Celyad Oncology SA · EURONEXT:CYAD
Celyad Oncology SA — Investor Day (September 2020)
56 slides from Celyad Oncology SA's investor day presentation, Sep 29, 2020
Slide 1: Celyad Oncology Research & Development Day Webinar
Celyad Oncology Research & Development Day Webinar William Blair Growth Stock Conference September 29, 2020
Slide 2: Disclaimers
Disclaimers This may contain forward-looking statements, within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995. Forward-looking statements may include statements regarding: the timing of the expansion cohort of Phase 1 alloSHRINK trial and t
Slide 3: Research & Development Day – Today's Agenda
Celyad Oncology’s Research & Development Day – Today’s Agenda Topic Discussant Welcome & Introductions Filippo Petti Immuno-oncology and Treatment Landscape for mCRC Richard Kim, MD – Moffitt Cancer Center Update on CYAD-101 alloSHRINK Phase 1 Trial Frederic Lehman, MD Merck Clinical Collaboration –
Slide 4: Celyad Oncology – Novel Perspective on CAR T Development
Celyad Oncology – Novel Perspective on CAR T Development Differentiation within Pioneer in Ahead of the Class Robust Intellectual Allogeneic CAR T NKG2D CAR Ts in Solid Tumors Property Estate • Leader in non-gene • Multiple NKG2D • CYAD-101 represents a • Nine foundational U.S. edited allogeneic CAR
Slide 5: Allogeneic CAR T Competitive Landscape
Allogeneic CAR T Competitive Landscape Hematological Malignancies Solid Tumors Target Indication Preclinical Clinical Target Indication Preclinical Clinical BCMA MM 2 3 NKG2DL mCRC 1 1 CD19 ALL/NHL 5 3 B7H3 Solid tumors 1 -- CD20 NHL 1 1 CD70 RCC 1 1 CD22 CLL/NHL -- 1 GPC3 HCC 1 -- CD38 MM 1 -- Meso
Slide 6: Overview of mCRC
Overview of mCRC Richard Kim, MD Professor, Section Chief of Gastrointestinal Oncology Moffitt Cancer Center
Slide 7: Current Landscape of Treatment of metastatic Colorectal cancer (mCRC)
Current Landscape of Treatment of metastatic Colorectal cancer (mCRC) Richard Kim M.D. Professor Section Chief of GI Oncology Department of Gastrointestinal Oncology Moffitt Cancer Center Tampa, FL 6
Slide 8: Impact of Colorectal Cancer (CRC)
Impact of Colorectal Cancer (CRC) • CRC US statistics: – 3rd highest incidence rate (~135,000/yr) – 2nd highest mortality rate (~49,000/yr) • CRC Global statistics: – 3rd highest incidence rate ( ~ 1.2million/yr) – 4th highest mortality rate (~608,000/yr) • The burden of disease is clearly evident…
Slide 9: Metastatic CRC Treatment Today
Metastatic CRC Treatment Today Over a Dozen Molecules to Personalize Patient Therapy Patient X Patient Y Patient Z Pembrolizumab or Nivolumab 8
Slide 10: Current Landscape in mCRC
Current Landscape in mCRC • Bevacizumab and epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) are competing for first-line patients in KRAS wild type (wt) CRC • Bevacizumab, ramucirumab and aflibercept are competing for second-line patients with each other, and with EGFR mAbs in K
Slide 11: Patients Relapsing or Refractory to Chemotherapy
Patients Relapsing or Refractory to Chemotherapy Two drugs currently available: • Regorafenib • TAS-102 (trifluridine/tipiracil) 10
Slide 12: Comparison of Regorafenib, TAS-102 after mCRC Progression
Comparison of Regorafenib, TAS-102 after mCRC Progression Agent Regorafenib TAS-102 Trial CORRECT[1] CONCUR2 RECOURSE3 TERRA4 Prior 100% BEV 60% 100% BEV 20% BEV biologics 100% EGFR mAbs 53% EGFR mAbs 18% EGFR mAbs 18% Prior Rego Rego BSC + PL Rego BSC + PL TAS-102 BSC + PL TAS-102 BSC + PL (n = 505
Slide 13: How about immunotherapy in mCRC?
