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

Transcription

1 Bringing Breakthrough Pioneering Therapies to Patients with Life-Threatening Diseases Corporate Presentation September 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 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 Celyad: Company overview 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 Phase I 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 CYAD-01 (CAR-T NKG2D) pipeline CLINICAL STAGE Autologous platform HEMATO CANCER INDICATIONS SOLID CANCER INDICATIONS CM-CS1 Phase 1 Trial - Completed THINK - Acute Myeloid Leukemia THINK - Multiple Myeloma THINK - Ovarian cancer THINK - Colorectal cancer THINK - Pancreatic cancer THINK - Bladder cancer THINK - Triple Negative Breast cancer SHRINK - Combo with chemotherapy LINK - Loco-regional administration PRECLINICAL STAGE Allogeneic platform 4

5 CYAD-01: A unique construct arming T-cells with a NK receptor to target and destroy cancer cells One natural construct that capitalizes 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 A single NK cell receptor binding 8 different ligands NKG2D can bind to any of eight naturally occurring ligands known to be overexpressed in more than 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 6

7 NKG2D expresses ligands in broad range of cancer indications 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) 7

8 Classical CAR-T A cell transplant paradigm Next Generation CYAD-01 Increasing deliverability and safety CYAD-01 : A novel paradigm to CAR-T The next frontier of cell therapy Less controlled In Vivo Expansion with potential for serious adverse events Persistence of CAR-T leading to the need to have control mechanisms Controlled dosing and PK to reduce adverse events and increase Effectiveness Managing kinetics through classical multiple infusion approach Primary modes of action through direct cytotoxicity Rapid clinical response but some relapse including Antigen Loss Variants Multiple Multiple modes MOA of action for increased for increased effectiveness effectiveness Induced adaptative immunity driving a progressive clinical response 8

9 CYAD-01 Modes of action identified from syngeneic mouse models Eradication of established tumors by multiple infusions of CYAD-01 with no pre-conditioning chemotherapy Short term persistence (7-10 days) Direct target cell killing Modulation of the local tumor microenvironment Reduced number of Tregs within tumor Alteration of myeloid compartment; reduced IL-6/IL-10 Anti-angiogeneic effect driven through targeting of tumor endothelial cells expressing NKG2D ligands Identification of CD8 + and CD4 + T-cell responses induced by CYAD- 01 therapy that drive prolonged anti-tumor immunity 9

10 CYAD-01 Syngeneic Models OVARIAN CANCER LEUKEMIA MULTIPLE MYELOMA 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): Multiple dosing No pre-conditioning 22/09/

11 CYAD-01: Mediate cytotoxicity and cytokine release during challenge with tumor cells Demoulin et al. Future Oncology

12 CYAD-01: Cell activity in vivo activity against established Panc-1 tumor cells Demoulin et al. Future Oncology

13 T a rg e t c e ll k illin g (% ) In vitro potency of CYAD-01 Cytotoxicity Cytotoxicity mediated by CYAD-01 CAR-T cells produced under GMP compliant conditions Kinetics of killing of pancreatic tumor cells by CYAD-01 CAR-T cells 13

14 CYAD-01 autologous clinical program includes various studies CM-CS-1 Study Open-label dose escalation Phase I study Single IV administration of CYAD-01 AML and MM relapsing post standard of care THINK Study Open-label dose escalation Phase I study Multiple IV administrations of CYAD-01 as stand alone according specific product profile 7 different cancer indications 14

15 CYAD-01: 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 NKG2D CAR-T NKG2D Phase 1 safety trial CAR-T NKG2D THINK Phase 1 trial 1 administration Low dose Hematological tumors No Lymphodepletion 3 administrations Optimal dose Hematological & solid tumors No Lymphodepletion 15

16 CYAD-01: Phase I safety trial successfully completed Single administration, dose-escalation Phase I autologous CAR-T NKG2D study in patients with CAR-T NKG2D Phase I Safety trial Cohort 1 Cohort 2 Cohort 3 Cohort 4 1 administration Low dose Hematological tumors 1x10 6 CAR-T NKG2D Cells 3x10 6 CAR-T NKG2D Cells 1x10 7 CAR-T NKG2D Cells 3x10 7 CAR-T NKG2D Cells N= N= 12 Acute Myeloid Leukemia and Multiple Myeloma Dana Farber, last patient included in September Strong safety profile, including no cell-related neurotoxicity, auto-immunity, or CAR-T related death. Unexpected signs of activity 4 patients showing unexpected benefit. 1 AML patient showed stabilization of hematological parameters at 6 months. 16

17 Hematological tumors Solid tumors CYAD-01: THINK trial study design targeting seven refractory cancers Phase I dose escalation segment Phase I dose expansion segment x10 8 1x10 9 3x10 9 All solid tumor types Recommended dose Bladder TN Breast Colorectal Ovarian Pancreatic 3x10 8 1x10 9 3x10 9 All hematological tumor types AML/MDS MM Recommended dose 17

