Celyad Oncology Sa · EURONEXT:CYAD
Celyad Oncology Sa — Technical Presentation (July 2021)
51 slides from Celyad Oncology Sa's technical presentation, Jul 21, 2021
Slide 1: Research and Development Day Virtual Webinar
Research and Development Day Virtual Webinar July 20, 2021 Exhibit 99.2
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation may contain forward-looking statements, within the meaning ha applicable securities laws, including we Private Securities Litigation Reform Act of 1995. Fi next steps for our armored CAR T franchise and our plans to build next Tonesation Slogan candidates
Slide 3: Today's Agenda
Today’s Agenda Topic Speaker Welcome & Introductions Filippo Petti Redefining Allogeneic CAR T Filippo Petti Update on CYAD-211 for r/r MM Charlie Morris, M.D. shRNA Platform Armored CAR T Franchise Introduction to CYAD-203 Optimized for Multiplexed CAR Ts Future programs David Gilham, Ph.D. Update
Slide 4: Redefining Allogeneic CAR T
elyad Oncology Redefining Allogeneic CAR T
Slide 5: Evolution of CAR T Landscape Towards Off-the-Shelf Approaches
Evolution of CAR T Landscape Towards Off-the-Shelf Approaches Allogeneic CAR Ts offer several benefits compared to autologous CAR Ts Quality of Therapy Cost Effective Derived from healthy donor T cells Opportunity to optimize manufacturing process to decrease variability between therapies Speed / Ac
Slide 6: Expected Real-World Benefits of Our Approach to Allogeneic CAR T
Expected Real-World Benefits of Our Approach to Allogeneic CAR T Differentiation Factor Key Characteristics Expected Real-World Benefit(s) All-in-One Vector Single vector for all elements of the CAR T therapy Lower cost of goods sold (COGS) – vector costs are a major contributor to COGS. Using a sin
Slide 7: CYAD-211 for r/r MM
elyad = Oncology : PS CYAD-211 or ri MM y = i
Slide 8: Background on CYAD-211
Background on CYAD-211 CYAD-211 is our first allogeneic CAR T candidate utilizing our All-in-One vector approach based on the shRNA technology CYAD-211 co-expresses: CAR with a BCMA-specific engager Allogeneic technology – single shRNA targeting CD3ζ component of TCR complex Selection marker – trunc
Slide 9: Keys to establishing technology proof-of-concept
Keys to establishing technology proof-of-concept No evidence of GvHD Cell kinetics Initial clinical activity shRNA as a Novel Allogeneic Technology for CAR T
Slide 10: CYAD-211 – IMMUNICY-1 Phase 1 Trial Study Design
Open-label, Phase 1 dose-escalation trial in relapsed or refractory multiple myeloma patients CYAD-211 – IMMUNICY-1 Phase 1 Trial Study Design (1) Patient Background Primary objective: safety and recommended dose of CYAD-211 Dose escalation: 30x106, 100x106 and 300x106 cells per infusion Standard pr
Slide 11: CYAD-211 – Summary of Initial Clinical Data – EHA June 2021
Positive Systemic Cell Engraftment EHA: European Hematology Association; DLT: Dose-limiting toxicity; GvHD: Graft versus Host Disease. | Data from uncleaned database (May 24, 2021). Of the six patients dosed at the first two dose levels (30x106 and 100x106 cells per infusion): No DLTs, no GvHD and n
Slide 12: CYAD-211 Case Study – Response in Individual Lesions in Patient 5
CYAD-211 Case Study – Response in Individual Lesions in Patient 5 1 month prior to infusion (SUV 6.2) D57 post infusion (SUV 5) 1 month prior to infusion (SUV 2.5 – 1.6 x 0.8 cm) D57 post infusion Resolved Left Maxillary Bone Right Lower Lobe (Superior segment)
Slide 13: Cell Kinetics Updated with First Patient at Dose Level 3
Cell Kinetics Updated with First Patient at Dose Level 3 Duration and depth of lymphodepletion was variable in dose level 1 patients while patients in dose levels 2 and 3 showed similar lymphodepletion CYAD-211 cell levels detected by PCR-based methods in all patients Consistent with a dose dependen
Slide 14: Keys to establishing technology proof-of-concept
Keys to establishing technology proof-of-concept No evidence of GvHD Cell kinetics Initial clinical activity ü ü ü shRNA as a Novel Allogeneic Technology for CAR T
Slide 15: Next Steps for CYAD-211 IMMUNICY-1 Trial
Enrollment ongoing in dose level 3 (300x106 cells per infusion) Plan to explore higher dose preconditioning regimens after dose level 3 Additional data from the dose escalation trial expected during second half 2021 Next Steps for CYAD-211 IMMUNICY-1 Trial
Slide 16: shRNA Platform – Armored CAR T Franchise
shRNA Platform – Armored CAR T Franchise
Slide 17: Armored CAR Ts to Target the Tumor Microenvironment
CAR Cytokine Autocrine effect – CAR T function Paracrine effect – Impact the tumor microenvironment Armored CAR Ts to Target the Tumor Microenvironment
Slide 18: Armored CARs Using Interleukin-18 (IL-18)
Armored CARs Using Interleuken-18 (IL-18)
Slide 19: Expected Mechanism of Action – IL-18 Influence on CAR T Cells
Expected Mechanism of Action – IL-18 Influence on CAR T Cells Local Environment Strong proliferation and anti-tumor activity in vivo Tbethigh FoxO1low CAR T phenotype through autocrine activity of IL-18 and CAR stimulation Mouse models: IL-18 Increased CD206- M1 macrophages Increased NKG2D+ NK cells
Slide 20: Background on CYAD-203
CYAD-203 – Armored NKG2D Receptor Allogeneic CAR T for Solid Tumors CYAD-203 is a novel allogeneic, armored CAR T candidate using shRNA technology within our All-in-One vector approach. CYAD-203 co-expresses: NKG2D-based CAR Allogeneic technology – single shRNA targeting CD3ζ component of TCR comple
Slide 21: IL-18 Secretion Enhances Activity of NKG2D Receptor CAR T Cells
IL-18 Secretion Enhances Activity of NKG2D Receptor CAR T Cells Proof-of-principle of IL-18 established in preclinical models NKG2D CAR + IL-18 NKG2D CAR + IL-18 + shRNA CD3ζ
Slide 22: Next Steps for Armored CAR T Franchise
Next Steps for Armored CAR T Franchise Investigational New Drug (IND) enabling studies ongoing Anticipate submission of IND application in mid-2022 To our knowledge, CYAD-203 on track to be first IL-18 secreting allogeneic CAR T candidate Additional Armored CAR Ts CYAD-203 Program Currently evaluati
Slide 23: shRNA Platform – Optimized for Multiplexed CAR Ts
shRNA Platform – Optimized for Multiplexed CAR Ts
Slide 24: Evolution of shRNA Technology for Next-Generation Allogeneic CAR T
Evolution of shRNA Technology for Next-Generation Allogeneic CAR T CYAD-211 and CYAD-203 employ a single shRNA targeting CD3ζ (CD247) Targeting multiple genes with shRNA to optimize functionality is an obvious next step given the breadth of the technology At ASCO 2020, demonstrated concurrent knockd
Slide 25: Ongoing shRNA Multiplex Research Focused on Key Targets
Ongoing shRNA Multiplex Research Focused on Key Targets CD3ζ (CD247) Beta-2-microglobulin (β2M) FAS (CD95) Component of the TCR complex Knockdown of TCR designed to prevent Graft versus Host Disease (GvHD) shRNA targeting approach validated through CYAD-211 program Component of the MHC Class I molec
Slide 26: Multiplexing with First Generation shRNA Scaffold
Multiplexing with First Generation shRNA Scaffold FAS HLA-I TCRαβ aBCMA CAR shRNA CD3z shRNA B2M shRNA FAS - - - - + - - - + + + - + + - + + + + + First Generation BCMA CAR CD3ζ β2M FAS BCMA: B-cell maturation antigen
Slide 27: First Generation shRNA Scaffold – Transduction Efficiency
First Generation shRNA Scaffold – Transduction Efficiency Targeting multiple genes using first generation shRNA scaffold impacts transduction efficiencies
