800 TCR / National Heart, Lung, and Blood Institute, Loyola University Medical Center, T-Cure Biosci - LARVOL DELTA

HERV-E TCR Transduced Autologous T Cells in People With Metastatic Clear Cell Renal Cell Carcinoma (clinicaltrials.gov) - P1 | N=17 | Active, not recruiting | Sponsor: National Heart, Lung, and Blood Institute (NHLBI) | Trial completion date: Dec 2032 ➔ Mar 2026

Metastases • Trial completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Improving killing of renal cell carcinoma through the combined effects of TCR engineered CD4+ and CD8+ T cells (AACR 2024) - P1 | "In conclusion, these data show that CD4+ BZ-4 T cells transfected with the CD8 co-receptor acquire the ability to lyse RCC tumors at levels comparable to that observed in CD8+ BZ-4 T cells. Additional experiments are planned to evaluate whether mixtures of CD8+ BZ-4 T cells with CD4+ BZ-4-8 T cells will augment the ability of TCR modified T cells to proliferate in vivo and kill human RCC tumors compared to CD8+ BZ-4 T cells alone in tumor bearing NSG mice."

Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD4 • CD8

Final results of a phase I trial of HERV-E TCR transduced T cells for the treatment of HLA-A*11 patients with metastatic clear cell renal cell carcinoma (mccRCC). (ASCO-GU 2024) - P1 | "Proof of concept that HERV-T cells can induce tumor regression without evidence of causing off-target toxicities has been established by this trial. Infused HERV-E T cells were detectable transiently in vivo and induce effector cytokine production. Our initial results support the further development of HERV-E-directed therapies that focus on methods to improve in vivo persistence of TCR engineered T-cells and to target HERV-E antigens expressed on more commonly expressed HLA alleles."

Clinical • Metastases • P1 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • HLA-A

HERV-E TCR Transduced Autologous T Cells in People With Metastatic Clear Cell Renal Cell Carcinoma (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: National Heart, Lung, and Blood Institute (NHLBI) | Recruiting ➔ Active, not recruiting | N=24 ➔ 16 | Trial primary completion date: Apr 2024 ➔ Oct 2023

Enrollment change • Enrollment closed • Metastases • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Phase I results of human endogenous retrovirus type-E (HERV-E) TCR transduced T-cells in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC). (ASCO 2023) - P1 | "Cyclophosphamide & fludarabine were given followed by HERV-E TCR infusion & IL-2 administration...86% had ≥ 3 prior treatment lines (range 1-7): 36% had high-dose IL2, 57% Ipilimumab-Nivolumab & 50% ≥ 3 lines of anti-VEGFR therapy... This is the first trial evaluating TCR-engineered T-cells targeting a human endogenous retrovirus in ccRCC. The manufacturing method utilized produced large numbers of highly purified CD8+ HERV-E reactive T-cells that were not associated with any dose limiting toxicities when given at doses up to 5x107 cells/kg. For pts in DL4, HERV-E TCR were observed to proliferate in vivo, traffic to a metastatic site, and induce tumor regression in one mccRCC pts."

Clinical • Metastases • P1 data • Clear Cell Renal Cell Carcinoma • Dermatology • Febrile Neutropenia • Genito-urinary Cancer • Hematological Disorders • Neutropenia • Oncology • Renal Cell Carcinoma • Respiratory Diseases • Solid Tumor • CD34 • CD8 • HLA-A

HERV-E TCR Transduced Autologous T Cells in People With Metastatic Clear Cell Renal Cell Carcinoma (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: National Heart, Lung, and Blood Institute (NHLBI) | Trial completion date: Dec 2022 ➔ Dec 2032 | Trial primary completion date: Dec 2022 ➔ Apr 2024

Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

HERV-E TCR Transduced Autologous T Cells in People With Metastatic Clear Cell Renal Cell Carcinoma (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: National Heart, Lung, and Blood Institute (NHLBI); Trial completion date: Dec 2021 ➔ Dec 2022; Trial primary completion date: Dec 2021 ➔ Dec 2022

Clinical • Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

HERV-E TCR Transduced Autologous T Cells in People With Metastatic Clear Cell Renal Cell Carcinoma (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: National Heart, Lung, and Blood Institute (NHLBI); Trial completion date: Dec 2020 ➔ Dec 2021; Trial primary completion date: Dec 2020 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

T-Cure Bioscience Announces Expansion of Collaboration With the National Institutes of Health for T Cell Receptor (TCR) Therapy Targeting HERV-E for the Treatment of Kidney Cancer (Businesswire) - "T-Cure Bioscience, Inc…announced that the Company has extended its ongoing research collaboration with the National Heart Lung and Blood Institute (NHLBI), through a formal Collaborative Research and Development Agreement (CRADA) to advance the Company’s HERV-E targeting TCR therapy for renal cell cancer. Additionally, T-Cure has amended an existing license to expand to worldwide rights for the intellectual property it licensed from NHBI related to the anti-HERV-E TCR product."

Licensing / partnership • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma