Bringing Breakthrough Pioneering Therapies to Patients with Life-Threatening Diseases Corporate Presentation January 2018 - Celyad

 
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Bringing Breakthrough Pioneering Therapies to Patients with Life-Threatening Diseases Corporate Presentation January 2018 - Celyad
Bringing Breakthrough Pioneering Therapies to
       Patients with Life-Threatening Diseases

                      Corporate Presentation

                                January 2018
Bringing Breakthrough Pioneering Therapies to Patients with Life-Threatening Diseases Corporate Presentation January 2018 - Celyad
Disclaimer
In addition to historical facts or statements of current condition, this presentation contains forward-looking statements, including
statements about the potential safety and feasibility of CYAD-01 cell therapy, including current and planned preclinical and clinical trials for
Celyad’s product candidates; the clinical and commercial potential of these product candidates and the adequacy of Celyad’s financial
resources; Celyad’s intellectual property portfolio, including plans related thereto; Celyad’s expectations regarding its strategic
collaborations and license agreements with third parties, including Novartis, Celdara Medical, and Dartmouth College, and the potential
impact of such collaborations on Celyad’s future financial condition; and Celyad’s expected cash burn, which reflect Celyad’s current
expectations and projections about future events, and involve certain known and unknown risks, uncertainties and assumptions that could
cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These forward-
looking statements are further qualified by important factors and risks, which could cause actual results to differ materially from those in the
forward-looking statements, including risks associated with conducting clinical trials; the risk that safety, bioactivity, feasibility and/or
efficacy demonstrated in earlier clinical trials or preclinical studies may not be replicated in subsequent trials or studies; risks associated with
the timely submission and approval of anticipated regulatory filings; the successful initiation and completion of clinical trials, including its
clinical trials for CYAD-01; risks associated with the satisfaction of regulatory and other requirements; risks associated with the actions of
regulatory bodies and other governmental authorities; risks associated with obtaining, maintaining and protecting intellectual property,
Celyad’s ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties; risks associated
with competition from others developing products for similar uses; risks associated with Celyad’s ability to manage operating expenses; and
risks associated with Celyad’s ability to obtain additional funding to support its business activities and establish and maintain strategic
business alliances and business initiatives. A further list and description of these risks, uncertainties and other risks can be found in Celyad’s
U.S. Securities and Exchange Commission (SEC) filings and reports, including in its Annual Report on Form 20-F filed with the SEC on April 4,
2017 and subsequent filings and reports by Celyad. Given these uncertainties, the reader is advised not to place any undue reliance on such
forward-looking statements. These forward-looking statements speak only as of the date of publication of this document. Celyad expressly
disclaims any obligation to update any such forward-looking statements in this document to reflect any change in its expectations with
regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless required by law or
regulation.

                                                                                                                                                  2
Bringing Breakthrough Pioneering Therapies to Patients with Life-Threatening Diseases Corporate Presentation January 2018 - Celyad
Focused on the discovery and development
of specialized cell-based therapies to target cancer

• Novel and proprietary CAR-T platform targeting treatment of solid and
  hematological tumors

• Lead candidate, CYAD-01 (CAR-T NKG2D), currently enrolling in THINK trial

• CAR-T NKG2D target supported with complete response in one AML patient

• Expertise in cell manufacturing with intense focus on process improvements

• Strong IP position

• Collaborations with world-class corporate, academic institutions

                                                                          3
Bringing Breakthrough Pioneering Therapies to Patients with Life-Threatening Diseases Corporate Presentation January 2018 - Celyad
Stress ligands, the making of an ubiquitous CAR-T

                                            SIGNAL 1
                       CD19-CAR-T                         CYAD-01 CAR-T

                                            SIGNAL 2
                            scFv
                                                              NKG2D

•   Derived from a
                                    CD8TM                             •   Derived from
    (murine) antibody                                                     human NK receptor

•   2nd generation CAR-                                       DAP10   •   Similar primary and
                                    CD28
    T signaling                                        CD3ζ               secondary signaling
                                    CD3ζ
•   scFv targeting                                                    •   NKG2D receptor
    specific cancers                                                      targeting stress
                                                                          signals present on
                                                                          many cancers

                                                                                         4
Bringing Breakthrough Pioneering Therapies to Patients with Life-Threatening Diseases Corporate Presentation January 2018 - Celyad
NKG2D binds to 8 stress induced ligands, expressed in a broad range
of cancer indications

                                                          Expression of at least one of
                                                          NKG2D ligands:
                                                          •    Triple negative breast: 88%
                                                          •    Colorectal: 88%
                                                          •    Ovarian: 68%
                                                          •    Bladder: 78% of the primary
                                                               tumors and 100% of the
                                                               metastases
                                                          •    Pancreatic: 86%
                                                          •    NSCLC Lung: 92% (100%
                                                               non-squamous NSCLC)

   Dulphy N., Toubert A. et al. 2017. Unpublished data.        Celyad 2017. Unpublished data, IHC.

