Celyad Oncology Sa · EURONEXT:CYAD
Celyad Oncology Sa — ASH 2019 Annual Meeting
57 slides from Celyad Oncology Sa's conference presentation, Dec 9, 2019
Slide 1: Pioneering innovative therapies for patients with life-threatening diseases
Pioneering innovative therapies for patients with life-threatening diseases ASH 2019 Presentation Update on r/r AML and MDS Program December 9, 2019
Slide 2: Disclaimers
Disclaimers This presentation may contain forward-looking statements, including statements regarding: the safety and clinical activity of CYAD-01 and CYAD-02; statements regarding the ongoing and planned clinical development of CYAD-01 and CYAD-02, including the timing of trials, enrollment, data re
Slide 3: Today's Agenda – CAR-T Therapy for the Treatment of r/r AML and MDS
Today’s Agenda – CAR-T Therapy for the Treatment of r/r AML and MDS Topic Discussant Welcome & Introductions Filippo Petti CYAD-01 Phase 1 Clinical Update Samer Al-Homsi, MD – NYU Langone Health CYAD-01 Case Reports Frédéric Lehmann, MD CYAD-02 and Next Steps for AML/MDS Program Frédéric Lehmann, MD
Slide 4: Leader in NKG2D-based CAR-T Therapies, Autologous and Allogeneic Approaches
Leader in NKG2D-based CAR-T Therapies Focused on Both Autologous and Next-Generation Allogeneic Approaches 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 investig
Slide 5: 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 6: CYAD-01 Phase 1 Clinical Update
Samer Al-Homsi, MD Clinical Professor of Medicine Perlmutter Cancer Center NYU Langone Health New York, New York CYAD-01 Phase 1 Clinical Update
Slide 7: CYAD-01 Development Program in r/r AML and MDS: THINK Poster
CYAD-01 Development Program in r/r AML and MDS Poster 3826 Results from the completed dose escalation of the hematological arm of the phase I THINK study evaluating multiple infusions of NKG2D-based CAR T-cells as standalone therapy in relapsed/refractory acute myeloid leukemia and myelodysplastic s
Slide 8: THINK Phase 1 Trial Design
CYAD-01 Development Program in r/r AML and MDS THINK Phase 1 Trial ▪ The THINK trial is an open-label, dose-escalation Phase 1 trial assessing the safety and clinical activity of multiple CYAD-01 administrations without prior preconditioning chemotherapy ▪ The dose escalation segment of the trial ev
Slide 9: THINK Patient and Tumor Characteristics
THINK Phase 1 Trial – Patient and Tumor Characteristics Biweekly schedule Dose dense schedule Dose Level 1 Dose Level 2 Dose Level 3 Total Dose Level 2 Dose Level 3 Total 3x108 1x10 9 3x109 1x10 9 3x10 9 N=6 N=3 N=7 N=16 N=4 N=5 N=9 Age (years): Mean (Range) 64.8 (52-79) 74.0 (60-83) 60.1 (29-80) 64
Slide 10: THINK Treatment Related Adverse Events
THINK Phase 1 Trial – Treatment Related Adverse Events (2) Biweekly schedule 8 Dose Level 1 (3x10 ) Dose Level 2 (1x109) Dose Level 3 (3x109) Total 6 patients (15 infusions) 3 patients (12 infusions) 7 patients (24 infusions) 16 patients (51 infusions) All Grades Grade 3 Grade 4 All Grades Grade 3 G
Slide 11: THINK Treatment Related Adverse Events, Continued
THINK Phase 1 Trial – Treatment Related Adverse Events (2), Continued Dose dense schedule 9 Dose Level 2 (1x10 ) Dose Level 3 (3x109 ) Total 4 patients (15 infusions) 5 patients (15 infusions) 9 patients (30 infusions) All Grades Grade 3 Grade 4 All Grades Grade 3 Grade 4 All Grades Grade 3 Grade 4
Slide 12: THINK Safety Overview Key Takeaways
THINK Phase 1 Trial – Safety Overview Key Takeaways ▪ Encouraging safety data to date with 11 patients out of 25 experiencing grade 3/4 treatment-related AEs ▪ Two DLTs reported at 3 billion (dose level 3) cells per infusion: ▪ One CRS grade 4 with the biweekly schedule (out of 24 infusions) ▪ One C
