On April 14, 2023 NuCana plc (NASDAQ: NCNA) announced two posters to be presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held from April 14-19, 2023 (Press release, Nucana BioPharmaceuticals, APR 14, 2023, View Source [SID1234630089]).
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Title: NUC-7738 causes reduction of soluble and exosome-associated PD-L1 in melanoma cell lines and patients
Presentation date and time: April 19th from 9.00am – 12.30pm
Abstract number: 5962
This study investigates the dynamic between NUC-7738 and the secreted forms of PD-L1 (soluble PD-L1 and exosomal PD-L1) both in a melanoma cell line and in patients treated with NUC-7738. Data from this study demonstrate that NUC-7738 reduced mRNA and protein levels of soluble PD-L1 in a melanoma cell line and that patients treated with NUC-7738 had reduced levels of exosomal PD-L1 compared to pre-treatment levels. These data indicate that NUC-7738 has the potential to act as an immune sensitizer and as an effective combination partner for PD-L1 pathway inhibitors. NUC-7738 is currently being studied in combination with pembrolizumab for patients with advanced solid tumors in the Phase 2 part of the NuTide:701 study.
Title: NUC-7738 promotes alternative polyadenylation site usage and reduces glutaminase GAC isoform
Presentation date and time: April 16th from 1.30pm – 5.00pm
Abstract number: 277
This study investigates the effect of NUC-7738 on isoforms of glutaminase 1. Glutaminase is often upregulated in cancer cells. Additionally, the GAC isoform drives more metabolically active cancers and has been associated with poorer patient outcomes. NUC-7738 reduced the expression of GAC in renal and pancreatic cancer cell lines in both hypoxic and normoxic conditions. Furthermore, tissue from patients with kidney cancer that was treated with NUC-7738 ex vivo demonstrated reduced levels of GAC. These data highlight a potentially meaningful anti-cancer strategy for NUC-7738 in metabolically active tumors that are able to sustain high rates of growth and proliferation in unfavorable conditions, including hypoxia.
Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer said: "We are excited with these data as we believe they demonstrate NUC-7738’s multi-faceted mechanisms of action and are highly supportive of our clinical development strategy. We are currently investigating NUC-7738 in combination with pembrolizumab in the Phase 2 part of the NuTide:701 study and look forward to sharing data from this study in 2023."