On March 8, 2022 NuCana plc (NASDAQ: NCNA) reported the release of two abstracts to be presented as posters at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held from April 8 to 13, 2022 (Press release, Nucana BioPharmaceuticals, MAR 8, 2022, View Source [SID1234609674]).
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Abstract 4992: NUC-3373 Potentiates Immune-Mediated Cytotoxicity of CRC Cells
NUC-3373 causes colorectal cancer (CRC) cell lines to release damage associated molecular patterns (DAMPs), molecular signals that can activate immune cells leading to immunogenic cell death (ICD). The addition of nivolumab, an anti-PD-1 antibody, to NUC-3373 enhanced tumor cell death in a model where cancer cells were incubated alongside human-derived immune cells, highlighting NUC-3373’s potential as an attractive combination partner for checkpoint inhibitors.
Abstract 1835: NUC-3373 Targets the DNA-Directed Pathway More Effectively than 5-FU
NUC-3373 and 5-FU exert their anti-cancer effects through the metabolite, FUDR-MP (or FdUMP), which inhibits thymidylate synthase (TS), a critical enzyme for cancer cell growth and survival. Pre-clinical and clinical data show that NUC-3373 generates far higher levels of FUDR-MP than 5-FU and is more effective at inhibiting TS activity. Data indicate that NUC-3373 also induces anti-cancer activity via the DNA-targeting metabolite, FdUTP. Furthermore, NUC-3373 avoids the RNA damage associated with 5-FU’s dose-limiting toxicities of diarrhea, myelosuppression and mucositis.
Through a more targeted, DNA-directed pathway, NUC-3373 may provide, if approved, a potentially more effective, safer and convenient therapeutic option than 5-FU for patients with cancer.
Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer said: "We believe these data demonstrate NUC-3373’s advantages over 5-FU and are highly supportive of our clinical development strategy. Our Phase 1/2 study of NUC-3373 in patients with colorectal cancer (NuTide:302) continues to generate data which will support our Phase 3 study for NUC-3373 in second-line colorectal cancer patients. In addition, NUC-3373 is entering a Phase 1/2 study (NuTide:303) in patients with solid tumors to identify additional indications for development, including in combination with checkpoint inhibitors."