A Leader in Engineered Cell Therapy Treatments

C O R P O R A T E
P R E S E N T A T I O N
S T R I C T L Y
C O N F I D E N T I A L
A Leader in Engineered Cell Therapy Treatments
Clinical Platforms Targeting
Cardiovascular Disease and Oncology
June 2015
N Y S E
C Y A 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 :
DISCLAIMERS
Celyad SA (“Celyad”) has filed a registration statement (including a preliminary prospectus) with the U.S. Securities and
Exchange Commission, or SEC, for the offering to which this presentation relates. Before you invest, you should read the
preliminary prospectus in that registration statement and other documents Celyad has filed with the SEC for more
complete information about Celyad and this offering. You may get these documents for free by visiting EDGAR on the
SEC website at www.sec.gov. Alternatively, Celyad or any underwriter or any dealer participating in the offering will
arrange to send you the prospectus if you request it by contacting UBS Securities LLC, Attention: Prospectus Department,
299 Park Avenue, New York, NY 10171, telephone, (888) 827-7275.
Forward Looking Statements
These slides and the accompanying oral presentation contain forward ‐looking statements and information. The use of
words such as “may,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,”
“future,” “potential,” or “continue,” and other similar expressions are intended to identify forward looking statements.
For example, all statements we make regarding timely submission and approval of anticipated regulatory filings; the
successful initiation and completion of clinical trials, including Phase III clinical trials for C-Cure® and Phase I clinical trial
for CAR-NKG2D, additional clinical results validating the use of adult autologous stem cells to treat heart failure and CAR
T-cell autologous therapy to treat cancer; satisfaction of regulatory and other requirements; actions of regulatory bodies
and other governmental authorities; obtaining, maintaining and protecting intellectual property, our ability to enforce our
patents against infringers and defend our patent portfolio against challenges from third parties, competition from others
developing products for similar uses, our ability to manage operating expenses, and our ability to obtain additional funding
to support our business activities and establish and maintain strategic business alliances and new business initiatives.
All forward‐looking statements are based on estimates and assumptions by our management that, although we believe to
be reasonable, are inherently uncertain. All forward‐looking statements are subject to risks and uncertainties that may
cause actual results to differ materially from those that we expected. These statements are also subject to a number of
material risks and uncertainties that are described in the preliminary prospectus. Any forward ‐looking statement
speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward
looking statement, whether as a result of new information, future events or otherwise, except as required by law.
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CELYAD IN SUMMARY
A leader in engineered cell therapy treatments with clinical
programs in cardiovascular disease and oncology
•
Goal of becoming global leader in engineered cell therapies by building franchises in
multiple indications based on core expertise
•
Developing reprogramming technologies invented at Mayo Clinic and Dartmouth College
–
C-Cure: Phase III trial in ischemic heart failure in Europe and Israel, CHART-1
–
CAR T-cell technology: Enrolling patients in Phase I clinical trial in MM and AML at Dana Farber
Cancer Institute (Harvard Medical School) with lead product candidate, CAR-NKG2D
•
IP and product portfolio allowing possible targeting of other indications in cardiovascular
diseases and oncology
•
GMP production facilities
•
CHART-1 efficacy read-out expected Q2 – Q3 2016
•
Headquarters in Belgium, with subsidiaries in the U.S. and Asia
*As of 31 December 2014
3
CELYAD PLATFORMS
Technology platforms supported by scientific research
•
•
Cardiopoiesis platform
CAR T-Cell platform
Invented at Mayo Clinic, exclusively
licensed to Celyad
A technology to treat heart failure
Invented at Dartmouth College,
exclusively licensed to Celyad
An approach to cancer immunotherapy
Cardiovascular
Oncology
Ischemic Heart Failure
Other Potential Indications:
• Congestive Non-Ischemic Heart
Failure
•
•
•
Acute Myeloblastic Lymphoma (AML)
Multiple Myeloma (MM)
Other Potential Indications:
• Ovarian
4
CELYAD OPPORTUNITIES
CAR T-Cell
C-Cure®
Product
Pre-clinical
Phase I
Phase II
Ischemic HF– CHART-1 (Europe and IL)
Phase III
Status / Milestones
•Full data readout expected: Q2-Q3
2016
Ischemic HF– CHART-2 (US and Europe)
• Start of enrollment expected:
•2H 2015, pending FDA release of
existing clinical hold
AML & MM – US
•Interim data set expected: various
times
•Full data readout expected; Q3-2016
Solid and blood cancers
expressing NKG2D
ligands
Allogeneic
Platform
NKp30
B7H6
•Pre-clinical development
•Pre-clinical development
•Pre-clinical development
•Pre-clinical development
