Slide 1: 2021 American Society of Hematology Meeting Update
2021 American Society of Hematology Meeting Update December 13, 2021 Exhibit 99.2
Slide 2: Forward Looking Statements
Forward Looking Statements This release may contain forward-looking statements, within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding the clinical activity and safety and tolerability
Slide 3: ASH 2021 Virtual Webcast – Agenda
ASH 2021 Virtual Webcast – Agenda Topic Discussant Welcome & Introductions Filippo Petti Chief Executive Officer shRNA Background David Gilham, Ph.D. Chief Scientific Officer CYAD-02 CYCLE-1 Phase 1 Trial Results Charles Morris, M.D. Chief Medical Officer CYAD-211 IMMUNICY-1 Phase 1 Trial Results Ch
Slide 4: Redefining Next-Generation Allogeneic CAR T Development
Redefining Next-Generation Allogeneic CAR T Development All-in-One vector approach Two proprietary allogeneic technologies shRNA – short hairpin RNA TIM – TCR Inhibitory Molecule Armored CAR T franchise focused on IL-18 cytokine Potential for non-gene edited shRNA as a viable platform to develop all
Slide 5: shRNA Background
David Gilham, Ph.D. Chief Scientific Officer shRNA Background
Slide 6: shRNA – Novel Platform for Allogeneic CAR T Development
shRNA – Novel Platform for Allogeneic CAR T Development shRNA: short hairpin RNA; mRNA: messenger ribonucleic acid; TCR: T cell receptor. Generating T cells with desired phenotypic and functional properties Controlling the level of gene knockdown Multiplexing to knockdown multiple genes Celyad is fo
Slide 7: First-in-Human shRNA Platform Timeline
First-in-Human shRNA Platform Timeline 2018 2022 Today Exclusive agreement with Horizon Discovery (shRNA platform) October 2018 IND clearance for CYCLE-1 study June 2019 First patient treated in CYCLE-1 study January 2020 IND clearance for IMMUNICY-1 study July 2020 First patient treated in IMMUNICY
Slide 8: Potential Advantages of Non-Gene Edited Allogeneic CAR Ts Using shRNA
Potential Advantages of Non-Gene Edited Allogeneic CAR Ts Using shRNA No double strand breaks – expected minimal risk of genomic instability and translocation Not all allogeneic CAR Ts are created equal All-in-One vector – long clinical history including maintenance of transgenic payload integrity1,
Slide 9: Expected Real-World Benefits of Our Approach to Allogeneic CAR T
Expected Real-World Benefits of Our Approach to Allogeneic CAR T Gene Knockdown Aims to Optimize Therapy Shorter Manufacturing Time Lower Cost of Goods Sold Ability to potentially simultaneously knockdown multiple gene targets of interest shRNA can target genes that are not suitable for gene editing
Slide 10: shRNA as a Novel Allogeneic Technology for CAR T
Technology continues to show promise as a platform No evidence of GvHD Cell kinetics Initial clinical activity shRNA as a Novel Allogeneic Technology for CAR T
Slide 11: CYAD-02 CYCLE-1 Trial Results
Charles Morris, M.D. Chief Medical Officer CYAD-02 CYCLE-1 Trial Results
Slide 12: CYAD-02 – Next-Generation Autologous NKG2D CAR T
CYAD-02 – Next-Generation Autologous NKG2D CAR T CYAD-02 incorporates shRNA technology to silence the expression of the NKG2D ligands MICA and MICB Targeting MICA and MICB with a single shRNA leads to decrease of ligand expression on T cells and enhanced in vitro expansion compared to first-generati
Slide 13: CYAD-02 CYCLE-1 – Phase 1 Trial to Determine Recommended Dose
Open-label, dose-escalation trial in relapsed or refractory AML and MDS patients CYAD-02 CYCLE-1 – Phase 1 Trial to Determine Recommended Dose Study Design Treatment Schedule Twelve AML and MDS with relapsed or refractory (r/r) disease patients treated Similar patient population as DEPLETHINK Phase
Slide 14: CYAD-02 vs. CYAD-01 Response in r/r AML and MDS Patients
+ indicates patient is ongoing. No objective responses observed 5/17 patients with SD including 1 with anti-leukemic activity 2 MDS patients achieved a marrow complete response (mCR) both at dose level 3 (DL3) 8/12 patients with stable disease (SD) including 4 with anti-leukemic activity defined as
Slide 15: Kinetics of CYAD-02 vs. CYAD-01 at Dose Level 3
CYAD-02 cells were detected post-infusion in all patients in the CYCLE-1 study Median peak engraftment trending higher for CYAD-02 compared to CYAD-01 Overall, CYAD-02 presents longer persistence compared to CYAD-01 One patient at dose level 3 in the CYCLE-1 study received a delayed infusion of CAR
Slide 16: CYAD-02 CYCLE-1 Summary
CYAD-02 CYCLE-1 Summary Data support the use of shRNA platform for CAR T development Single shRNA can target two independent genes to enhance the phenotype of the CAR T cells Overall good tolerability profile of CYAD-02 post CyFlu preconditioning Two objective responses (mCR) at dose level 3 leading
Slide 17: CYAD-211 IMMUNICY-1 Phase 1 Trial Update
Charles Morris, M.D. Chief Medical Officer CYAD-211 IMMUNICY-1 Phase 1 Trial Update
Slide 18: CYAD-211 – Novel Allogeneic CAR T Candidate for r/r MM
Background on CYAD-211 First allogeneic CAR T candidate utilizing our All-in-One vector approach based on shRNA technology CYAD-211 co-expresses: CAR with a BCMA-specific engager Allogeneic technology – single shRNA targeting CD3ζ component of TCR complex Selection marker – truncated cell surface ta
Slide 19: CYAD-211 – Preclinical Differentiation Among BCMA CAR T Candidates
CYAD-211 – Preclinical Differentiation Among BCMA CAR T Candidates * First experiment performed with one donor. Other donors are currently being investigated to determine whether there is a donor effect. CYAD-211 and peer candidate CAR T cells screened for repeated antigen stimulation After each rou
Slide 20: CYAD-211 – IMMUNICY-1 First-in-Human Trial
Open-label, Phase 1 dose-escalation trial in r/r multiple myeloma patients CYAD-211 – IMMUNICY-1 First-in-Human Trial Study Design Treatment Schedule Primary objective: Safety and identification of recommended dose of CYAD-211 Secondary objective: Clinical anti-tumor activity and CYAD-211 cell expan
Slide 21: IMMUNICY-1 – Patient Backgrounds and Safety Data
IMMUNICY-1 – Patient Backgrounds and Safety Data Twelve patients enrolled in three dose levels Most patients had high-risk cytogenetics according to mSMART 25% had extramedullary disease Heavily pre-treated patients: Median prior lines of therapy: four 83% exposed to all three major MM drug classes
Slide 22: CYAD-211 – Clinical Responses and Duration of Responses to Progression
Three patients achieved partial response (PR), one in each dose-level, while eight patients had stable disease (SD) One patient with SD (4.5 months) showed evidence of reduction in size of plasmacytomas CYAD-211 – Clinical Responses and Duration of Responses to Progression Data from uncleaned databa
Slide 23: CYAD-211 – Cell Kinetic Data from IMMUNICY-1
CYAD-211 – Cell Kinetic Data from IMMUNICY-1 Calls for Further Exploration of Lymphodepletion All patients had detectable CYAD-211 cells in the peripheral blood, although engraftment was short lasting Data suggests expansion and persistence of cells might be more dependent on the depth and period of
Slide 24: CYAD-211 IMMUNICY-1 Summary
Data and observations support the potential of shRNA allogeneic therapies as a feasible approach to CAR T that may overcome challenges associated with autologous and gene edited CAR Ts Three patients achieved partial response (one in each dose level) Eight patients had stable disease One patient wit
Slide 25: Final Remarks
Filippo Petti Chief Executive Officer Final Remarks
Slide 26: shRNA as a Novel Allogeneic Technology for CAR T
Technology continues to show promise as a platform shRNA as a Novel Allogeneic Technology for CAR T No evidence of GvHD Cell kinetics Initial clinical activity ü ü ü
Slide 27: Next Steps for shRNA CAR T Candidates and Platform
Next Steps for shRNA CAR T Candidates and Platform CYAD-211 Enrolling in cohorts 4 and 5 to evaluate enhanced lymphodepletion CYAD-211 redosing also allowed by the protocol CYAD-02 Evaluating potential partnership opportunities for autologous NKG2D franchise shRNA Platform Continue exploring platfor
Slide 28: 2021 American Society of Hematology Meeting Update
2021 American Society of Hematology Meeting Update December 13, 2021