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

Transcription

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

2 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 forwardlooking 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

3 Focused on the discovery and the 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 validated with first complete response in AML Unique expertise in cell manufacturing Strong IP position Partnerships with first-class corporate, academic institutions 3

4 Stress ligands, the making of an ubiquitous CAR-T CD19-CAR-T SIGNAL 1 CYAD-01 CAR-T scfv SIGNAL 2 NKG2D Derived from a (murine) antibody CD8TM Derived from human NK receptor 2 nd generation CAR- T signaling scfv targeting specific cancers CD28 CD3ζ CD3ζ DAP10 Similar primary and secondary signaling NKG2D receptor targeting stress signals present on most cancers 4

5 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 Unpublished data. Celyad Unpublished data, IHC. 5

6 Beyond direct cell killing, inducing multi faceted attack on the tumor RELEASE OF THE IMMUNOSUPPRESSION OF THE TUMOR MICROENVIRONMENT DIRECT TUMOR CELL KILLING Immunosuppressive cells CYAD-01 Tumor cells Blood vessels 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 Lonez et al BMJ Open 7:e

7 CYAD-01 preclinical models showing activity with multiple injections and without pre-conditioning OVARIAN CANCER LYMPHOMA MULTIPLE MYELOMA Barber et al J Immunol. 183(4): Zhang et al., 2007 Cancer Res; 67: (22) Barber et al., 2011 Gene Ther. 18(5):

8 FIM Phase I Study: CYAD-01 showed acceptable safety profile and shows early signs of activity Safety Phase I 1 administration No lymphodepletion Low sub-therapeutic doses Hematological tumors (AML/MM) Run at Dana Farber Cancer Institute CYAD-01 is safe at the dose levels tested One r/r AML Patient at highest dose (3x10 7 ) showed normalization of all hematologic parameters for 6 months 8

9 THINK Study (THerapeutic Immunotherapy w/ NKG2D-based therapy) THINK Trial o 3 dose levels (3x10 8,1x10 9 and 3x10 9 ) Washout period 1st CYAD-01 (D1) 2nd CYAD-01 (D2) 3rd CYAD-01 (D3) Tumor assessment 3 administrations Primary Endpoint: Safety &Tolerability Secondary Endpoint: Efficacy as Monotherapy (w/o preconditioning) Hematological & solid tumors D-35 D-21 D1 D15 D29 D43 D57 Apheresis End safety 13 weeks w/o any other non-investigational cancer therapy Seven advanced refractory tumor indications Global development: EU and USA 9

10 THINK Study: Primary endpoint Safety Interim Data THINK: Safety Profile in 15 Patients All adverse events if >= 2 patients Solid (n=8) and hematologic (n=7) cancer patients patients Dose-level 1 (solid and hematologic cohorts) and dose-level 2 (solid cohort) All AEs are unrelated to the investigational treatment 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,

11 Dose 2 Dose 1 Dose 1 Secondary Endpoint: Early readout: Clinical activity in 3/3 Relapsed Refractory AML Patients treated at the prespecified dose Best Response to date Months CRi Demethylation Agent CR (MRD- Post HSCT) SD HI Demethylation Agent Allo- HSCT Treatment Cycle 1 End of Treatment Evaluation CRi Complete remission with incomplete hematological recovery CR (MRD-) Complete response without minimal residual disease SD HI Stable disease with hematological improvement HSCT Hematopoietic stem cell transplant 1 Patient reached MLFS, allowing HSCT. Patient further improved to CR MRD negative status, ongoing at 6 month 3/3 patients showed blast reduction during treatment administration All patients had hematological improvements 11

12 Preliminary take away from AML patients with CYAD-01 as monotherapy at intended dose (w/o preconditioning) CYAD-01 active against AML tumor in 3/3 patients treated at the intended dose Blast reduction in BM in patients up to and including at least the third injection Hematological parameters improving in patients No safety concerns (low grade CRS, no neurotoxicity) Next steps in THINK: Complete Dose level 2 and 3; Expansion cohort according to ORR with multiple cycles of treatment 12