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THE CARDIOPOIESIS
PLATFORM
C-Cure – An Autologous Cell Therapy Targeting Ischemic Heart Failure
6
C-CURE THERAPY FOR THE TREATMENT OF HEART
FAILURE
Large Market,
Unmet Need
Validated
Science
Advanced
Clinical
Development
•
Cardiovascular diseases are leading cause of death
in the world in 2012
•
1 million primary HF-related hospitalizations annually
in the U.S. as of 2013
•
C-Cure Phase II data published in Journal of
American College of Cardiology:
improvement in Ejection Fraction, ESV, 6-min walk
test
•
Ongoing Pivotal Phase III trial in Europe and Israel
•
Futility data disclosed March 2015
•
Full data set from this trial expected in Q2 – Q3 2016
7
AVAILABLE THERAPIES – UNMET NEED TO TREAT
FAILING HEARTS
NYHA Classes I & II
Mild HF
Medications:
ACE inhibitors
Angiotensin – 2 receptor
blockers
Beta blcokers
Diuretics
NYHA Class III
Moderate HF
+ Devices
Biventricular
Pacemakers &
Defibrillators
(CRTD)
ICD
NYHA Class IV
Severe HF
Transplantation
Hemodynamic
Support
LVAD
Immunosupressors
C-Cure target population is NYHA classes II, III, IV
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SCIENCE &
RESULTS
9
BRINGING REPROGRAMED PRECURSOR
CARDIAC CELLS TO THE DISEASED TISSUES
Introduction of
functioning myocytes
to induce repair
Cardiopoietic cells
are injected back
into the heart using
C-Cathez®
Bone
marrow
drawn from
the patient
Stem cells are
selected and
expanded
1. Behfar et al., “Cardiopoeitic programming of embryoinic stem cells for tumor-free heart
Stem cells are differentiated to
become cardiopoietic cells,
through the use of a proprietary
combination of cytokines and
growth factors
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C-CURE PHASE II DESIGN
•
Phase II, multicenter, prospective, randomized, open, parallel two-arm study with
blinded core lab analysis
•
Primary endpoints: safety and feasibility
Phase II
•
Measurement of efficacy assessed by LVEF
(n = 45)
C-Cure group
Heart Failure of Ischemic
Origin
Main Inclusion Criteria:
•
NYHA Class II and III
•
LVEF: ≥15% and ≤40%
•
History of Myocardial Infarction (MI)
•
Stable treatment
Control group
Source: Bartunek, J., et al., Cardiopoietic stem cell therapy in heart failure The C-CURE multicenter randomized trial with lineagespecified biologics. J Am Coll Cardiol, 2013.
11
C-CURE TREATED PATIENTS SHOWED IMPROVED
CARDIAC FUNCTION
Patients treated with C-Cure showed improved left ventricular ejection fraction1
* P<0.0001
*
37
34.5 +/-1.1
Ejection Fraction (%)
35
33
Treatment
Cell
Therapy
31
Control
Control
29
27.8 +/-2
28.0 +/-1.8
27.5 +/-1
27
25
Baseline
12
6 Month
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.
12
C-CURE TREATED PATIENTS SHOWED IMPROVED
CARDIAC STRUCTURE
C-Cure treated patients demonstrated
improved cardiac structure1
End-diastolic
volume (EDV)
End-systolic
volume (ESV)
Control
30
-5
20
LV Mass Index (g/m2)
0
Δ Volume (mL)
-10
-15
-20
-25
-35
Treatment
10
0
-10
-20
-30
-30
13
C-Cure treated patients demonstrated
a reduction of heart mass1
Control
Treatment
* P<0.001
-40
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.
13
C-CURE TREATED PATIENTS SHOWED
SIGNIFICANTLY IMPROVED EXERCISE CAPACITY
Patients treated with C-Cure demonstrated improved walking
distance at 6 months in the 6 minute walk distance test with 77m1 increase
Control
100
Treatment
*P<0.01
80
Δ Distance (m)
60
40
20
0
-20
-40
14
From 419m to 404m;
∆-15m, baseline 419m
From 394m to 456m;
∆+62m, baseline 394m
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.
14
PHASE II DATA DEMONSTRATES IMPROVEMENT OF
HEART FAILURE PATIENTS
•
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
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.
15
C-CURE: PHASE III TRIALS DESIGN
Phase III cell therapy trial using reprogrammed cells for Heart
Failure patients (CHART-1) – 240 patients trial
C-Cure
CHART-1
EMA Approved
NYHA class III and IV
NYHA class III and IV
Composite endpoint at 9 month:
Mortality, WHF, 6MWT, QoL,
LVEF, ESV
Clinical enpdoint at 9 month;
6MWT
Currently ongoing in over 30 sites
in Europe and Israel
Anticipate start in second half 2015
in the U.S. and Europe, pending
release of FDA clinical hold
End of enrolment
March 2015
Futility analysis
March 2015
Data read-out
CHART-2
Pending FDA Clearance
Expected Q2-Q3 2016
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CAR T-CELL
PORTFOLIO FOR
ONCOLOGY
17
HOW DOES CAR T-CELL THERAPY WORK FOR
THE PATIENT
18
NKG2D: THE STARTING POINT OF INNOVATION
•
NKG2D is a receptor that is expressed on Natural
Killer (NK) cells
•
An activating receptor that triggers cell killing by NK
cells against “self”
•
Killing activity is dependent on NKG2D ligand
expression
•
There are several NKG2D ligands generally
expressed by cells under stress conditions
•
Numerous tumor cells express NKG2D ligands:
ovarian, bladder, breast, lung and liver cancers, as
well as leukemia, lymphoma and myeloma
Cell activation
Use NKG2D to construct new CAR for fighting
multiple tumors
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NKG2D Ligand Expression in Tumor Cells
Expression of NKG2D ligands
on human tumor cells
Tumor Type
Carcinoma