Slide 28: Multiplexing with Novel Second Generation shRNA Scaffold
Multiplexing with Novel Second Generation shRNA Scaffold FAS HLA-I TCRαβ First Generation Second Generation aBCMA CAR shRNA CD3z shRNA B2M shRNA FAS - - - - + - - - + + + - + + - + + + + + + + + - + + - + + + + + CD3ζ β2M FAS BCMA CAR
Slide 29: Second Generation shRNA Scaffold – Transduction Efficiency
Second Generation shRNA Scaffold – Transduction Efficiency Broad increase in transduction efficiencies with second generation shRNA scaffold
Slide 30: Next Steps for Multiplexing Research – Illustrative shRNA Targets
Next Steps for Multiplexing Research – Illustrative shRNA Targets CD3z TRAC β2M HLAII CD52 MICA/B CD28 PI3Kd PERSISTENCE FAS DGK PD1, TIGIT, LAG3, TIM3, CTL4A, TGFbR ALLOGENICITY FITNESS RESISTANCE to TME RESISTANCE to AICD CD38 CD7 MICA/B THERAPY SPECIFIC Bold/italicized/underlined targets currentl
Slide 31: shRNA Platform – Future Programs
shRNA Platform – Future Programs
Slide 32: Allogeneic CAR T Competitive Landscape – Key Targets of Interest
Allogeneic CAR T Competitive Landscape – Key Targets of Interest Hematological Solid Tumors CD123 CD20 PSMA HER2 CD70 GPC3 CD19 CS1 CD38 BCMA CD22 CD33 NKG2D MSLN MUC1 ROR1 Claudin 18.1 NKG2D B7H3 FAP TAG72 CD70 Target represented by number of clinical/preclinical candidates in development B7H6 5T4
Slide 33: Allogeneic CAR T Competitive Landscape – Key Targets of Interest
Allogeneic CAR T Competitive Landscape – Key Targets of Interest Hematological Solid Tumors CD123 CD20 PSMA HER2 CD70 GPC3 CD19 CS1 CD38 BCMA CD22 CD33 NKG2D MSLN MUC1 ROR1 Claudin 18.1 NKG2D B7H3 FAP TAG72 CD70 Target represented by number of clinical/preclinical candidates in development Source: C
Slide 34: Allogeneic CAR T Competitive Landscape – Key Targets of Interest
Allogeneic CAR T Competitive Landscape – Key Targets of Interest Hematological Solid Tumors CD123 CD20 PSMA HER2 CD70 GPC3 CD19 CS1 CD38 BCMA CD22 CD33 NKG2D MSLN MUC1 ROR1 Claudin 18.1 NKG2D B7H3 FAP TAG72 CD70 Target represented by number of clinical/preclinical candidates in development B7H6 5T4
Slide 35: Allogeneic CAR T Competitive Landscape – Key Targets of Interest
Allogeneic CAR T Competitive Landscape – Key Targets of Interest Hematological Solid Tumors CD123 CD20 PSMA HER2 CD70 GPC3 CD19 CS1 CD38 BCMA CD22 CD33 NKG2D MSLN MUC1 ROR1 Claudin 18.1 NKG2D B7H3 FAP TAG72 CD70 Target represented by number of clinical/preclinical candidates in development Source: C
Slide 36: Update on CYAD-101 for mCRC
elyad Oncology Update on CYAD-101 for mCRC
Slide 37: Background on CYAD-101
Background on CYAD-101 NKG2D receptor-based CAR, TCR Inhibitory Molecule (TIM) and selection marker All-in-One vector approach based on TIM technology Single transduction Avoids multiple genetic modifications and cost associated with additional GMP grade materials TIM inhibits CD3ζ and reduces signa
Slide 38: CYAD-101 – alloSHRINK Phase 1 Trial
Patient population mCRC after at least one metastatic treatment line FOLFIRI segment: PD under FOLFIRI Treatment schedule Three CYAD-101 infusions administered Q2W 48 hrs post preconditioning chemotherapy Primary objective: Safety (GvHD, CRS, CRES) Secondary objective: Clinical activity Exploratory
Slide 39: alloSHRINK – CYAD-101 Following FOLFOX Showed Encouraging ORR
FOLFOX Preconditioning Cohorts Values below LOD (10 copies/µg DNA) set at LOD Arrows indicate CYAD-101 infusions alloSHRINK – CYAD-101 Following FOLFOX Showed Encouraging ORR 15 patients were treated at 3 dose-levels Absence of GvHD No treatment-related adverse events ≥ Grade 3 1x109 CYAD-101 cells/
Slide 40: Case Study – alloSHRINK Patient 01
