Core Viewpoint - Mural Oncology has decided to discontinue all clinical development of nemvaleukin alfa following unsatisfactory results from the ARTISTRY-6 and ARTISTRY-7 trials, and will explore strategic alternatives to maximize shareholder value [1][2][3] Company Developments - Mural Oncology will reduce its workforce by approximately 90% as part of its restructuring efforts [1] - The company had approximately $144.4 million in cash, cash equivalents, and marketable securities as of December 31, 2024 [1] - Mural has engaged Lucid Capital Markets, LLC as its financial advisor to assist in exploring strategic alternatives [1][3] Clinical Trial Results - The ARTISTRY-6 trial did not achieve its primary endpoint in evaluating nemvaleukin as a monotherapy for mucosal melanoma [2] - Preliminary data from ARTISTRY-6 cohort 3, which assessed less-frequent intravenous dosing in cutaneous melanoma patients, also did not show sufficient activity to warrant continuation [2] - Interim overall survival results from the ARTISTRY-7 trial in platinum-resistant ovarian cancer contributed to the decision to halt development of nemvaleukin [2] Strategic Alternatives - Mural is considering various strategic alternatives, including potential offers for acquisition, mergers, or other business combinations [3] - The company is currently in an "offer period" as defined by the Irish Takeover Rules, which may affect the exploration of strategic alternatives [5][6] Regulatory Considerations - Mural is subject to the Irish Takeover Panel Act and must comply with specific disclosure requirements during the strategic evaluation process [5][10]

Core Insights - Mural Oncology has decided not to progress the ARTISTRY-7 phase 3 trial of nemvaleukin alfa in combination with KEYTRUDA® for platinum-resistant ovarian cancer due to lack of statistically significant improvement in overall survival compared to chemotherapy [1][6] - The median overall survival was reported as 10.1 months for the combination therapy versus 9.8 months for chemotherapy, with a hazard ratio of 0.98 indicating no significant benefit [1] - The company remains focused on its upcoming topline results from the ARTISTRY-6 trial in mucosal melanoma, expected in Q2 2025 [2][4] Company Overview - Mural Oncology is a clinical-stage immuno-oncology company developing cytokine-based immunotherapies, with a focus on leveraging its protein engineering platform [9] - The lead candidate, nemvaleukin, is designed to enhance antitumor effects while minimizing toxicities associated with traditional IL-2 therapies [7] - The company has treated over 800 patients across its broader clinical program, demonstrating a favorable safety profile for nemvaleukin [3][9] Clinical Trials - The ARTISTRY-7 trial involved 456 patients and was designed to compare nemvaleukin with pembrolizumab against investigator's choice chemotherapy, focusing on overall survival as the primary endpoint [6] - The ARTISTRY-6 trial is currently evaluating nemvaleukin in mucosal melanoma, with topline data readouts expected in Q2 2025, alongside preliminary data for cutaneous melanoma in the same timeframe [4][8]

Company Status and Growth - The company qualifies as an "emerging growth company" and may remain so until December 31, 2028, unless certain financial thresholds are exceeded, such as a market value of $700 million or annual gross revenues of $1.235 billion [555]. - The company is permitted to provide only two years of audited financial statements and is exempt from auditor attestation requirements for internal control over financial reporting while it remains an emerging growth company [558]. - The company may continue to qualify as a smaller reporting company, allowing it to take advantage of certain disclosure exemptions [556]. Financial Outlook and Shareholder Returns - The company anticipates significant additional capital will be needed in the future, which may lead to substantial dilution for existing shareholders if equity securities are issued [564]. - The company does not intend to pay dividends in the foreseeable future, with returns to shareholders likely limited to share appreciation [569]. - The company currently does not intend to pay dividends, as it lacks distributable reserves under Irish law [592]. Compliance and Regulatory Challenges - The company is subject to increased costs and demands on management resources due to compliance with public company regulations, including the Sarbanes-Oxley Act [575]. - The company is required to furnish a report on internal control over financial reporting, which is costly and challenging, and may not be completed within the prescribed timeframe [577]. Market Volatility and Share Price Influences - The company may face volatility in share price due to various factors, including adverse clinical trial results and regulatory decisions [561]. - The company’s share price may be influenced by the actions of activist shareholders, which could lead to periods of volatility [568]. - The company’s financial results may not be comparable to other public companies due to its election to adopt new accounting standards at the same time as private companies [558]. Strategic Transactions and Financial Impact - The company may engage in strategic transactions such as acquisitions, which could impact liquidity and increase expenses [580]. - Future acquisitions may require additional financing, potentially affecting financial condition and results of operations [580]. - The company is restricted from entering certain transactions for a four-year period due to a tax matters agreement [581]. Legal and Tax Considerations - Irish law may afford less protection to holders of the company's securities compared to U.S. laws [582]. - The company may face challenges in enforcing U.S. court judgments in Ireland due to the lack of a reciprocal treaty [587]. - Any takeover offer will be subject to the Irish Takeover Rules, which may restrict the company's actions during the offer period [588]. - Transfers of ordinary shares may be subject to a 1% Irish stamp duty if not held through the Depository Trust Company [589]. - Future financing arrangements may impose restrictions that could adversely affect the company's ability to obtain financing [591]. - Changes in tax laws could adversely affect the company and its shareholders, with potential retroactive applications impacting financial conditions [601]. - Non-U.S. governments may enact tax laws in response to U.S. tax rule changes, potentially affecting the company's global financial position [602]. Cash Management and Financial Strategy - The company has broad discretion in the use of cash, cash equivalents, and marketable securities, which may not enhance operating results or shareholder value [603]. - Unfavorable global economic conditions could adversely affect the company's business and financial results [598].

Financial Performance - As of December 31, 2024, cash, cash equivalents, and marketable securities were $144.4 million, down from $270.9 million in 2023[12][25] - Net loss for Q4 2024 was $34.3 million, significantly reduced from $59.5 million in Q4 2023[16] - For the three months ended December 31, 2024, the net loss was $34,274,000 compared to a net loss of $59,537,000 for the same period in 2023, representing a 42.4% improvement[27] - The net loss per ordinary share for the year ended December 31, 2024, was $7.58, compared to $12.43 in 2023, showing a 39.5% improvement[27] - The operating loss for the year ended December 31, 2024, was $138,262,000, down from $196,238,000 in 2023, a decrease of 29.6%[27] Expenses - Research and development expenses for Q4 2024 were $28.7 million, a decrease of 32% compared to $42.2 million in Q4 2023[13] - General and administrative expenses for Q4 2024 were $7.2 million, down 56% from $16.3 million in Q4 2023[15] - Total operating expenses for the year ended December 31, 2024, were $138,262,000, down from $196,238,000 in 2023, indicating a reduction of 29.6%[27] - Research and development expenses decreased to $110,666,000 in 2024 from $165,532,000 in 2023, reflecting a 33.1% decline[27] - General and administrative expenses decreased to $27,596,000 in 2024 from $30,706,000 in 2023, a reduction of 6.9%[27] Assets and Equity - The total assets as of December 31, 2024, were $169.4 million, a decrease from $301.7 million in 2023[25] - Total equity as of December 31, 2024, was $140.5 million, down from $263.8 million in 2023[25] Income and Other Financial Metrics - Other income for the year ended December 31, 2024, was $9,748,000, significantly higher than $951,000 in 2023[27] - The company reported an increase in other income for the three months ended December 31, 2024, to $1,580,000 from $951,000 in the same period of 2023[27] - The income tax provision for the year ended December 31, 2024, was zero, compared to a provision of $12,160,000 in 2023[27] Clinical Trials and Future Plans - The ARTISTRY-7 trial reached 75% of overall survival events necessary for the planned interim analysis, expected in late Q1/early Q2 2025[3][6] - Top-line data from the ARTISTRY-6 trial in mucosal melanoma is expected in Q2 2025, with a target response rate of 25%[7] - The company plans to submit a Biologics License Application (BLA) for nemvaleukin in combination with pembrolizumab in 2025 if the interim analysis meets the pre-specified hazard ratio of 0.727[6] Cash Runway - Mural's cash runway has been extended into Q1 2026 through operational efficiencies[1] - The weighted average ordinary shares outstanding increased to 16,954,577 in 2024 from 16,689,740 in 2023[27]

