIb; 2016
Solid tumors
• Target identification 2015
• Start Phase IIb; 2016
… and preferred access to all technologies developed
by Mayo Clinic Center for Regenerative Therapies
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THE CARDIOPOIESIS
PLATFORM
C-Cure – An Autologous Cell Therapy Targeting Heart Failure
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BRINGING REPROGRAMED PRECURSOR CARDIAC
CELLS TO THE DISEASED TISSUES
Cardiac
Regeneration
Cardiac Progenitor
cells are injected
back into the heart
using C-Cathez® and
terminally
differentiate
Bone
marrow
drawn from
the patient
Unique reprogramming technology1
Stem cells are
selected and
expanded
1. Behfar et al., “Cardiopoeitic programming of embryoinic stem cells for tumor-free heart
Stem cells are differentiated towards the
cardiac lineage to become cardiopoietic cells,
through the use of a proprietary combination of
proteins and cytokines
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COMPELLING PHASE II DATA DEMONSTRATES
HEALING OF HEART FAILURE
•
Statistically and clinically significant increase in cardiac function (ejection fraction)
(p<0.0001)1
•
Statistically and clinically significant improvement in cardiac structure (end systolic
volume (p<0.001)1
•
Statistically and clinically significant improvement in exercise capacity (6 minute walk
distance test) (p<0.01)1
“…This improvement in ejection fraction is dramatic, particularly given
the duration between the ischemic injury and cell therapy. It compares
favourably with our most potent therapies in heart failure.” 2
Professor Charles E. Murry, MD, PhD, University of Washington
Director at the Center for Cardiovascular Biology; Co-Director, ISCRM
1: Bartunek, J., et al., Cardiopoietic stem cell therapy in heart failure The C-CURE multicenter randomized trial with lineage-specified biologics.
J Am Coll Cardiol, 2013.
2: Murry CE, Cardiopoietry in Motion: Primed Mesenchymal Stem Cells for Ischemic Cardiomyopathy. J Am Coll Cardiol, 2013.
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C-CURE, A CLINICALLY VALIDATED BREAKTHROUGH
THERAPY FOR THE TREATMENT OF HEART FAILURE
Large Market,
Unmet Need
Validated
Science
Advanced
Clinical
Development
•
Heart failure is the leading cause of hospitalization
in patients over age of 65
•
1 million EU and US patients with potential to benefit
from C-Cure treatment
•
Multi billion dollar market opportunity based on
patient population
•
C-Cure phase II data published in JACC:
Statistically and clinically significant
improvement in Ejection Fraction, ESV, EDV, 6-min
walk test
•
Ongoing Pivotal Phase III trials in Europe, Israel
and U.S.
•
Interim data expected April 2015
•
Full data set from European trial in Q2 2016
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CAR T-CELL
PORTFOLIO FOR
ONCOLOGY
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A NEW ERA OF IMMUNO-ONCOLOGY HAS
ARRIVED
Cytotoxics
1965
Combination
chemotherapy
ALL
CAR*-T cells:
Monoclonal Abs
CAR
T cells
the cutting edge
in oncology
Small Molecules
2001
Imatinib
Gleevec
CML
Bcr-abl
2006
2011
2014
2015
Trastuzumab
Herceptin
Ipilumumab
Yervoy
CAR19
NKG2D
Adjuvant Breast
Metastatic
Melanoma
risk reduct. 52%
OS 1y: 25% to 46%
ALL & CLL
RR at 1m: 90%
OS 6m: 68%
MM & AML
100% survival
in precl model
90% CR
OS 5y: 31% to 59%
* CAR: Chimeric Antigen Receptor
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HOW DOES CAR-T CELL THERAPY WORK FOR
THE PATIENT
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CARDIO3 BIOSCIENCES’ CAR-T CELL TECHNOLOGY
Classical CAR construct
C3BS CAR construct
• Uses scFv derived from antibodies
• Uses NK cell receptors; no need for
antibodies
• One CAR construct targets one tumor
• May not be suitable for repeated injections
• Mostly autologous
• Highly crowded space
• One CAR construct targets multiple tumors
