An 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

Phase I Study of NT-175, an autologous T cell therapy product genetically engineered to
express an HLA-A*02:01-restricted T cell receptor (TCR), targeting TP53 R175H mutant
malignancies

Key Inclusion Criteria (Module 1)

- Subjects must be at least 18 years of age

- Subject must be diagnosed with one of the histologies below:

- NSCLC

- Colorectal adenocarcinoma

- HNSCC

- Pancreatic adenocarcinoma

- Breast cancer

- Ovarian cancer

- Any other solid tumor

- Tumors must harbor a TP53 R175H variant mutation and subject must be HLA-A*02:01
positive (at least 1 allele)

- Subject has advanced solid cancer, defined as unresectable, advanced, and/or
metastatic disease (Stage III or IV) after at least 1 line of approved systemic
standard of care (SOC) treatment regimen and for which there are no available
curative treatment options.

- Subject has at least 1 measurable lesion

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

- Adequate hematological, renal, hepatic, pulmonary, and cardiac function

Key Exclusion Criteria (Module 1)

- Any another primary malignancy within the 3 years prior to enrollment

- Known, active primary central nervous system (CNS) malignancy

- History of prior adoptive cell and gene therapy, allogeneic stem cell transplant or
solid organ transplantation.

- History of clinically significant cardiac disease within the 6 months prior to
enrollment or heart failure at any time prior to enrollment.

- Systemic therapy within at least 2 weeks or 3 half-lives, whichever is shorter,
prior to enrollment.

- Any form of primary immunodeficiency.

- Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed
with Li-Fraumeni syndrome.

Key Inclusion Criteria (Module 2 - hematological malignancies)

- At least 18 years of age

- Diagnosis of AML or MDS that allows for efficacy assessments

- Confirmation of TP53 R175H variant mutation in cancer cells

- Subject must be HLA-A*02:01 positive (at least 1 allele)

- ECOG performance status of 0 to 1

Key Exclusion Criteria (Module 2 - hematological malignancy)

- Acute promyelocytic leukaemia or isolated extramedullary disease

- Another primary malignancy within 2 years (with exceptions)

- HSCT within 100 days or immunosuppression for GvHD within 4 weeks

- History of CNS or other extramedullary leukaemic involvement unless a lumbar
puncture is negative for leukemic cells

- Prior stroke, ischemic attack, significant cardiac disease, heart failure

- Prior adoptive modified cell therapy

- Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed
with Li-Fraumeni syndrome.