A Leader in Engineered Cell Therapy Treatments

A Leader in Engineered Cell Therapy Treatments

Clinical Platforms Targeting

Cardiovascular Disease and Oncology

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

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DISCLAIMERS

This presentation is being made in reliance upon Section 105(c) of the Jumpstart Our Business Startup Act of 2012, and is intended solely for investors that are either qualified institutional buyers or institutions that are accredited investors (as such terms are defined under Securities and Exchange Commission (SEC) rules). This presentation shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. Any such offering of securities will only be made by means of a

registration statement (including a prospectus) filed with the SEC, after such registration statement becomes effective. No such registration statement has been filed as of the date of this presentation.

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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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Goal of becoming global leader in cell therapies by building franchises in multiple

indications based on core expertise

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Developing reprogramming technologies invented at Mayo Clinic and Dartmouth College

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C-Cure: Phase III trial in ischemic heart failure in Europe and Israel, CHART-1

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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

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IP and product portfolio allowing possible targeting of other indications in cardiovascular

diseases and oncology

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GMP production facilities

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CHART-1 efficacy read-out expected middle of 2016

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Headquarters in Belgium, with subsidiaries in US and Asia

A leader in cell therapy treatments with clinical programs

in cardiovascular disease and oncology

MANAGEMENT AND BOARD

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Executive Management Team

Chief Executive Officer

Patrick Jeanmart, representative of PaJe SPRL, acting as

Chief Financial Officer Vincent Brichard, representative of

ViaNova SPRL, acting as

VP Immuno-Oncology

Peter De Waele, representative of Advanced Therapies Consulting Ltd., acting as

VP Research & Development

Georges Rawadi VP Business Development Warren Sherman Chief Medical Officer

Board of Directors

LSS Consulting SPRL, represented by its permanent representative Christian Homsy William Wijns

Serge Goblet

Jean-Marc Heynderickx Danny Wong

R.A.D. Life Sciences BVBA, represented by its permanent representative Rudy Dekeyser Chris de Jonghe

Pienter-Jan BVBA, represented by its permanent representative Chris Buyse

Hanspeter Spek

TOLEFI SA, represented by its permanent representative Serge

Goblet

Scientific and clinical Advisors

Charles Sentman, PhD Prof & Director of Immunology Center, Dartmouth College Milton Packer, MD, PhD UT Southwestern, Columbia

University and Presbyterian Medical Center

Stefan Anker, MD, PhD Charité Berlin, Imperial College London, EMA expert

CAR T-Cell platform

Invented at Dartmouth College,

exclusively licensed to Celyad

An approach to cancer immunotherapy

Technology platforms supported by scientific research

CELYAD PLATFORMS

Cardiopoiesis platform

Invented at Mayo Clinic, exclusively

licensed to Celyad

A technology to treat heart failure

Oncology

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Acute Myeloblastic Lymphoma (AML)

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Multiple Myeloma (MM)

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Other Potential Indications:

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Ovarian

•

…

Cardiovascular

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Ischemic Heart Failure

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Other Potential Indications:

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Congestive Non-Ischemic Heart

Failure

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CELYAD OPPORTUNITIES

C

-Cure

®

Ischemic HF– CHART-1 (Europe and IL)

CA

R

T

-Ce

ll

AML & MM – US

Solid and blood cancers expressing NKG2D ligands

•Full data readout expected: Q2-Q3 2016

• Start of enrollment expected: •2H 2015, pending FDA release of existing clinical hold

•Interim data set expected: various times

•Full data readout expected; Q3-2016

•Start Phase IIb expected: 2016

Product

Pre-clinical

Phase I

Phase II

Phase III

Status / Milestones

Allogeneic

Platform

NKp30

• Start Phase I expected: 2016

B7H6

Ischemic HF– CHART-2 (US and Europe)

• Start Phase I expected: 2016

THE CARDIOPOIESIS

PLATFORM

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Heart failure affects 1 - 2% of the adult population in developed

countries

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In 2012, approximately

5.7 million heart failure patients in the U.S.

alone

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5-year survival rate for heart failure patients is 50%

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$60 billion estimated in direct costs on heart failure in 2014 in the

U.S.