How about immunotherapy in mCRC? 12
Slide 14: Background
Background • In non-selected colorectal cancer patients PD-1 blockade seems to be ineffective • Average tumor has dozens of somatic mutations • Mismatch repair deficient tumors harbor thousands of mutations • Somatic mutations have the potential to generate neo-antigens which can be recognized by im
Slide 15: Approved Checkpoint Inhibitors in mCRC
Approved Checkpoint Inhibitors in mCRC • Pembrolizumab (anti–PD-1) – For MSI-H or dMMR CRC that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan • Nivolumab (anti–PD-1) – For MSI-H or dMMR CRC that has progressed following treatment with a fluoropyrimidine, oxa
Slide 16: Pembrolizumab in MMRD/P CRC: Efficacy
Pembrolizumab in MMRD/P CRC: Efficacy Outcome MMRD CRC (n = 28) MMRP CRC (n = 25) Median follow-up, mos 9.3 6 ORR, % (95% CI) 57 (39-73) 0 (0-13) Response, % ▪ CR 11 0 ▪ PR 46 0 ▪ SD (Wk 12) 32 16 ▪ PD 4 44 ▪ NE (no 12-wk scan) 7 40 Disease control rate, % (95% CI) 89 (73-96) 16 (6-35) Median PFS, m
Slide 17: NCCN Guidelines - mCRC
MOFFITT MEDICAL GROUP G NCCN Guidelines - mCRC CONTINUUM OF CARE - SYSTEMIC THERAPY FOR ADVANCED OR METASTATIC DISEASE* based therapy without irinotecan SUBSEQUENT THERAPY? FOLFIRIP or irinotecan® POLFIRIS + (bevacizumab® [preferred] or ziv-aflibercept?:!° or ramucirumab®* or Irinotecan®* (bevacizum
Slide 18: Can we convert non-immunogenic tumor into immunogenic tumor?
Can we convert non-immunogenic tumor into immunogenic tumor? 17
Slide 19: Therapeutic Outcome Correlates with T cell Presence
Therapeutic Outcome Correlates with T cell Presence • Higher T cell levels in tumor microenvironment increases chance of survival in CRC patients From: Galon et al 2006, Science 18
Slide 20: Immunotherapies Under Development for GI Tumors
Immunotherapies Under Development for GI Tumors Several IO approaches are currently being investigated clinically • Immune checkpoint inhibitors in combination with chemo-/radiotherapy • Immune checkpoint inhibitors + TKIs • CAR-T cell therapies • Oncolytic viruses • Vaccines 19
Slide 21: Combination Strategy for MSS Colorectal Cancer
Combination Strategy for MSS Colorectal Cancer Regorafenib: Approved for all CRC Nivolumab: Approved for MSI-H CRC • The response rate of either agent alone in microsatellite stable patients is <5% 20
Slide 22: REGONIVO Regorafenib + Nivolumab
REGONIVO REGOMUNE REGONIVO (Kim) Regorafenib + Nivolumab Regorafenib + Avelumab Regorafenib + Nivolumab (25 mCRC pts)1 (n=47)2 (n=28)3 Median Age (range) 55 (31 – 77) 62 (26 – 83) 55 (31 – 79) Male/female, % 72 / 28 74 / 26 61 / 39 PS 0/1, % 100 / 0 60 / 40 39 / 61 Right/left sided tumors, % 20 / 80
Slide 23: Conclusions
Conclusions • Next generation sequencing (NGS) testing is essential to optimize clinical outcomes for patients with advanced CRC • ALL pts should be tested for MMR/MSI status • VEGF and EGFR mAbs competing for first-line patients in RAS wt CRC • Regorafenib and TAS-102 are options in refractory mCRC