                                                                                                     5
Bringing Breakthrough Pioneering Therapies to Patients with Life-Threatening Diseases Corporate Presentation January 2018 - Celyad
Beyond direct cell killing, inducing multi faceted attack on the tumor

                                                                  RELEASE OF THE IMMUNOSUPPRESSION OF
                                                                      THE TUMOR MICROENVIRONMENT

                                                            Immunosuppressive cells
          DIRECT TUMOR
           CELL KILLING

                          Tumor cells                               Blood vessels

CYAD-01                                                         ANTI-NEOANGIOGENEIC EFFECT DRIVEN
                                                             THROUGH TARGETING OF TUMOR ENDOTHELIAL
                                                                 CELLS EXPRESSING NKG2D LIGANDS
                                        Host Immune cells

                                                     ADAPTIVE IMMUNE RESPONSE: SPECIFIC ANTITUMOR
                                                          RESPONSE POST CYAD 01 TREATMENT

                                                                                                                     6
                                                                             Lonez et al. 2017 BMJ Open 7:e017075.
CYAD-01 preclinical models showing activity with multiple
  injections and without pre-conditioning

      OVARIAN CANCER                                   LYMPHOMA                              MULTIPLE MYELOMA

Barber et al. 2009 J Immunol. 183(4):2365-72   Zhang et al., 2007 Cancer Res; 67: (22)   Barber et al., 2011 Gene Ther. 18(5):509-16

                                                                                                                                 7
FIM Phase I Study: CYAD-01 showed acceptable safety profile and
early signs of activity

2015                       2016

         Safety Phase I
                                  • Conducted at Dana Farber Cancer Institute
                                  • No treatment related SAEs
     ▪    1 administration        • One relapsed refractory AML Patient at highest dose (3x107) showed
     ▪    No lymphodepletion        normalization of all hematologic parameters for 6 months
     ▪    Low sub-therapeutic
          doses
     ▪    Hematological tumors
          (AML/MM)

                                                                                                    8
THINK Study (THerapeutic Immunotherapy with NKG2D-based
therapy)

                                               o 3 dose levels (3x108,1x109 and 3x109)
              THINK Trial
                                                                         1st CYAD-01 (D1)
                                                                                   2nd CYAD-01 (D2)
                                                                                                                      Tumor
                                                                                             3rd CYAD-01 (D3)
                                           Washout period                                                             assessment

                                           D-35      D-21           D1        D15        D29       D43          D57
▪ 3 administrations                                                                                       End safety
                                                            Apheresis
▪ Primary Endpoint: Safety &
  Tolerability                        13 weeks w/o any other non-investigational cancer therapy
▪ Secondary Endpoint: Efficacy as
                                       ▪   Seven advanced refractory tumor indications
  Monotherapy (w/o preconditioning)
▪ Hematological & solid                ▪   Global development: EU and USA
  tumors

                                                                                                                                   9
THINK Study: Primary endpoint – Safety – Interim Data

                                       THINK: Safety & Tolerability Data in 15 Patients
   All adverse events if occurred in >= 2 patients
   Solid (n=8) and hematologic (n=7) cancer patients
   Dose-level 1 (solid and hematologic cohorts) and dose-level 2 (solid cohort and one patient
   hematologic cohort)

   Adverse Events                                    Grade 3           Grade 4           Grade 5         Total % of Patients*
                                                 Events (Patients) Events (Patients) Events (Patients)
   Anaemia                                            3 (2)                                                    13.3%
   Back pain                                          3 (2)                                                    13.3%
   Febrile neutropenia                                3 (2)                                                    13.3%
   General physical health deterioration              2 (2)                                                    13.3%
   Hypophosphataemia                                  4 (2)                                                    13.3%
   Lymphocyte count decreased                         5 (2)                                                    13.3%

   Data as of December 31, 2017

                                                                                                                                10
Secondary Endpoint: Early readout: Clinical activity in 3/3 Relapsed
     Refractory AML Patients treated at the per-protocol dose
          Best
          Response
          to date  Months               1                   2                   3                   4                      5            6
Level 1
 Dose

            CRi                                                                             Demethylation Agent

            CR
Level 1

          (MRD-
 Dose

           Post
          HSCT)
Level 2
 Dose

           SD HI                                                                                                  Demethylation Agent

