On September 12, 2022 NuCana plc (NASDAQ: NCNA) reported that data from the ongoing NuTide:701 study of NUC-7738 in an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting (Press release, Nucana BioPharmaceuticals, SEP 12, 2022, View Source [SID1234619427]).

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Oral 455MO: NUC-7738 in Patients with Advanced Solid Tumors- Phase 1 results from the NuTide:701 Phase 1 / 2 Study

Data on NUC-7738 from the Phase 1 part of NuTide:701 showed encouraging signals of anti-tumor activity across a range of tumor types, particularly melanoma. Promising data were observed in a variety of solid tumors with numerous patients staying on treatment for extended periods, including one patient with metastatic melanoma who became eligible for complete surgical resection following eleven months of treatment with NUC-7738. NUC-7738 also had a favorable safety profile with low rates of treatment-related AEs (TRAEs), very few Grade 3 TRAEs and no patients experiencing Grade 4 or 5 TRAEs.

Dr. Stefan Symeonides, Senior Lecturer in Experimental Cancer Medicine at the Edinburgh Cancer Research Centre and lead author of the ESMO (Free ESMO Whitepaper) presentation, said: "NUC-7738 has shown an excellent safety profile and encouraging signals of anti-tumor activity in this study which is enrolling patients who have exhausted all standard therapies. We are excited to further investigate the activity of NUC-7738 in melanoma and other tumor types."

"We remain very encouraged by what we have observed with NUC-7738," said Hugh S. Griffith. "NUC-7738’s precise mode of action of disrupting RNA polyadenylation in cancer cells thereby altering the expression of genes associated with key cellular processes is very exciting. The positive signals observed in Part 1 of the NuTide:701 study, combined with NUC-7738’s differentiated mode of action, provide a strong scientific rationale to expedite its development and enrich the Phase 2 part of the study for patients with melanoma. This part of the study will also include a cohort combining NUC-7738 with pembrolizumab, which is a standard of care for melanoma patients. We have begun enrolling patients into the Phase 2 part of the study and look forward to sharing these data."

About NUC-7738
NUC-7738 is a phosphoramidate transformation of 3′-deoxyadenosine (3′-dA), also known as cordycepin. 3’-dA has demonstrated potent anti-cancer activity in non-clinical studies, but has not been successfully developed as an anti-cancer agent due to its rapid breakdown by adenosine deaminase (ADA). NUC-7738 is designed to generate the active anti-cancer metabolite of 3’-dA directly inside cancer cells, thus overcoming 3’-dA’s key limitations of breakdown, transportation and activation. The cytotoxic effect of NUC-7738 is largely attributed to the generation of the main active anti-cancer metabolite, 3′-dATP which interferes with RNA polyadenylation, causing changes in the expression of genes involved in various cellular processes, leading to cancer cell death.