Slide 24: Thank you! GI Oncology Questions
Thank you! GI Oncology Questions richard.kim@moffitt.org 23
Slide 25: Update on CYAD-101 alloSHRINK Phase 1 Trial
Update on CYAD-101 alloSHRINK Phase 1 Trial Frederic Lehmann, MD VP Head Global Clinical Development & Medical Affairs
Slide 26: CYAD-101 – TIM-based Allogeneic CAR T Candidate for mCRC
CYAD-101 – TIM-based Allogeneic CAR T Candidate for mCRC Background on CYAD-101 and alloSHRINK Phase 1 Trial • CYAD-101 co-expresses NKG2D receptor, novel allogeneic TCR Inhibitory Molecule (TIM) and selection marker • The expression of TIM results in the competitive inhibition of CD3ζ and reduces s
Slide 27: alloSHRINK Trial – Change in Tumor Burden From Baseline
alloSHRINK Trial – Change in Tumor Burden From Baseline RAS BRAF UNK UNK Mutated Wild-type Key Summary 40 PD • Tumor burden decrease was 30 observed in eight out of 15 PD evaluable patients, including six 20 PD(1) PD(1) SD of nine patients at dose level 3 10 SD % change from screening • Clinical act
Slide 28: alloSHRINK Trial – Median Progression-Free Survival
alloSHRINK Trial – Median Progression-Free Survival All patients (15 pts) – mPFS: 3.9 months Dose Level 3 (9 pts) – mPFS: 4.6 months In addition, mPFS for patients with ≥ 3 prior metastatic lines and RAS mutation was 3.9 months and 4.5 months, respectively 27
Slide 29: alloSHRINK Trial – Next Steps
alloSHRINK Trial – Next Steps alloSHRINK Expansion Cohort • Recommended dose: 1 billion cells per infusion • Trial amended to evaluate three infusions of CYAD-101 following FOLFIRI preconditioning chemotherapy • Enrollment criteria allows for recruitment of mCRC patients who have progressed under pr
Slide 30: MSD Clinical Collaboration – KEYNOTE-B79 Trial
MSD Clinical Collaboration – KEYNOTE-B79 Trial David Gilham, PhD Chief Scientific Officer
Slide 31: CYAD-101 with KEYTRUDA in Refractory mCRC
CYAD-101 with KEYTRUDA® in Refractory mCRC Background on KEYNOTE-B79 Trial • Today, we announced a clinical trial collaboration with MSD, a tradename of Merck & Co., Inc., to conduct the Phase 1b KEYNOTE-B79 clinical trial • KEYNOTE-B79 will evaluate CYAD-101 following FOLFIRI preconditioning chemot
Slide 32: How Could NKG2D CAR T Combine with PD-1 Therapy in Solid Tumors
How Could NKG2D CAR T Combine with PD-1 Therapy in Solid Tumors NKG2D CAR T Directly Targets Tumors and Remodels the Local TME • NKG2D CAR T cells have been observed to sculpt the myeloid environment towards a M1 phenotype in a murine ovarian tumor model (1) • Increased infiltration of activated mac
Slide 33: alloSHRINK Trial – Preliminary Analysis of T cell Repertoire
alloSHRINK Trial – Preliminary Analysis of T cell Repertoire T Cell alpha chain Repertoire Key Takeaways • Partial responder, 100 M dose • Following treatment with CYAD-101 and FOLFOX preconditioning, these preliminary data show an increase in the breadth of the large clone (>0.1% of the population)
Slide 34: Additional Approach to Further Evaluate CYAD-101 in mCRC?