                                                                     •   1 Patient reached MLFS, allowing HSCT. Patient further improved to CR
                     Treatment Cycle 1                                   MRD negative status, ongoing at 6 month
                                                                     •   3/3 patients showed blast reduction during treatment administration
                                                                     •   All patients had hematological improvements
           Allo-     End of Treatment
                                                                     •   4th patient treated at dose lower then per-protocol dose did not show
           HSCT      Evaluation
                                                                         signs of clinical activity
   CRi – Complete remission with incomplete hematological recovery
   CR (MRD-) – Complete response without minimal residual disease
   SD HI – Stable disease with hematological improvement                                                                                11
   HSCT – Hematopoietic stem cell transplant                                              Data as of December 31, 2017
Preliminary take away from AML patients with CYAD-01 as
monotherapy at per-protocol dose (without preconditioning)

•   CYAD-01 active against AML tumor in 3/3 patients treated at the intended dose
•   Blast reduction in Bone Marrow in patients up to and including at least the third
    injection
•   Hematological parameters improving in patients
•   No significant Adverse Events (low grade (
CYAD-01 AML Clinical Development Plan

                                                                     Boosting potency:
                 Prolong durability as
                                                                      •   Expansion
                     stand-alone
                                                                    • Tumor debulking

                             Multiple Treatment                                   THINK
                             Cycles in Expansion

 First FOCUS ON AML
                                                        Standard CAR-T
   in Hematological              Enhance
                                                        preconditioning             AML
        Tumors               engraftment and
                                                      regimen to induce        preconditioning
                               proliferation
                                                       lymphodepletion
                              Increase potency     Combination with 2nd line
                             through debulking                                    AML SoC
                                                      standard of care
                                                   chemotherapy regimen

                               Broaden patient     Donor-derived CYAD-01
                                                                                  SIBLINK
                                 population          infused in patients in
                                                   remission post allo-graft
                                                                                                 13
Secondary Endpoint: Early readout: Signals of activity in Colorectal
Cancer and Ovarian Cancer

• Two out of four metastatic colorectal cancer patients treated at per-
  protocol dose reported as “stable disease” up to 3-months follow-up*+
• No toxicity signals to date

      ➢ Next anticipated steps: Higher dose, longer follow-up + SHRINK and
        LINK

*   Median progression free survival in these patients under standard of care is between 1.9 and 3.2 months
    (e.g. regorafinib or trifluridine/tipiracil).
+   Fifth CRC patient treated at a dose lower then per-protocol dose did not show signs of clinical activity

    Sources: Grothey et al., 2013 Lancet. 381(9863):303-12; Li et al., 2015. Lancet Oncol. 16(6):619-29;
             Moriwaki et al., 2017. Oncologist. 2017 Sep 11.                                                   14
CYAD-01 clinical development plan in CRC
                                                                 Boosting potency through:
            Prolong durability as                                     • Expansion
                stand alone                                        • Tumor debulking
                                                                        • Homing

                          Multiple Treatment
                                                                                  THINK
                          Cycles in Expansion

                                                    Standard CAR-T
                              Enhance                                             CRC pre-
                                                preconditioning regimen
                          engraftment and                                       conditioning
                            proliferation
First FOCUS ON
                                                1st line standard of care
  CRC in Solid             Increase potency     chemotherapy regimen           SHRINK SOC
    Tumors                through debulking       for metastatic CRC            (FOLFOX)

                                                 Local infusion in hepatic
                                                  artery for primary liver
                          Favor tumor homing                                       LINK
                                                    metastasis of CRC
                                                                                               15
Intensely Focused on Manufacturing Improvements in Anticipation
of Commercial Ready Product
• Evolution from drug product manufactured in academic setting (DFCI) towards a
  commercial-ready process that is reproducible and scalable, with attractive COGs

•   Legacy method (LY process) failed to consistently yield drug product with target T cell
    numbers

     •   Of 15 patients treated at December 31, 2017, 10 were dosed at per-protocol intended dose and 5 were
         treated at lower doses

•   New manufacturing process is currently being used in the clinic

     •   mAb manufacturing process inhibits NKG2D expression on the T cell surface during production
     •   Enables significantly higher cell numbers than the legacy process
     •   Validated in both in vivo and ex vivo models
     •   CMC amendments to THINK protocol are in effect with applicable regulators
     •   First patient treated January 2018

•   Continued focus on next-generation process improvements, including automated
    and closed system approach
                                                                                                               16
Clinical Development Plan

   Product        Indication   Clinical Study     Preclinical   Phase 1       Next Anticipated
                                                                                Milestones
                               THINK                                      Complete Dose Escalation

                               Pre-conditioning                           File IND
                     AML
                               Standard of Care                           File IND

                               SIBLINK                                    File IND
    CYAD-01
                               THINK                                      Complete Dose Escalation

                               SHRINK                                     First Patient First Visit
                     CRC
                               LINK                                       First Patient Dosing

                               Pre-Conditioning                           File IND

    CYAD-101
                     CRC       SHRINK Allo                                File IND
   (Allogeneic)

                                                                                                      17
CYAD-101: Non gene edited allogeneic option

•    Engineered for CYAD-01 (NKG2D-based CAR-T cell)
•    Alloreactivity controlled through co-expression of an inhibitory peptide (termed a T cell
     receptor inhibitory molecule – TIM) to reduce TCR-signaling and thereby reduce Graft
     versus Host Disease (GvHD).

