CYAD-221 / Celyad Oncology - LARVOL DELTA

Celyad Oncology Reports First Half Year 2024 Financial Results and Recent Business Highlights (Businesswire) - "Multispecific NKG2D-based CAR T-cell platform...PSMA/NKG2DL tandem CAR T-cells, that encompass the extracellular domain of the natural NKG2D receptor fused to an anti-PSMA CAR to overcome antigen heterogeneity and improve anti-tumor efficacy against prostate cancer were developed and demonstrated functionality in vitro against prostate cancer cell lines expressing or not the tumor-associated antigen PSMA; In vivo proof-of-concept of the company’s CD19/NKG2DL tandem CAR T-cell candidate was also provided in a B-ALL relapse model, showing that this multi-specific CAR T-cell candidate has an enhanced anti-tumor efficacy against heterogeneous lymphoma tumors, or to counteract antigen loss, as compared to currently existing treatment options."

Preclinical • Genito-urinary Cancer • Hematological Malignancies • Lymphoma • Oncology • Prostate Cancer • Solid Tumor

Celyad Oncology reports third quarter 2023 financial results and recent business highlights (GlobeNewswire) - "Our data provides the proof-of-concept that NKG2DL are valuable targets in a multispecific CAR approach...we showed that CD19/NKG2DL multispecific CAR T-cells, and in particular dual receptors, are highly effective in vitro against CD19+ and CD19- cell lines and against CD19+ primary B-cell acute lymphoblastic leukemia (B-ALL) cells. In vivo, CD19/NKG2DL tandem CAR T-cells outperforms dual CAR T-cells in controlling tumor growth in an aggressive B-ALL relapse model; In vitro data generated with BCMA/NKG2DL and PSMA/NKG2DL multispecific CAR T-cells further validate this approach and its application in other hematological and solid indications...More data and evidence in the context of the multi-specific CAR platform and shRNA multiplexing approach will be shared in the first quarter of 2024, with the aim of a clinical evaluation of assets and initiation of clinical trials either by the Company and/or through strategic partnerships afterwards."

Clinical • Preclinical • Hematological Malignancies • Oncology • Solid Tumor

A phase I study assessing the safety and clinical activity of multiple doses of a NKG2D-based CAR-T therapy, CYAD-01, administered concurrently with the neoadjuvant FOLFOX treatment in patients with potentially resectable liver metastases from colorectal cancer (AACR 2018) - P1,P1/2; "...To address the challenge related to the immunosuppressive TME, the SHRINK trial (Standard cHemotherapy Regimen and Immunotherapy with NKR-2) has been developed to assess the safety and clinical activity of multiple infusion CYAD-01 treatment (every 2 weeks x 3 infusions) in patients undergoing standard-of-care FOLFOX (Folinic acid, Fluorouracil (5-FU) and Oxaliplatin) chemotherapy, as neoadjuvant treatment, for the treatment of colorectal metastatic disease with potentially resectable metastases (NCT03310008)...The expansion segment will then enroll 21 additional patients to further evaluate the safety and potential signs of activity of the CYAD-01 therapy when administered concurrently with chemotherapy. Peripheral blood samples, as well as tumor biopsies from patients at baseline and at resection, will be collected to determine, among others, CYAD-01 persistence, NKG2D ligand expression and systemic cytokine levels in peripheral blood post-infusion.

Clinical • IO Biomarker • P1 data • Colorectal Cancer • Hepatocellular Cancer

A phase I study assessing the safety and clinical activity of multiple hepatic transarterial administrations of a NKG2D-based CAR-T therapy CYAD-01, in patients with unresectable liver metastases from colorectal cancer (AACR 2018) - P1,P1/2; "Peripheral blood samples, as well as tumor biopsies will be collected to determine systemic CYAD-01 kinetics and within the liver tumor tissues, NKG2D ligand expression and systemic cytokine levels in peripheral blood post-infusion. This study will enroll 12 patients in case of no DLT and is open for recruitment."

Clinical • IO Biomarker • P1 data • Colorectal Cancer • Hepatocellular Cancer

A NKG2D-based CAR-T therapy in a multinational phase I dose escalation and expansion study targeting multiple solid and hematologic tumor types. (ASCO 2017) - P1; "The expansion segment will then enroll 96 additional patients in 7 separate cohorts for each indication with 3 steps of statistical analysis (overall futility, cohort futility and final evaluation). The study is open for recruitment in both EU and US."

P1 data • Acute Myelogenous Leukemia • Biosimilar • Bladder Cancer • Colorectal Cancer • Gynecologic Cancers • Inflammation • Myelodysplastic Syndrome • Pancreatic Cancer • Triple Negative Breast Cancer

The THINK clinical trial: Preliminary evidence of clinical activity of NKG2D chimeric antigen receptor T cell therapy (CYAD-01) in acute myeloid leukemia (AACR 2018) - P1/2; "Interestingly, even at this early stage of the evaluation, there is variation in the phenotype of the CYAD-01 cells (e.g. CD4/CD8 ratio) and an early observation of a relative increase in the systemic levels of SDF-1 and RANTES in the patient who achieved MLFS. In summary, we report the first objective response to CAR-T in r/r AML using CYAD-01 without preconditioning chemotherapy and with no significant toxicities, highlighting the potential of targeting NKG2D ligands in AML."

