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NuCana Presents Data at the AACR 2024 Annual Meeting Highlighting the Ability of NUC-7738 to Profoundly Alter Tumour Biology in a Paired Biopsy Clinical Study

April 10, 2024 – Biotechnology, Clinical Trials, Pharmaceutical – AARC 2024, NuCana, clinical trials, oncology

NUC-7738 reprogrammes cancer cell lipid metabolism to make tumours less aggressive and promote cancer cell death
NUC-7738 alters ribosome biogenesis and the regulation of genes critical for cancer growth and survival

9 April 2024 — California, US — NuCana announced two posters being presented today at the American Association of Cancer Research (AACR) Annual Meeting.

Title: Exposing the Heterogeneity of the Lipidome in the TME of Cutaneous Melanoma Following Treatment with NUC-7738 in Combination with anti-PD-1 Therapy
Presentation date and time: 9 April 2024 from 1:30pm-5:00pm
Abstract number: 6222

The tumour microenvironment (TME) is a complex interplay of various cell types, extracellular matrix, signalling molecules and physical factors that collectively influence tumour growth. Lipids play an important role in the TME, contributing to various aspects of cancer progression and therapy resistance. A novel methodology, including imaging mass spectrometry, was developed to investigate the spatial relationship between the lipidome and TME using paired biopsies from patients treated with NUC-7738. NUC-7738 was found to increase polyunsaturated fatty acids within the TME, which is indicative of a shift to a less aggressive cancer type and to decrease monounsaturated fatty acids which are associated with malignant behaviour and chemotherapy resistance. In addition, NUC-7738 was shown to reduce lipids associated with protection against cancer cell death and to increase lipids associated with cancer cell death. Multi-modal imaging indicated that this lipid reprogramming is a result of the alteration in enzymes associated with lipid metabolism.

Title: RNA Regulatory Disruption by 3’-dATP: A Novel Approach to Inhibit Ribosome Biogenesis in Cancer
Presentation date and time: 9 April 2024 from 1:30pm-5:00pm
Abstract number: 5650

Ribosome biogenesis is a complex process that plays a pivotal role in protein translation which can become dysregulated in cancer. Thus, ribosome targeting therapies are an attractive treatment modality for anti-cancer medicines. This study investigates the impact of NUC-7738, which generates high intracellular levels of the active anti-cancer metabolite 3’-deoxyadenosine triphosphate (3’-dATP), on the generation of mRNAs and proteins associated with ribosome biogenesis. Data from cancer cell lines, confirmed using paired biopsies of patients treated with NUC-7738, demonstrated that NUC-7738 significantly modulated the levels of RNAs which are important for translational control of protein synthesis. Furthermore, data also highlight NUC-7738’s potential to influence the regulation of genes critical for cancer cell growth and survival.

Hugh S Griffith, NuCana’s founder and CEO said: “We are excited to present these results as we believe they demonstrate NUC-7738’s multi-faceted mechanisms of action. They also further explain the compelling clinical data we have generated with NUC-7738 as a monotherapy and in combination with pembrolizumab. We recently presented clinical data from the ongoing NuTide:701 study of NUC-7738 in combination with pembrolizumab which demonstrated that NUC-7738 may potentiate the activity of pembrolizumab in patients who were refractory to PD-1 inhibitor-based therapy. Our translational data help us to understand these clinical observations and guide the optimal development pathway for NUC-7738. We look forward to sharing additional data for NUC-7738 in 2024.”

About NuCana
NuCana is a clinical-stage biopharmaceutical company focused on significantly improving treatment outcomes for patients with cancer by applying our ProTide technology to transform some of the most widely prescribed chemotherapy agents, nucleoside analogues, into more effective and safer medicines. While these conventional agents remain part of the standard of care for the treatment of many solid and haematological tumours, they have significant shortcomings that limit their efficacy and they are often poorly tolerated. Utilising our proprietary technology, we are developing new medicines, ProTides, designed to overcome the key limitations of nucleoside analogues and generate much higher concentrations of anti-cancer metabolites in cancer cells. NuCana’s pipeline includes NUC-3373 and NUC-7738. NUC-3373 is a new chemical entity derived from the nucleoside analogue 5-fluorouracil, a widely used chemotherapy agent. NUC-3373 is currently being evaluated in three ongoing clinical studies: a phase 1b/2 study (NuTide:302) in combination with leucovorin, irinotecan or oxaliplatin, and bevacizumab in patients with metastatic colorectal cancer; a randomised phase 2 study (NuTide:323) in combination with leucovorin, irinotecan and bevacizumab for the second-line treatment of patients with advanced colorectal cancer; and a phase 1b/2 modular study (NuTide:303) of NUC-3373 in combination with the PD-1 inhibitor pembrolizumab for patients with advanced solid tumours and in combination with docetaxel for patients with lung cancer. NUC-7738 is a transformation of 3’-deoxyadenosine, a novel anti-cancer nucleoside analogue. NUC-7738 is in the phase 2 part of a phase 1/2 study in patients with advanced solid tumours which is evaluating NUC-7738 as a monotherapy and in combination with pembrolizumab. Visit: www.nucana.com.