Nemvaleukin Alfa

Based on overall survival data observed in interim analysis in platinum-resistant ovarian cancer, Mural will not progress trial to final analysis Continued demonstration of favorable tolerability profile generally consistent with previously reported data; over 800 patients treated across the greater nemvaleukin clinical program The company remains on track to share topline results from potentially registrational, phase 2 trial in mucosal melanoma, ARTISTRY-6, Cohort 2, evaluating nemvaleukin monotherapy in Q2 2025 WALTHAM, Mass and DUBLIN, March 25, 2025 (GLOBE NEWSWIRE) -- Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company, today announced that the ARTISTRY-7 phase 3 trial of nemvaleukin alfa in combination with Merck’s (known as MSD outside the US and Canada) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) versus investigator’s choice chemotherapy in patients with platinum-resistant ovarian cancer (PROC) will not continue to final analysis and the company will cease development of nemvaleukin for PROC. In the pre-specified interim analysis conducted by the independent data monitoring committee, nemvaleukin in combination with pembrolizumab did not achieve a statistically significant improvement in overall survival versus investigator’s choice chemotherapy alone and the company believes the study is highly unlikely to achieve success at the final analysis. Median overall survival was 10.1 months for patients treated with nemvaleukin in combination with pembrolizumab and 9.8 months for patients treated with investigator’s choice chemotherapy (hazard ratio: 0.98). “We are disappointed for ovarian cancer patients desperately lacking new treatment options. There has been a great deal of work across the industry in this immunologically cold tumor, yet there are still few treatment options that improve survival in this very difficult-to-treat tumor type. We are still on track to report topline data from our potentially registrational trial in mucosal melanoma later next quarter and will assess all available data to inform our next steps,” said Caroline Loew, Ph.D., CEO of Mural Oncology. Nemvaleukin has a well characterized and favorable safety profile, both as a monotherapy and in combination with pembrolizumab, with over 800 patients treated across the broader clinical program. In the interim analysis of ARTISTRY-7, the safety profile was generally consistent with previously reported data. Nemvaleukin is currently being evaluated in a potentially registrational, phase 2 trial, ARTISTRY-6, cohort 2 in mucosal melanoma, with a topline data readout expected in Q2 2025. Preliminary data readouts for less-frequent intravenous dosing of nemvaleukin in patients with cutaneous melanoma are expected in the second quarter of 2025 for cohort 3 of ARTISTRY-6 (monotherapy) and the second half of 2025 for cohort 4 of ARTISTRY-6 (combination therapy), subject to patient enrollment. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About the ARTISTRY-7 Trial ARTISTRY-7 is a phase 3 trial comparing nemvaleukin in combination with pembrolizumab vs. investigator choice single agent chemotherapy in patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, with a primary endpoint of overall survival. This four-arm trial also contains two smaller single agent arms, a pembrolizumab and a nemvaleukin arm, to assess contribution of components. A total of 456 patients were enrolled over the four arms of the trial in an approximate 3:1:1:3 randomization. Only arms 1 (nemvaleukin in combination with pembrolizumab) and 4 (investigator’s choice chemotherapy) were designed to be assessed for statistical comparisons. The pre-specified interim analysis was conducted at 77% events (219 events) needed for the final analysis. About Nemvaleukin Nemvaleukin alfa (nemvaleukin) is an engineered fusion protein designed to leverage IL-2’s antitumor effects while mitigating the hallmark toxicities that limit its use. Nemvaleukin selectively binds to the intermediate-affinity IL-2 receptor (IL-2R) and is sterically occluded from binding to the high-affinity IL-2R. Because of this molecular design, nemvaleukin treatment leads to preferential expansion of antitumor CD8+ T cells and natural killer cells, with minimal expansion of immunosuppressive regulatory T cells. Nemvaleukin is currently being evaluated in a potentially registrational trial, ARTISTRY-6, cohort 2 in mucosal melanoma, with a topline readout expected in Q2 2025. Preliminary data readouts for less-frequent intravenous dosing of nemvaleukin in patients with cutaneous melanoma are expected in the second quarter of 2025 for cohort 3 of ARTISTRY-6 (monotherapy) and the second half of 2025 for cohort 4 of ARTISTRY-6 (combination therapy), subject to patient enrollment. About Mural Oncology Mural Oncology is leveraging its novel protein engineering platform to develop cytokine-based immunotherapies for the treatment of cancer. By combining our expertise in cytokine biology and immune cell modulation and our protein engineering platform, we are developing medicines to deliver meaningful and clinical benefits to people living with cancer. Our mission is to broaden the potential, and reach, of cytokine-based immunotherapies to improve the lives of patients. Our lead candidate, nemvaleukin, is currently being evaluated