Additional Approach to Further Evaluate CYAD-101 in mCRC? Following Preconditioning with CyFlu CYAD-01 Kinetics in mCRC Patients • Rationale: cell kinetic data from CYAD-01 Following FOLFOX Following CyFlu (autologous) program demonstrate increased cell kinetics parameters following CyFlu including:
Slide 35: Expanding the Clinical Development of CYAD-101
Expanding the Clinical Development of CYAD-101 alloSHRINK KEYNOTE-B79 Future Trials • Encouraging initial data from • Evaluate CYAD-101 following • Opportunity to further assess CYAD-101 following FOLFOX FOLFIRI preconditioning CYAD-101’s potential clinical preconditioning chemotherapy chemotherapy,
Slide 36: shRNA-based Allogeneic Platform
shRNA-based Allogeneic Platform Peggy Sotiropoulou, PhD Head of Research & Development
Slide 37: Developing a Next-Generation, Non-Gene Edited Allogeneic Platform
Developing a Next-Generation, Non-Gene Edited Allogeneic Platform Review of Proprietary shRNA Platform • In 2018, the Company entered into an exclusive agreement with Horizon Discovery Group for the use of its shRNA SMARTVector technology to develop next-generation, non-gene edited allogeneic platfo
Slide 38: shRNA vs. CRISPR-Cas9: Equivalent Knockdown of TCR
shRNA vs. CRISPR-Cas9: Equivalent Knockdown of TCR Cell Surface TCR Complex Intensity of TCRα/β TCR Stimulation Assay 10000 8 0 0 0 1 .0 0 .8 6 0 0 0 TCR/ MFI IF N (n g / m l) C D 2 5 M F I 0 .6 C T R (tC D 1 9 ) 5000 4 0 0 0 s h R N A C D 3 0 .4 C R IS P R C D 3 8 0 0 0 1 .0 2 0 0 0 8 0 0 0 1
Slide 39: CYAD-211 – First shRNA-based Allogeneic Candidate
CYAD-211 – First shRNA-based Allogeneic Candidate Cell Expansion TCR Function TCR Expression 1.2 1000 CYAD-211 cell expansion OKT3-induced IFNγ 100 0.8 (ng/ml) (fold) 10 0.4 1 Donor 1 Donor 2 Donor 3 0.0 Control CYAD-211 CYAD-211, BCMA-targeting CAR-T cells incorporating shRNA targeting CD3ζ, effici
Slide 40: CYAD-211 Demonstrates High In vivo Activity with No Signs of Alloreactivity
CYAD-211 Demonstrates High In vivo Activity with No Signs of Alloreactivity Mean Weight Graft-vs-Host Disease Anti-tumor Activity 30 100 100 Percent survival Percent survival 25 Weight (g) 20 50 50 Vehicle Control T cells 15 Vehicle Control T cells CYAD-211 Control T cells CYAD-211 CYAD-211 0 10 0 0
Slide 41: CYAD-211 – Novel, shRNA-based anti-BCMA CAR-T for Multiple Myeloma
CYAD-211 – Novel, shRNA-based anti-BCMA CAR-T for Multiple Myeloma Background on IMMUNICY Phase 1 Trial • Open-label, Phase 1 dose-escalation trial to determine the recommended dose in multiple myeloma patients with relapsed or refractory disease • In addition, set to establish proof-of-concept usin
Slide 42: Next-Generation Multiplexed shRNA-based Candidates
Next-Generation Multiplexed shRNA-based Candidates Peggy Sotiropoulou, PhD Head of Research & Development
Slide 43: Concurrent Knockdown of Multiple shRNAs from a Single Vector – Case Study 1
Concurrent Knockdown of Multiple shRNAs from a Single Vector – Case Study 1 Protein Response to TCR Protection from Expression Mitogenic Stimuli CD52-targeted lysis TCR CD52 100 100 over no OKT3 treatment 15 percentage positive percentage positive 30000 0 g/ml % IFN+ cells 10 g/ml C3/iC3 MFI 10
Slide 44: Concurrent Knockdown of Multiple shRNAs from a Single Vector – Case Study 2
Concurrent Knockdown of Multiple shRNAs from a Single Vector – Case Study 2 shRNA screening mRNA Expression Protein Expression 2.0 b2-microglobulin (relative to Mock transduced) 0.8 CD3ζ (relative to Mock transduced) 1.5 0.6 Fold change Fold change 1.0 0.4 0.5 0.2 HLA-ABC TCRαβ 0.0 0.0 3ζ 3ζ A 2M Mo
Slide 45: Concurrent Knockdown of Multiple shRNAs from a Single Vector – Case Study 3