Core Insights - Mural Oncology is focused on advancing its clinical-stage immuno-oncology therapies, particularly the nemvaleukin program, with significant data readouts expected in 2025 [2][18]. Upcoming Milestones - Interim overall survival analysis for the phase 3 ARTISTRY-7 trial in platinum-resistant ovarian cancer is anticipated in late Q1/early Q2 2025 [4][18]. - Top-line data from the phase 2 ARTISTRY-6 trial in mucosal melanoma is expected in Q2 2025 [4][18]. - Preliminary data for less-frequent intravenous dosing of nemvaleukin alfa in ARTISTRY-6 for cutaneous melanoma is expected in 1H 2025 for monotherapy and 2H 2025 for combination therapy [4][8][9]. Financial Performance - As of December 31, 2024, Mural's cash, cash equivalents, and marketable securities totaled $144.4 million, extending the cash runway into Q1 2026 [11][16]. - Research and development expenses decreased to $28.7 million in Q4 2024 from $42.2 million in Q4 2023, attributed to reduced employee-related expenses and trial winding down [12][13]. - General and administrative expenses also decreased to $7.2 million in Q4 2024 from $16.3 million in Q4 2023, primarily due to lower employee-related expenses [14]. Clinical Development - The ARTISTRY-7 trial is evaluating nemvaleukin alfa in combination with pembrolizumab against single-agent chemotherapy in platinum-resistant ovarian cancer, with a high statistical bar for success at the interim analysis [4][18]. - The ARTISTRY-6 trial, cohort 2, targets a response rate of 25% in patients with unresectable or metastatic mucosal melanoma, with Orphan Drug Designation granted by the FDA [7][18]. - Mural is also developing MURA-8518 and MURA-7012, targeting IL-18 and IL-12 respectively, with plans for IND submission for MURA-8518 in 1H 2026 [10][19][20].

Group 1 - Mural Oncology plc is a clinical-stage immuno-oncology company focused on developing engineered therapies targeting cytokine pathways [1][2] - The company's lead candidate, nemvaleukin alfa, is in potentially registrational trials for platinum-resistant ovarian cancer and mucosal melanoma, with results expected in late Q1/early Q2 and Q2 of 2025, respectively [2] - CEO Caroline Loew, Ph.D., will present at the TD Cowen 45th Annual Health Care Conference on March 4, 2025, at 3:10 p.m. ET, with a live webcast available [1]

