NUC-3373 Plus Pembrolizumab Continues to Show Favorable Efficacy and Safety Profile in Heavily Pre-treated Patients

Latest Data Cut-Off Shows Patient with Melanoma Remains Progression-Free at 23 Months with a Durable Partial Response

Preclinical Data Corroborate Immunogenic Effects of NUC-3373 Observed in Patients

 NuCana plc (NASDAQ: NCNA) (“NuCana” or the “Company”) announced the publication of new data on NUC-3373. The update includes results from the NuTide:303 clinical study, published on medRxiv, the preprint server for health sciences, together with complementary preclinical findings published in the peer-reviewed journal Public Library of Science ONE (PLOS ONE).

NUC-3373, a potent thymidylate synthase inhibitor that induces DNA damage in cancer cells, has previously shown encouraging activity in combination with the PD-1 inhibitor pembrolizumab in the Phase 1/2b modular study, NuTide:303. In Module 1 of this study, 12 patients with advanced solid tumors who had exhausted all standard treatment options and had previously received PD-1 inhibitors were treated with NUC-3373 plus pembrolizumab.

Encouraging signals of durable activity were observed, including:

• A 100% reduction in tumor lesion size (classified as a partial response due to the presence of non-target lesions) in a patient with urothelial carcinoma of the bladder who remained on treatment for over 15 months; and
• An 81% reduction in target lesions in a patient with metastatic melanoma resistant to prior pembrolizumab therapy, who continues to remain progression-free at 23 months.

These promising clinical findings are further supported by preclinical data. The published results demonstrate that NUC-3373 in a model in vitro system:

• Promotes the release of immunogenic damage-associated molecular patterns (DAMPs);
• Enhances activation of first-line defense immune cells, including natural killer (NK) cells; and
• In combination with a PD-1 inhibitor, enhances tumor cell death by activating lymphocytes, regardless of the tumor’s genomic stability status.

“It is becoming increasingly clear that the majority of future standards of care for advanced cancers will rely on combination regimens incorporating novel immuno-oncology backbones,” said Professor David Harrison, Head of Translational Medicine at NuCana. “The combination of NUC-3373 with pembrolizumab has demonstrated both a favorable safety profile and evidence of efficacy and durable disease control in this patient cohort.”

Andrew Kay, NuCana’s Executive Chairman, added: “The complementary mechanisms of action of NUC-3373 and PD-1 inhibition provide a strong rationale for synergy. We are currently evaluating optimal combinations and indications for further clinical studies of NUC-3373, while continuing to maintain our anticipated cash runway into 2029. We are committed to advancing these assets and working toward our vision of delivering significantly improved treatment outcomes for patients with cancer.”