CYAD-02 / Celyad Oncology - LARVOL DELTA

Proof-of-concept of a non-gene editing technology using shRNA down-regulation to engineer and optimize CAR T-cell functionality (SITC 2023) - P1 | "This construct (CYAD-211) was then evaluated in a Phase I clinical trial (NCT04613557) to validate the shRNA technology...This construct (CYAD-02) was also evaluated in a Phase I clinical trial (NCT04167696)...Conclusions Our data provide proof of principle that single shRNA-mediated knockdown can generate fully functional allogeneic CAR T-cells in humans without any signs of GvHD or can improve CAR T-cell characteristics while maintaining a good safety profile and efficacy. We are currently validating the technology to downregulate multiple-genes of interest simultaneously thereby providing a platform approach that could support the future of cell therapy."

CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Oncology • NKG2D

[VIRTUAL] First Results from the Dose Escalation Segment of the Phase I Clinical Study Evaluating Cyad-02, an Optimized Non Gene-Edited Engineered NKG2D CAR T-Cell Product, in Relapsed or Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients (ASH 2020) - P1 | "Results As compared to CYAD-01, CYAD-02 cell expansion in vitro was 3-fold increased...The study evaluates three dose-levels of CYAD-02 (1x108, 3x108 and 1x109 cells/infusion), administered as a single infusion after non-myeloablative preconditioning chemotherapy (cyclophosphamide 300 mg/m²/day and fludarabine 30 mg/m²/day, daily for 3 days, CyFlu) according to a classical Fibonacci 3+3 design...This next generation NKG2D CAR T-cell product is currently investigated in the CYCLE-1 Phase I study in r/r AML/MDS patient population, a difficult to target disease due in part to the absence of truly AML-specific surface antigens, its rapid clinical progression and the absence of disease control by the CyFlu preconditioning. Both the anti-MICA and MICB shRNA hairpin and the OptimAb manufacturing process for CYAD-02 aim to improve CAR T-cell persistence and clinical responses."

CAR T-Cell Therapy • Clinical • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • NKG2D

Co-Expression of an shRNA Targeting MICA/Micb Improves the Clinical Activity of a NKG2D-Based CAR T in Patients with Relapsed / Refractory AML/MDS (ASH 2021) - P1, P1/2 | "In clinical trials, CYAD-01 showed a good tolerability profile but with a disappointing level of clinical activity when combined with cyclophosphamide / fludarabine preconditioning (DEPLETHINK trial, NCT03466320)...The knockdown of MICA/MICB appears to have a positive contribution to the initial clinical activity of CYAD-02 as compared to that achieved with the first generation CYAD-01 CAR T, together with good safety and tolerability...One approach to further drive the potency of NKG2D-based CAR T cells would likely be armoring the CAR T through using the T cell as a vehicle to secrete cytokines alongside the CAR. Overall, shRNA knockdown technology provides a means to modify CAR T function and here shows that single shRNA can target two independent genes to enhance the phenotype of the CAR Ts."

Clinical • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Inflammation • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • IL15 • IL7 • NKG2D

Celyad Oncology Reports Full Year 2020 Financial Results and Recent Business Highlights (GlobeNewswire) - “Upcoming Milestones; Additional proof-of-concept data from the initial dose cohorts of the Phase 1 IMMUNICY-1 trial of CYAD-211 for r/r MM are expected by the end of Q2 2021; Preliminary data from the expansion segment of the alloSHRINK trial evaluating CYAD-101 following FOLFIRI preconditioning chemotherapy in refractory mCRC patients are expected in Q2 2021; Initiation of the Phase 1b KEYNOTE-B79 trial evaluating CYAD-101 with KEYTRUDA® in mCRC patients with MSS/pMMR disease is anticipated by in the first half of 2021; Additional data from dose level 3 of Phase 1 CYCLE-1 trial of CYAD-02 for r/r AML and MDS are anticipated in the first half of 2021.”

New P1 trial • P1 data • Acute Myelogenous Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • Solid Tumor

Celyad Oncology Presents Updates on shRNA-Based CAR T Programs at the 63rd ASH Annual Meeting and Exposition (GlobeNewswire) - P1, N=27; CYCLE-1 (NCT04167696); Sponsor: Celyad Oncology SA; "Celyad Oncology SA...announced that data from the Phase 1 CYCLE-1 trial of CYAD-02 for the treatment of relapsed or refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) and the Phase 1 IMMUNICY-1 trial of CYAD-211 for the treatment of r/r multiple myeloma were presented at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition...Data from autologous NKG2D receptor CAR T candidate CYAD-02 using shRNA shows a single shRNA can target two independent genes to enhance the phenotype of the CAR T cells. The dual knockdown of genes MICA/MICB with a single shRNA has a positive contribution to the initial clinical activity of CYAD-02 as compared to the first-generation, autologous NKG2D receptor CAR T, CYAD-01."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Celyad Oncology Announces Third Quarter 2021 Financial Results and Recent Business Highlights (GlobeNewswire) - "Upcoming Anticipated Milestones: Additional data from the Phase 1 IMMUNICY-1 trial of CYAD-211 and the Phase 1 CYCLE-1 trial of CYAD-02 are expected at the upcoming ASH meeting in December 2021."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Celyad Oncology to Present Updates from Allogeneic and Autologous CAR T Programs at 63rd ASH Annual Meeting and Exposition (GlobeNewswire) - "The poster will focus on the Company’s shRNA-based anti-BCMA allogeneic CAR T candidate CYAD-211 for the treatment of relapsed/refractory (r/r) multiple myeloma (r/r MM). The oral session will focus on the Company’s autologous NKG2D receptor-based CAR T candidate CYAD-02 for the treatment of r/r acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS)."

