Pioneering breakthrough therapies for patients with life-threatening diseases. Investor Presentation July 2018

Transcription

1 Pioneering breakthrough therapies for patients with life-threatening diseases Investor Presentation July 2018

2 Forward-Looking Statements This presentation may contain forward-looking statements, including statements regarding the safety and efficacy of CYAD-01 and the new mab manufacturing method used to manufacture this drug product candidate; statements concerning the ongoing and planned clinical development of CYAD-01. Forward-looking statements may involve known and unknown risks, uncertainties and other factors which might cause actual results, financial condition and liquidity, performance or achievements of Celyad, or industry results, to differ materially from those expressed or implied by such forward-looking statements. In particular it should be noted that the interim data summarized above are preliminary in nature. The THINK trial is not complete. There is limited data concerning safety and clinical activity following treatment with the CYAD-01 drug product candidate. These results may not be repeated or observed in ongoing or future studies involving the CYAD-01 drug product candidate. 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 statements about: the initiation, timing, progress and results of our preclinical studies and clinical trials, and our research and development programs; our ability to advance drug product candidates into, and successfully complete, clinical trials; our ability to successfully manufacture drug product for our clinical trials, including with our new mab manufacturing process and with respect to manufacturing drug product with the desired number of T cells under our clinical trial protocols; our reliance on the success of our drug product candidates, including our dependence on the regulatory approval of CYAD-01 in the United States and Europe and subsequent commercial success of CYAD-01, both of which may never occur; the timing or likelihood of regulatory filings and approvals; our ability to develop sales and marketing capabilities; the commercialization of our drug product candidates, if approved; the pricing and reimbursement of our drug product candidates, if approved; the implementation of our business model, strategic plans for our business, drug product candidates and technology; the scope of protection we are able to establish and maintain for intellectual property rights covering our drug product candidates and technology; our ability to operate our business without infringing, misappropriating or otherwise violating the intellectual property rights and proprietary technology of third parties; cost associated with enforcing or defending intellectual property infringement, misappropriation or violation; product liability; and other claims; regulatory development in the United States, the European Union, and other jurisdictions; estimates of our expenses, future revenues, capital requirements and our needs for additional financing; the potential benefits of strategic collaboration agreements and our ability to enter into strategic arrangements; our ability to maintain and establish collaborations or obtain additional grant funding; the rate and degree of market acceptance of our drug product candidates, if approved; our financial performance; developments relating to our competitors and our industry, including competing therapies and statements regarding future revenue, hiring plans, expenses, capital expenditures, capital requirements and share performance. 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 6, 2018 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 and Celyad s actual results may differ materially from those expressed or implied by these forward-looking statements. Celyad expressly disclaims any obligation to update any such forwardlooking 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 in a nutshell Novel cell therapy platform focused on developing the next wave of CAR-T innovation Lead candidate, CYAD-01, a CAR-T therapy leveraging the natural killer receptor NKG2D, being developed for the treatment of hematologic and solid tumors CAR-T NKG2D approach supported by data to date in Phase I/II THINK trial, with activity observed in several AML patients (including one complete response) and in patients with CRC and ovarian cancer Pursuing both autologous and allogeneic approaches Strong intellectual property position Collaborations with world-class pharma companies, including Novartis and Ono Pharma, as well as leading academic institutions 3

4 Agenda CAR-T; It s here and now Celyad building on experience and daring to invent Upcoming milestones and financial considerations 4

5 Beyond current momentum for CAR-T therapies: Towards the next wave of CAR-T technologies Next Generation CAR-T aims to: Improve outcomes Address solid tumors Overcome the complexities of current approaches 5

6 Agenda CAR-T; It s here and now Celyad building on experience and daring to invent Upcoming milestones and financial considerations 6

7 Three integrated strategies to optimize each element of the CAR-T construct to tackle both liquid and solid tumors CD19 NKG2D B7H6 Target Homing NKG2D: one construct targeting multiple tumor types Targets already validated with current generation CAR-T (e.g. CD19) in indications that are harder to treat, leveraging the CARGO platform Targets validated as antibody based cancer treatments CARPOOL Signalling Improving signal transfer between target and T-cell (CAR engineering) CARGO T-cell Activity Engineering the cell to increase tumor infiltration, and targeting the tumor microenvironment for both hematologic and solid tumors 7

8 Celyad s strategy has produced a deep pipeline of CAR-T therapies CYAD-01 NKG2D CYAD-101 NKG2D CYAD-02 NKG2D CYAD-03 NKG2D CYAD-04 CD19 CYAD-05 B7H6 8

9 CYAD-01 binding of stress-induced ligands provides an opportunity to target a broad range of cancers NKG2D Target Expression of at least one of NKG2D ligands (updated): Bladder: 96% Colorectal: 100% NSCLC Lung: 100% Ovarian: 84% Pancreatic: 90% Triple negative breast: 100% DAP10 Costimulatory domain CD3ζ Source: Dulphy N., Toubert A. et al unpublished data; Celyad 2017 Unpublished data, IHC 9