• Suitable for repeated injections
• Autologous and possibly allogeneic
• Unique signaling and strong IP position
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CARDIO3 BIOSCIENCES CAR-TCELL PIPELINE
Pipeline Development
CAR-NKG2D
CAR-NKp30
CAR-B7H6
Allogeneic platform (TIM*)
*TIM: TCR Inhibitory Molecule
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CAR-NKp30 and CAR-B7H6 Overview
•
Both receptor based and antibody based CARs
•
In vitro and in vivo POC obtained
•
In preclinical development
•
Potential for use against ovarian cancer, gastrointestinal stromal tumors
(GIST), breast cancer, lymphoma, leukemias, sarcomas, prostate cancer
•
Strong IP position
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ALLOGENEIC CAR-T CELL PLATFORM
•
Based on co-expression of CAR molecules and TCR Inhibitory Molecules (TIMs) from
same retrovirus DNA
•
TIMs inhibit TCR expression and/or dysfunction TCR signaling, resulting in loss of capacity
of engineered T-cell to recognize allogenic HLAs and to generate GvHD reaction
•
Cardio3 allogeneic platform uses T-Cells from healthy donors and generates “off-the-shelf”
CAR T-Cells to potentially treat hundreds or thousands of cancer patients
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A UNIQUE CAR-T CELL PORTFOLIO FOR THE
CANCER TREATMENT
• Not another CD19 CAR
• No need for antibody platform because it uses natural NK receptors
• Potential to target varieties of tumor types including liquid and solid
tumors
• Pipeline with multiple products; lead product currently in Phase I
• Allogeneic T-Cell platform allows manufacturing of “off-the-shelf”
products
• Strong and differentiated IP position
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CURRENT CAR-T COMPETITIVE LANDSCAPE
Player/partner
Academic
coll
Autologous
/Allogeneic
Lead
product
Clinical
phase
Main
indication
Novartis
Upenn
Auto
CAR-CD19
Phase I
CLL/ALL
✓
Servier/Cellectis
UCL
Allo
CAR-CD19
No
CLL/ALL
✗
Pfizer/Cellectis
UCL
Allo
No
No
No
✗
Celgene/bluebird
Baylor Col
Auto
CAR-CD19
No
CLL/ALL
✗
Juno
MSKC &
FHCRC
Auto
CAR-CD19
Phase I/II
CLL/ALL/
NCI
Auto
Kite
NHL*
CAR-CD19
Phase I/IIa
B-Cell
malignancies
Glioblastoma
& EGFRVIII
Bellicum Pharma
None
Auto
CD19
No
CLL/ALL
Cardio3 Biosciences
Dartmouth
Univ
Auto
CAR-NKG2D
Phase I
AML/MM
*NHL: Non-Hodgkin Lymphoma
Clinical PoC
✓
✓
✗
✗
✗
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Financial
Shareholder
Information
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ANTICIPATED CLINICAL MILESTONES
CAR T-Cell
C-CURE
H1 2015
End of
Enrolment
CHART-1
H2 2015
Injection of last
CHART-1
patient
Futility
Analysis
H1 2016
H2 2016
Readout CHART-1
full data set
End of
Enrolment
CHART-2
Initiation of
CHART-2 in US
NKG2D Phase I – interim readouts after each cohort
Recruitment
of 1st patient
Results of
first cohort
Results of
second cohort
Results of
third cohort
Readout NKG2D
full data set
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SHAREHOLDERS AND FUNDING HISTORY
Shareholder structure as per March 2, 2015
Tolefi SA
Medisun
28,90%
SRIW
PMV
45,18%
Founders & Mgt
7,24%
Mayo Foundation for Education and
Research
Celdara
5,10%
1,19%
2,69%
4,25%
Others
5,46%
• €146M raised since inception
• Public company since July 2013 (Euronext Brussels & Paris)
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CORPORATE HIGHLIGHTS
• Year end 2014 financials released on March 26
• Solid performance since IPO
– +277% since July 5 2013
– Average daily volume in 2015; 36Kshares/day, or €1.5M/day
• Multiple near term catalysts, culminating with NKG2D and
CHART-1 efficacy read-out in Q2 2016
• Strong focus on US investors for further capital raising
– US is main market place of C-Cure and CAR-T technologies
– Ongoing US IR and communication strategy
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