Previous Metastatic Lines and Response Case Study – alloSHRINK Patient 01 (Partial Response, Dose Level 1) Male, 74 years old; ECOG 1 | Left colon | RAS wild type; BRAF wild type; MSS CONFIRMED PARTIAL RESPONSE Responses on CYAD-101 + FOLFOX preconditioning SD FOLFOX CETUXIMAB PR FOLFOX PANITUMUMAB
Slide 41: Case Study – alloSHRINK Patient 08
CONFIRMED PARTIAL RESPONSE No better clinical response under FOLFOX alone Male, 62 years old; ECOG 0 | Rectum cancer | RAS mutated; BRAF wildtype; MSS CEA = 10.9 µg/L CEA = 6.3 µg/L Case Study – alloSHRINK Patient 08 (Partial Response, Dose Level 3) Previous Metastatic Lines and Response Responses o
Slide 42: Shorter Persistence of CYAD-101 Cells Observed After FOLFIRI vs. FOLFOX
Cell Engraftment following FOLFIRI NKG2D copies/µg DNA Cell Engraftment following FOLFOX Values below LOD (10 copies/µg DNA) set at LOD Arrows indicate CYAD-101 infusions Values below LOD (10 copies/µg DNA) set at LOD Arrows indicate CYAD-101 infusions Shorter Persistence of CYAD-101 Cells Observed
Slide 43: alloSHRINK Expansion Cohort Update
alloSHRINK Expansion Cohort Update Best Tumor Burden Response Cell Engraftment following FOLFIRI NKG2D copies/µg DNA Values below LOD (10 copies/µg DNA) set at LOD Arrows indicate CYAD-101 infusions CYAD-101 following FOLFIRI generally well-tolerated No objective response observed with nine of ten p
Slide 44: Shorter Persistence of CYAD-101 Cells Observed After FOLFIRI vs. FOLFOX
No relevant differences between CYAD-101 batches used CYAD-101 cells may be impacted (lysis) by irinotecan metabolite In vitro testing is ongoing to investigate lead hypothesis Cell Engraftment following FOLFIRI Cell Engraftment following FOLFOX Shorter Persistence of CYAD-101 Cells Observed After F
Slide 45: KEYNOTE-B79 Trial – CYAD-101 with KEYTRUDA in Refractory mCRC
mCRC: Metastatic colorectal cancer; MoA: Mechanism of action; TME: Tumor microenvironment KEYNOTE-B79 Trial – CYAD-101 with KEYTRUDA® in Refractory mCRC alloSHRINK Highlights Expected Complementary MoAs Encouraging clinical activity observed in incurable mCRC patients Therapy well tolerated. No evid
Slide 46: KEYNOTE-B79 Phase 1b Trial Design
KEYNOTE-B79 Phase 1b Trial Design Primary objective: Safety (GvHD, CRS, CRES) Secondary objective: Clinical activity Exploratory evaluation: CYAD-101 engraftment FOLFOX Screening D1 Long-term safety follow-up Y15 D15 D29 D52 D73 M26 D3 D17 D31 FOLFOX FOLFOX CYAD-101 End of treatment phase CYAD-101 C
Slide 47: Next Steps for CYAD-101 Program
alloSHRINK Phase 1 KEYNOTE-B79 Phase 1b Next Steps for CYAD-101 Program Continue to monitor patients Analyze SN-38 serum levels in study patients Evaluate sensitivity of CYAD-101 cells to SN-38 in vitro Regulatory process for review of protocol complete in U.S. and Belgium Study initiation by early
Slide 48: Final Remarks and Q&A
Final Remarks and Q&A Company proprietary material – do not copy or distribute
Slide 49: Building Next Generation Allogeneic Candidates
Building Next Generation Allogeneic Candidates MM: Multiple myeloma; mCRC: Metastatic colorectal cancer; MDS: Myelodysplastic syndrome; MSS: Microsatellite stable; pMMR: Proficient mismatch repair; r/r: relapse/refractory. Second Half 2021 2022 CYAD-211 for r/r MM Report additional clinical activity
Slide 50: Differentiated Pipeline of Allogeneic CAR T Candidates
Differentiated Pipeline of Allogeneic CAR T Candidates TARGET INDICATION IND ENABLING Phase 1 PHASE 2 PHASE 3 CYAD-101 NKG2DL mCRC CYAD-203 NKG2DL + IL-18 Solid tumors CYAD-211 BCMA r/r MM MM: Multiple myeloma; BCMA: B-cell maturation antigen; IL-18: Interleuken-18; mCRC: Metastatic colorectal cance
Slide 51: Research and Development Day Virtual Webinar
Research and Development Day Virtual Webinar July 20, 2021