Celyad Oncology Sa · EURONEXT:CYAD
Celyad Oncology Sa — SITC 2019 (Society for Immunotherapy of Cancer 34th Annual Meeting)
50 slides from Celyad Oncology Sa's conference presentation, Nov 9, 2019
Slide 1: SITC 2019 Presentation: Update on mCRC Program
Pioneering innovative therapies for patients with life-threatening diseases SITC 2019 Presentation Update on mCRC Program November 9, 2019
Slide 2: Disclaimers
Disclaimers Certain statements in this presentation constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act and Section 21E of the Securities Exchange Act and are usually identified by the use of words such as "anticipates," "believes," "estimates," "expects,"
Slide 3: Today's Agenda – CAR-T Therapy for the Treatment of Advanced mCRC
Today’s Agenda – CAR-T Therapy for the Treatment of Advanced mCRC Topic Discussant Welcome & Introductions Filippo Petti Current Treatment Landscape of mCRC Richard Kim, MD – Moffitt Cancer Center Update on CYAD-101 alloSHRINK Phase 1 Trial Frédéric Lehmann, MD Next Steps for Solid Tumor Franchise D
Slide 4: Clinical-stage Biopharmaceutical Company Focused on a Differentiated Approach to CAR-T Therapies
Clinical-stage Biopharmaceutical Company Focused on a Differentiated Approach to the Development of CAR-T Therapies Developing NKG2D-based CAR-T therapies which encompass eight different stress ligands expressed on the surface of both hematological malignancies and solid tumor cells Initial programs
Slide 5: Overview of mCRC
Richard Kim, MD Associate Professor Section Chief of Gastrointestinal Oncology Moffitt Cancer Center Tampa, Florida Overview of mCRC
Slide 6: Current Treatment Landscape of Metastatic Colorectal Cancer (mCRC)
Current Treatment Landscape of Metastatic Colorectal Cancer (mCRC) Richard Kim M.D. Associate Professor Section Chief of GI Oncology Department of Gastrointestinal Oncology Moffitt Cancer Center Tampa, FL
Slide 7: Impact of Colorectal Cancer (CRC)
Impact of Colorectal Cancer (CRC) • CRC US Statistics: – 3rd highest incidence rate (~135,000/year) – 2nd highest mortality rate (~49,000/year) • CRC Global Statistics: – 3rd highest incidence rate ( ~ 1.2million/year) – 4th highest mortality rate (~608,000/year) • The burden of disease is clearly e
Slide 8: 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
Slide 9: 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 10: Key Points in the Medical Management of mCRC
Key Points in the Medical Management of mCRC • We can “cure” some patients with limited metastatic disease • Collaboration within an MDT essential • For the majority of patients the treatment goal is to extend life and maintain quality of life as long as possible • Patients benefit from access to al
Slide 11: Key Points in the Medical Management of mCRC, Continued
Key Points in the Medical Management of mCRC, Continued • We have biomarkers who identify cancers which do NOT respond to certain therapies, i.e. EGFR mAbs • Routine testing for extended RAS/ BRAF mutations, now also HER-2 • Biomarkers that select patients for a specific therapy are emerging • Misma
Slide 12: mCRC Treatment Decision Recommendations
mCRC Treatment Decision Recommendations 1L Illustration: RAS/BRAF wild4Ltype Chemo + Chemo + Other anticancer RAS Regorafenib therapy, BSC, or mutation anti-VEGF anti-VEGF or TAS-102 clinical trial RAS Chemo + Chemo + Regorafenib Other anticancer wild type anti-VEGF anti-EGFR or TAS-102 therapy, BSC
Slide 13: Patients Relapsing or Refractory to Chemotherapy
Patients Relapsing or Refractory to Chemotherapy Two drugs currently available • Regorafenib • TAS-102 (trifluridine/tipiracil)
Slide 14: Regorafenib Phase 3 CORRECT: Overall Survival (Primary Endpoint)
Regorafenib Phase 3 CORRECT: Overall Survival (Primary Endpoint) ▪ Primary endpoint met prespecified stopping criteria at second interim analysis (P ≤ .009279) Grothey. Lancet. 2013;381:303.
