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. The data support the potential and versatility of non-gene edited short hairpin RNA (shRNA) technology for the development of next-generation CAR T therapies. Key Highlights from the ASH Annual Meeting: CYAD-02 and CYCLE-1 Phase 1 Trial Update: 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. A favorable tolerability profile for CYAD-02 with a low rate of Grade = 3 cytokine release syndrome in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome (r/r AML /MDS). 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. Two MDS patients achieved a marrow complete response at dose level 3. Of the eight patients with stable disease, six had anti-leukemic activity. Comparison of cellular kinetics for CYAD-02 and CYAD-01 trend towards increased engraftment and persistence of CYAD-02 versus CYAD-01, potentially associated with the knockdown of MICA/MICB and reduced fratricide in vivo. CYAD-211 and IMMUNICY-1 Phase 1 Trial Update: Trial observations from allogeneic shRNA-based anti-BCMA CAR T candidate CYAD-211 support the continued development of shRNA-based allogeneic CAR T therapies as a feasible approach to overcome potential drawbacks and risks associated with autologous and gene-edited allogeneic CAR T therapies. CYAD-211 demonstrated a good tolerability profile and evidence of clinical activity in the dose-escalation segment with three out of 12 total patients with relapsed or refractory multiple myeloma (r/r MM) evaluated for activity achieving partial response, one in each dose-level, while eight patients had stable disease. All patients had detectable CYAD-211 cells in the peripheral blood; preconditioning chemotherapy led to earlier-than-expected recovery of host lymphocytes limiting persistence of CAR T cells. The next segment of the IMMUNICY-1 trial will evaluate enhanced lymphodepleting regimens with the aim to improve persistence. In addition, the protocol also allows for CYAD-211 redosing in certain patient. Enrollment in the cohorts evaluating enhanced lymphodepletion is ongoing. Additional data from the CYAD-211 IMMUNICY-1 trial are expected in mid-2022.