nemvaleukin alfa (ALKS 4230) / Mural Oncology - LARVOL DELTA

Less Frequent Intravenous Dosing of Nemvaleukin Alfa in Patients With Advanced Solid Tumors: The Phase 1/2 ARTISTRY-3 trial. (PubMed, Oncologist) - P1/2 | "Less frequent IV doses of nemvaleukin demonstrated pharmacodynamic proof of mechanism and was tolerable with some disease stabilization."

Journal • P1/2 data • Hematological Disorders • Neutropenia • Oncology • Solid Tumor

Nemvaleukin alfa monotherapy in patients with advanced melanoma and renal cell carcinoma: results from the phase 1/2 non-randomized ARTISTRY-1 trial. (PubMed, J Immunother Cancer) - P1/2 | "Nemvaleukin demonstrated pharmacodynamic proof of mechanism, with single-agent antitumor activity and manageable safety in patients with advanced melanoma and RCC."

Journal • Monotherapy • P1/2 data • Genetic Disorders • Genito-urinary Cancer • Hematological Disorders • Melanoma • Neutropenia • Oncology • Renal Cell Carcinoma • Skin Cancer • Solid Tumor • CD8

Phase 3 Study of Nemvaleukin Alfa in Combination With Pembrolizumab in Patients With Platinum-Resistant Epithelial Ovarian Cancer (ARTISTRY-7) (clinicaltrials.gov) - P3 | N=456 | Terminated | Sponsor: Mural Oncology, Inc | Trial completion date: May 2027 ➔ May 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: May 2026 ➔ Jan 2025; Study terminated due to business and strategic decision.

Platinum resistant • Trial completion date • Trial primary completion date • Trial termination • Epithelial Ovarian Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Nemvaleukin Alfa Monotherapy and in Combination With Pembrolizumab in Patients With Advanced Cutaneous or Mucosal Melanoma - ARTISTRY-6 (clinicaltrials.gov) - P2 | N=173 | Terminated | Sponsor: Mural Oncology, Inc | Trial completion date: Sep 2026 ➔ May 2025 | Recruiting ➔ Terminated; Study terminated due to business and strategic decision.

Monotherapy • Trial completion date • Trial termination • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • BRAF

Mural Oncology Announces Plans to Explore Strategic Alternatives (GlobeNewswire) - "Mural Oncology plc...announced that following review of data from its phase 2 ARTISTRY-6 trial in melanoma and previously announced results from the phase 3 ARTISTRY-7 trial in platinum-resistant ovarian cancer, the company is discontinuing all clinical development of nemvaleukin alfa and plans to immediately commence the exploration of strategic alternatives focused on maximizing shareholder value."

Discontinued • Platinum resistant • Mucosal Melanoma • Ovarian Cancer

Mural Oncology Provides Update on Phase 3 ARTISTRY-7 Trial of Nemvaleukin in Combination with KEYTRUDA (pembrolizumab) in Patients with Platinum-Resistant Ovarian Cancer (GlobeNewswire) - P3 | N=456 | ARTISTRY-7 (NCT05092360) | Sponsor: Mural Oncology, Inc | "Mural Oncology plc...announced that the ARTISTRY-7 phase 3 trial of nemvaleukin alfa in combination with Merck’s...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)."

Discontinued • P3 data • Ovarian Cancer

Phase 2 ARTISTRY-6 trial (GlobeNewswire) - "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."

P2 data • Cutaneous Melanoma • Mucosal Melanoma

Nemvaleukin | Clinical Results from the ARTISTRY-1 Trial (YouTube) - "Key highlights from the trial, which were published in the Journal for ImmunoTherapy of Cancer, showed that nemvaleukin was generally well tolerated, with durable responses observed in both monotherapy and combination therapy across a range of heavily pretreated advanced solid tumors, including PROC, which does not typically respond to immunotherapies."

Video

Mural Oncology Announces Fourth Quarter and Year End 2024 Financial Results and Highlights Upcoming Clinical Milestones (GlobeNewswire) - "Interim analysis of overall survival in potentially registrational phase 3 ARTISTRY-7 trial in platinum-resistant ovarian cancer expected in late Q1/early Q2 2025; Top-line data readout of potentially registrational phase 2 ARTISTRY-6 (cohort 2) trial in mucosal melanoma expected in Q2 2025; Preliminary data readouts for less-frequent intravenous dosing of nemvaleukin alfa in the ARTISTRY-6 trial in patients with cutaneous melanoma expected in 1H 2025 for monotherapy (cohort 3) and 2H 2025 for combination therapy (cohort 4); The company plans to submit a Biologics License Application (BLA) for nemvaleukin in combination with pembrolizumab for the treatment of PROC in 2025."