Slide 13: THINK Time to Response & Duration of Response
THINK Phase 1 Trial – Time to Response & Duration of Response Summary ▪ According to the ELN 2017 (AML) or Revised IPSS (MDS) guidelines for the 19 patients evaluable (1) for clinical activity: ▪ Biweekly schedule (11 patients) - Five objective response (CR/PR) - One stable disease (≥ 3m) ▪ Dose den
Slide 14: Anti-Leukemic Activity According to Dose-Level
Phase 1 Trial – Anti-Leukemic Activity According to Dose-Level Best Change in Bone Marrow Blast Count from Baseline (1) Summary ▪ Anti-leukemic activity with bone marrow blasts decreased in 8 patients including 5 objective responses and 1 SD for ≥ 3 months according to the ELN2017 recommendations (A
Slide 15: Anti-Leukemic Activity According to Disease Risk Stratification
Phase 1 Trial – Anti-Leukemic Activity According to Disease Risk Stratification Best Change in Bone Marrow Blast Count from Baseline (1) Summary ▪ Preliminary analysis of patient tumor ELN 2017 (AML) / Revised IPSS (MDS) classification shows that four out of the five patients with objective response
Slide 16: THINK CYAD-01 Engraftment
THINK Phase 1 Trial – CYAD-01 Engraftment CYAD-01 Engraftment Without Preconditioning Summary ▪ Evidence of dose- dependent engraftment of CYAD-01 cells ▪ No strong evidence of correlation of dose with clinical activity in the study to date Red dots indicate the patients with Complete or partial res
Slide 17: THINK Summary
THINK Phase 1 Trial – Summary Encouraging Results with CYAD-01 Without Preconditioning Chemotherapy ▪ CYAD-01 without preconditioning chemotherapy is generally well-tolerated following multiple dose schedule in patients with relapsed/refractory AML and MDS ▪ Encouraging anti-leukemic activity, despi
Slide 18: CYAD-01 Development Program: DEPLETHINK Poster
CYAD-01 Development Program in r/r AML and MDS Poster 3844 Interim results from the phase I DEPLETHINK trial evaluating the infusion of a NKG2D CAR T-cell therapy post a non-myeloablative conditioning in relapsed or refractory acute myeloid leukemia and myelodysplastic syndrome patients A Samer Al-H
Slide 19: DEPLETHINK Phase 1 Trial Design
CYAD-01 Development Program in r/r AML and MDS DEPLETHINK Phase 1 Trial ▪ DEPLETHINK Phase 1 trial is an open-label, dose-escalation trial assessing a single infusion of CYAD-01 following treatment with the preconditioning regimen of cyclophosphamide (300 mg/m²) and fludarabine (30 mg/m²), or CyFlu
Slide 20: DEPLETHINK Patient and Tumor Characteristics
DEPLETHINK Phase 1 Trial – Patient and Tumor Characteristics All patients Dose Level 1 Dose Level 2 1x108 3x108 N=9 N=6 (1) N=3 Age (years): Mean (Range) 63.6 (50-73) 61.7 (50-73) 67.3 (58-73) Gender: Male/Female 6/3 4/2 2/1 ECOG performance score at screening (Grade 0/1/2) 5/3/1 4/2/0 1/1/1 LVEF (%
Slide 21: DEPLETHINK Treatment Related Adverse Events
DEPLETHINK Phase 1 Trial – Treatment Related Adverse Events Dose Level 1 Dose Level 2 Induction Consolidation Induction Consolidation with preconditioning without preconditioning with preconditioning without preconditioning (1x108) (1x109 or 3x109) (3x108) (3x109) N=6 (6 infusions) N=2 (4 infusions)
Slide 22: DEPLETHINK CYAD-01 Engraftment
DEPLETHINK Phase 1 Trial – CYAD-01 Engraftment Comparison of Cell Engraftment Key Summary ▪ The two first dose levels of CYAD-01 (produced with mAb manufacturing process) demonstrate dose-dependent cell engraftment ▪ The addition of the cyclophosphamide and fludarabine (CyFlu) as preconditioning che
Slide 23: DEPLETHINK Preliminary Results
DEPLETHINK Phase 1 Trial – Preliminary Results Study Ongoing to Evaluate CYAD-01 Following Preconditioning Chemotherapy ▪ To date, nine patients have been enrolled in the dose-escalation trial at the first two dose levels evaluating CYAD-01 produced with mAb manufacturing process ▪ CYAD-01 following
Slide 24: CYAD-01 Case Reports
Frédéric Lehmann, MD Celyad SA Vice President Clinical Development & Medical Affairs CYAD-01 Case Reports
Slide 25: THINK Overview: Patient Disposition and Best Objective Response
THINK Phase 1 Trial – Overview Patient Disposition and Best Objective Response THINK Phase 1 Trial THINK solid tumors 17 patients THINK hematological malignancies 25 patients Three multiple myeloma patients 22 relapsed/refractory AML/MDS patients 13 patients 9 patients Biweekly schedule Dose dense s
Slide 26: THINK Patient Case Report
THINK Phase 1 Trial – Patient Case Report Additional Details of Select Patient 26
Slide 27: THINK Patient Case Report (Biweekly Schedule)
THINK Phase 1 Trial – Patient Case Report (Biweekly Schedule) Key Facts Blood and Bone Marrow Parameter Measurements ▪ r/r AML patient in dose level 1 CRh CRMRD- 100% donor chimerism (300 million cells per infusion) ▪ Male, 52 years old ▪ ELN 2017 – Intermediate ▪ Baseline bone marrow blasts at 7% ▪
Slide 28: THINK Patient Case Report (Biweekly Schedule)
THINK Phase 1 Trial – Patient Case Report (Biweekly Schedule) Additional Details of Select Patient 28
Slide 29: THINK Patient Case Report (Biweekly Schedule)
THINK Phase 1 Trial – Patient Case Report (Biweekly Schedule) Key Facts ▪ r/r AML patient in dose level 1 (300 million cells per infusion) ▪ Male, 73 years old ▪ ELN 2017 – Favorable ▪ Baseline bone marrow blasts at 10% ▪ Previously reported as Complete Remission with incomplete hematological recove
Slide 30: THINK Patient Case Report (Biweekly Schedule)
THINK Phase 1 Trial – Patient Case Report (Biweekly Schedule) Additional Details of Select Patient 30
Slide 31: THINK Patient Case Report (Biweekly Schedule)
THINK Phase 1 Trial – Patient Case Report (Biweekly Schedule) Key Facts Blood and Bone Marrow Parameter Measurements ▪ r/r AML patient in dose level 2 (1 billion cells per infusion) ▪ Male, 60 years old ▪ ELN 2017 – Adverse ▪ Previous treatments ▪ Azacytidine: May 16 – Jan. 18 ▪ Anti-leukemic activi
Slide 32: THINK Patient Case Report
THINK Phase 1 Trial – Patient Case Report Additional Details of Select Patient 32
Slide 33: THINK Patient Case Report (Dose-dense Schedule)
THINK Phase 1 Trial – Patient Case Report (Dose-dense Schedule) Key Facts Blood and Bone Marrow Parameter Measurements ▪ r/r AML patient in dose level 3 (3 billion cells per infusion) ▪ Male, 78 years old ▪ ELN 2017 – Adverse ▪ Previous treatments ▪ Azacytidine: Jan17 – Mar17 ▪ MDMX/MDM2 dual inhibi
Slide 34: Anti-Leukemic Activity According to Disease Risk Stratification
Phase 1 Trial – Anti-Leukemic Activity According to Disease Risk Stratification Best Change in Bone Marrow Blast Count from Baseline (1) Summary ▪ Encouraging initial clinical activity in non-Adverse (AML) and non-Very High (MDS) patients warrants additional investigation of NKG2D-based CAR-T therap
Slide 35: CYAD-02 and Next Steps for AML/MDS Program
Frédéric Lehmann, MD Celyad SA Vice President Clinical Development & Medical Affairs CYAD-02 and Next Steps for AML/MDS Program
Slide 36: CYAD-02 – Next-Generation NKG2D-based CAR-T Candidate