Clinical data • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Celyad Oncology Reports First Half 2021 Financial Results and Recent Business Highlights (GlobeNewswire) - "Upcoming Anticipated Milestones: Report additional data from the dose-escalation Phase 1 CYCLE-1 trial evaluating CYAD-02 in r/r AML and MDS by year-end 2021."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Celyad Oncology Presents Updates on Allogeneic CAR T Clinical Candidates and shRNA-based Preclinical Concepts at Research & Development Day (GlobeNewswire) - "Upcoming milestones: (i) Additional clinical activity data for the Phase 1 IMMUNICY-1 trial of CYAD-211 for r/r MM are expected during second half 2021; (ii) Study initiation for KEYNOTE-B79 Phase 1b is expected early fourth quarter 2021; (iii) Submission of an IND application for CYAD-203 is expected in mid-2022; (iv) Report additional data from the dose-escalation Phase 1 CYCLE-1 trial evaluating CYAD-02 in relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome in mid-2021."

IND • New P1 trial • P1 data • Acute Myelogenous Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Microsatellite Instability • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Celyad Oncology Provides Updates on Allogeneic and Autologous CAR T Programs at 62nd ASH Annual Meeting and Exposition (Businesswire) - "Celyad...today announced updates from the company’s shRNA-based anti-B cell maturation antigen (BCMA) allogeneic CAR T candidate, CYAD-211, and autologous NKG2D receptor-based CAR T candidates, CYAD-01 and CYAD-02....Clinical activity data from the full dose-escalation trial are expected during second half 2021....Based on clinical futility observed to date of CYAD-01 from the Phase 1 THINK trial the company has decided to discontinue the development of CYAD-01 for the treatment of r/r AML / MDS....The dose level 3 cohort of the CYCLE-1 trial is ongoing. Additional safety and efficacy data from the trial are expected during the first half of 2021."

Discontinued • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Fate and Celyad’s CAR therapies in oncology offer potential to amplify efficacy with multiple doses (Pharmaceutical-technology.com) - "Phase I FT596 results in B-cell lymphomas/ CLL are expected at either the American Society of Hematology (ASH) meeting in December or an investor meeting in early 2021, as per a second analyst report. Phase I data for CYAD-01 and CYAD-02 in relapsed/refractory (r/r) acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) are expected by YE20, as per the company’s August corporate presentation. Celyad’s allogeneic CYAD-101 is being tested in a Phase I alloSHRINK trial (NCT03692429) in metastatic colorectal cancer (CRC), which has a primary completion date of November 2020."

P1 data • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Celyad Oncology to Present Updates from Allogeneic and Autologous CAR T Programs at 62nd ASH Annual Meeting and Exposition (GlobeNewswire) - "Celyad Oncology SA...today announced that three abstracts have been accepted for presentation at the 62^nd American Society of Hematology (ASH) Annual Meeting and Exposition, which will be held virtually from December 5-8, 2020. The presentations will focus on the company’s anti-BCMA allogeneic CAR T candidate, CYAD-211, and autologous NKG2D receptor-based CAR T candidates CYAD-01 and CYAD-02."

Clinical data • P1 data • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Celyad Oncology Reports Half Year 2020 Financial Results and Second Quarter Business Highlights (Businesswire) - "Plan to begin enrollment in the expansion cohort of the Phase 1 alloSHRINK trial evaluating CYAD-101 following FOLFIRI preconditioning chemotherapy in refractory mCRC patients with MSS disease during the fourth quarter of 2020; Report additional data from the CYAD-01 program in r/r AML and MDS, including the dose-expansion cohort of the Phase 1 THINK trial by year-end 2020; Report preliminary data from the dose-escalation Phase 1 CYCLE-1 trial evaluating CYAD-02 in r/r AML and MDS by year-end 2020; Expect to initiate the dose-escalation Phase 1 trial evaluating CYAD-211 in r/r MM by year-end quarter 2020."

Enrollment status • New P1 trial • P1 data • Acute Myelogenous Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Celyad announces first quarter 2020 financial results and recent business highlights (Businesswire) - "Upcoming Milestones....Report preliminary data from CYAD-01 produced with OptimAb manufacturing process including expansion cohort of Phase 1 THINK and dose-escalation Phase 1 DEPLETHINK trials during second half of 2020; Report preliminary data from dose-escalation Phase 1 CYCLE-1 trial for CYAD-02 by year-end 2020."