13 CYAD-01 AML Clinical Development Plan Prolong durability as stand-alone Boosting potency: Expansion Tumor debulking Multiple Treatment Cycles in Expansion THINK First FOCUS ON AML in Hematological Tumors Enhance engraftment and proliferation Standard CAR-T preconditioning regimen to induce lymphodepletion AML preconditioning Increase potency through debulking Combination with 2 nd line standard of care chemotherapy regimen AML SoC Broaden patient population Donor-derived CYAD-01 infused in patients in remission post allo-graft SIBLINK 13

14 CD 19 malignancies AML is a large unmet medical need, distinct from B cell malignancies AML NCY 26.9% 5 Y Survival ALL NCY 68.2% 5 Y Survival DLBCL NCY 53% 5 Y Survival 14

15 Secondary Endpoint: Early readout: Signals of activity in CRC and Ovarian Cancers Two out of three metastatic colorectal cancer patients reported as stable disease up to 3-months follow-up* No toxicity signals to date Next 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. Regarifinib or trifluridine/tipiracil). Sources: Grothey et al., 2013 Lancet. 381(9863):303-12; Li et al., Lancet Oncol. 16(6):619-29; Moriwaki et al., Oncologist Sep

16 CYAD-01 clinical development plan in CRC Prolong durability as stand alone Boosting potency through: Expansion Tumor debulking Homing Multiple Treatment Cycles in Expansion THINK First FOCUS ON CRC in Solid Tumors Enhance engraftment and proliferation Increase potency through debulking Standard CAR-T preconditioning regimen 1 st line standard of care chemotherapy regimen for metastatic CRC CRC preconditioning SHRINK SOC (FOLFOX) Favor tumor homing Local infusion in hepatic artery for primary liver metastasis of CRC LINK 16

17 Celyad Consolidated Clinical Development Plan AACR ASCO ASH AACR ASCO ASH Clinical Trial AML THINK Expansion AML Pre-conditioning AML SOC AML SIBLINK CYAD-02 AML CRC THINK CRC SHRINK CRC LINK CRC Pre-conditioning CRC CYAD-101 Allo 17

18 CYAD-101: Making allogeneic options feasible 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 GvHD. 22/01/

19 S u r v iv a l (% ) B io lu m in e s c e n c e (p h o to n s / s e c / m m 2 ) Abrogation of GvHD by the expression of TIM8 in allogeneic T cells The expression of TIM8 inhibits xgvhd in the NSG mouse Tumor growth (orthotopic colorectal tumor in NSG mice) is decreased following treatment with CYAD C o n tro l tc D 1 9 T c e lls T IM 8.NCYAD-101 K R 2 * * 5 0 D o n o r T c e lls D o n o r T IM 8 T c e lls N o T c e lls 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 Vehicle tcd19 TIM8. CYAD

20 Summary: Towards CAR-T leadership NKG2D platform; Leveraging Stress Ligands based CAR-T Building on early signals Improving outcomes Autologous Cell Manufacturing Paradigm shift Process Development Improved yields and CoGs Allogeneic CAR T Cell Therapy Strong IP position Patents concerning TCR knockdown in CAR T cell therapy providing exclusivity in the field Towards BTD/PRIME in AML and CRC Execution Automation 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 and CRC Towards Point of Care Processing Enabling large indications Allogeneic TIM Platform Developing broad based Allogeneic CAR T products 20

21 Corporate partnerships July 11th 2016: Celyad grants exclusive license to ONO for the development and commercialization of allogeneic CYAD-01 T-cell immunotherapy in Japan, Taiwan and Korea (=10% of the worldwide pharmaceutical market) License in exchange for $12.5M upfront, $300M in potential milestones and double-digit royalties May 2nd, 2017: Celyad grants to Novartis a nonexclusive license for its allogeneic TCR-deficient CAR-T cells patents for two undisclosed targets Deal value: $96 million. Celyad to receive upfront, development and commercial milestones payments and single 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

22 Financial snapshot Cash Position: 40 million as of Sept 30, 2017 Enabling company s activities through first half of 2019 Ticker: Nasdaq (CYAD), Euronext Paris & Euronext Brussels (CYAD.BB) 22

23 Management team 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 7. Philippe Dechamps, CLO 8. Philippe Nobels, Global Head Of Human Resources /01/

24 Thank you Contact: BELGIUM Celyad SA Axis Business Park Rue Edouard Belin, 2 B-1435 Mont-Saint-Guibert +32(0) USA Celyad Inc. Seaport East 2 Seaport Lane Boston, MA