FDA filing • P2 data • P3 data • Cutaneous Melanoma • Melanoma • Ovarian Cancer

Upcoming catalysts: Late Q1/early Q2 2025: Interim data readout of ARTISTRY-7 (GlobeNewswire) - "Mural's potentially registrational phase 3 trial in PROC. The trial is evaluating nemvaleukin in combination with pembrolizumab versus investigator’s choice single agent chemotherapy....The data will remain blinded to the company until after the independent data monitoring committee (IDMC) has reviewed the interim analysis, which is expected to be in late Q1/early Q2 2025....If the hazard ratio meets this pre-specified higher bar for success at the interim analysis (0.727, or a 27.3% reduction in the risk of death assuming exactly 215 OS events), the company plans to submit a Biologics License Application (BLA) for nemvaleukin in combination with pembrolizumab for the treatment of PROC in 2025....The company expects to report these final OS results in the second quarter of 2026, subject to event accrual."

DSMB • FDA filing • P3 data • Ovarian Cancer

Upcoming catalysts:…Data readout of…ARTISTRY-6 (GlobeNewswire) - "(i) Q2 2025: Top-line data readout of Cohort 2 of ARTISTRY-6, Mural’s potentially registrational phase 2 trial of nemvaleukin monotherapy in patients with unresectable or metastatic mucosal melanoma previously treated with immune checkpoint blockade. Nemvaleukin has been granted Orphan Drug Designation by the FDA for the treatment of mucosal melanoma...; (ii) 1H 2025: Preliminary data readout of Cohort 3 of ARTISTRY-6, an evaluation of a less-frequent intravenous (LFIV) dose of nemvaleukin monotherapy in patients with cutaneous melanoma. Patient enrollment in this cohort is now complete...; (iii) 2H 2025: Preliminary data readout of Cohort 4 of ARTISTRY-6, an evaluation of a LFIV dose of nemvaleukin in combination with pembrolizumab in patients with cutaneous melanoma."

P2 data • Cutaneous Melanoma • Mucosal Melanoma

Tumor microenvironment pharmacodynamic effect of nemvaleukin less frequent intravenous dosing in multiple solid tumors: results from the phase 1/2 ARTISTRY-3 study (SITC 2024) - P1/2 | "Background Nemvaleukin alfa (nemvaleukin) is a novel engineered cytokine with antitumor activity both as monotherapy and in combination with pembrolizumab in multiple solid tumors when administered intravenously (IV) at 6 μg/kg once daily, days 1–5 in a 21-day cycle (q5d).1 ARTISTRY-3 (NCT04592653) is a phase 1/2, open-label study evaluating less frequent IV dosing (LFD) of nemvaleukin in advanced solid tumors. Ethics Approval Multiple ethics committees and IRBs were involved and the trial protocol was approved by the institutional review boards/independent ethics committees at each site. Institution details for each site are available at the ARTISTRY-3 clinicaltrials.gov trial page: 'https://clinicaltrials.gov/study/NCT04592653?term=artistry-3&rank=1#contacts-and-locations.'Download figure Open in new tab Download powerpoint Abstract 217 Figure 1 Treg, CD8+, and NK and subsets densities (#/mm2) within and surrounding tumor parenchymaView this..."

Biomarker • P1/2 data • PK/PD data • Tumor microenvironment • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Ovarian Cancer • Solid Tumor • CD4 • CD8

Nemvaleukin alfa, a modified interleukin-2 cytokine, as monotherapy and with pembrolizumab in patients with advanced solid tumors (ARTISTRY-1). (PubMed, J Immunother Cancer) - P1/2 | "Nemvaleukin was well tolerated and demonstrated promising antitumor activity across heavily pretreated advanced solid tumors. Phase 2/3 studies of nemvaleukin are ongoing."

Journal • Metastases • Monotherapy • Genetic Disorders • Genito-urinary Cancer • Hematological Disorders • Melanoma • Neutropenia • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Skin Cancer • Solid Tumor • CD8 • IL2

Mural Oncology Announces Publication Highlighting Promising Clinical Antitumor Activity Shown in its ARTISTRY-1 Clinical Trial of Nemvaleukin, its Lead Engineered Fusion Protein, in the Journal for ImmunoTherapy of Cancer (GlobeNewswire) - P1/2 | N=243 | ARTISTRY-1 (NCT02799095) | Sponsor: Mural Oncology, Inc | "Key Findings:...Monotherapy: 10% overall response rate (ORR) with nemvaleukin monotherapy (7/68; 95% CI 4 to 20), with all seven confirmed partial responses (melanoma, n=4; renal cell carcinoma, n=3). 33.3% ORR in patients with mucosal melanoma, with two partial responses (one confirmed, one unconfirmed) in six evaluable patients.....Combination therapy: 13% ORR with nemvaleukin and pembrolizumab (19/144; 95% CI 8 to 20), with five confirmed complete responses and 14 confirmed partial responses. Six responses were in PD-(L)1 inhibitor-approved and five in PD-(L)1 inhibitor-unapproved tumor types. 21% ORR in patients with PROC: Notably, there were three confirmed responses (two complete, one partial) in 14 evaluable patients with PROC....ARTISTRY-1...data readouts expected in late Q1/early Q2 2025 for platinum-resistant ovarian cancer (PROC) and Q2 2025 for mucosal melanoma."