P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Celyad reports full year 2019 financial results and provides business update (GlobeNewswire, Celyad SA) - “Report additional data from the dose-escalation segment of the CYAD-101 alloSHRINK Phase 1 trial during the second quarter of 2020; Submit IND application for an shRNA-based allogeneic BCMA CAR-T candidate, CYAD-211, for the treatment of patients with r/r MM by mid-2020; Report preliminary data from expansion cohort of the Phase 1 THINK and dose-escalation Phase 1 DEPLETHINK trials evaluating CYAD-01 produced with OptimAb manufacturing process during second half of 2020, due to enrollment delays caused by the COVID-19 pandemic; Begin expansion segment of the CYAD-101 alloSHRINK Phase 1 trial during the second half of 2020; Report preliminary data from the dose-escalation Phase 1 CYCLE-1 trial for CYAD-02 by year-end 2020.”

IND • P1 data

Celyad successfully doses first patient with CYAD-02 in CYCLE-1 trial for r/r AML and MDS (GlobeNewswire, Celyad SA) - "Celyad...today announced the successful administration of the next-generation, NKG2D-based candidate CYAD-02 to a relapsed/refractory acute myeloid leukemia (r/r AML) patient enrolled in the Phase 1 CYCLE-1 trial...Enrollment in the CYCLE-1 trial will continue over the coming months and we expect to report preliminary data from the study during the second half of 2020."

Enrollment open • P1 data

Celyad successfully doses first patient with CYAD-02 in CYCLE-1 trial for r/r AML and MDS (GlobeNewswire) - "Celyad...announced the successful administration of the next-generation, NKG2D-based candidate CYAD-02 to a relapsed/refractory acute myeloid leukemia (r/r AML) patient enrolled in the Phase 1 CYCLE-1 trial...Enrollment in the CYCLE-1 trial will continue over the coming months and we expect to report preliminary data from the study during the second half of 2020."

Enrollment open • P1 data

CYCLE-1: Study in Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Patients to Determine the Recommended Dose of CYAD-02 (clinicaltrials.gov) - P1; N=27; Recruiting; Sponsor: Celyad (formerly named Cardio3 BioSciences); Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Next Generation NKG2D-based CAR T-cells (CYAD-02): Co-expression of a Single shRNA Targeting MICA and MICB Improves Cell Persistence and Anti-Tumor Efficacy in vivo (ASH 2019) - "The product candidate CYAD-01 are chimeric antigen receptor (CAR) T-cells encoding the full length human NKG2D fused to the intracellular domain of CD3ζ. Conclusions By using a single vector encoding the NKG2D-based CAR next to a shRNA targeting MICA and MICB and combined with improved cell culture methods, CYAD-02, the next-generation of NKG2D-based CAR T-cells, demonstrated enhanced in vivo persistence and anti-tumor activity. Following FDA acceptance of the IND application, a Phase 1 dose-escalation trial evaluating the safety and clinical activity of CYAD-02 for the treatment of r/r AML and MDS is scheduled to start in early 2020."

CAR T-Cell Therapy

Celyad presents update on r/r AML and MDS program at 61st ASH Annual Meeting (GlobeNewswire) - P1/2, N=52; DEPLETHINK (NCT03466320); Sponsor: Celyad; “CYAD-01 produced with the mAb manufacturing process was generally reported to be well-tolerated following preconditioning chemotherapy. At the first CYAD-01 infusion of the consolidation cycle (3 billion cells per infusion), one patient experienced both grade 4 cytokine release syndrome (CRS) and grade 3 CAR-T cell-related encephalopathy and another patient experienced grade 3 CRS. Both patients recovered following the appropriate treatment, including tocilizumab….To date, no objective response has been observed at the first two dose levels of the trial in patients treated with CYAD-01 produced with the mAb manufacturing process….Preliminary data evaluating CYAD-01 produced with the OptimAb manufacturing process from cohorts 3 and 4 are expected by the end of first half 2020....[for CYAD-02] Enrollment in the CYCLE-1 trial is expected to begin in early 2020 with preliminary data anticipated during second half 2020."

Enrollment status • P1 data • P1/2 data

Celyad presents update on r/r AML and MDS program at 61st ASH Annual Meeting (GlobeNewswire, Celyad SA) - P1/2, N=146; THINK (NCT03018405); Sponsor: Celyad; “CYAD-01 without preconditioning chemotherapy was generally reported to be well-tolerated, with 11 out of 25 patients experiencing grade 3/4 treatment-related adverse events (AEs). Cytokine release syndrome (CRS) occurred in 13 patients, with four grade 3 and two grade 4 events, which showed rapid resolution following the appropriate treatment, including tocilizumab. Two dose-limiting toxicities were reported at dose level 3 (3 billion cells per infusion), including one CRS grade 4 (biweekly) and one CRS grade 3 (dose dense schedule)….Five out of the eight patients exhibited an objective response….Company plans to progress to the expansion segment of the THINK trial to further evaluate CYAD-01 produced with the OptimAb manufacturing process. Enrollment in the expansion segment of the trial is expected to begin in first quarter 2020 with preliminary data anticipated by the end of first half 2020.”

Enrollment status • P1/2 data • Trial status