ThisCART19A / Fundamenta Therap - LARVOL DELTA

Intracellular Retention of Tcrαβ/CD3 to Generate Novel Allogeneic CAR-T Cells (ThisCART19A) with Enhanced Antitumor Potency for Treating B-ALL (ASH 2023) - P1 | "All patients received intravenous fludarabine (30mg/m2/d), cyclophosphamide (300mg/m2/d) and etoposide (100mg/d) for 5 days followed by a single infusion of thisCART19A. We report for the first time that intracellular retention of TCRαβ/CD3 complex can successfully manufacture allogeneic CAR-T cells, with superior activation potential. In patients with R/R B-ALL, ThisCART19A demonstrated acceptable safety, robust expansion and encouraging clinical response profiles. With streamlined single-vector-based production and enhanced CAR signaling, ThisCART platform represents an attractive alternative to gene-editing-based allogeneic CAR-T platforms."

CAR T-Cell Therapy • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Neutropenia • Oncology • Thrombocytopenia • CD22

A study of a new mechanism: Intracellular retention allo-CART safety and efficacy for extranodal bulky B-NHL. (ASCO 2024) - P1 | "In response, we developed ThisCART19A, a non-genetic editing and off-the-shelf anti-CD19 CAR T-cell therapy incorporating intracellular retention of membrane proteins, representing a novel approach that downregulates surface expression of TCRαβ/CD3 complexes...69%)patient experienced grade 4 ICANS and relieved after intravenous dexamethasone treatment... This CART19A exhibited favorable safety, remarkable expansion potential, and efficacy profiles in the treatment of r/r bulky lymphoma. Notably, it achieved a high ORR of 90%, providing a favorable window of opportunity for subsequent consolidation and intensification treatments. Moreover, this transition from a bulky to a non-bulky disease state reduces the intricacy of follow-up treatments."

Clinical • IO biomarker • Hematological Disorders • Infectious Disease • Non-Hodgkin’s Lymphoma

Clinical validation and mechanistic insights of ThisCART: A novel allogeneic platform enhancing CAR-T signaling via intracellular TCRαβ/CD3 retention (AACR 2024) - P1 | "Our lead product, ThisCART19, has demonstrated superior efficacy compared to conventional AutoCART19 in preclinical and early clinical studies for B-ALL. In the clinical trial NCT04384393, we assessed the safety and efficacy of ThisCART19 in patients with B-cell malignancies...Pt1 experienced Grade 1 CRS that resolved without treatment, and Pt2 experienced Grade 2 CRS that resolved after tocilizumab and corticosteroids... The ThisCART platform marks a transformative advancement in allogeneic CAR-T cell therapy. By enhancing CAR signaling autonomously through a unique intracellular retention of TCRαβ/CD3 complexes, ThisCART has shown promising safety and efficacy in early clinical trials. Its potential in reshaping the treatment landscape for hematological and autoimmune disorders positions ThisCART as a crucial development in cellular therapeutics."

Clinical • IO biomarker • Late-breaking abstract • Hematological Malignancies • Leukemia • Oncology

CAR-T for Autoimmune Hemolytic Anemia Patients Who Have Failed Three or More Lines of Therapy (clinicaltrials.gov) - P1 | N=13 | Recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting ➔ Recruiting

Enrollment open • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

CAR-T for Autoimmune Hemolytic Anemia Patients Who Have Failed Three or More Lines of Therapy (clinicaltrials.gov) - P1 | N=13 | Not yet recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China

New P1 trial • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

Upgrading the non-gene-editing, allogeneic ThisCART platform for extending persistence in vivo. (ASCO 2023) - "To our knowledge, ThisCART19C represents the first application of viral evading strategy in promoting the clinical persistence of allogeneic CAR-T cells. Its efficient processing, potent cytotoxicity and favored preclinical safety profile warrant clinical investigation. >"

IO biomarker • Preclinical • Graft versus Host Disease • Immunology • Oncology • HLA-B • HLA-E

Safety, Efficacy and Pharmacokinetics of ThisCART19A in Patients With Refractory or Relapsed B Cell Lymphoma (clinicaltrials.gov) - P1/2 | N=12 | Not yet recruiting | Sponsor: Chongqing University Cancer Hospital

New P1/2 trial • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD4

ThisCART19A for B-NHL Relapsed After Auto-CAR T (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: The First Affiliated Hospital of Soochow University

New P1 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

ThisCART19A Bridging to alloHSCT for R/R B-ALL (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: The First Affiliated Hospital of Soochow University

New P1 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD19

Assessment of Safety and Efficacy of ThisCART19A in Adult Patients With B Cell Malignancies After Failure of Autologous Chimeric Antigen Receptor T- Cell(CAR-T) Therapy (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Henan Cancer Hospital

CAR T-Cell Therapy • New P1 trial • Acute Lymphocytic Leukemia • Hematological Malignancies • Oncology

PRELIMINARY ANALYSES OF A NON-GENE-EDITING ALLOGENTIC CAR-T IN CD19+ RELAPSED OR REFRACTORY NON-HODGIN’S LYMPHOMA (EHA 2022) - P1 | "Standard or enhanced l ymphodepletion with f l udarabine and cyclophosphamide was followed by infusion of ThisCART19A at a dose range of 0.2-60x10 6 cells/kg . Conclusion ThisCART19A cells demonstrate d potent CD19-dependent cytotoxicity and no xenogentic GvHD in murine models . In th is preliminary analys is on evaluable lymphoma subjects, ThisCART19A exhibited a n acceptable safety and an encouraging clinical response profiles , both comparable to those for marketed autologous products."

Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases • CD19

Safety and Efficacy of ThisCART19A Bridging Hematopoietic Stem Cell Transplantation in Patients With Refractory or Relapsed B-cell Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P1 | N=19 | Not yet recruiting | Sponsor: Fundamenta Therapeutics, Ltd.

New P1 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation • ABL1 • BCR • CD19 • CD22 • FGFR • IKZF1 • IL7R • JAK1 • JAK2 • PDGFRA • PDGFRB • SH2B3 • TCF3

Safety, Efficacy and Pharmacokinetics of ThisCART19A in Patients With Refractory or Relapsed B Cell Lymphoma (clinicaltrials.gov) - P1 | N=15 | Not yet recruiting | Sponsor: Zhengzhou University

New P1 trial • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CD19 • CXCL8 • IL10 • IL17A • IL2 • IL22 • IL4 • IL5 • IL6

Safety and Efficacy of ThisCART19 in Patients With Refractory or Relapsed B Cell Malignancies (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: Fundamenta Therapeutics, Ltd.; Trial primary completion date: Nov 2021 ➔ Nov 2022

CAR T-Cell Therapy • Clinical • Trial primary completion date • Oncology • CD19

Safety and Clinical Activity of ThisCART19 in Patients With r/r Non-Hodgkin's B Cell Lymphoma (clinicaltrials.gov) - P1; N=20; Recruiting; Sponsor: Fundamenta Therapeutics, Ltd.

Clinical • New P1 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

Safety and Efficacy of ThisCART19 in Patients With Refractory or Relapsed B Cell Malignancies (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: Fundamenta Therapeutics, Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Hematological Malignancies • Leukemia • Lymphoma • Oncology • CD19

Safety and Efficacy of ThisCART19 in Patients With Refractory or Relapsed B Cell Malignancies (clinicaltrials.gov) - P1; N=30; Not yet recruiting; Sponsor: Fundamenta Therapeutics, Ltd.

Clinical • New P1 trial • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology