On November 12, 2021 Celyad Oncology SA (Euronext & Nasdaq: CYAD), a clinical-stage biotechnology company focused on the discovery and development of chimeric antigen receptor T cell (CAR T) therapies for cancer, reported three poster presentations on the Company’s allogeneic CAR T therapy programs at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting taking place in Washington D.C. and virtually November 10-14, 2021 (Press release, Celyad, NOV 12, 2021, View Source [SID1234595448]).

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"With these presentations, we demonstrate how we continue to execute on our strategic vision to develop differentiated next generation CAR Ts using our non-gene edited allogeneic approaches which are intended to provide multiple real-world benefits to patients," said David Gilham, Ph.D., Chief Scientific Officer of Celyad Oncology. "We believe our CAR T cells are the only allogeneic CAR T cells currently in human clinical trials that avoid generating double-strand DNA breaks. Combining with multiplexed shRNA and cytokine armoring, we believe this approach provides us with a dynamic platform for the generation of future allogeneic candidates."

Charles Morris, M.D., Chief Medical Officer of Celyad Oncology said, "In addition to the encouraging preclincal data presented, we are also on the cusp of initiating the KEYNOTE-B79 Phase 1b clinical trial in collaboration with MSD. We believe that KEYNOTE-B79 will be the first clinical trial to evaluate an allogeneic CAR T with an anti-PD-1 therapy in solid tumors. We look forward to evaluating whether the expected highly complementary mechanism of actions of CYAD-101 and KEYTRUDA could help to drive important clinical benefit in patients with refractory metastatic colorectal cancer with microsatellite stable disease where a high unmet medical need exists. We look forward to initiating the study in the coming weeks and providing clinical updates to the CYAD-101 program in 2022."

Key Highlights from SITC (Free SITC Whitepaper) Annual Meeting

Poster 107 – Armoring NKG2D CAR T cells with IL-18 improves in vitro and in vivo anti-tumor activity

This poster demonstrates the key role of Interleukin-18 (IL-18) in driving increased effector function of the NKG2D CAR T cells.
These data support the ongoing development of the Company’s shRNA-based allogeneic, IL-18-armored CAR T candidate CYAD-203 as well as future allogeneic IL-18-armored CAR T candidates.
Poster 146 – Evolving multiplexed shRNA to generate tailored CAR T cell therapy

Multiplexing short hairpin RNA (shRNA) within a single vector format ensures co-linked expression of the shRNA with therapeutic transgenes.
We continue to develop second-generation shRNA scaffold using multiplexed technology to produce novel allogeneic clinical candidates with bespoke, desired phenotypes and function produced using methods that avoid the generation of double strand DNA breaks.
Poster 407 – A Phase 1b KEYNOTE-B79 trial evaluating non-gene edited allogeneic CAR T-cells, CYAD-101, post FOLFOX preconditioning, followed by pembrolizumab, in refractory metastatic colorectal cancer patients

Clinical and translational results from the alloSHRINK Phase 1 trial evaluating the TCR Inhibitory Molecule (TIM)-based allogeneic NKG2D CAR T-cell product candidate CYAD-101 (NCT03692429) in patients with metastatic colorectal (mCRC) cancer suggest that treatment with sequential checkpoint inhibition following CYAD-101 with FOLFOX preconditioning could drive more durable clinical responses.
The KEYNOTE-B79 trial will therefore evaluate the safety and clinical activity of multiple infusions of CYAD-101 administered post FOLFOX preconditioning chemotherapy, followed by treatment with KEYTRUDA (pembrolizumab) in mCRC patients with microsatellite stable disease, according to a Simon’s two stage trial design.
The KEYNOTE-B79 clinical trial is expected to begin in fourth quarter 2021.
These ePosters will be available on the SITC (Free SITC Whitepaper) website starting today at 1 p.m. CET / 7 a.m. ET and in the Scientific Publications section of Celyad Oncology’s website.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.