                                                                                     01/02/2018   18
Impact on GvHD off the expression of TIM8 in allogeneic T cells

                                 The expression of TIM8 inhibits                                                                                            Tumor growth (orthotopic colorectal tumor in NSG mice)
                                   xGvHD in the NSG mouse                                                                                                      is decreased following treatment with CYAD-101

                                                                                                                                            10   11       C o n tro l
                       100

                                                                                                            (p h o to n s / s e c / m m )
                                                                                                                                                          tC D 1 9 T c e lls

                                                                                                            2
                                                                               B io lu m in e s c e n c e
                                                                                                                                            10   10               CYAD-101
                                                                                                                                                          T IM 8 .N KR2
S u r v iv a l ( % )

                                                                                                                                                                                                   **

                                                                                                                                                  9
                        50                                                                                                                  10

                                     D o n o r T c e lls
                                                                                                                                                  8
                                     D o n o r T IM 8 T c e lls                                                                             10

                                     N o T c e lls
                         0                                                                                                                        7
                                                                                                                                                                                                                                 TIM8.
                             0                20                  40      60
                                                                                                                                            10                                                               Vehicle   tCD19
                                                                                                                                                      0    5            10       15           20        25                     CYAD-101
                                           D a y s p o s t in fu s io n                                                                                        D a y s p o s t in fu s io n

                                                                                                                                                                                                                                  19
Summary: Towards CAR-T leadership

    NKG2D platform;
                                      Autologous Cell
Leveraging Stress Ligands                                           Allogeneic CAR T Cell Therapy
                                 Manufacturing Paradigm shift
      based CAR-T

   Building on early signals          Process Development                   Strong IP position
    Improving outcomes              Improved yields and CoGs        Patents concerning TCR knockdown
                                                                      in CAR T cell therapy providing
                                                                        broad coverage in the field

  Initial focus on AML and CRC             Automation
           Execution             Making Autologous Cell Therapies
                                    feasible and cost effective        Allogeneic NKG2D Platform
                                                                     Development of TIM8-CYAD 01
                                                                             (CYAD-101)
 Continuing Development Plan
Broaden indications beyond AML   Towards Point of Care Processing        Allogeneic TIM Platform
           and CRC                   Enabling large indications     Developing broad based Allogeneic
                                                                            CAR –T products

                                                                                                   20
Corporate collaborations

                                                         •   May 2nd, 2017: Celyad grants to Novartis a non-
                                                             exclusive license for its allogeneic TCR-deficient
                                                             CAR-T cells patents for two undisclosed targets
•   July 11th 2016: Celyad grants exclusive license to
    ONO for the development and commercialization of     •   Deal value: $96 million. Celyad to receive
    allogeneic CYAD-01 T-cell immunotherapy in Japan,        upfront, and potential development and
    Taiwan and Korea                                         commercial milestones payments and single
                                                             digit royalties
•   License in exchange for $12.5M upfront, $300M in
    potential milestones and double-digit royalties      •   Celyad retains all rights to grant further licenses
                                                             to third parties for the use of allogeneic CAR-T
                                                             cells. Deal can be turned into exclusive license

                                                                                                            21
Financial snapshot

 Cash Position:

 • Approximately €34 million as of December 31, 2017*

 • Enabling company’s activities through first half of 2019

 Ticker: Nasdaq (CYAD), Euronext Paris & Euronext Brussels (CYAD.BB)

* Preliminary estimate abd unaudited

                                                                       22
Management team

                          1.   Christian Homsy, CEO
                          2.   Patrick Jeanmart, CFO
                          3.   Jean-Pierre Latere, COO
                          4.   Frédéric Lehmann, VP Clinical Development & Medical Affairs
                          5.   David Gilham, VP R&D
                          6.   Georges Rawadi, VP Business Development & IP
      1       2       3   7.   Philippe Dechamps, CLO
                          8.   Philippe Nobels, Global Head Of Human Resources

      4       5       6
                                        6

      7       8
                  7        8
                                                                          01/02/2018   23
Thank you
Contact: investors@celyad.com

BELGIUM                     USA
Celyad SA                   Celyad Inc.
Axis Business Park          Seaport East
Rue Edouard Belin, 2        2 Seaport Lane
B-1435 Mont-Saint-Guibert   Boston, MA. 02210
+32(0) 10 39 41 00          +1 857-990-6900

                            www.celyad.com
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