Celyad s CAR-T NKR-2 Program Conference Call Presentation Wednesday, December 7 th 2016 2:00pm CET / 8:00am EST
Forward Looking Statements 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 and C-Cure, 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 forward-looking statements, including risks associated with on-going ex parte re-examination of the Company s U.S. patent number 9,181,527, including the risk that the U.S. Patent and Trademark Office may decide to cancel all or a portion of the claims contained therein, 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 III clinical trials for C-Cure and 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. C3BS-CQR-1, C-Cure, NKG2D CAR T-cell, CAR-T NKR-2, C-CathezTM, Celyad, CHART-1, CHART-2 and OnCyte logos are signs internationally protected under applicable Intellectual Property Laws. Mayo Clinic holds equity in Celyad as a result of intellectual property licensed to the Company. We kindly remind you that the conference call will be audio recorded and posted on Celyad s website until 10 days after th call. 2
Agenda 1. Data readout from the CAR-T NKR-2 Phase I trial presented at ASH 2016. 2. CAR-T NKR-2: unique construct and specificities. 3. Design and rationale for the upcoming THINK trial. This presentation will be followed by a Q&A session. 3
Data readout from the CAR-T NKR-2 Phase I trial presented at ASH 2016 4
CAR-T NKR-2 Phase I Trial Primary Objectives: Safety and Feasibility 2015 2016 NKR-2 Safety Phase I Cohort 1 Cohort 2 Cohort 3 1 administration Low dose Liquid tumors 1x10 6 NKR-2 Cells 3x10 6 NKR-2 Cells 1x10 7 NKR-2 Cells N= 3 3 3 Single administration, dose-escalation Phase I autologous NKR-2 study in patients with Acute Myeloid Leukemia and Multiple Myeloma [Dana Farber * last patient Sept 2016] Strong safety signals, including no cases of CRS, cell-related neurotoxicity, autoimmunity, or CAR-T related death. Cohort 4 3x10 7 NKR-2 Cells «1/100 dose» 3 N= 12 5
No Dose Limiting Toxicity AE monitoring Grade 3 Grade 4 No DLTs No cytokine release syndrome, NG2D CAR-Trelated neurotoxicity, severe auto-immunity, or significant infusion reactions. 94 AEs reported, 17(18%) Grade 3, 7 (7%) Grade 4. 4 patients (22%) experienced Grade 3 and 2 patients (17%) had Grade 4 Aes. All were consider NOT related to NKG2D CAR T infusion, but rather 2/2 disease progression 2 patients in cohort 4 developed Grade I maculopapular rash between 1 and 3 months. In patient 13, probably attributed to CAR T cells. Total incidence, 4 Patients 3 Patients 1- Parainfluenza 1- Neutropenia, 1- Elevated LFTs Cohort 1 (n=3) thrombocytopenia, biliary 2- Anemia sepsis 1- Hypernatremia 1- Influenza A Cohort 2 (n=3) 1- Cord Compression 0 1- Thromboembolism Cohort 3 (n=3) 1- Febrile neutropenia 1- Intracochlear bleed Cohort 4 (n=3) 1- Thrombocytopenia 1 GI bleed/anemia 6
CAR-T NKR-2 Phase I results: Clinical outcome As of Dec, 2016, 7 of 12 subjects had died of their disease. Overall survival is 4.8 mos. Patient 3 (MM-dose 1x10 6 ) is demonstrating longevity on subsequent myeloma therapies, despite aggressiveness of disease prior to infusion. Patient 5 maintained stable disease (bordering on PR) for 6 months on a subsequent IDH-1 inhibitor trial despite having a mutated allele frequency of <5% IDH and 54% p53 mutation at infusion. Patient 7 (AML, dose 1x10 7 ), despite 50% blasts and p53 mutation at infusion, demonstrated relative peripheral blood hematologic stability for 3 months. Marrow results were not available. If retrospectively, a definition of stable disease used in other AML trials was applied (<50% change in BM blasts, maintained for 12 weeks, without further therapy), Patient 13 (AML, dose 3x10 7 ) demonstrates stable disease at 3+ months. He has improvement in all hematologic parameters. 7