in a potentially registrational trial, ARTISTRY-6, cohort 2 in mucosal melanoma, with a topline readout expected in Q2 2025. Preliminary data readouts for less-frequent intravenous dosing of nemvaleukin in patients with cutaneous melanoma are expected in the second quarter of 2025 for monotherapy and the second half of 2025 for combination therapy. Mural Oncology has its registered office in Dublin, Ireland, and its primary facilities in Waltham, Mass. For more information, visit Mural Oncology’s website at www.muraloncology.com and follow us on LinkedIn, Bluesky, and X. Forward Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: the company’s pipeline and development programs, including the expected timing of data readouts from the ARTISTRY-6 trial, the potential of the company’s product candidates and programs to address unmet medical needs, the continued progress of its pipeline and programs, and the sufficiency of Mural’s cash resources for the period anticipated. Any forward-looking statements in this press release are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include, among others, the inherent risks and uncertainties associated with competitive developments, preclinical development, clinical trials, recruitment of patients, product development activities and regulatory approval requirements; that preclinical or interim results and data from ongoing clinical studies of the company’s cytokine programs and product candidates may not be predictive of future or final results from such studies, results of future clinical studies or real-world results; future clinical trials or future stages of ongoing clinical trials may not be initiated or completed on time or at all; the company’s product candidates, including nemvaleukin, could be shown to be unsafe or ineffective; changes in the cost, scope and duration of development activities; the U.S. Food and Drug Administration may make adverse decisions regarding the company’s product candidates; and those other risks and uncertainties set forth in the company’s filings with the Securities and Exchange Commission (“SEC”), including its Annual Report on Form 10-K for the fiscal year ended December 31, 2024 and in subsequent filings the company may make with the SEC. All forward-looking statements contained in this press release speak only as of the date of this press release. The company anticipates that subsequent events and developments will cause its views to change. However, the company undertakes no obligation to update such forward-looking statements to reflect events that occur or circumstances that exist after the date of this press release, except as required by law. Contact: Katie Sullivan katie.sullivan@muraloncology.com

Plus, news about Relmada Therapeutics and Mural Oncology: Cassava Sciences finally stops work on Alzheimer’s drug: After a Phase 3 study of simufilam failed in November, Cassava said it was discontinuing a second Phase 3 trial. On Tuesday, the company said that trial failed, too, and it would stop work on simufilam in Alzheimer’s by the end of June. The drug did not meet primary, secondary or exploratory biomarker endpoints. “These results were unambiguous,” CEO Rick Barry said in a press statement. The SEC last year accused the drug’s co-developer Hoau-Yan Wang, a CUNY School of Medicine professor, of manipulating clinical trial results. Former CEO Remi Barbier and SVP of neuroscience Lindsay Burns paid more than $40 million to settle charges they made misleading statements about the Phase 2 studies. They allegedly told investors that the drug had significant therapeutic benefits when it did not. The company then continued studying the treatment. Cassava said Tuesday that it started preclinical studies of simufilam for epilepsy in people with tuberous sclerosis complex. Its stock $SAVA was down about 21% on Tuesday morning. — Lei Lei Wu Alumis inks deal in Japan: The California immunology biotech will get $40 million in upfront and near-term payments from Kaken Pharmaceutical as part of a licensing deal for rights to its oral TYK2 inhibitor in Japan. The Tokyo-based drugmaker also promised about $140 million in biobucks as part of the licensing deal for Alumis’ ESK-001 in dermatology indications. Alumis shares $ALMS were up about 22% on Tuesday morning. It is currently working on a merger with Acelyrin . — Kyle LaHucik Relmada Therapeutics’ bladder cancer deal: The Florida biotech will pay $3.5 million upfront and issue 3 million, or 10%, of its shares to Trigone Pharma for worldwide rights to an experimental bladder cancer drug. Called NDV-01, the drug is a sustained-release and intravesical formulation of gemcitabine and docetaxel. Relmada will take over development and other work for NDV-01 once an ongoing Phase 2 wraps up. Relmada gets rights to all regions except India, Israel and South Africa. Trigone could receive another $200 million in milestone payments and 3% royalties on net sales. The move comes a few months after Relmada’s depression drug failed another Phase 3 trial. — Kyle LaHucik Mural Oncology to stop a Phase 3 study in ovarian cancer: The biotech said an interim survival analysis showed that its IL-2 drug, called nemvaleukin alfa, plus Merck’s Keytruda was unlikely to succeed versus chemotherapy. Mural’s stock $MURA fell 60% on Tuesday morning. — Lei Lei Wu