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 solid
tumors.

- Subjects must be at least 18 years of age, at the time of signing the informed
consent.

- Subjects must be capable of giving signed informed consent

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

- NSCLC

- Colorectal adenocarcinoma

- HNSCC

- Pancreatic adenocarcinoma

- Breast cancer

- Any other solid tumor

- Tumors must harbor a TP53 R175H variant mutation (confirmed by an FDA-approved test),
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 per computed tomography (CT) scan or magnetic
resonance imaging (MRI).

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at the time of
enrollment

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

- Per Investigator judgement, subject is likely to complete study visits and/or
procedures per the protocol and comply with study requirements for study participation

Exclusion Criteria:

- Any another primary malignancy within the 3 years prior to enrollment (except for
non-melanoma skin cancer, carcinoma in situ (eg, cervix, bladder, breast) or low-grade
prostate cancer

- 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 stroke or transient ischemic attack within the 12 months prior to
enrollment.

- 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.

- History of severe immediate hypersensitivity reaction to cyclophosphamide,
fludarabine, or rIL-2; or known sensitivity or allergy to methotrexate, gentamicin, or
other aminoglycosides.

- Any form of primary immunodeficiency.

- Live vaccine ≤ 4 weeks prior to enrollment or plans to have a live vaccine prior to
planned lymphodepleting chemotherapy and/or NT-175 treatment.

- Active immune-mediated disease requiring systemic steroids or other immunosuppressive
treatment (except if related to prior checkpoint inhibitor therapy)

- Female of childbearing potential who is lactating or breast feeding at the time of
enrollment.

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