Mural Oncology plc is a clinical-stage immuno-oncology company that is leveraging its innovative protein engineering platform to develop novel, engineered cytokine therapies designed to address areas of unmet need for patients with a variety of cancers. The company's pipeline is led by its lead product candidate, nemvaleukin alfa, which is currently being evaluated in two potentially registrational clinical trials, with key data readouts expected in the first half of 2025.
Business Overview and History
Mural Oncology was established in May 2017 as a private company limited by shares and was later de-shelved in 2023 in connection with the separation of Alkermes plc's oncology business. In August 2023, the company's legal status under Irish law was altered to that of a public limited company. Prior to the separation, Mural Oncology's operations were managed as part of Alkermes' consolidated business, and its historical financial statements reflect the operating results and financial position of the oncology business as it was historically managed by Alkermes.
On November 13, 2023, Mural Oncology entered into several agreements with Alkermes, including a separation agreement, a tax matters agreement, an employee matters agreement, and transition services agreements. These agreements provided a framework for Mural Oncology's relationship with Alkermes following the separation. On November 14, 2023, in connection with the separation, Mural Oncology received a cash contribution of $275 million from Alkermes.
The separation was effected through the distribution of Mural Oncology's ordinary shares to Alkermes' shareholders on November 15, 2023. On November 16, 2023, Mural Oncology commenced trading as an independent, publicly traded company on the Nasdaq Global Market under the ticker symbol MURA.
Since its inception, Mural Oncology has been focused on developing immunotherapies that leverage the power of cytokines to enhance the body's immune response against cancer. The company's lead product candidate, nemvaleukin alfa, is an engineered cytokine fusion protein that selectively binds to the intermediate-affinity interleukin-2 (IL-2) receptor. Nemvaleukin is designed to preferentially activate antitumor effector natural killer (NK) cells and CD8+ T cells while minimizing the expansion of immunosuppressive T regulatory (Treg) cells.
In addition to nemvaleukin, Mural Oncology is also advancing two earlier-stage programs targeting the interleukin-18 (IL-18) and interleukin-12 (IL-12) pathways, which have also demonstrated therapeutic potential in cancer. The company expects to nominate development candidates for these programs by the end of 2024.
Financial Overview
As a clinical-stage biotechnology company, Mural Oncology has not yet generated any revenue from product sales. The company has incurred significant operating losses since its inception, reporting a net loss of $128.51 million for the year ended December 31, 2024. This was primarily driven by the company's ongoing research and development (R&D) activities, which amounted to $110.67 million in 2024, as well as general and administrative (G&A) expenses of $27.60 million.
Financials
Mural Oncology's financial position as of December 31, 2024, included $144.38 million in cash, cash equivalents, and short-term investments, which the company believes will be sufficient to fund its current operating plan into the first quarter of 2026. However, the company's financial statements include a going concern disclosure, as it anticipates continuing to incur significant losses and negative cash flows from operations for the foreseeable future.
For the most recent quarter (Q3 2024), Mural Oncology reported no revenue and a net loss of $34.27 million. The decrease in net loss compared to the prior year period was primarily due to a decrease in research and development expenses as the ARTISTRY-1 and ARTISTRY-2 trials wound down, partially offset by higher general and administrative expenses related to the company operating as an independent public company.
Liquidity
As of December 31, 2024, Mural Oncology had $144.38 million in cash, cash equivalents, and short-term investments. The company believes this will be sufficient to fund its current operating plan into the first quarter of 2026. This cash runway projection takes into account the company's efforts to optimize its operations and control costs, which have enabled it to extend its anticipated cash runway.
The company's liquidity position is further characterized by the following metrics: - Cash and Cash Equivalents: $115.46 million as of December 31, 2024 - Current Ratio: 5.84 - Quick Ratio: 5.84
These ratios indicate that Mural Oncology has a strong short-term liquidity position, with ample current assets to cover its current liabilities. However, the company will likely need to raise additional capital in the future to fund its ongoing operations and clinical development programs.
Pipeline and Clinical Progress
Nemvaleukin Alfa (ARTISTRY Program)
Nemvaleukin alfa, Mural Oncology's lead product candidate, is currently being evaluated in two potentially registrational clinical trials:
1. ARTISTRY-6 (Cohort 2): This phase 2 trial is assessing nemvaleukin as a monotherapy in patients with advanced mucosal melanoma. The company expects to report topline results from this cohort in the second quarter of 2025.
2. ARTISTRY-7: This ongoing phase 3 trial is evaluating nemvaleukin in combination with pembrolizumab in patients with platinum-resistant ovarian cancer (PROC). Mural Oncology expects to report interim overall survival (OS) results from this trial in late the first quarter or early the second quarter of 2025.
In addition to these potentially registrational trials, Mural Oncology is also exploring alternative dosing regimens for nemvaleukin in the ARTISTRY-6 trial. Cohort 3 is evaluating a less frequent intravenous (IV) dosing of nemvaleukin as a monotherapy in patients with cutaneous melanoma, with preliminary data readouts expected in the first half of 2025. Cohort 4 of ARTISTRY-6 is assessing the less frequent IV dosing of nemvaleukin in combination with pembrolizumab in patients with cutaneous melanoma, with preliminary data expected in the second half of 2025.