Ovarian

Bladder

Breast

Lung

Hepatocellular

Colon

Renal

Prostate
Leukemia

AML

CML

CLL
Lymphoma
Multiple Myeloma
Melanoma
Ewing Sarcoma
Glioma
Neuroblastoma
Spear et al., Cancer Immunity (2013)
Reference
(40, 43, 148-151)
(152)
(40, 153-155)
(40, 156, 157)
(158)
(40, 41)
(40, 159, 160)
(40, 161)
(39, 162-164)
(39, 165, 166)
(167, 168)
(169)
(138, 170)
(42, 171, 172)
(56, 173)
(38, 108)
(104)
20
CAR-NKG2D T-CELLS INDUCE LONG-TERM TUMOR
FREE SURVIVAL IN ANIMAL MODELS
100% survival in murine models ovarian cancer
Wild-type
NKG2D T-Cells (n=12)
WT
CH
CAR-NKG2D
T-Cells (n=12)
Percent survival
100
50
0
0
50
100
150
200
Time (in days)
250
CAR-NKG2D CAR T-Cells showed efficacy in multiple
tumor models, including multiple myeloma (MM), ovarian
cancer and lymphoma
1.
2.
3.
4.
Barber, A. et al., J. Immunol (2009) 183(4):2365-72;
2. Barber, A. et al., J. Immunol (2009) 183(11):6939-47;
3. Barber, A. et al., J. Immunol (2008) 180(1):72-8
4. Barber A. et al.,Exp. Hematol. (2008) 36(10):1318-28
21
NKG2D CAR T-CELLS INDUCE DURABLE ANTITUMOR IMMUNITY
Treatment with NKG2D CAR T-Cells
led to long-term survival of mice
injected with 5T33MM tumor cells
(MM model)
Survivors were either re-challenged with
5T33MM cells or injected with RMA cells
a different tumor type; naive used as
control
Survivors were used to re-challenge
100% of animals rechallenged with the
same tumor type survived
W T (n = 1 1 )
5 T s u rv iv :R
C H (n = 1 3 )
Naïve - RMA-RL (n=11) 5 T s u rv 5 T 3
Survivor - RMA-RL (n=6)N a ï v e :R M A
Naïve - 5T33MM-L (n=7)
N a ï v e :5 T 3 3
Survivor - 5T33MM-L (n=7)
100
Wild-type NKG2D T-Cells (n=11)
CAR-NKG2D T-Cells (n=13)
50
0
P e r c e n t s u r v iv a l
P e r c e n t s u r v iv a l
100
50
0
0
20
40
60
T im e(in
Time
days)
80
100
0
20
40
60
80
T im e(in days)
Time
Following CAR T-Cell therapy, long-term protection demonstrated
against parental tumor, even if NKG2D ligand negative
1. Barber, A. et al., Gene Ther. (2011) 18(5): 509–516
22
CAR-NKG2D T-CELLS PHASE I DESIGN
• Phase I being conducted at Dana Farber Cancer Institute, Boston
• Dose escalation 3+3 design; primary objective: feasibility and safety
• Enrolling refractory/relapsed AML or MM patients
• Safety measures cover conventional risks
• Biomarker measurement to assess efficacy
• Additional 12 patients may be included in dose expansion part of the
trial
• First patient infused in April 2015; no treatment-related safety
concerns reported during 30 day follow-up period
• Full data read-out expected by the middle of 2016
23
ALLOGENEIC T-CELL PLATFORM
•
Based on the engineering of T-cells that lack expression of a functional T-cell receptor,
while at the same time expressing a CAR that can trigger the killing of cancer cells
•
Functional T-cell receptors on a donor T-cell are responsible for eliciting an adverse
immune reaction (GVHR); goal of our program is to eliminate the GVHR
•
Celyad allogeneic platform may allow manufacture of an "off-the-shelf" CAR T-cell therapy
product to potentially transform the treatment of cancer
24
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FINANCING STRATEGY – EXECUTIVE SUMMARY
• Celyad was a private company until July 2013
• Raised 42M€ through four successive financing rounds
• Went public in July 2013 on Euronext Brussels and Euronext Paris –
IPO of 26M€
• Additional funding rounds since public company
