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

From Structure to Therapy: Engineering Improved T Cell Receptors for Renal Cell Carcinoma (EACR 2026) - P1 | "A phase I clinical trial using HERV-E TCR transduced autologous T cells was completed by the Nishimura lab in collaboration with the National Institute of Health (NIH)... Most importantly, our studies have shown how an innovative computational tool like AlphaFold has the potential to advance immunotherapy. Predicting TCR structures and how they bind peptide-MHC complexes enables us to use structure-guided design to improve TCR recognition of tumor targets. We are demonstrating this in one model for HERV-E TCR therapy against RCC, however this has the potential of being applied to all TCR-modified therapies against all cancers."

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

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: Mar 2026 ➔ Mar 2029

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

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

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