CYAD-02 – Next-Generation NKG2D-based CAR-T Candidate Differentiated Profile for the Treatment of r/r AML ▪ Utilizes Horizon Discovery’s short hairpin RNA (shRNA) SMARTvector technology to target the NKG2D ligands MICA and MICB ▪ Single shRNA knock down the expression of both ligands ▪ Offers opport
Slide 37: CYAD-02 – Overview of Phase 1 CYCLE-1 Trial
CYAD-02 – Second Autologous Candidate in r/r AML and MDS Program Overview of Phase 1 CYCLE-1 Trial ▪ In June 2019, the Food & Drug Administration accepted the Investigational New Drug application for CYAD-02 ▪ CYCLE-1 Phase 1 dose-escalation trial will evaluate the safety and clinical activity of CY
Slide 38: Comparing Phase 1 Preconditioning Trials: DEPLETHINK and CYCLE-1
Comparing Phase 1 Preconditioning Trials in r/r AML and MDS Program DEPLETHINK CYCLE-1 CAR-T Candidate CYAD-01 CYAD-02 Receptor NKG2D NKG2D shRNA / Targets -- ✓ / MICA and MICB Manufacturing Process of Cells mAb OptimAb OptimAb Preconditioning Regimen CyFlu (1) CyFlu (1) Bridging Therapy -- ✓ / Ph
Slide 39: Broad r/r AML and MDS Program – Next Steps
Broad r/r AML and MDS Program – Next Steps Assessing Multiple Autologous Approaches THINK DEPLETHINK CYCLE-1 ▪ Given encouraging data from ▪ Dose escalation segment of ▪ Enrollment in dose- CYAD-01 without trial ongoing at dose level 2 escalation trial on track to preconditioning, next steps (300 mi
Slide 40: r/r AML and MDS Program – Additional Thoughts
David Gilham, PhD Celyad SA Vice President Research & Development r/r AML and MDS Program – Additional Thoughts
Slide 41: History of NKG2D-based CAR-T r/r AML and MDS Program
History of NKG2D-based CAR-T r/r AML and MDS Program Academic process, low cell dose, fresh cell product CM-CS1 (DFCI) Safety confirmed at low cell dose (Baumeister et al. (2019) Cancer Immol Res) Develop manufacturing process of CYAD-01 – cryopreserved product (LY process) CYAD-01 yield increase th
Slide 42: Insights of Genetic Analysis from AML: ELN 2017 Stratification
AML Classification Insights of Genetic Analysis from AML ELN 2017 Stratification – Risk Category and Select Genetic Abnormality Favorable Intermediate Adverse ▪ t(8;21)(q22;q22.1); ▪ Mutated NPM1 and FLT3‐ITDHigh ▪ t(6;9)(p23;q34.1); DEK‐NUP214 RUNX1‐RUNX1T1 ▪ Wild‐type NPM1 without ▪ t(v;11q23.3);
Slide 43: History of NKG2D-based CAR-T r/r AML and MDS Program
History of NKG2D-based CAR-T r/r AML and MDS Program Academic process, low cell dose, fresh cell product CM-CS1 (DFCI) Safety confirmed at low cell dose (Baumeister et al. (2019) Cancer Immol Res) Develop manufacturing process of CYAD-01 – cryopreserved product (LY process) CYAD-01 yield increase th
Slide 44: OptimAb Manufacturing Process
OptimAb OptimAb Manufacturing Process Review of Manufacturing Processes Used in CYAD-01 Program LY and mAb Processes OptimAb Process ▪ Incorporates pan-PI3K inhibitor ▪ Incorporates selective-PI3K inhibitor 44
Slide 45: OptimAb: Cell Yield and Phenotype Between Manufacturing Processes
OptimAb Comparison of Cell Yield and Phenotype Between Manufacturing Processes Cell Expansion during Manufacturing Early Memory T cells 60 50 Central memory T cells 40 Fold expansion (D4-harvest) 40 30 20 20 10 0 0 LY mAb OptimAb LY mAb OptimAb (8-days) (10-days) (8-days) ▪ High cell yield in mAb (t
Slide 46: OptimAb: In vitro Functional Activity Between Manufacturing Processes
OptimAb Comparison of In vitro Functional Activity Between Manufacturing Processes Cytokine Production (1) Cytolytic Activity % cancer cells killed (24h) 100 50 80 40 IFN- (ng/mL) 60 30 40 20 20 10 0 0 LY mAb OptimAb LY mAb OptimAb ▪ Increased potency with OptimAb ▪ Similar in vitro killing activit
