CYAD-101 is an investigational, non-gene edited allogeneic (healthy donor derived) CAR T candidate engineered to co-express the chimeric antigen receptor based on NKG2D, a receptor expressed on natural killer (NK) cells that binds to eight stress-induced ligands and the novel inhibitory peptide TIM (TCR Inhibitory Molecule). The expression of TIM reduces signaling of the TCR complex by interfering with the CD3ζ component of the TCR complex.

CYAD-101 is currently being evaluated in the Phase 1 alloSHRINK trial for the treatment of relapsed/refractory metastatic colorectal cancer (mCRC). An expansion cohort of the alloSHRINK trial evaluating CYAD-101 following FOLFIRI preconditioning chemotherapy is expected to begin during the fourth quarter of 2020.

CYAD-103 is a preclinical, non-gene edited allogeneic CAR T candidate. Similar to CYAD-101, CYAD-103 is engineered to co-express the chimeric antigen receptor based on NKG2D, a receptor expressed on natural killer (NK) cells that binds to eight stress-induced ligands and the novel inhibitory peptide TIM (TCR Inhibitory Molecule). In addition to NKG2D and TIM, the company is exploring additional add-on components to the CAR T construct to improve clinical activity of the next-generation candidate for the treatment of solid tumors.

CYAD-211 is a preclinical, short hairpin RNA (shRNA)-based allogeneic CAR T candidate for the treatment of relapsed or refractory multiple myeloma (r/r MM). CYAD-211 is engineered to co-express a B-cell maturation antigen (BCMA) chimeric antigen receptor and a single shRNA hairpin which interferes with the expression of the CD3ζ component of the TCR complex.

Celyad Oncology plans to submit an Investigational New Drug (IND) application for CYAD-211 during mid-2020 and the allogeneic candidate is expected to enter the clinic by year-end 2020.

CYAD-221 is a preclinical, short hairpin RNA (shRNA)-based allogeneic CAR T candidate for the treatment of B-cell malignancies. CYAD-221 is engineered to co-express a CD19 chimeric antigen receptor and an shRNA hairpin which interferes with the expression of the CD3ζ component of the TCR complex.

CYAD-231 is a dual specific CAR T candidate targeting NKG2D and an undisclosed membrane protein. The short hairpin RNA (shRNA)-based allogeneic CAR T candidate is in preclinical development.

CYAD-01 is an investigational CAR T therapy in which a patient's T cells are engineered to express a chimeric antigen receptor based on NKG2D, a receptor expressed on natural killer (NK) cells that binds to eight stress-induced ligands expressed on tumor cells.

CYAD-01 continues to advance in Phase 1 trials – THINK and DEPLETHINK – for the treatment of patients with relapsed or refractory acute myeloid leukemia and myelodysplastic syndromes (r/r AML/MDS). In December 2019, the Company presented the data from the CYAD-01 Phase 1 THINK and DEPLETHINK clinical trials at the American Society of Hematology annual meeting. In February 2020, the Company began recruitment in the expansion cohort of the THINK trial evaluating CYAD-01 as a monotherapy. Both the expansion cohort of the THINK trial and the dose-escalation DEPLETHINK trial are now assessing CYAD-01 produced with the Company’s proprietary OptimAb manufacturing process.

CYAD-02 is an investigational CAR T therapy that engineers an all-in-one vector approach in patient’s T cells to express both (i) the NKG2D chimeric antigen receptor, a receptor expressed on natural killer (NK) cells that binds to eight stress-induced ligands expressed on tumor cells, and (ii) short hairpin RNA (shRNA) technology to knockdown the expression of NKG2D ligands MICA and MICB on the CAR T cells. In preclinical models, shRNA-mediated knockdown of MICA and MICB expression on NKG2D CAR T cells has shown enhanced in vitro expansion, as well as enhanced in vivo engraftment and persistence, of the CAR T cells, as compared to first-generation NKG2D-based CAR T cells.

In January 2020, the Company announced enrollment had begun in the Phase 1 dose-escalation CYCLE-1 trial evaluating the next-generation NKG2D-based CAR T candidate for the treatment of relapsed or refractory acute myeloid leukemia and myelodysplastic syndromes (r/r AML/MDS). The CYCLE-1 trial will evaluate the safety and clinical activity of a single infusion of CYAD-02 produced with the OptimAb manufacturing process following preconditioning chemotherapy with cyclophosphamide and fludarabine. The trial will evaluate three dose levels of CYAD-02 up to one billion cells per infusion.