Bringing Breakthrough Pioneering Therapies to Patients with Life-Threatening Diseases. Corporate Presentation. March 2017

Transcription

1 Bringing Breakthrough Pioneering Therapies to Patients with Life-Threatening Diseases Corporate Presentation March 2017

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 CAR-T NKR-2 cell therapy, which reflect our 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, which could cause actual results to differ materially from those in the forwardlooking statements, including risks associated with conducting clinical trials; the risk that safety, bioactivity, feasibility and/or efficacy demonstrated in earlier clinical or pre-clinical studies may not be replicated in subsequent studies; risk associated with the timely submission and approval of anticipated regulatory filings; the successful initiation and completion of clinical trials, including Phase I clinical trial for CAR-T NKR-2; 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, our ability to enforce our patents against infringers and defend our patent portfolio against challenges from third parties; risks associated with competition from others developing products for similar uses; risks associated with our ability to manage operating expenses; and risks associated with our ability to obtain additional funding to support our 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 the Company s Securities and Exchange Commission filings and reports, including in the Company s Annual Report on Form 20-F filed with the SEC on April 8, 2016 and future filings and reports by the Company. 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. The Company 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 Celyad: Company Overview 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, CAR-T NKR-2, currently enrolling in Phase 1 THINK trial in 7 indications. Unique expertise in cell manufacturing co-located with our head office in Belgium. Led by experienced management team and supported by strong scientific advisory board. Partnerships with first-class corporate, academic and medical institutions. Well capitalized to advance robust CAR-T pipeline. 3

4 Celyad s Robust Immuno-Oncology Pipeline CLINICAL STAGE Autologous platform HEMATO CANCER INDICATIONS SOLID CANCER INDICATIONS CAR-T NKR-2 SAFETY Phase 1 Trial THINK - Acute Myeloid Leukemia THINK - Multiple Myeloma THINK - Ovarian cancer THINK - Colorectal cancer THINK - Pancreatic cancer THINK - Bladder HEMATOLOGICAL cancer INDICATIONS THINK - Triple Negative Breast cancer SHRINK - Combo with chemotherapy LINK - Loco-regional administration PRECLINICAL STAGE Allogeneic platform B7/H6 CAR-T CAR-T NKp30 4

5 A Unique Construct Arming T-cells with a NK Receptor to Target and Destroy Cancer Cells One natural construct that capitalized on the two main pillars of the immune system: NK cells and T-cells. A natural co-stimulating domain: DAP 10 Same signaling domain as other CAR-T: CD3ζ. 5

6 Classical CAR-T A Cell Transplant Paradigm Next Generation CAR-T NKR-2 Increasing Deliverability and Safety CAR-T NKR-2: A Novel Paradigm to CAR-T The Next Frontier of Cell Therapy Lymphodepletion Making Space for the Graft Less Controlled In Vivo Expansion with Potential for Serious Adverse Events Persistence of CAR-T leading to the need to have Control Mechanisms Primary MOA through Direct Cytotoxicity No Lymphodepletion Leveraging the patient Immune System Controlled Dosing and PK to reduce Adverse Events and increase Effectiveness Managing kinetics through classical multiple infusion approach Multiple MOA for increased Effectiveness Rapid clinical response but some relapse including Antigen Loss Variants Induced adaptive immunity driving a progressive clinical response 6

7 Significant Survival Benefit Shown in Animal Models Prolonged survival in multiple dose murine models of Ovarian, Myeloma, Lymphoma, Melanoma and Pancreatic cancers. MULTIPLE MYELOMA LYMPHOMA Reduced Pancreatic Cancer in Humanized Mice 1. Barber, A. et al., J. Immunol (2009) 183(4): Barber, A. et al., J. Immunol (2009) 183(11): Barber, A. et al., J. Immunol (2008) 180(1): Barber A. et al., Exp. Hematol. (2008) 36(10):

8 Multiple Modes Of Action: Targeting the Tumor Micro Environment Eliminates Tumor T Regs Recruits Macrophages to the Tumor Number CD4+Foxp3+ of cells x 10^5 x Peritoneal cells #521- Number of CD4+Foxp3+ cells x 10^5 CD4 + Foxp3 + *** naïve WT CH Naive Control NKR-2 Barber et al. J Immunol CCL2 Spear, et al. J. Immunol Reduces Myeloid Suppression in the Tumor NKR-2 Control T cells 8 Spear, et al. J. Immunol. 2012

9 Multiple Modes of Action: Disrupting Tumor Blood Supply wtnkg2d chnkg2d CAR-T NKR-2 targets the tumor s neovasculature, and deprives it from the oxygen and nutrients needed to grow and survive 9

10 P e rc e n t s u rv iv a l P e rc e n t s u rv iv a l Multiple Modes Of Action: Preventing Relapse Acquired adaptive immunity for long-term recurrence protection in Multiple Myeloma (MM) model Treatment with CAR-T NKR-2 cells led to long-term survival of mice injected with 5T33MM tumor cells. Survivors were used to re-challenge Survivors were either re-challenged with 5T33MM cells or with RMA cells; naive used as control. 100% of animals re-challenged with the same tumor type survived W T (n = 1 1 ) C H (n = 1 3 ) T s u rv iv :R M A -R L 5 T s u rv 5 T 3 3 M M N a ïve :R M A -R L 5 0 Wild-type NKG2D T-Cells (n=12) NKR-2 T-Cells (n=13) 5 0 Na ïve:5t33m M T im e T im e Barber, A. et al., Gene Ther. (2011) 10

