GYA01 / Gyala Therap - LARVOL DELTA

Safety and Efficacy of GYA01 (CART84) in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) and Acute Lymphoblastic T Leukemia Patients (T-ALL). (clinicaltrials.gov) - P1/2 | N=33 | Recruiting | Sponsor: Gyala Therapeutics

New P1/2 trial • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • CD4 • CD8

Establishing a Decentralized GMP Manufacturing Model for GYA01, a Novel Anti-CD84 CAR-T Therapy: Design, Validation, and Comparability (EHA-EBMT-CART 2026) - "cell count and viability %CVs were 13.1% and 5.5%, respectively; CAR+ detection %CV was 9.17%, and CD3, CD4, CD8 subpopulations, as well as potency test, showed %CVs ranging from 0.1 to 14.65%. All six GMP batches were successfully completed in 10–11 days without deviations. In-process parameters and qualitative safety CQAs were equivalent across both MUs."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • CD4 • CD8

Cytokine-driven Modulation of CART84 Phenotype and Function for AML Therapy (EHA-EBMT-CART 2026) - "Conclusions : Collectively, IL-21 supplementation during CART84 manufacturing promotes a memory-enriched, metabolically robust phenotype and enhances antitumor efficacy in vitro . These findings suggest that incorporating IL-21 into CAR T-cell production protocols could improve the functional persistence and overall quality of CART84 products for immunotherapy ."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • CD4 • CD8 • IL15 • IL2 • IL21 • IL7

Gyala Therapeutics…announced the initiation of a Phase I/IIa clinical trial of GYA01 following authorization from the Spanish Agency of Medicines and Medical Devices (AEMPS). (PRNewswire) - "The study will evaluate GYA01, a first-in-class CAR-T cell therapy targeting the CD84 protein, in patients with relapsed or refractory acute myeloid leukemia (AML) or T-cell acute lymphoblastic leukemia (T-ALL), diseases with poor prognosis and limited treatment options....Gyala Therapeutics and Hospital La Fe have received €3.7 million in funding from Spain's Ministry of Science, Innovation and Universities through the CPP 2024 program to conduct the study."

Financing • Trial status • Acute Myelogenous Leukemia • T Acute Lymphoblastic Leukemia

CART Cell Therapy Targeting CD84 Alone or in Combination with CD19 for the Treatment of B-Cell Malignancies (ASH 2024) - "Moreover, it has been reported that patients with lower pre-therapy median CD19 density had increased risk of relapse after axicabtagene ciloleucel. In summary, CART84 cells demonstrated cytotoxicity towards B-ALL and aggressive B-cell lymphoma, both in vitro and in vivo, highlighting their potential as a therapeutic option for relapsed CD19negative B-cell malignancies. Furthermore, the "IF-BETTER" CD19/CD84-targeted dual CART cells, enhanced with their co-receptor, offer a promising approach for addressing CD19low B-ALL and B-cell lymphomas, while maintaining the safety profile of CD19-directed CART cell therapy."

CAR T-Cell Therapy • Combination therapy • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Burkitt Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • TFRC

Gyala Therapeutics unveils first-in-class CAR-T therapy targeting CD84 showing strong preclinical efficacy in hard-to-treat leukemias (PRNewswire) - "Strong and specific cytotoxicity against AML, T-ALL, and aggressive B-cell lymphoma cell lines, as well as primary patient samples. Significant efficacy in animal models, eradicating disease and prolonging survival."

Preclinical • Acute Myelogenous Leukemia • T Acute Lymphoblastic Leukemia

Gyala secures €3 million financing from Invivo Partners, Nara Capital and CDTI Innvierte to launch a Phase I trial in AML patients in H2 2025 (PRNewswire)

Financing • New P1 trial • Acute Myelogenous Leukemia • T Acute Lymphoblastic Leukemia

A novel chimeric antigen receptor T-cell therapy targeting CD84 for the treatment of acute myeloid and T-cell lymphoblastic leukemias. (PubMed, Leukemia) - "Furthermore, CART84 eliminated primary leukemic blasts while exhibiting low cytotoxicity against CD34+ HSPC in vitro and in humanized mouse models in vivo, suggesting a low risk of myelotoxicity. These results support CD84 as a promising target for AML and T-ALL and provide the foundation for our upcoming first-in-human phase I/II clinical trial using CD84-directed CAR T cell therapy for patients with R/R AML and T-ALL (EudraCT 2024-519966-31-00)."

Journal • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • CD34

HARNESSING CMV-VSTS FOR ALLOGENEIC CART84 THERAPY TO TARGET AML (EHA 2025) - "To better preserve CMV specificity in thawed CMV-VSTs, we tested OKT-3 as an activation method prior to transduction, which successfully maintained CMV specificity but resulted in low CAR84 expression.Additionally, we evaluated ARI-0001, an academic CD19-targeting CAR, as a control. Given the limited CAR84 expression in CMV-VSTs, efforts continue to optimize CAR84 expression while maintaining CMV specificity. This study highlights CMV-VSTs as a potential allogeneic CART platform and underscores the need for further refinement of transduction protocols to enhance therapeutic efficacy."

IO biomarker • Acute Myelogenous Leukemia • Cytomegalovirus Infection • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology • CD28 • CD4 • CD8

CAR T-CELL THERAPY TARGETING CD84 ALONE OR IN COMBINATION WITH CD19 FOR THE TREATMENT OF B-CELL MALIGNANCIES (EHA 2024) - "CART84 cells are highly cytotoxic towards aggressive B-cell lymphoma both in vitro and in vivo. CART84showed specific proliferation and cytokine secretion when co-cultured with CD84+ tumour cells. Furthermore, CD19/CD84-directed dual CAR T cells successfully expanded and displayed cytotoxicity againstCD19+/CD84+ NALM-6 cells in vitro, but not towards CD19-/CD84+ MOLM-13 cells."

CAR T-Cell Therapy • Combination therapy • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Burkitt Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19