Apr 10, 2021
NuCana presented two posters on NUC-3373, its ProTide transformation of the active anti-cancer metabolite of 5-fluorouracil (5-FU), a very widely used anti-cancer drug. NUC-3373 has been designed to overcome the main challenges associated with 5-FU and capecitabine, including cancer-resistance mechanisms, the generation of toxic metabolites and unfavorable pharmacokinetic profile.
This poster describes further encouraging interim data from 38 patients with metastatic colorectal cancer. In this difficult-to-treat group, who had received a median of four prior lines of therapy, NUC-3373, with or without leucovorin, demonstrated a 62% disease control rate (defined as stable disease lasting more than 8 weeks) in the efficacy-evaluable population. Three patients experienced reductions in their target lesions of 40%, 28% and 15% and several patients achieved a longer progression-free survival on NUC-3373 than they had on their prior therapy. NUC-3373 also continues to demonstrate a favorable safety profile with no FBAL or FUTP-associated Grade 3 or 4 toxicities, such as hand-foot syndrome, GI or hematological adverse events.
The second NUC-3373 poster showed that NUC-3373-treated colon cancer cells are able to activate a natural killer (NK) cell response. NUC-3373 was shown to induce the release of damage associated molecular patterns (DAMPs) which may restore NK cell-mediated immune responses by reducing inhibitory signals. Thus, NUC-3373 has the potential to evoke immunogenic cell death and may enhance the clinical utility of immunotherapy agents.
NuCana presented two posters on NUC-7738, a ProTide transformation of a novel nucleoside analog, 3’-deoxyadenosine or 3’-dA. NUC-7738, which has several potential anti-cancer mechanisms of action, is being evaluated in a Phase I study in patients with advanced solid tumors who have exhausted all standard therapies.
The first poster describes additional interim data from the ongoing Phase I study. These data demonstrate NUC-7738’s encouraging anti-cancer activity and favorable tolerability profile. Three case studies were described detailing patients who achieved tumor reductions and prolonged stable disease on NUC-7738.
The second poster describes how NUC-7738 was designed to overcome the key cancer resistance mechanisms which have prevented the clinical development of 3’-dA. NUC-7738 was shown to efficiently generate high and prolonged intracellular levels of the active anti-cancer metabolite, 3’-dATP, and to cause cell death by activation of apoptotic pathways, as well as through inhibition of NFkB nuclear translocation.
NuCana presented a poster that further demonstrated Acelarin’s activity in biliary tract cancer cells. Specifically, the poster described how Acelarin (NUC-1031) is converted to the active anti-cancer metabolite (dFdCTP) and demonstrated that it is incorporated into DNA, inducing persistent double-strand breaks. This leads to cell cycle arrest and DNA damage resulting in apoptosis in biliary tract cancer cells.
Abstracts and full session details can be found at www.aacr.org
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 analogs, into more effective and safer medicines. While these conventional agents remain part of the standard of care for the treatment of many solid and hematological tumors, their efficacy is limited by cancer cell resistance mechanisms and they are often poorly tolerated. Utilizing our proprietary technology, we are developing new medicines, ProTides, designed to overcome key cancer resistance mechanisms and generate much higher concentrations of anti-cancer metabolites in cancer cells. NuCana’s robust pipeline includes three ProTides in clinical development. Acelarin and NUC-3373, are new chemical entities derived from the nucleoside analogs gemcitabine and 5-fluorouracil, respectively, two widely used chemotherapy agents. Acelarin is in a Phase III study for patients with advanced biliary tract cancer and a Phase III study for patients with metastatic pancreatic cancer for which enrollment has been suspended. NUC-3373 is in a Phase I study for the potential treatment of a wide range of patients with advanced solid tumors and a Phase Ib study for patients with metastatic colorectal cancer. Our third ProTide, NUC-7738, is a transformation of a novel nucleoside analog (3’-deoxyadenosine) and is in a Phase I study for patients with advanced solid tumors.
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