11 Controlled Safety Profile: No Lymphodepletion Sustaining a competent immune system allows for the induction of an adaptive anti-tumor immune response and avoids the potentially acute and enduring toxicities associated with chemotherapy. Single Dose Cy Control T cells NKR-2 + Cy NKR-2 Myeloma cancer model was used with or without lymphodepletion using Cyclophosphamide. Barber et al. Gene Therapy,

12 A Single NK Cell Receptor Binding 8 Different Ligands NKG2D can bind to any of eight naturally occurring ligands known to be overexpressed in over 80% of solid and hematological tumors NKG2D Binding Ligands MICA MICB ULBPs 1-6 NKG2D ligands are expressed by stressed cells during infection, tumorigenesis or DNA damage 12

13 CAR-T NKR-2 Multiple Targets Expression of at least one of NKG2D ligands: Triple negative breast cancers : 88% Colorectal cancers : 88% Ovarian cancers: 68% Bladder cancers: 78% of the primary tumors and 100% of the metastases Pancreatic cancers: 86% NSCLC Lung cancers: 92% (100% non-squamous NSCLC) 13

14 CAR-T NKR-2, Potential Best-In-Class CAR-T Therapy 80% of all cancers Single receptor can recognize multiple tumor antigens Target the majority of solid and hematological tumors Impressive Preclinical Results 100% Cancer-free survival in multiple aggressive tumor models Long-term adaptive immune response Targeting tumors through multiple angles Attack the tumor cells Activate and recruit anti-tumor immune cells Eliminate immune suppressive cells from the tumor micro environment Disrupt the tumor s blood supply Promote adaptive immunity Controlled Safety Profile No lymphodepleting pre-conditioning Low persistence of engineered cells Major in vivo cell expansion unnecessary 14

15 CAR-T NKR-2 Clinical Development Plan THINK: A multinational (EU/US), open-label, dose escalation Phase 1 study to assess the safety and clinical activity of multiple administrations of CAR-T NKR-2 CAR-T NKR-2 Phase 1 Safety trial CAR-T NKR-2 THINK Phase 1 trial 1 administration Low dose Hematological tumors 3 administrations Optimal dose Hematological & solid tumors 15

16 NKR-2 Phase 1 Safety Trial Successfully Completed Single administration, dose-escalation Phase I autologous CAR-T NKR-2 study in patients with CAR-T NKR-2 Phase 1 Safety trial Cohort 1 Cohort 2 Cohort 3 Cohort 4 1 administration Low dose Hematological tumors 1x10 6 CAR-T NKR-2 Cells 3x10 6 CAR-T NKR-2 Cells 1x10 7 CAR-T NKR-2 Cells 3x10 7 CAR-TNKR-2 Cells N= Acute Myeloid Leukemia and Multiple Myeloma Dana Farber, last patient included in September Strong safety profile, including no cases of CRS, cell-related neurotoxicity, auto-immunity, or CAR-T related death. Unexpected signs of activity 4 patients showing prolonged survival, 1 AML patient showing stabilization of hematological parameters at 7 months. «1/100 dose» N= 12 16

17 THINK trial study design 17

18 2017 and 2018 Clinical Milestones Q Q Q Q Q Q Q THINK 1 st Patient EU 1 st Patient US Enrollment Dose 1 Completed Reporting Dose 1 Enrollment Dose 2 Completed Reporting Dose 2 Enrollment Dose 3 Completed Reporting Dose 3 Start Phase I Expansion Segment Dose Escalation Data Results Enrollment Expansion Segment Completed Topline Data PFS 6-Month Data SHRINK Initiate Study Enrollment Completed Topline Data PFS 6-Month Data LINK Initiate Study Enrollment Completed Topline Data PFS 6-Month Data B7H6 Initiate Study 18

19 Intellectual Property and Financial Snapshot Intellectual Property: Three patent families covering autologous products, pipeline and allogeneic platform Allogeneic patent provides fundamental exclusivity in the field of CAR-T cells that are TCR-deficient, regardless of method used to inhibit TCR Financial Snapshot: Cash Position: 82 million as of December 31, 2016 Enabling company s activities until Q Ticker: Nasdaq (CYAD), Euronext Paris & Euronext Brussels (CYAD.BB) 19

20 Corporate, Academic and Medical Partnerships CAR-T NKR-2 was invented by Dr. Charles Sentman at Dartmouth College and is exclusively licensed to Celyad. Celyad licensed allogeneic CAR-T NKR-2 to Ono Pharmaceutical in Japan, Taiwan and Korea in exchange for $12.5M upfront, $300M in potential milestones and double-digit royalties. 20

21 Experienced 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. Dieter Hauwaerts, VP Operations 7. Georges Rawadi, VP Business Development & IP 8. Philippe Dechamps, Chief Legal Officer 9. Philippe Nobels, Global Head Of Human Resources

22 Celyad ADR programme Celyad ADRs trade on NASDAQ Symbol CYAD Cusip Ratio 1 ORD:1 ADR DR ISIN US ORD ISIN BE Depositary Citibank Benefits of ADRs to US investors Clear and settle according to US standards. Offer the convenience of stock quotes and dividend payments in US dollars. Can be purchased/sold in the same way as other US stocks via a US broker. Provide a cost-effective means of international portfolio diversification. For questions about creating Celyad ADRs, please contact Citi: New York Michael O Leary michael.oleary@citi.com London Mike Woods michael.woods@citi.com

23 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