NT-175 / AstraZeneca - LARVOL DELTA

Initial phase 1 study results of NT-175 engineered T-cell therapy in TP53 R175H–mutated unresectable advanced solid tumors. (ASCO 2026) - P1 | "Patients (pts) received lymphodepletion with fludarabine and cyclophosphamide followed by a single NT-175 infusion along with subcutaneous recombinant IL-2. Manufacturing and treatment with autologous NT-175 eTCR T cells was safe and feasible in pts with heavily pre-treated metastatic TP53-mutated malignancies. Further, NT-175 demonstrated encouraging preliminary antitumor activity across multiple histologies, with most notable early signals in PDAC and may offer a prolonged treatment-free interval in pts with refractory solid tumors."

IO biomarker • Metastases • P1 data • Breast Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Leiomyosarcoma • Oncology • Pancreatic Adenocarcinoma • Sarcoma • Solid Tumor • HLA-A • IL2 • TGFB1 • TGFBR2 • TP53

More than 85 abstracts will feature 10 approved and 13 potential new medicines from the Company, including 25 oral presentations. Highlights include (AstraZeneca Press Release) - "BLUESTAR: Updated safety and efficacy results from the BLUESTAR Ph I/IIa trial of the B7-H4-directed ADC puxitatug samrotecan (Puxi-Sam) in patients with relapsed/metastatic B7-H4-positive endometrial and ovarian cancer...PRIMAVERA: Safety and preliminary efficacy from the first-in-human Phase I PRIMAVERA trial of the protein arginine methyltransferase 5 (PRMT5) inhibitor AZD3470 as monotherapy in relapsed/refractory classic Hodgkin lymphoma (Oral Abstract #7003)...Phase I initial results for NT-175 T-cell receptor therapy in TP53 R175H-mutated unresectable, advanced and/or metastatic solid tumours including pancreatic adenocarcinoma (Oral Abstract #2506)...POTOMAC: Five-year overall survival and patient-reported outcomes from the Phase III POTOMAC trial of Imfinzi plus Bacillus Calmette-Guérin (BCG) induction and maintenance therapy in patients with high-risk non-muscle-invasive bladder cancer (Rapid Oral Abstract #4624)."

First-in-human • P1 data • P1/2 data • P3 data • P53mut • Bladder Cancer • Breast Cancer • Classical Hodgkin Lymphoma • Colorectal Cancer • Endometrial Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Pancreatic Adenocarcinoma • Squamous Cell Carcinoma of Head and Neck

NT-175-201: A Study of NT-175 in Adult Subjects With Unresectable, Advanced, and/or Metastatic Solid Tumors That Are Positive for HLA-A*02:01 and the TP53 R175H Mutation (clinicaltrials.gov) - P1 | N=45 | Recruiting | Sponsor: AstraZeneca | Trial primary completion date: Sep 2028 ➔ Jul 2029

P53mut • Trial primary completion date • Breast Cancer • Colorectal Cancer • Head and Neck Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • TP53

NT-175-201: A Study of NT-175 in Adult Subjects With Unresectable, Advanced, and/or Metastatic Solid Tumors That Are Positive for HLA-A*02:01 and the TP53 R175H Mutation (clinicaltrials.gov) - P1 | N=46 | Recruiting | Sponsor: AstraZeneca | N=162 ➔ 46 | Trial completion date: Aug 2039 ➔ Jul 2029

Enrollment change • Trial completion date • Breast Cancer • Colorectal Cancer • Head and Neck Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • TP53

NT-175-201: A Study of NT-175 in Adult Subjects With Unresectable, Advanced, and/or Metastatic Solid Tumors That Are Positive for HLA-A*02:01 and the TP53 R175H Mutation (clinicaltrials.gov) - P1 | N=162 | Recruiting | Sponsor: AstraZeneca | Trial primary completion date: Aug 2026 ➔ Sep 2028

Trial primary completion date • Breast Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • HLA-A • TP53

A Study of NT-175 in Adult Subjects With Unresectable, Advanced, and/or Metastatic Solid Tumors That Are Positive for HLA-A*02:01 and the TP53 R175H Mutation (clinicaltrials.gov) - P1 | N=162 | Recruiting | Sponsor: Neogene Therapeutics, Inc. | N=24 ➔ 162

Enrollment change • Metastases • Breast Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • HLA-A • TP53

Open-label, phase 1, multicenter study to evaluate the safety and preliminary anti-tumor activity of NT-175 in human leukocyte antigen-a*02:01-positive adult subjects with unresectable, advanced and/or metastatic solid tumors that are positive for the TP53 R175H mutation. (ASCO 2024) - "Subjects will undergo lymphodepletion chemotherapy with fludarabine and cyclophosphamide followed by a single infusion of NT-175 and subcutaneous recombinant IL-2 administration for up to 8 days. Translational analysis will evaluate potential biomarkers for insights into mechanism of action, response prediction, or resistance mechanisms. The study was activated in March 2023 and is open to accrual; 5 patients have been enrolled as of 4 Jan 2024."

Clinical • Metastases • P1 data • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CD4 • CD8 • HLA-A • IL2 • TGFB1 • TGFBR2 • TP53

Non-clinical evaluation of NT-175, an autologous T cell product engineered to express an HLA-A*02:01-restricted TCR targeting TP53 R175H and resistant to TGF-b inhibition. (ASCO 2024) - "Non-clinical studies revealed a favorable safety and efficacy profile for NT-175 and supported further clinical development of a TGF-β-resistant TCR-edited T-cell product for mutant TP53-targeted cancer immunotherapy."

Clinical • IO biomarker • Oncology • CD4 • CD8 • HLA-A • TGFB1 • TGFBR2 • TP53

A Study of NT-175 in Adult Subjects With Unresectable, Advanced, and/or Metastatic Solid Tumors That Are Positive for HLA-A*02:01 and the TP53 R175H Mutation (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Neogene Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Breast Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • HLA-A • TP53

A Study of NT-175 in Adult Subjects With Unresectable, Advanced, and/or Metastatic Solid Tumors That Are Positive for HLA-A*02:01 and the TP53 R175H Mutation (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Neogene Therapeutics, Inc.

Metastases • New P1 trial • Breast Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • HLA-A • TP53