Slide 15: TAS-102 Phase 3 RECOURSE: Overall Survival (Primary Endpoint)
TAS-102 Phase 3 RECOURSE: Overall Survival (Primary Endpoint) Mayer. NEJM. 2015;372:1909.
Slide 16: 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 17: How about retreating advanced patients with chemotherapy?
How about retreating advanced patients with chemotherapy?
Slide 18: FOLFOX Re-Challenge Strategy in mCRC: RE-OPEN Phase 2 Study
FOLFOX Re-Challenge Strategy in mCRC: RE-OPEN Phase 2 Study Study objective • To investigate the effectiveness of reintroducing oxaliplatin in mCRC patients Key patient inclusion criteria Treatment schedule Primary Endpoint • Received prior chemotherapy • Oxaliplatin (85 mg/m²) administered as a 2-h
Slide 19: RE-OPEN Phase 2 Results
RE-OPEN Phase 2 Results Tumor Response after 12 weeks Waterfall Plot for Best Tumor Response mPFS = 98 days and mOS = 300 days Suenaga, Drug Design Development and Therapy, June 2015
Slide 20: How about immunotherapy in mCRC?
How about immunotherapy in mCRC?
Slide 21: 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 22: Outcomes of Checkpoint Inhibitors Approved in dMMR mCRC
Outcomes of Checkpoint Inhibitors Approved in dMMR mCRC Outcome Pembrolizumab Nivolumab Nivolumab + Ipilimumab KEYNOTE-164 CheckMate-142 CheckMate-142 N = 61 N = 53 N = 82 Median follow-up 13.2 m 21.0 m 13.4 m ORR, % (95% CI) 28% 26% 46% Response, % • CR NA 8% 4% • PR 28% 19% 42% • SD 23% 30% NA Dis
Slide 23: 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
Slide 24: Conclusions
Conclusions • Treatment of advanced metastatic colorectal cancer patients previously exposed to oxaliplatin and irinotecan remains a high unmet medical need • Though multiple salvage products are approved and recommended in this setting, response rates and overall outcomes remain poor • Despite the
Slide 25: Thank you!
Thank you! GI Oncology Questions richard.kim@moffitt.org
Slide 26: Update on CYAD-101 alloSHRINK Trial
Frédéric Lehmann, MD Celyad SA Vice President Clinical Development & Medical Affairs Update on CYAD-101 alloSHRINK Trial
Slide 27: NKG2D – Novel Receptor in CAR-T Therapy Development
NKG2D – Novel Receptor in CAR-T Therapy Development Review of NKG2D Receptor ▪ NKG2D is an activating receptor expressed on natural killer (NK) cells NKG2D which plays an important role in protection against infection and cancer Receptor ▪ Receptor binds to eight stress induced ligands: MICA, MICB,
Slide 28: Multiple Targets to Generate Allogeneic T-cells
Multiple Targets to Generate Allogeneic T-cells TCRα (TRAC) is a common target TCR complex is for gene edited approaches responsible for (i.e. CRISPR-Cas9, TALENs, ZFNs) GvHD Attenuation of the TCR complex CD3ζ is the rate-limiting factor to is necessary for the TCR complex moving to the creating ce
Slide 29: CYAD-101 – Investigational, Non-gene Edited Allogeneic CAR-T Therapy for mCRC
CYAD-101 – Investigational, Non-gene Edited Allogeneic CAR-T Therapy for the Treatment of mCRC CYAD-101 Co-expresses NKG2D Receptor and TIM ▪ The expression of TIM (TCR Inhibitory Molecule) results in the competitive inhibition of CD3ζ and reduces signaling of the TCR CYAD-101 complex, leading to th
Slide 30: CYAD-101 alloSHRINK Trial – First-in-Human Phase 1 Study Overview
CYAD-101 alloSHRINK Trial – First-in-Human Phase 1 Study Overview ▪ Evaluates CYAD-101 administered concurrently with FOLFOX chemotherapy in mCRC patients ▪ Patients with non-resectable recurrent/progressing mCRC after prior metastatic chemotherapy lines including oxaliplatin and irinotecan-based ch
Slide 31: alloSHRINK Trial – Background Characteristics
alloSHRINK Trial – Background Characteristics Patient and Tumor Characteristics Prior Treatment Characteristics All Patients (N=12) All Patients (N=12) Mean Age (Range), years 57 (25-74) Prior Adjuvant Treatment 2 (16.7%) Male / Female 8/4 Number of Prior Lines of Metastatic Treatment ECOG Grade 0 /
Slide 32: alloSHRINK Trial – Overview of Adverse Events (AEs)
alloSHRINK Trial – Overview of Adverse Events (AEs) Incidence of AEs Patient Incidence of Treatment Related-AEs All Patients (N=12) All Patients (N=12) (35 infusions) (35 infusions) All Treatment- All Treatment- All AEs Grade ≥ 3 related AEs related AEs Any Grade 131 (100%) 16 (100%) Total Patients
Slide 33: alloSHRINK Trial – Best Tumor Responses
alloSHRINK Trial – Best Tumor Responses Clinical Outcomes Key Summary All Patients (N=12) ▪ All responses were observed at the first tumor assessment scheduled 8-12 days Best overall responses – n (%) after the third infusion of CYAD-101 ▪ Best overall response includes two Partial response (PR) 2 (
Slide 34: alloSHRINK Trial – Change in Tumor Burden From Baseline
alloSHRINK Trial – Change in Tumor Burden From Baseline Analysis of Evaluable Patients (1) Key Summary Chromosomal instability pathway RAS Mutated ▪ Tumor burden decrease was BRAF UNK UNK Wild-type observed in six out of 11 30 evaluable patients, including 20 PD(2) PD(2) SD four out of seven patient
Slide 35: alloSHRINK Trial – Time to Response and Duration of Treatment
alloSHRINK Trial – Time to Response and Duration of Treatment Prior metastatic agent(s) FX: FOLFOX; FiRi: FOLFIRI; FiRiX: FOLFIRINOX; Cetux: Cetuximab; Pmab: Panitumumab; Bev: Bevacizumab; LTFU: Lost to follow-up. PR: Partial response; SD: Stable disease; PD: Progressive disease. (1) Include regoraf
Slide 36: alloSHRINK Trial – CYAD-101 Cell Kinetics
alloSHRINK Trial – CYAD-101 Cell Kinetics Analysis of Peripheral Blood by Dose Cohort 1x108 cells/infusion 3x108 cells/infusion 1x109 cells/infusion (3 patients) (3 patients) (6 patients) ▪ CYAD-101 cells were detected in the peripheral blood for up to 40 days after the first infusion ▪ Host-versus-
Slide 37: alloSHRINK Trial – Comparing Kinetics Between CYAD-101 and CYAD-01
alloSHRINK Trial – Comparing Kinetics Between CYAD-101 and CYAD-01 Similar Overall Cell Kinetics between NKG2D-based CAR-Ts Following FOLFOX ▪ CYAD-101 (allogeneic) and CYAD-01 (autologous) CAR-T cells administered after FOLFOX show similar peak engraftments in the 14 days after each of all three in
Slide 38: alloSHRINK Trial – Summary
alloSHRINK Trial – Summary Encouraging Results for Off-the-Shelf CAR-T Therapy, CYAD-101 ▪ alloSHRINK trial is the first study to evaluate a non-gene edited, allogeneic CAR-T cell therapy for the treatment of a solid cancer indication ▪ Results demonstrate favorable safety profile for CYAD-101 with
Slide 39: Next Steps for Solid Tumor Franchise
David Gilham, PhD Celyad SA Vice President Research & Development Next Steps for Solid Tumor Franchise
Slide 40: Next Steps for CYAD-101 alloSHRINK Trial in Refractory mCRC
Next Steps for CYAD-101 alloSHRINK Trial in Refractory mCRC Dose-Escalation Segment Dose-Expansion Segment ▪ In October, enrollment completed in dose ▪ Expansion activities ongoing including: level three cohort (1x109 cells per infusion) ▪ Preparation for cell production of CYAD- ▪ Next milestone: u