Trial conclusions Among AML/MDS and MM patients, a single dose of NKG2D CAR-T cells without lymphodepletion was feasible and well tolerated without DLTs over a range of 1x10 6 to 3x10 7 T cells. Objective clinical responses were not seen. However, cases of unexpected survival and/or improvement in hematologic parameters were noted in both AML and MM patients, some with and some without subsequent therapy. NKG2D CAR-T-specific activity against autologous tumor-containing cells was demonstrated in vitro in the 2 patients tested. This paves the way for studies of multiple infusions and higher doses of NKG2Dexpressing CAR-T cells in numerous malignancies. 8
The CAR-T NKR-2: unique construct and specificities 9
NKG2D receptor: the starting point of innovation NKG2D is an activating receptor that is expressed on NK cells. Killing activity is dependent on NKG2D ligand expression & independent of inhibitory signalling. NKG2D ligands: MICA, MICB, ULBPs 1-6. NKG2D ligands are absent or expressed at very low levels in normal tissues. NKG2D ligands are expressed by: Cells under stress conditions (DNA damage Infection, or Malignancy). (Tumor) Neo-vascularization in murine tumor models. Regulatory T-Cells and MSDC (in murine models). Numerous tumor types express NKG2D ligands (80%) including: bladder (78%), breast (TNB 88%), colorectal (88%), leukemia, myeloma, ovarian and pancreatic (86%)*. Both membrane and soluble ligands. *Source: Celyad November 2016 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 CAR-T NKR-2 Induces of a Lasting Adaptive Immunity Acquired adaptive immunity for long-term recurrence protection in Multiple Myeloma (MM) model Survivors were used to re-challenge 100% of animals re-challenged with the same tumor type survived 1 0 0 W T (n = 1 1 ) C H (n = 1 3 ) 1 0 0 5 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 0 0 2 0 4 0 6 0 8 0 1 0 0 T im e 0 0 2 0 4 0 6 0 8 0 T im e Barber, A. et al., Gene Ther. (2011) 11
CAR-T NKR-2 has demonstrated promising preclinical results in mice Human NKR-2 cells destroy human tumor in mice Pancreatic cancer 12
CAR-T NKR-2 Mechanisms of Action Beyond Direct Killing Attack the tumor cells Prevent the tumor cells from evading the immune system via modulation of the immunosuppressive tumor microenvironment. Disrupt the tumor s blood supply by targeting of NKG2D ligands expressed upon tumor neovasculature. Activate and recruit anti-tumor immune cells to control any minimal residual disease Promote adaptive immunity. Controlled Safety Profile No lymphodepleting pre-conditioning. Low persistence of engineered cells. Major in vivo cell expansion unnecessary. Impressive Preclinical Results 100% Cancer-free survival in five tumor models. 100% Long-term adaptive immune response. 13
Design and rationale for the upcoming THINK trial 14
CAR-T NKR-2 clinical development plan 2013 2015 2016 Q2-2018 PRECLINICAL NKR-2 Safety Phase I THINK Trial Animal Proof of Concept 1 administration Low dose Liquid tumors 3 administrations Optimal dose Liquid & solid tumors 15
THINK Study design Phase I Expansion 2 Liquid tumors 5 Solid tumors Open-label study in the 7 indications 3+3 design to determine Maximum Tolerated Dose (MTD) on basis of Phase I Dose Limiting Toxicity Tested dose: 3x10 8, 1x10 9, 3x10 9 Patients treated with the recommended dose based on MTD determined in Phase I arm to assess clinical activity 16
THINK Cancer indications 5 Solid tumors Colorectal cancer (CRC), Epithelial ovarian and fallopian tube carcinoma Urothelial carcinoma Triple-negative breast cancer (TNBC) Pancreatic cancer 2 Hematological tumors Acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) Multiple myeloma (MM) All these tumor types responded well to the treatment in mice and overexpress NKG2D ligands (average: 85% in primary tumor samples). Bladder = 100% in metastases. 17
Upcoming Milestones Start of multiple dose THINK solid & liquid tumor trial in Belgium before yearend. Start of multiple dose THINK solid & liquid tumor trial in the US in the next weeks. Interim data from multiple dose THINK trial in Q3 2017. Start of THINK expansion phase in 2H17 in EU and US. Final data from THINK trial expected 2H18. 18
Contacts BELGIUM Celyad SA Axis Business Park Rue Edouard Belin, 2 B-1435 Mont-Saint-Guibert +32(0) 10 39 41 00 USA Celyad Inc. Seaport East 2 Seaport Lane Boston, MA. 02210 +1 857-990-6900 www.celyad.com