10 NKG2D CYAD-01 seeks to target many of the challenges facing current CAR-T therapies Challenges related to current CAR approaches Haematologic cancers Haematologic and solid cancer types Responses only observed with preconditioning First responses observed in absence of preconditioning One CAR construct typically targets one antigen and one cancer type One CAR construct targets multiple ligands and multiple cancer types May not be suitable for repeated injections No targeting of tumor microenvironment (TME) or tumor vasculature No adaptive immunity Suitable for repeated injections implying different target product profile TME and tumor vasculature modes of action demonstrated in preclinical settings Adaptive immune response observed in preclinical settings 10

11 Multifaceted attack enables CYAD-01 to address solid tumors 2 REDUCTION OF THE IMMUNO-SUPPRESSIVE FACTORS IN THE TME 1 DIRECT CELL KILLING OF TUMOR Immunosuppressive cells CYAD-01 Tumor cells 3 Blood vessels ANTI-ANGIOGENEIC EFFECT BY TARGETING OF TUMOR ENDOTHELIAL CELLS EXPRESSING NKG2D LIGANDS Host Immune cells 4 ADAPTIVE IMMUNE & SPECIFIC ANTITUMOR RESPONSE POST TREATMENT Source: Lonez et al BMJ Open 7:e

12 In preclinical models, CYAD-01 demonstrated broad activity across both hematologic and solid tumors, without the need for preconditioning treatment LYMPHOMA MULTIPLE MYELOMA OVARIAN CANCER Zhang et al., 2007 Cancer Res; 67: (22) Barber et al J Immunol. 183(4): Barber et al., 2011 Gene Ther. 18(5):

13 CYAD-01 clinical development plan 2019/ /2018 Towards confirmatory trial(s) 2015/2016 Safety First in human trial Evaluating optimal approaches Ongoing Stand alone Combination with standard of care to reduce tumor burden prior to CAR-T Preconditioning to trigger in vivo expansion of CAR-T Potential BTD strategies in different patient populations e.g. Low tumor burden in RR AML Preconditioning in fit RR patients in AML and CRC SOC for CRC and AML to reduce tumor burden in earlier lines 13

14 Based on tolerability and signs of clinical activity in Phase I, CYAD-01 is currently being evaluated in the THINK 1 trial THINK Trial (Phase I) Stand alone/no-preconditioning Study Design One cycle: Enrollment of patients with hematologic malignancies & solid tumors Three administrations Primary endpoints: Safety & tolerability Secondary endpoint: Efficacy as monotherapy Two cycles amendment: Second cycle of treatment administered to patients with signs of clinical activity 2 D-35 Washout period D-21 Apheresis 1st CYAD-01 (D1) 2nd CYAD-01 (D2) 3rd CYAD-01 (D3) D1 D15 D29 13 weeks w/o any other cancer therapy 3 dose levels evaluated: 3x10 8,1x10 9 and 3x10 9 D43 D57 End safety Tumor assessment 4th CYAD-01 (D1) 5th CYAD-01 (D2) 6th CYAD-01 (D3) Tumor assessment C2 D1 (D71 max) C2 D15 C2 D29 C2 D43 C2 D57 End safety (1) THINK: THerapeutic Immunotherapy with NKG2D-based Therapy (2) Complete response/remission (CR) or partial response/remission (PR) or stable disease (SD) according the tumor evaluation guidelines Cycle 2 14

15 Same patient Same patient THINK Interim Safety Data (April 5 th, 2018) : All related AEs Grade 3 Patients, n (%) DL NKR-2 (n = 4) THINK SOLID ARM (28 doses/ 11 patients) DL NKR-2 (n = 4) DL NKR-2 Grade 3 Grade 4 Grade 5 Grade 3 Grade 4 Grade 5 Grade 3 Grade 4 Grade 5 Cytokine release syndrome (CRS) 1 1* Acute respiratory distress syndrome 1* Lymphocyte count decreased 1* Chills 1 (n = 3) Patients, n (%) DL NKR-2 (n = 6) THINK HEMATOLOGICAL ARM (23 doses/ 9 patients) DL NKR-2 Grade 3 Grade 4 Grade 5 Grade 3 Grade 4 Grade 5 Cytokine release syndrome 1 Platelet count decreased 1 Lymphocyte count decreased 1 1* Hypoxia 1* Pneumonitis 1* (n = 3) * All events in same patient. Patients are only counted once for each preferred term and are listed by maximum grade toxicity Adverse events data disclosed above is preliminary and subject to further review, and classification. As such, adverse events reflected above may change as a result of such further analysis 15

