Mural Oncology Shares ARTISTRY-3 Data at ASCO Annual Meeting

Mural Oncology plc, a clinical-stage immuno-oncology company, has shared promising data from its ARTISTRY-3 clinical trial, which focuses on evaluating less frequent intravenous dosing of nemvaleukin alfa (nemvaleukin). This development was announced ahead of the American Society of Clinical Oncology (ASCO) annual meeting scheduled from May 31 to June 4 in Chicago. Nemvaleukin, Mural’s leading candidate, is an engineered interleukin-2 (IL-2) cytokine designed to harness the therapeutic benefits of high-dose native IL-2 while reducing its toxic side effects.

In the ARTISTRY-1 trial, Mural mimicked the high-dose IL-2 regimen using five daily intravenous infusions over a three-week cycle. In contrast, the ARTISTRY-3 trial tested escalating doses of less frequent intravenous infusions, which were well tolerated at all levels. The safety profile was consistent with nemvaleukin’s known mechanism of action, showing no dose-limiting toxicities. Notably, higher doses per three-week cycle did not reveal new safety concerns. Desired pharmacodynamic effects, such as the expansion of antitumor CD8+ T cells and natural killer (NK) cells, were observed with minimal expansion of immunosuppressive regulatory T cells (Tregs).

Dr. Sarina Piha-Paul, Associate Professor at The University of Texas MD Anderson Cancer Center, noted, "Nemvaleukin showed deep and durable responses in previous trials, leading us to explore a more patient-friendly dosing schedule. All tested schedules in ARTISTRY-3 demonstrated desired pharmacodynamic effects, including immune cell expansion, with no new tolerability issues despite higher doses."

Following a thorough review of safety, pharmacokinetics, pharmacodynamics, and efficacy data, Mural, in collaboration with its safety review committee, recommended a dose of 30 µg/kg on days 1 and 8 as the phase 2 dose. This schedule provides a seven-day recovery window, offering flexibility for both patients and providers. The new dosing regimen, delivering twice the dose over a three-week cycle compared to the standard five-day regimen, is being evaluated as a single agent and in combination with pembrolizumab in Mural's ARTISTRY-6 trial for cutaneous melanoma. Preliminary data from this trial are expected in 2025.

Dr. Caroline Loew, CEO of Mural Oncology, stated, "ARTISTRY-3 aimed to see if a more convenient dosing schedule could maximize nemvaleukin's dose without additional tolerability issues. The data presented at ASCO confirmed pharmacodynamic proof and favorable tolerability. We are incorporating this new regimen into additional cohorts of the ARTISTRY-6 phase 2 trial."

Nemvaleukin alfa, Mural's novel engineered cytokine, is designed to enhance the antitumor effects of the IL-2 pathway while reducing its toxicities. It selectively binds to the intermediate-affinity IL-2 receptor, promoting the expansion of antitumor CD8+ T cells and NK cells with minimal expansion of Tregs. Nemvaleukin showed promising responses in both monotherapy and combination therapy in ARTISTRY-1, Mural's initial Phase 1/2 trial.

Currently, nemvaleukin is under evaluation in two potentially registrational trials for platinum-resistant ovarian cancer and mucosal melanoma. ARTISTRY-3 is a Phase 1/2 open-label trial testing IV nemvaleukin in patients with selected advanced solid tumors who have undergone standard treatments. It evaluates doses between 10 µg/kg and 40 µg/kg across three dosing schedules: once per three-week cycle; days 1 and 8 of a three-week cycle; and days 1 and 4 of a three-week cycle.

Mural Oncology, headquartered in Dublin, Ireland, with primary facilities in Waltham, Massachusetts, leverages its protein engineering platform to develop cytokine-based immunotherapies for cancer treatment. Their mission is to broaden the potential and reach of these therapies to improve cancer patients' lives.