Company: NCNA
Filing Date: 2025-03-20
Form Type: 20-F
Source: 0000950170-25-042709
Chunk: 131

Company: NuCana plc
Filing Date: 2025-03-20
Form: 20-F
Item: Item 4
Chunk 131
---
1 clinical trial, NuTide:301, in patients with advanced solid tumors; a Phase 1b/2 clinical trial, NuTide:302, in combination with other agents, for patients with metastatic colorectal cancer; and a randomized Phase 2 clinical 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.
<{self.tag} alt="{self.alt}" src="{self.src}">
 Unlike 5-FU, NUC-3373 consists of the active anti-cancer metabolite, FUDR-MP, and a protective phosphoramidate moiety. This moiety protects FUDR-MP making it resistant to breakdown by the enzyme DPD, which reduces the generation of toxic byproducts such as FBAL. It also confers a more predictable pharmacokinetic profile including a longer half-life, estimated at between 6 to 14 hours in plasma, and a better distribution into tissues. These properties allow NUC-3373 to be administered through a short infusion of approximately 2 hours. The chemical structure of the ProTide alters the lipophilicity of the molecule, allowing NUC-3373 to enter cancer cells without the need for membrane transporters. Once inside the cancer cell, the phosphoramidate moiety is cleaved off, resulting in deprotection and the release of FUDR-MP. This bypasses the need for any activating enzymes, resulting in significantly higher levels of the active anti-cancer metabolite, which we believe will lead to improved efficacy as compared to 5-FU. Furthermore, the metabolic pathways utilized by NUC-3373 avoid the generation of the toxic metabolite FUTP so toxicities such as neutropenia, mucositis and diarrhea should be significantly reduced.
 
 The metabolism of NUC-3373 compared to 5-FU as described above is illustrated in the following graphic.
 

 
NUC-3373 Preclinical Data
 
 NUC-3373 has greater anti-cancer activity than 5-FU. In preclinical studies, NUC-3373 was not reliant on activating enzymes, including OP