CAR T-Cell Therapy • Clinical • IO biomarker • Acute Myelogenous Leukemia • Multiple Myeloma • Myelodysplastic Syndrome • Pancreatic Cancer

Celyad Oncology Announces April 2021 Conference Schedule (Businesswire) - "Celyad Oncology SA...discovery and development of chimeric antigen receptor T cell (CAR T) therapies for cancer...announced that the company plans to participate at the following conferences in April 2021: Cell & Gene Meeting on the Mediterranean; Dates: April 6-9, 2021...2021 Virtual Wells Fargo Biotech Corporate Access Day; Date: Thursday, April 8, 2021; Kempen & Co. Life Sciences Conference - European Cell, Gene & RNA; Date: Wednesday, April 28, 2021."

Clinical • Oncology

NKG2D as a chimeric antigen receptor - DAP 10 provides optimal co stimulation for NKG2D based CARs (AACR 2018) - "Next to cytokine release, cytolytic activity was also assessed which interestingly showed no difference in any of the conditions even when the CD4/CD8 cell ratio was different.In conclusion NKG2D CAR T cells only showed increased cytokine release when DAP10 was overexpressed, all other conditions did not lead to any changes when compared to the NKG2D CAR T cells currently tested in the clinic. This implies that NKG2D is optimally costimulated through the DAP 10 co-signaling, and that this co-signaling is a least as potent as traditional CD28 or 4-1BB based co stimulation."

Oncology

NKG2D chimeric antigen receptor T cells yield promising preliminary results in THINK phase I clinical trial (AACR 2018) - No abstract available.

CAR T-Cell Therapy • Clinical • P1 data • Oncology

[VIRTUAL] Single vector multiplexed shRNA provides a non-gene edited strategy to concurrently knockdown the expression of multiple genes in CAR T cells. (ASCO 2020) - "A first-in-human clinical trial evaluating the first-generation single shRNA-vector in the context of a BCMA-targeting CAR as a non-gene edited approach to allogeneic CAR T cell therapy will be initiated in 2020. The proof of principle study here shows that multiple shRNAs are active within a single viral vector thereby avoiding the need for bespoke individual clinical reagents to target multiple genes. The multiplexed shRNA vector system is now in further development to explore whether this strategy can enhance the therapeutic potential of CAR T cells."

CAR T-Cell Therapy • IO Biomarker • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • AGK • B2M • CD52

alloSHRINK - Standard cHemotherapy Regimen and Immunotherapy With Allogeneic NKG2D-based CYAD-101 Chimeric Antigen Receptor T-cells (clinicaltrials.gov) - P1; N=36; Not yet recruiting; Sponsor: Celyad (formerly named Cardio3 BioSciences)

New P1 trial • Biosimilar • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

"Novartis licenses CAR-T patents from bluebird, Celyad https://t.co/cEbJwnjNcN #biotech $NVS @Novartis" - cmiller1225

Head-to-Head • Biosimilar

LINK: Hepatic Transarterial Administrations of NKR-2 in Patients With Unresectable Liver Metastases From Colorectal Cancer (clinicaltrials.gov) - P1; N=18; Recruiting; Sponsor: Celyad (formerly named Cardio3 BioSciences)

New P1 trial • Biosimilar • Colorectal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

THINK: A Dose Escalation Phase I Study to Assess the Safety and Clinical Activity of Multiple Cancer Indications (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Celyad (formerly named Cardio3 BioSciences)

New P1 trial • Acute Myelogenous Leukemia • Biosimilar • Bladder Cancer • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Leukemia • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • Ovarian Cancer • Pancreatic Cancer • Triple Negative Breast Cancer

Early Signs of Clinical Activity in Aml Patients Receiving NKG2D CAR T Cell Therapy in the Absence of Pre-Conditioning Chemotherapy: An Alternative Strategy to CAR T Cell Therapy (ASGCT 2018) - P1/2; "These results demonstrate the on-going translation of CYAD-01 with interesting early signs of activity in patients with advanced refractory cancer. Continuing to understand the mode of action of CYAD-01 CAR T cells remains essential as well as considering whether combinations of therapy may potentially synergize with CYAD-01."

CAR T-Cell Therapy • Clinical • Acute Myelogenous Leukemia • Biosimilar • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

DEVELOPMENT OF A NEXT GENERATION ALLOGENEIC CAR-T CELL PLATFORM WITHOUT GENE EDITING (EHA 2019) - "...Allogeneic CAR-T therapeutic products could allow treatment of multiple patients with cells from the same healthy donor, increasing product consistency, likely reducing manufacturing costs and avoiding the time delay required to generate an autologous T cell product.Aims Allogeneic CAR-T cell therapy is dependent upon eliminating the activity of the endogenous T Cell Receptor (TCR) within the engineered T cell, thereby preventing the induction of a graft versus host response and resultant potentially life-threatening toxicity. We have explored RNA interference to modulate the TCR and to assess the potential of short hairpin RNA (shRNA) as a platform technology for Allogeneic CAR T cell therapy.Methods shRNAs targeting the CD3ε and CD3ζ chains of the TCR complex were expressed in primary T cells where the efficacy of the individual shRNAs to downregulate the CD3 component and subsequent impact upon TCR expression assessed...Our testing continues, involving the..."

CAR T-Cell Therapy • IO Biomarker