18 CYAD-01: THINK trial (solid arm) promising early results at first dose level Promising early results at first dose level (3x10 8 ) Two metastatic colorectal cancer patients reported as Stable Disease at 3- months follow-up* Refractory pancreatic patient was in progression at the same time point No toxicity signals reported up to now Higher doses, longer follow-up + SHRINK and LINK * According to recent studies conducted on similar patient populations, median progression free survival in these patients under standard of care is between 1.9 and 3.2 months. Sources: Patients With Metastatic Colorectal Cancer Treated With Regorafenib or Placebo After Failure of Standard Therapy (CORRECT), Grothey A., Lancet Oncol Aug;16(8): ; Asian Subjects With Metastatic Colorectal Cancer Treated With Regorafenib or Placebo After Failure of Standard Therapy (CONCUR), Li J., Lancet Oncol Jun;16(6):

19 CYAD-01 autologous clinical program includes various studies CM-CS-1 Study Open-label dose escalation Phase I study Single IV administration of CYAD-01 AML and MM relapsing post standard of care THINK Study Open-label dose escalation Phase I study Multiple IV administrations of CYAD-01 as stand alone according specific product profile 7 different cancer indications SHRINK Study Open-label dose escalation Phase I study Multiple IV administrations of CYAD-01, combined with FOLFOX Potentially resectable liver metastases from colorectal cancer LINK Study Open-label dose escalation Phase I study Multiple hepatic transarterial administrations Unresectable liver metastases from colorectal cancer SIBLINK Study Open-label dose escalation Phase I study Multiple IV administration of SIBLING CYAD-01 AML relapsing post allo-hct 19

20 2017 and 2018 clinical milestones Q Q Q Q H H SOLID Enrollment Dose 1 Completed Reporting Dose 1 Completion enrollment Dose 2 Reporting Dose 2 Completion enrollment Dose 3 Start Expansion Segment Reporting Dose 3 Enrollment Expansion Segment Completed PFS 6- Month Data THINK HEMATO Topline Data 1st Patient EU Completion enrollment Dose 1 Reporting Dose 1 Completion enrollment Dose 2 Reporting Dose 2 & 3 Completion enrollment Dose 3 Top line data Expansion Segment PFS 6- Month Data Start Phase I Expansion Segment 20

21 2017 and 2018 clinical milestones Q Q Q Q H H SHRINK LINK Initiate Study Topline Data PFS 6-Month Data Initiate Study Topline Data PFS 6-Month Data SIBLINK Initiate Study Topline Data 21

22 Intellectual Property Overview Three patent families covering autologous products pipeline CYAD-01 (CAR-T NKG2D): two granted US patents, covering chimeric NK cell receptor CAR-Ts CAR-T B7H6: pending applications in US, Europe, China and Japan on B7-H6 CAR-Ts B7-H6 is a ligand of the NKp30 receptor CAR-T NKp30: pending US application on chimeric NKp30 receptor CAR-Ts One patent family covering allogeneic platform (see next slide) 22

23 Intellectual Property Allogeneic platform One patent family covering allogeneic platform: Three granted US patents, covering TCR-deficient T-cells, methods of producing them, and methods to use them to treat cancer >10 applications pending in different jurisdictions Allogeneic patent provides fundamental exclusivity in the field of CAR-T cells that are TCR-deficient, regardless of method used to inhibit TCR Opportunity for licensing (e.g. Novartis) Can be combined with autologous pipeline 23

24 Financial snapshot Cash Position: 69 million as of June 30, 2017 Enabling company s activities through 2019 Ticker: Nasdaq (CYAD), Euronext Paris & Euronext Brussels (CYAD.BB) 24

25 Academic partnerships Institut Curie is a world class research institution focusing on cancer and immunity, and positioning translational science at the heart of its approach CAR-T platform developed by Celyad was invented by Prof. Charles Sentman at Dartmouth College and is exclusively licensed to Celyad Ongoing research collaboration with Prof Sentman and his team March 2016: Celyad entered into a 3 year collaboration with Institut Curie Collaboration with Professor Sebastian Amigorena to dissect the molecular interactions of the NKR2 chimeric antigen receptor with individual NKG2D ligands to better understand NKR2 CAR-T cell responses generated upon successful target binding Collaboration with Dr Franck Perez concerning methods to facilitate targeting of NK receptor ligands including the B7H6 target 25

26 Corporate partnerships ONO is a leader in cancer-immunotherapy in Japan with the first approved checkpoint inhibitors, OPVIDO 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 Novartis is a global healthcare company based in Switzerland that provides solutions to address the evolving needs of patients worldwide May 2nd, 2017: Celyad grants to Novartis a nonexclusive license for its allogeneic TCR-deficient CAR-T cells patents 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 26

27 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, Chief Legal Officer 8. Philippe Nobels, Global Head Of Human Resources /09/

28 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

29 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