Slide 41: Preconditioning Chemotherapy – A Closer Look
Preconditioning Chemotherapy – A Closer Look Standard CAR-T Preconditioning Standard CAR-T FOLFOX Preconditioning (i.e. CyFlu) Lymphodepletion Strongly lymphodepleting Less intense lymphodepletion as compared to CyFlu with a nadir of 9-14 days after first dose Non-myeloablative Yes Yes Induction of
Slide 42: Preconditioning Chemotherapy – Standard CAR-T versus FOLFOX Preconditioning
Preconditioning Chemotherapy – A Closer Look Standard CAR-T Preconditioning versus FOLFOX Preconditioning Standard CAR-T FOLFOX Preconditioning (i.e. CyFlu) Preconditioning Lymphodepletion Strongly lymphodepleting Less intense lymphodepletion as compared to CyFlu with a nadir of 9-14 days after firs
Slide 43: Potential Approaches to Further Evaluate CYAD-101 in mCRC
Potential Approaches to Further Evaluate CYAD-101 in mCRC Following Preconditioning with CyFlu In Combo with Checkpoint Inhibitor ▪ Rationale: cell kinetic data from CYAD-01 ▪ Rationale: mCRC is considered to be (autologous) program demonstrate increase non-responsive to immune-based cell kinetics p
Slide 44: Strategic Focus to Develop Best-in-Class Allogeneic CAR-Ts for Solid Tumors
Strategic Focus to Develop Best-in-Class Allogeneic CAR-Ts for Solid Tumors Expanding the CYAD-100 Series ▪ Builds upon CYAD-101’s encouraging clinical data, in particular tolerability profile ▪ Continue to leverage our TIM technology to create allogeneic NKG2D-based CAR-T therapies ▪ Enhance cell c
Slide 45: Enhancing Cell Characteristics of Next-Generation Allogeneic Candidates
Enhancing Cell Characteristics of Next-Generation Allogeneic Candidates Improving Activity with Cytokine X Targeting B2M with shRNA 10 11 CYAD-01 (photons / sec / mm2) CYAD-02 10 10 Bioluminescence CYAD-03 10 9 Background 10 8 10 7 10 6 10 5 0 20 40 60 Time (days) HCT-116 xenograft based orthotopic
Slide 46: CYAD-100 Series – Allogeneic TIM/NKG2D-based CAR-T Franchise
CYAD-100 Series – Allogeneic TIM/NKG2D-based CAR-T Franchise Focus on Targeting Solid Tumors with Off-the-Shelf Candidates ▪ alloSHRINK trial is the first study to evaluate a non-gene edited, allogeneic CAR-T cell therapy product candidate for the treatment of a solid cancer indication ▪ Provides pr
Slide 47: Final Remarks and Q&A
Final Remarks and Q&A
Slide 48: Updated CAR-T Therapy Pipeline with Introduction of CYAD-103
Updated CAR-T Therapy Pipeline with Introduction of CYAD-103 Product Target Study Design Preclinical IND Submission Phase 1 Standalone w/o THINK Hematological malignancies and Solid tumors Preconditioning Autologous THINK Schedule optimization CYAD-01 NKG2DL Cohort 10/11 w/o Preconditioning r/r AML
Slide 49: Summary of Conference Presentations
Summary of Conference Presentations Society for Immunotherapy of Cancer's 34th Annual Meeting Results from the complete dose escalation part of alloSHRINK evaluating CYAD-101 in P330 mCRC patients Results from the complete dose escalation part of SHRINK evaluating CYAD-01 in mCRC P331 patients P147
Slide 50: Pioneering innovative therapies for patients with life-threatening diseases
Pioneering innovative therapies for patients with life-threatening diseases SITC 2019 Presentation Update on mCRC Program November 9, 2019
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