16 Dose Level 2 Dose Level 1 Dose Level 1 THINK early readout: Clinical activity reported in relapsed refractory AML patients treated at the per-protocol dose Best Response to date Months 1 CRi CR (MRD- Post HSCT) SD HI Treatment Cycle 1 Allo- HSCT End of Treatment Evaluation Demethylation Agent Demethylation Agent CYAD-01 active against AML tumor in 3/3 patients treated at the intended dose Blast reduction in Bone Marrow in all patients up to and including at least the third injection Hematological parameters improving in all patients No significant Adverse Events (low grade i.e.<grade 3, cytokine release syndrome, no neurotoxicity) Next anticipated steps: Complete Dose level 3; Expansion cohort according to Objective Response Rate As of June 2018, 5 more patients are currently in treatment or follow-up 16

17 Case report of complete response in AML patient AML Patient in Dose Level 1 of THINK (3x10 8 CYAD-01/injection) BM before treatment: 7% blasts BM evaluation at day +28: 2% blasts with normocellularity and trilineage hematopoiesis Patient in Morphologic leukemia-free state (CR- MLFS) Confirmed at day +56 Progressive hematological recovery after treatment Patient at 6 month; CR, MRD- Source: Sallman et al. Haematologica

18 THINK early readout: Signals of activity in colorectal cancer and ovarian cancer As of December 31 st : Two out of four metastatic colorectal cancer patients reported as stable disease up to 3- months follow-up 1,2 One of out one ovarian cancer patient treated at per-protocol dose reported as stable disease up to 2-months follow-up Next anticipated steps: multiple injections, longer follow-up + SHRINK and LINK As of June 30th 2018, 6 more CRC patients have been treated (1) 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). (2) Fifth CRC patient treated at a dose lower then per-protocol dose did not show signs of clinical activity Source: Grothey et al., 2013 Lancet. 381(9863):303-12; Li et al., Lancet Oncol. 16(6):619-29; Moriwaki et al., Oncologist Sep

19 CYAD-01: Defining the optimal approach to AML and CRC Ongoing Planned CYAD-01 Patient population Hematological Acute Myeloidindications Leukemia Colorectal Cancer Patient population Relapsed refractory w/o preconditioning THINK Stand alone (multiple injections) THINK Relapsed refractory w/o preconditioning Relapsed refractory with preconditioning DEPLETHINK AML Preconditioning (Cy-Flu) DEPLETHINK CRC Relapsed refractory with preconditioning 1st line, unsuitable for induction therapy EPITHINK Concurrent with standard of care SHRINK 1st line metastatic with standard of care Relapsed post allograft SIBLINK Other LINK 1st line, w/ unresectable liver metastases 19

20 CYAD-101 represents a potential allogeneic option without gene editing CD3ε CD3γ TCRα TCRβ CD3δ CD3ε NKG2D Target Engineered CYAD-01 (NKG2D-based CAR-T cell) Alloreactivity controlled through co-expression of an inhibitory peptide (T cell receptor inhibitory molecule TIM) to reduce TCR-signaling and thereby reduce Graft versus Host Disease (GvHD) DAP10 Costimulatory domain TIM8 TIM8 CD3ζ 20

21 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 ) In preclinical models, tumor growth was decreased following treatment with CYAD-101 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 CYAD-101 T IM 8.N K R 2 * * 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-101 Manuscript in preparation 21

22 Corporate collaborations May 2, 2017: Celyad grants to Novartis a non-exclusive license for its allogeneic TCR-deficient CAR-T cells patents for two undisclosed targets Deal value: $96 million plus Royalties July 11, 2016: Celyad grants exclusive license to ONO for the development and commercialization of CYAD- 101 T-cell immunotherapy in Japan, Taiwan and Korea License in exchange for $12.5M upfront, $300M in potential milestones and double-digit royalties Celyad retains all rights to grant further licenses 22

23 Agenda CAR-T; It s here and now Celyad building on experience and daring to invent Upcoming milestones and financial considerations 23

24 Milestones Safety profile SITC timing Full Phase 1 CRC data Preclinical on 02, CARGO, CARPOOL, 04 and 05 Start Phase 2B AML Proof of concept CARGO Proof of concept Allogeneic ASH timing Full data set CYAD-01 AML stand-alone Interim report on DEPLETHINK and EPITHINK 24

25 Financial Snapshot Key Financial Figures Cash Position: 25 million as of March 31, 2018* Net proceeds from the global offering: 43 million Cash at Q Net proceeds Enabling company s activities until mid-2020 Ticker: Nasdaq (CYAD) Euronext Paris & Euronext Brussels (CYAD.BB) 25

26 Celyad highlights: building leadership in CAR-T space Comprehensive CAR-T strategy Leveraging stress ligands of NKG2D constructs Building on early signals and improving outcomes Indications extension after initial focus on AML and CRC Autologous Cell Manufacturing Paradigm shift Process improvement with particular focus on yields and COGS Automation for feasible and cost effective autologous cell therapies Towards point of care processing to enable more common indications Allogeneic CAR-T Cell Therapy Broad coverage of the field thanks to a strong IP position, in particular patents around TCR knockdown in CAR-T cell therapy Development of allogeneic NKG2D platform (CYAD-101) and TIM platforms (broad based allogeneic CAR T products) 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. Philippe Dechamps, CLO 7. Philippe Nobels, VP Human Resources

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