– Private round of 25M€ in June 2014
– Global Offering of 100M$ in June 2015; IPO on Nasdaq and PIPE on
Euronext
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Going public versus staying private – the
Celyad experience
• C3BS funding history until May 2013
Round A*
Round B
Round C
Round D
DATE
AMOUNT IN ‘M€
02/2005
12/2008
10/2010
05/2013
3.5
7.2
12.1
19.0
Total equity funding
41.8
Non-dilutive funding
18.2
Total funding
60.0
• CQR-1 Phase III trial approved end of 2012
• 20M€+ needed to finance European Phase III trial until primary
endpoint
Going public versus staying public – the C3BS
experience
• Limited outcome of roadshows conducted all over Europe and US
despite positive Phase II data
• ATMP specificities : being leader in a pioneer field with a complex
business model is not consider as positive by the VC’s
• Conclusion: Going public was the last financing option to finance our
phase III program and remain a standalone company
Key success factors
• Solid equity story
– Late stage company
– Matured pipeline (strong phase II data)
– External validation of the science/technology platform (partnership,
publications)
– Clear path to market (clinical and regulatory pathways)
•
•
•
•
•
Strong management team
Strong news flow
Positive and stable market sentiment
Appropriate planning (timing and IPO size)
Selection of adequate financial partners/investment
banks
Key success factors
• Place of listing; be listed where you are visible and know
• Solid financial base at IPO
– Min of 6 months of cash at IPO
– Strong commitment by existing shareholders/new shareholders to build
momentum in the IPO book. Minimum of 50% of the contemplated
amount is required.
• ATMP specificities;
– Maturity of the project – Being approved to initiate Phase III in EU was a
must have in our experience
– Public institutional funds are less afraid of pioneer fields than VC’s
– Larger base of public institutional funds than VC’s and Private Equity
funds
What are the don’ts?
• Do not over size the transaction
• Do not overestimate the market appetite for IPO’s
• Do not underestimate the workload for the key managers
(CEO and CFO) involved in the IPO process – it comes
on top of your daily tasks…
• Be skeptical during banks pitches – it is a selling
exercise
IPO planning
 6 months process is confortable, less is feasible but challenging!
Source; Kempen, April 2013
Euronext versus Nasdaq
Opportunities
Risks
NASDAQ
- Valuation
- Larger base of lifesciences funds
- Bigger size/tickets
- Local visibility (branch,
main competitor)
- Post market liquidity
- Expensive
EURONEXT
- Local visibility
- Good biotech index
performance
- Belgian success stories
- Cheaper process
- Limited IPO’s in
Amsterdam and Brussels
since 2009.
- Smaller size/tickets
ALTERNEXT
- Less
constraints/reporting
- Liquidity
Consequences on day-to-day CFO role and
responsibilities
• Complete different job than being a CFO of a private
company;
– Public exposure
– Manage market expectations
– Investor relations
• Requires staffing of additional heads in the Finance and
Admin department;
– Corporate communication
– Legal officer
– Financial controller
• Upgrade of internal control procedures
• External reporting (quarterly, semi annual and annual report)
• Cash management!
6/07/2015
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THANK YOU
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