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1: McMurray, JJV et al., 2005, The Lancet, 365, pp1877-1889 2: Company estimates

3: Go, A.S. et al., Heart Disease and Stroke Statistics 2013 Update:, 4: Voigt, J., et al. (2014). “A Reevaluation of the Costs of Heart Failure and Its A Report From the American Heart Association Implications for Allocation of Health Resources in the United States.” Clinical Cardiology

THE HEART FAILURE MARKET OPPORTUNITY

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One in five people over the age of 40 will develop heart failure

during his or her life

C-CURE THERAPY FOR THE TREATMENT OF HEART

FAILURE

Large Market,

Unmet Need

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Cardiovascular diseases are leading cause of death

in the world in 2012

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1 million primary HF-related hospitalizations annually

in U.S.

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C-Cure phase II data published in JACC:

improvement

in Ejection Fraction, ESV, 6-min walk

test

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Ongoing Pivotal Phase III trial

in Europe and Israel

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Futility data disclosed March 2015

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Full data set from European trial in the middle of 2016

Validated

Science

Advanced

Clinical

Medications: ACE inhibitors Angiotensin – 2 receptor blockers Beta blcokers Diuretics + Devices Biventricular Pacemakers & Defibrillators (CRTD) ICD Hemodynamic Support LVAD Immunosupressors Transplantation 10

AVAILABLE THERAPIES

– UNMET NEED TO TREAT

FAILING HEARTS

C-Cure target population is NYHA classes II, III, IV

Mild HF

NYHA Class III Moderate HF

NYHA Class IV Severe HF

SCIENCE &

RESULTS

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Bone marrow drawn from

the patient

Stem cells are selected and

expanded

Cardiopoietic cells are injected back into the heart using

C-Cath_ez®

1. Behfar et al., “Cardiopoeitic programming of embryoinic stem cells for tumor-free heart

Introduction of functioning myocytes

to induce repair

Stem cells are differentiated to become cardiopoietic cells, through the use of a proprietary

combination of cytokines and growth factors

BRINGING REPROGRAMED PRECURSOR

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Phase II, multicenter, prospective open-label study with blinded core lab analysis

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Endpoints: safety and feasibility. For efficacy - LVEF

Main Inclusion Criteria:

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NYHA Class II and III

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LVEF: ≥15% and ≤40%

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History of Myocardial Infarction (MI)

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Stable treatment

Phase II

(n = 45)

C-Cure group

Control group

Heart Failure of Ischemic

Origin

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. 27.8 +/-2 28.0 +/-1.8 27.5 +/-1 34.5 +/-1.1 25 27 29 31 33 35 37 Baseline E je c tion Fra c tion (% ) Cell Therapy Control

*

*

Patients treated with C-Cure showed improved left ventricular ejection fraction

Treatment

Control

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C-CURE TREATED PATIENTS SHOWED IMPROVED

CARDIAC FUNCTION

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-35 -30 -25 -20 -15 -10 -5 0 End-diastolic volume (EDV) End-systolic volume (ESV) Δ V ol ume (m L) Control Treatment -40 -30 -20 -10 0 10 20 30 Control Treatment L V Ma ss In d e x (g /m 2 )

C-Cure treated patients demonstrated

improved cardiac structure

C-Cure treated patients demonstrated

a reduction of heart mass

* P<0.001

C-CURE TREATED PATIENTS SHOWED IMPROVED

CARDIAC STRUCTURE

-40 -20 0 20 40 60 80 100 Control Δ Di sta n ce (m )

Patients treated with C-Cure demonstrated improved walked

distance at 6 month in the 6 minute walk distance test with 77m

*P<0.01

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.