Concurrent Knockdown of Multiple shRNAs from a Single Vector – Case Study 3 mRNA Levels Protein Levels HLA-ABC CD3 TCR CD52 MFI fold change B2M DGK CD3ζ CD52 1.0 Fold change 1.0 0.5 0.5 0.0 0.0 sh A sh A sh A sh A A A A A sh A sh A sh A sh A sh A sh A sh A sh A sh A A sh A A sh A A sh A A 1x hRN 1x
Slide 46: Enhancing Cell Characteristics of Next-Generation Allogeneic CAR-T Cell Candidates
Enhancing Cell Characteristics of Next-Generation Allogeneic CAR-T Cell Candidates Improving Activity Enhancing Persistence through Inhibition with Activating Cytokines of Activation-Induced Cell Death CD19-CAR/shRNA 10 11 NKG2D-CAR 100 CD19-CAR/control shRNA (photons / sec / mm2) 10 10 NKG2D-CAR +
Slide 47: Multiplexing shRNAs to Create Differentiated, Allogeneic CAR-T Candidates
Multiplexing shRNAs to Create Differentiated, Allogeneic CAR-T Candidates • shRNA represents a next-generation allogeneic approach with flexibility, versatility and single step engineering based on an all-in-one-vector approach • Proof-of-concept of multiplexing with up to four shRNAs (~100 bp per s
Slide 48: Overview of Allogeneic and NKG2D Intellectual Property
Overview of Allogeneic and NKG2D Intellectual Property Stephen Rubino, PhD Chief Business Officer
Slide 49: Robust Intellectual Property for Allogeneic and NKG2D CAR Ts
Robust Intellectual Property for Allogeneic and NKG2D CAR Ts Key U.S. Patents Strategic Validation • Allogeneic T-Cell Technology • T cell receptor deficient T cell compositions • In May 2017, Celyad granted Novartis a non-exclusive license for allogeneic • Method of producing T cell receptor defici
Slide 50: Current Allogeneic Patent Portfolio – United States
Current Allogeneic Patent Portfolio – United States 9,821,011 10,689,617 15/383,717 15/815,261 Method of treating cancer Method of treating cancer, wherein CAR-T mediates T cell signaling 9,181,527 9,938,497 9,822,340 10,689,616 13/502,978 14/676,028 15/383,662 15/815,197 Method of producing TCR-def
Slide 51: Current Allogeneic Patent Portfolio – Rest of World
Current Allogeneic Patent Portfolio – Rest of World 9,181,527 AU2013/ AU2018/ 13/502,978 256424B2 253624A1 BR112014027 9,273,283 155-0 CN108384758 13/459,664 CN104395463 CN108795875 PCT/US2013/ Original 038921 EP2844742 EP3447125 applications from Dartmouth JP2018/ JP6411328 Issued 157824 Applicatio
Slide 52: Current NKG2D Patent Portfolio
Current NKG2D Patent Portfolio 7,994,298 8,252,914 10,336,804 16/415,309 11/575,878 13/155,909 14/600,799 Nucleic acid constructs Nucleic acid constructs encoding a Nucleic acid constructs encoding a chimeric chimeric receptor comprising a C- encoding a chimeric receptor receptor comprising a type l
Slide 53: Final Remarks and Q&A
elyad = Oncology Final Remarks and Q&A
Slide 54: Differentiated Pipeline of Next-Generation CAR T Candidates
Differentiated Pipeline of Next-Generation CAR T Candidates Allogeneic TARGET INDICATION PRECLINICAL PHASE 1 PHASE 2 PHASE 3 CYAD-101 NKG2DL mCRC CYAD-103 NKG2DL Solid tumors CYAD-211 BCMA r/r MM CYAD-221 CD19 B-cell maligancies CYAD-231 NKG2DL x Solid tumors Undisclosed Autologous TARGET INDICATION
Slide 55: Upcoming Anticipated Milestones
Upcoming Anticipated Milestones Second Half 2020 CYAD-101 in mCRC: Begin expansion cohort of alloSHRINK trial CYAD-211 in r/r MM: Initiate first-in-human, dose-escalation Phase 1 trial CYAD-01 in r/r AML and MDS: Report data from expansion cohort of Phase 1 THINK trial CYAD-02 in r/r AML and MDS: Re
Slide 56: Celyad Oncology Research & Development Day Webinar
Celyad Oncology Research & Development Day Webinar William Blair Growth Stock Conference September 29, 2020