On June 10, 2022 NuCana plc (NASDAQ: NCNA) reported that data to be presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress highlighting the activity of NUC-7738, a phosphoramidate transformation of 3’-deoxyadenosine (3’-dA), in a broad range of Acute Myeloid Leukemia (AML) cell lines. NUC-7738 has already shown promise as monotherapy in patients with solid tumors in a Phase 1/2 study (NuTide:701) and will also be combined with a PD-1 checkpoint inhibitor (Press release, Nucana BioPharmaceuticals, JUN 10, 2022, View Source [SID1234615873]).

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The data at EHA (Free EHA Whitepaper) 2022 show that NUC-7738 can suppress the expansion and survival of AML cells by reducing β-catenin signaling, a key pathway in AML. NUC-7738’s effect was observed in multiple different AML cell lines suggesting broad therapeutic potential. Furthermore, it was observed that NUC-7738 resulted in a reduction of the cells that are resistant to standard chemotherapy drugs and thought to be responsible for disease relapse.

These findings, combined with the anti-cancer activity and favorable safety profile of NUC-7738 observed in the NuTide:701 study provide a strong rationale for the evaluation of NUC-7738 in patients with leukemia.

The details of NuCana’s poster presentation at EHA (Free EHA Whitepaper) are as follows:

Title: NUC-7738 regulates β-catenin signaling resulting in reduced proliferation and self-renewal of AML cells
Abstract Number: P459
Presentation Date & Time: Friday June 10, 2022 from 16:30-17:45 CEST (e-poster online at 9:00 CEST)
Presenting Author: Akbar M. Shahid

Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer said: "NUC-7738 has entered Phase 2 development in patients with solid tumors and we have been encouraged by the clinical activity and favorable safety profile we have observed. The data presented at EHA (Free EHA Whitepaper) indicate that NUC-7738 may have applications beyond solid tumors and we are currently evaluating the optimal pathway for NUC-7738’s development for the treatment of hematologic malignancies."

About NUC-7738
NUC-7738 is a ProTide 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. Primarily, 3′-dATP interferes with RNA polyadenylation, causing changes in the expression of genes involved in metabolism, differentiation, and apoptosis, ultimately leading to metabolic stress, cessation of cancer-cell growth and cell death.