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From 394m to 456m; ∆+62m, baseline 394m From 419m to 404m;

∆-15m, baseline 419m

C-CURE TREATED PATIENTS SHOWED

SIGNIFICANTLY IMPROVED EXERCISE CAPACITY

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Statistically and clinically significant increase in cardiac function (ejection fraction)

(p<0.0001)

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Statistically and clinically significant improvement in cardiac structure (end systolic

volume (p<0.001)

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Statistically and clinically significant improvement in exercise capacity (6 minute walk

distance test) (p<0.01)

PHASE II DATA DEMONSTRATES IMPROVEMENT OF

HEART FAILURE PATIENTS

C-CURE: PHASE III TRIALS DESIGN

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Phase III cell therapy trial using reprogrammed cells for Heart

Failure patients (CHART-1)

C

-Cure

CHART-1

EMA Approved

NYHA class III and IV

Composite endpoint at 9 month:

Mortality, WHF, 6MWT, QoL,

LVEF, ESV

Currently ongoing in over 30 sites

in Europe and Israel

CHART-2

Pending FDA Clearance

NYHA class III and IV

Clinical enpdoint at 9 month;

6MWT

Anticipate start in second half

2015 in US and Europe, pending

release of FDA clinical hold

End of enrolment

March 2015

Futility analysis

March 2015

MANUFACTURING OF C-CURE

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Manufacturing process, ready for upscale and industrialization

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Pilot manufacturing facility with approximately 250 patient production

capacity, sufficient to meet current C-Cure clinical program needs

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Second manufacturing plant in Rochester, MN to increase production

capacity, provide redundancy and decrease logistical burden

CARDIOPOIESIS PATENT PORTFOLIO

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Seven patent families covering the cardiopoiesis platform issued by

Mayo and Celyad

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Lead product, C-Cure is covered by four granted patents in the U.S.

and New Zealand

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C-Cath

is a proprietary intramyocardial

injection catheter

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High local delivered retention compared to

existing devices

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Optimal biocompatibility through

decreased sheer stress

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Excellent safety profile

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Celyad invention with worldwide patent

applications

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CE marked since April 2012

C-CATH

EZ

: APPROVED PROPRIETARY CATHETER FOR

CAR T-CELL

PORTFOLIO FOR

ONCOLOGY

HOW DOES CAR T-CELL THERAPY WORK FOR

THE PATIENT

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NKG2D: THE STARTING POINT OF INNOVATION

Cell activation

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NKG2D is a receptor that is expressed on Natural

Killer (NK) cells

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An activating receptor that triggers cell killing by NK

cells against “self”

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Killing activity is dependent on NKG2D ligand

expression

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There are several NKG2D ligands generally

expressed by cells under stress conditions

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Numerous tumor cells express NKG2D ligands:

ovarian, bladder, breast, lung, liver, leukemia and

others

Use NKG2D to construct new CAR for fighting

multiple tumors

Human NKG2D Ligands

DNA damage

Infection, or

Malignancy

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MIC molecules may be induced in association with DNA damage, cell

stress, infection or malignant transformation

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System in which “self” alerts the immune system via upregulation of intrinsic

NKG2D ligands

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Tumor cells may express one or more ligands

MIC-B

Healthy

Cell

Tumor

Cell

ULBP

1-6

Tumor

Cell

Tumor

Cell

Tumor

Cell

MIC-A

NKG2D Ligand Expression in Tumor Cells

Expression of NKG2D ligands

on human tumor cells

Tumor Type Reference

Carcinoma  Ovarian (40, 43, 148-151)  Bladder (152)  Breast (40, 153-155)  Lung (40, 156, 157)  Hepatocellular (158)  Colon (40, 41)  Renal (40, 159, 160)  Prostate (40, 161) Leukemia  AML (39, 162-164)  CML (39, 165, 166)  CLL (167, 168) Lymphoma (169) Multiple Myeloma (138, 170) Melanoma (42, 171, 172) Ewing Sarcoma (56, 173) Glioma (38, 108) Neuroblastoma (104)

CELYAD'S CAR T-CELL TECHNOLOGY

Classical CAR construct

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One CAR construct targets one tumor

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May not be suitable for repeated injections

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Mostly autologous

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Many potential therapies under development

Our CAR construct

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Uses NK cell receptors

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One CAR construct has the potential to

target multiple tumors

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Suitable for repeated injections

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Autologous and possibly allogeneic

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CAR-NKG2D T-CELLS INDUCE LONG-TERM TUMOR

