Things didn’t go as planned with Mural Oncology in terms of another shot on goal for its lead IL-2 candidate, Nemvaleukin alfa. That’s because just today it announced that it had failed to achieve desired efficacy in two cohorts as part of the phase 2 ARTISTRY-6 study. One cohort [cohort 2] was evaluating the use of this drug as a monotherapy for the treatment of patients with mucosal melanoma. The hope was that the company would be able to at least achieve the primary endpoint of this study; however, it was not met with statistical significance.
Not to see a signal of efficacy is not a good thing at all, but the hope was that upon evaluation of the other cohort [cohort 3], which dealt with nemvaleukin alfa for the treatment of patients with cutaneous melanoma, it would at least see a signal of efficacy here. Unfortunately, the drug didn’t even perform well with respect to this other cancer type either.
Prior to these two cohorts having data announced, there was another failure with nemvaleukin alfa in the treatment of patients with platinum-resistant ovarian cancer. That is, the drug was being evaluated in the phase 3 ARTISTRY-7 study. It was announced just the other month, in March of 2025, that the primary endpoint of overall survival (OS) was not met upon an interim analysis being done by the Independent Data Monitoring Committee (IDMC).
The goal was to test the use of nemvaleukin alfa in combination with Merck’s anti-PD-1 therapy KEYTRUDA to treat patients with platinum-resistant ovarian cancer (PROC). This combination was to be compared to that of investigator’s choice of chemotherapy. With the interim analysis showing that the primary endpoint of OS was unlikely to be reached, the company chose not to continue it to final analysis.
The hope was that the ARTISTRY-6 study would have been successful to make up for the failure shown in ARTISTRY-7. The science was ideal as well, because IL-2 is a proven drug. High-dose recombinant human IL-2 was first approved in 1992 for the treatment of patients with renal cell carcinoma (RCC). With FDA approval of Melanoma following soon afterwards. The end game here was to engineer the drug of IL-2 to bind to intermediate-affinity IL2 receptor and not high-affinity trimeric interluekin-2 receptor.
The reason why the goal was to prevent binding to the latter receptor is because then it would bring about T-regulatory cells (T-regs). The bottom line is that these T-regs would inhibit T-cells and other immune cells for starters. Plus, it would bring about an increase in toxicities for patients as well. Thus, the hope was to only bind to intermediate IL-2 receptor to bring about CD8+ and natural killer (NK) cells to eliminate the tumor. While it was a solid endeavor to tackle, it didn’t pay off.
With both the ARTISTRY-7 and ARTISTRY-6 trials failing to establish shareholder value, management of Mural chose to explore strategic alternatives. What this would entail would be to perform a merger of some sort, a sale of the company, or another financial transaction. This type of move, though, didn’t come without a major change in the company. It was forced to reduce its workforce by as much as 90%. Of course, that makes sense, because it only had $144.4 million in cash left as of December 31st of 2024.
One would think that the strategic alternative is good news, but the company laid out risk factors at the bottom of its press release. It noted that it was currently not in any type of talks with another pharmaceutical company to achieve such a business transaction. Plus, there is no guarantee it will be able to complete some type of merger or business arrangement to boost shareholder value.
