Mural Oncology is winding down its lead clinical programme and enacting sweeping cuts to its workforce after its experimental cancer therapy, nemvaleukin, failed to deliver in two key studies.
The biotech, which spun out of Alkermes in 2023 with $275m in funding, will halt all development of nemvaleukin. It will also lay off around 90% of its staff and pursue strategic alternatives, including a potential sale or merger.
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Mural’s stock surged 134% following the 15 April announcement.
The latest setback came from the Phase II ARTISTRY-6 study (NCT03861793) in patients with mucosal melanoma. Nemvaleukin, an interleukin-2 (IL-2) cytokine, missed its primary endpoint. The results come just weeks after the drug also failed in the Phase III ARTISTRY-7 trial (NCT05092360) for platinum-resistant ovarian cancer. That study tested nemvaleukin in combination with MSD’s Keytruda (pembrolizumab).
Last month, Mural announced that the nemvaleukin/Keytruda combo didn’t achieve a statistically significant improvement in overall survival compared with chemotherapy alone. The biotech discontinued the ovarian cancer programme but continued to analyse Phase II data from the melanoma trial.
The company has now reported that one cohort in the ARTISTRY-6 trial failed to show meaningful benefit, while another yielded only preliminary results that did not support continued development. With no path forward for nemvaleukin, Mural has chosen to shut down all clinical activity around the candidate, ending an attempt to revive interest in IL-2 based immunotherapies.
The decision brings with it significant operational changes. Mural will cut 104 jobs, representing approximately 90% of its workforce. The company expects the layoffs to cost up to $10m and will record an additional $2m to $4m in non-cash impairment charges related to the disposal of property and equipment.
Nemvaleukin was Mural’s only clinical stage programme. Its discontinuation will be a major shift for the company, which now retains only two preclinical candidates dubbed MURA-8518, and MURA-7012. These candidates target IL-18 and IL-2, respectively.
As of the end of December 2024, Mural had $144.4m in cash on hand. The company has retained a financial adviser and says it will “explore potential strategic alternatives including, but not limited to, an offer for or other acquisition of the company, merger, business combination, or other transaction”.
This outcome reflects broader challenges in IL-2 drug development. Nemvaleukin was designed to improve on first-generation IL-2 therapies by limiting activation of regulatory T cells, which can suppress anti-tumour responses.
The result adds nemvaleukin to a growing list of IL-2 candidates that have fallen short in trials, following high-profile disappointments such as Nektar Therapeutics and Bristol Myers Squibb’s bempegaldesleukin. The IL-2 candidate failed to meet primary endpoints in multiple late-stage trials, including studies in melanoma, renal cell carcinoma, and urothelial cancer.
Originally launched with a $1.9bn investment, the programme was discontinued in 2022, leading Nektar to cut 70% of its workforce and shift focus to other pipeline assets.