FREE SURVIVAL IN ANIMAL MODELS

1. Barber, A. et al., J. Immunol (2009) 183(4):2365-72;

2. 2. Barber, A. et al., J. Immunol (2009) 183(11):6939-47;

3. 3. Barber, A. et al., J. Immunol (2008) 180(1):72-8

4. 4. Barber A. et al.,Exp. Hematol. (2008) 36(10):1318-28

100% survival in murine models ovarian cancer

CAR-NKG2D CAR T-Cells showed efficacy in multiple

tumor models, including multiple myeloma (MM), ovarian

cancer, lymphoma

NKG2D CAR T-CELLS INDUCE DURABLE

ANTI-TUMOR IMMUNITY

Survivors were either re-challenged with

5T33MM cells or injected with RMA cells

a different tumor cells; naive used as

control

Survivors showed 100% durable protection

against re-challenge

Treatment with NKG2D CAR T-Cells

lead to long-term survival of mice

injected with 5T33MM tumor cells

(MM model)

Survivors were used to re-challenge

0 2 0 4 0 6 0 8 0 1 0 0 0 5 0 1 0 0 T im e P e r c e n t s u r v iv a l W T ( n = 1 1 ) C H ( n = 1 3 )

Following CAR T-Cell therapy, long-term protection demonstrated

against parental tumor, even if NKG2D ligand negative

Wild-type NKG2D T-Cells (n=12) CAR-NKG2D T-Cells (n=12) 0 2 0 4 0 6 0 8 0 0 5 0 1 0 0 T im e P e r c e n t s u r v iv a l 5 T s u r v iv :R M A - R L 5 T s u r v 5 T 3 3 M M N aïv e :R M A - R L N aïv e :5 T 3 3 M M Naïve - RMA-RL (n=11) Survivor - RMA-RL (n=6) Naïve - 5T33MM-L (n=7) Survivor - 5T33MM-L (n=7)

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CAR-NKG2D T-CELLS PHASE I DESIGN

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Phase I to be performed at Dana Farber Cancer Institute, Boston

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Dose escalation 3+3 design; primary objective: feasibility and safety

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Enrolling refractory/relapsed AML or MM patients

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Safety measures cover conventional risks

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Biomarker measurement to assess efficacy

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Additional 12 patients may be included in dose expansion part of the

trial

ALLOGENEIC T-CELL PLATFORM

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Based on co-expression of CAR molecules and TCR Inhibitory Molecules (TIMs) from

same retrovirus DNA

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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

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Celyad allogeneic platform uses T-Cells from healthy donors and generates “off-the-shelf”

CAR T-Cells to potentially treat numerous cancer patients

STRONG IP POSITION

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Three patent families covering all CAR products pipeline and

allogeneic platform

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Distinguished IP on Celyad CAR constructs utilizing NK receptors

A CAR T-CELL PORTFOLIO FOR CANCER

TREATMENT

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Not another CD19 CAR

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No need for antibody platform because it uses natural NK receptors

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Potential to target variety of tumor types including liquid cancers and

solid tumors

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Multiple product candidates possible; lead product candidate

currently beginning Phase I

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Allogeneic T-cell platform may allow manufacturing of “off-the-shelf”

products

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ANTICIPATED CLINICAL MILESTONES

CAR

T

-Cell

C

-CURE

H1 2015

H2 2015

H1 2016

H2 2016

Futility

Analysis

End of

Enrolment

CHART-1

Expected Readout

CHART-1 full data

set

CAR-NKG2D Phase I – interim readouts after each cohort

Expected Readout

CAR-NKG2D full

data set

Recruitment

of 1

patient

Interim data to be reported throughout trial

Expected Initiation

of CHART-2 in

US, pending

release of FDA

clinical hold

SHAREHOLDERS AND FUNDING HISTORY

• $165M (€146M) raised since inception

• Public company since July 2013 (Euronext Brussels & Paris)

28.90% 7.24% 5.10% 5.46% 4.25% 2.69% 1.19% 45.18%

Shareholder structure as per March 2, 2015

Tolefi SA Medisun SRIW PMV

Founders & Mgt

Mayo Foundation for Education and Research

Celdara Others