The company's confidence in nemvaleukin's potential is bolstered by the durable responses observed across a range of solid tumor types, including in difficult-to-treat cancers like PROC, in the completed ARTISTRY-1 phase 1/2 clinical trial. These results, which were recently published in the Journal for ImmunoTherapy of Cancer, showed that nemvaleukin was generally well-tolerated and generated objective responses in both monotherapy and combination therapy settings.
IL-18 and IL-12 Programs
In addition to its lead nemvaleukin program, Mural Oncology is also advancing two earlier-stage programs targeting the IL-18 and IL-12 cytokine pathways. The company has nominated product candidates for both its IL-18 (MURA-8518) and IL-12 (MURA-7012) programs in 2024 and is currently conducting investigational new drug (IND)-enabling studies for the IL-18 candidate.
The IL-18 program is focused on engineering an IL-18 variant that is resistant to neutralization by the IL-18 binding protein, a natural regulator of IL-18 activity. Mural's approach aims to leverage IL-18's potent ability to reinvigorate exhausted T cells and activate other immune cell subsets for potential anti-tumor effects.
The IL-12 program is exploring a novel, tumor-targeted approach to IL-12 delivery, using split subunits of the cytokine that preferentially assemble and activate in the tumor microenvironment. This strategy is designed to limit systemic exposure and potentially improve the therapeutic index of IL-12-based cancer immunotherapies.
Mural Oncology expects to submit an IND application for its IL-18 program in the fourth quarter of 2025.
Operational Efficiency and Cash Runway
Mural Oncology has taken steps to operate efficiently as an independent public company following its separation from Alkermes. The company has successfully transitioned key corporate functions, including financial reporting, information technology, and other administrative services, that were previously provided by Alkermes.
As of December 31, 2024, Mural Oncology had $144.38 million in cash, cash equivalents, and short-term investments, which the company believes will be sufficient to fund its current operating plan into the first quarter of 2026. This cash runway projection takes into account the company's efforts to optimize its operations and control costs, which have enabled it to extend its anticipated cash runway.
Risks and Challenges
As a clinical-stage biotechnology company, Mural Oncology faces a number of risks and challenges that are common to the industry, including:
1. Clinical development risks: The success of the company's product candidates, including nemvaleukin, is dependent on the outcome of ongoing and future clinical trials. Delays or failures in these trials could significantly impact the company's timeline and ability to obtain regulatory approvals.
2. Regulatory approval risks: Even if Mural Oncology's product candidates demonstrate positive results in clinical trials, there is no guarantee that they will receive regulatory approval from the FDA or other non-U.S. regulatory authorities. The regulatory review process can be lengthy, complex, and unpredictable.
3. Commercialization risks: If approved, Mural Oncology will need to successfully commercialize its product candidates, which will require the company to build or partner with experienced commercial teams. Failure to effectively commercialize approved products could limit the company's revenue potential.
4. Financing risks: As a pre-revenue company, Mural Oncology is dependent on its ability to raise additional funding to advance its pipeline and operations. Failure to secure sufficient financing could jeopardize the company's ability to continue as a going concern.
5. Competition risks: Mural Oncology faces competition from other companies developing cytokine-based and other immunotherapy approaches, which could impact the commercial potential of the company's product candidates.
Despite these risks, Mural Oncology remains well-positioned to capitalize on the potential of cytokine-based immunotherapies, with two potentially registrational trials for nemvaleukin expected to provide key data readouts in the first half of 2025 and a growing pipeline of earlier-stage programs targeting IL-18 and IL-12.
Conclusion
Mural Oncology is a clinical-stage immuno-oncology company that is leveraging its innovative protein engineering platform to develop novel, engineered cytokine therapies designed to address areas of unmet need for patients with a variety of cancers. The company's lead product candidate, nemvaleukin alfa, is currently being evaluated in two potentially registrational clinical trials, with key data readouts expected in the first half of 2025. Additionally, Mural Oncology is advancing earlier-stage programs targeting the IL-18 and IL-12 cytokine pathways, with candidate nominations already completed in 2024.
As a pre-revenue, clinical-stage company, Mural Oncology faces a number of risks and challenges, including clinical development, regulatory, commercialization, and financing risks. However, the company's innovative approach to cytokine-based immunotherapies, its promising clinical data, and its efforts to operate efficiently as an independent public company position it well to capitalize on the potential of this emerging field of cancer treatment.
With multiple clinical milestones on the horizon and a growing pipeline of cytokine-based product candidates, Mural Oncology represents a compelling opportunity for investors interested in the evolving landscape of immuno-oncology. The company's financial position, while precarious, provides a runway into early 2026, giving Mural Oncology time to advance its key programs and potentially reach critical clinical milestones that could drive value creation for shareholders.