Clinical Trials and Data Readouts - Interim data readout for ARTISTRY-7, a phase 3 trial evaluating nemvaleukin in combination with pembrolizumab for platinum-resistant ovarian cancer (PROC), expected in late Q1/early Q2 2025, with 75% of overall survival (OS) events reached for interim analysis [3][6] - Top-line data readout for ARTISTRY-6, Cohort 2, evaluating nemvaleukin monotherapy for mucosal melanoma, expected in Q2 2025, with a target response rate of 25% [6][7] - Preliminary data readout for less-frequent intravenous (LFIV) dosing of nemvaleukin monotherapy in cutaneous melanoma expected in 1H 2025, with patient enrollment complete [3][13] - Preliminary data readout for LFIV dosing of nemvaleukin in combination with pembrolizumab for cutaneous melanoma expected in 2H 2025 [13] Pipeline Expansion and Development Candidates - Mural nominated two new development candidates: MURA-8518, a half-life extended, binding protein-resistant IL-18, and MURA-7012, targeted split sub-units of IL-12 [3][4] - MURA-8518 aims to overcome native IL-18 limitations by eliminating binding to IL-18BP and extending half-life, with an IND submission expected in Q4 2025 [4][11] - MURA-7012 is designed to limit systemic exposure by delivering IL-12 preferentially to the tumor microenvironment, with preclinical studies showing reduced serum toxicity [12] Financial and Operational Updates - Mural extended its cash runway projection into Q1 2026 through operational efficiencies [3][5] - The company has transformed into a robust organization with multiple expected data catalysts since becoming independent [5] Regulatory and Strategic Milestones - If ARTISTRY-7 interim analysis meets the hazard ratio threshold (0.727, 27.3% reduction in risk of death), Mural plans to submit a Biologics License Application (BLA) for nemvaleukin in combination with pembrolizumab for PROC in 2025 [6] - Final OS results for ARTISTRY-7 expected in Q2 2026, with a maximum hazard ratio for success of 0.788 (21.2% reduction in risk of death) [6] - Nemvaleukin has been granted Orphan Drug Designation by the FDA for mucosal melanoma [6] Company Overview - Mural Oncology is a clinical-stage immuno-oncology company developing engineered cytokine therapies for cancer, with a focus on platinum-resistant ovarian cancer and mucosal melanoma [9] - The company leverages its protein engineering platform to develop cytokine-based immunotherapies, aiming to improve clinical outcomes for cancer patients [9]

Core Insights - Mural Oncology's lead candidate, nemvaleukin, has shown promising tolerability and anti-tumor activity in the ARTISTRY-1 clinical trial, particularly in platinum-resistant ovarian cancer, which typically does not respond to immunotherapies [1][2][5] Clinical Trial Overview - ARTISTRY-1 was a phase 1/2 trial that evaluated nemvaleukin as both monotherapy and in combination with pembrolizumab, enrolling 286 patients across 32 sites in seven countries from July 2016 to March 2023 [3][5] - The trial demonstrated durable responses in heavily pretreated advanced solid tumors, supporting the foundation for two ongoing potentially registrational trials with data readouts expected in late Q1/early Q2 2025 for PROC and Q2 2025 for mucosal melanoma [4][10] Efficacy Results - Monotherapy with nemvaleukin resulted in a 10% overall response rate (ORR), with confirmed partial responses in melanoma and renal cell carcinoma [6] - Combination therapy with pembrolizumab yielded a 13% ORR, including five confirmed complete responses and 14 confirmed partial responses, with a notable 21% ORR in PROC patients [7] Safety and Tolerability - Nemvaleukin was well tolerated, with a low discontinuation rate of 4% due to adverse events, and the most common severe treatment-related adverse events were neutropenia and anemia [9] Mechanism of Action - Nemvaleukin is an engineered fusion protein designed to enhance the anti-tumor effects of the IL-2 pathway while reducing toxicity, leading to preferential expansion of CD8+ T cells and natural killer cells [11]

WALTHAM, Mass. and DUBLIN, Nov. 11, 2024 (GLOBE NEWSWIRE) -- Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company developing novel, investigational engineered cytokine therapies designed to address areas of unmet need for patients with a variety of cancers, today announced that members of the management team will participate in two upcoming investor conferences. Jefferies London Healthcare Conference 1x1 meetings with Caroline Loew, Ph.D., CEO, Vicki Goodman, MD, Chief Medical Officer ...

WALTHAM, Mass and DUBLIN, Sept. 23, 2024 (GLOBE NEWSWIRE) -- Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company developing novel, investigational engineered cytokine therapies designed to address areas of unmet need for patients with a variety of cancers, today announced the appointment of Sachiyo Minegishi to its board of directors, effective September 20. Ms. Minegishi will serve as Chair of the Audit Committee and will also be joining the company's Nominating and Corporate Govern ...