Company: NCNA
Filing Date: 2025-03-20
Form Type: 20-F
Source: 0000950170-25-042709
Chunk: 134

Company: NuCana plc
Filing Date: 2025-03-20
Form: 20-F
Item: Item 4
Chunk 134
---
. This leads to the release of molecules called DAMPs from the cancer cells as they die, or so-called immunogenic cell death, or ICD. This process of ICD is characterized by the cell surface exposure or extracellular release of calreticulin, or CRT, and high-mobility-group box 1 protein, or HMGB1, from dying cells, as depicted in the diagram below. These DAMPs help the immune system to recognize cancer cells in the body, thus promoting the further killing of cancer cells by immune cells.
 
 These experiments have shown that NUC-3373 is not only a targeted TS inhibitor but also induces DNA damage and can potentiate an immune response, as illustrated in the following graphic.
  
 Overall, these non-clinical studies suggest that NUC-3373 potentially has the ability to enhance the activity of immunotherapy agents by making tumors more visible to the immune system. This was demonstrated in a series of experiments in which cancer cells treated with NUC-3373 were exposed to immune cells in combination with the

immunotherapy agent nivolumab, a PD-L1 inhibitor. These experiments showed that the combination of NUC-3373 and nivolumab resulted in greater cancer cell death than either agent alone, indicating that NUC-3373 enhances the activity of immunotherapy.
 
NUC-3373 Clinical Data
 
 NUC-3373 has been evaluated in a Phase 1 trial in patients with advanced solid tumors, the NuTide:301 trial; a Phase 1b/2 trial, NuTide:302, in combination with other agents, for patients with metastatic colorectal cancer; and a randomized Phase 2 trial, NuTide:323, in combination with other agents, for the second-line treatment of patients with advanced colorectal cancer. NUC-3373 is currently being evaluated in a Phase 1b/2 modular clinical trial, NuTide:303, of NUC-3373 in combination with the PD-1 inhibitor pembrolizumab for patients with advanced solid tumors and in combination with docetaxel for patients with lung cancer.
NUC-3373 Development Strategy and Ongoing / Planned Clinical Trials
  We aim to develop NUC-3373 for multiple indications. In 2022, we initiated a Phase 1b/2 modular clinical trial, NuTide:303, of NUC-3373 in combination with the PD-1 inhibitor pembrolizumab for