Company: NCNA
Filing Date: 2025-03-20
Form Type: 20-F
Source: 0000950170-25-042709
Chunk: 141

Company: NuCana plc
Filing Date: 2025-03-20
Form: 20-F
Item: Item 4
Chunk 141
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ed and had progressed within 4 months, the PD-1 inhibitor nivolumab and had progressed within 4 months, and carboplatin plus pemetrexed and had progressed within 1 month.Following treatment with NUC-3373 plus docetaxel, the patient achieved ongoing stable disease for 13 months at the data cut-off. A second case study was a patient with squamous NSCLC who had previously received carboplatin plus paclitaxel plus pembrolizumab and achieved stable disease for 2 months, followed by maintenance pembrolizumab and progressed within 21 months. Following treatment with NUC-3373 plus docetaxel, the patient achieved stable disease for 7 months.
 

In 2025, we expect to announce data from the NuTide:303 trial of NUC-3373 in combination with pembrolizumab in patients with solid tumors.
 
Acelarin: A Transformation of Gemcitabine
 Acelarin was designed to overcome the key cancer resistance mechanisms associated with the nucleoside analog gemcitabine.
 Gemcitabine and its Limitations
 Gemcitabine is a nucleoside analog that is used as a chemotherapeutic to treat a wide range of tumors. There are key limitations that have been associated with a poor survival prognosis for gemcitabine therapy:
 1. Subject to breakdown. Gemcitabine, prior to being phosphorylated to its active form, is susceptible to being broken down chemically by metabolic enzymes, such as cytidine deaminase, or CDA, which irreversibly degrades up to 90% of gemcitabine to an inactive form.
 2. Requires active transport. Gemcitabine requires the membrane transporter hENT1 to enter cancer cells. Patients with a low level of hENT1 who receive gemcitabine have lower overall survival as compared to patients with a high level of hENT1.
 3. Requires activation within the cancer cell. Once gemcitabine enters cells, it must be activated by the addition of phosphate groups before it can exert its cell-killing effect. The rate-limiting addition of the first phosphate group is rapidly followed by the addition of a second and third phosphate group. The end result of this phosphorylation is the creation of the active anti-cancer metabolite, which is known as dFdCTP. A specific enzyme, deoxycytidine kinase, or dCK