Slide 47: OptimAb: In vivo Efficacy Between Manufacturing Processes
OptimAb Comparison of In vivo Efficacy Between Manufacturing Processes LY versus mAb (1) mAb versus OptimAb (2) 100 100 Percent survival Percent survival Vehicle Vehicle Control T cells Control T cells LY mAb 50 mAb 50 OptimAb 0 0 0 20 40 60 0 10 20 30 40 50 60 Time (Days) Time (Days) ▪ LY shows pot
Slide 48: Summary of Manufacturing Approaches for Autologous r/r AML Program
OptimAb Summary of Manufacturing Approaches for Autologous r/r AML Program OptimAb Manufacturing Process – Bringing Together the Best Qualities LY mAb OptimAb Cell yield + +++ ++ Memory phenotype +++ + +++ Potency (cytokine production) + + +++ Potency (cell killing) ++ ++ ++ In vivo efficacy ++ ++ +
Slide 49: History of NKG2D-based CAR-T r/r AML and MDS Program
History of NKG2D-based CAR-T r/r AML and MDS Program Academic process, low cell dose, fresh cell product CM-CS1 (DFCI) Safety confirmed at low cell dose (Baumeister et al. (2019) Cancer Immol Res) Develop manufacturing process of CYAD-01 – cryopreserved product (LY process) CYAD-01 yield increase th
Slide 50: History of NKG2D-based CAR-T r/r AML and MDS Program
History of NKG2D-based CAR-T r/r AML and MDS Program Academic process, low cell dose, fresh cell product CM-CS1 (DFCI) Safety confirmed at low cell dose (Baumeister et al. (2019) Cancer Immol Res) Develop manufacturing process of CYAD-01 – cryopreserved product (LY process) CYAD-01 yield increase th
Slide 51: Preconditioning Chemotherapy – 'Standard' CAR-T Preconditioning
Preconditioning Preconditioning Chemotherapy – A Closer Look in Hematological Indications ‘Standard’ CAR-T Preconditioning Product (Company) Indication(s) Cyclophosphamide Fludarabine Yescarta Adult DLBCL 500 mg/m² daily for three days, 30 mg/m² daily for three days, (Kite) D-5 to D-3 D-5 to D-3 Kym
Slide 52: Preconditioning Chemotherapy – Comparison to AML Therapy FLAG
Preconditioning Preconditioning Chemotherapy – A Closer Look in Hematological Indications Comparison to AML Therapy – FLAG Product (Company) Indication(s) Cyclophosphamide Fludarabine CYAD-01 /-02 AML and MDS 300 mg/m2 daily for three days 30 mg/m2 daily for three days (Celyad) FLAG AML Fludarabine
Slide 53: History of NKG2D-based CAR-T r/r AML and MDS Program
History of NKG2D-based CAR-T r/r AML and MDS Program Academic process, low cell dose, fresh cell product CM-CS1 (DFCI) Safety Safety confirmed at low cell dose (Baumeister et al. (2019) Cancer Immol Res) Develop manufacturing process of CYAD-01 – cryopreserved product (LY process) CYAD-01 yield incr
Slide 54: Final Remarks and Q&A
Final Remarks and Q&A
Slide 55: Multiple NKG2D-based CAR-T Candidates for r/r AML Program
Multiple NKG2D-based CAR-T Candidates for r/r AML and MDS Program Product Target Study Design Preclinical IND Submission Phase 1 THINK Standalone w/o r/r AML / MDS Autologous Preconditioning CYAD-01 NKG2DL DEPLETHINK Preconditioning with CyFlu r/r AML / MDS CYAD-02 NKG2DL CYCLE-1 Preconditioning wit
Slide 56: Upcoming Milestones for OptimAb-based r/r AML and MDS Program
Upcoming Milestones for OptimAb-based r/r AML and MDS Program First Quarter 2020 Second Quarter 2020 Second Half 2020 ▪ CYAD-01: Begin expansion ▪ CYAD-01: Report preliminary ▪ CYAD-01: Report additional segment of Phase 1 THINK trial data from expansion segment of data from THINK and evaluating CYA
Slide 57: Pioneering innovative therapies for patients with life-threatening diseases
Pioneering innovative therapies for patients with life-threatening diseases ASH 2019 Presentation Update on r/r AML and MDS Program December 9, 2019