P1/2 data • Mucosal Melanoma • Ovarian Cancer • Renal Cell Carcinoma

Mural Oncology Announces Third Quarter 2024 Financial Results and Provides Update on Pipeline Progress (GlobeNewswire) - "Mural is...evaluating a less-frequent intravenous (LFIV) dose of nemvaleukin in patients with cutaneous melanoma in ARTISTRY-6, Cohort 3 (monotherapy) and Cohort 4 (combination with pembrolizumab). The company continues to expect preliminary data readouts in the monotherapy cohort in the first half of 2025, and in the combination cohort in the second half of 2025. Mural plans to nominate development candidates for its IL-18 and IL-12 programs by the end of 2024. The company expects to submit an Investigational New Drug (IND) Application for its IL-18 program to the FDA in Q4 2025."

IND • P2 data • Cutaneous Melanoma

Mural Oncology Announces Third Quarter 2024 Financial Results and Provides Update on Pipeline Progress (GlobeNewswire) - "The company shared new information related to study design, statistical assumptions, and study execution at a virtual Investor Day in September 2024, including: Completion of enrollment in ARTISTRY-7, the company’s potentially registrational phase 3 trial in platinum-resistant ovarian cancer (PROC), with a total of 456 patients enrolled....Mural expects to report interim overall survival (OS) results in late Q1 or early Q2 based on an analysis performed at approximately 75% of OS events. If the hazard ratio meets the bar for success (0.727, or a 27.3% reduction in the risk of death assuming exactly 215 OS events), the company plans to file a Biologics License Application (BLA) in 2025 subject to discussions with the U.S. Food and Drug Administration (FDA). The company expects to report final results in the second quarter of 2026."

FDA filing • P3 data • Ovarian Cancer

Tumor microenvironment pharmacodynamic effect of nemvaleukin less frequent intravenous dosing in multiple solid tumors: results from the phase 1/2 ARTISTRY-3 study (Friday, Nov. 8: Abstract #217) (GlobeNewswire) - P1/2 | N=78 | ARTISTRY-3 (NCT04592653) | Sponsor: Mural Oncology, Inc | "Mural Oncology...shared...poster presentations at the 39th Annual Meeting of SITC....Paired biopsies were available from 8 patients across the three different dosing schedules of nemvaleukin....Collectively, LFIV nemvaleukin demonstrated tumor-site-specific pharmacodynamic activity and immune activation. Nemvaleukin treatment increased cytolytic NK and CD8 T cell densities in the tumor microenvironment. Density ratios of CD8 and NK cells relative to immune-suppressive Tregs were also favorable for the nemvaleukin LFIV regimen....Mural is currently running two late-stage, potentially registrational trials in platinum-resistant ovarian cancer (ARTISTRY-7) and mucosal melanoma (ARTISTRY-6, cohort 2), with data readouts expected in late Q1/early Q2 2025 and Q2 2025, respectively."

P1/2 data • P2 data • P3 data • Mucosal Melanoma • Ovarian Cancer

Mural Oncology to Present Clinical and Preclinical Data at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (GlobeNewswire) - "Mural Oncology plc...announced three upcoming poster presentations at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) taking place November 6-10, 2024 in Houston. The company will present tumor microenvironment pharmacodynamic data from the phase 1/2 ARTISTRY-3 study, an evaluation of less frequent dosing of nemvaleukin, Mural’s engineered interleukin-2 (IL-2). Additionally, Mural will share data from its two preclinical research programs in IL-18 and IL-12, including new preclinical efficacy data for IL-18."

P1/2 data • PK/PD data • Preclinical • Oncology • Solid Tumor

Mural Oncology’s First Virtual Investor Day to Highlight Late-Stage Clinical Progress (GlobeNewswire) - "Mural leadership will provide new clinical insight into the trial design, statistical assumptions, and progress of the company’s late-stage trials of nemvaleukin. ARTISTRY-7 Timing: With enrollment complete, the OS events required for interim analysis are estimated to occur by late Q4 2024 or early Q1 2025. Mural expects the interim analysis data readout to be available in late Q1 or early Q2 2025. If the hazard ratio meets the bar for success, the study will be declared positive and the company will plan to file a Biologics License Application (BLA) in 2025; ARTISTRY-6 Timing...In order to ensure adequate follow-up on all patients, Mural anticipates that the top-line readout will occur in the second quarter of 2025; Mural plans to nominate a development candidate for its IL-18 program by the end of 2024 and intends to submit an Investigational New Drug (IND) Application to the FDA in Q4 2025."

Clinical protocol • FDA filing • IND • P3 data • Melanoma • Oncology • Ovarian Cancer

Mural Oncology to Host First Virtual Investor Day on September 26, 2024 (GlobeNewswire) - "Mural Oncology plc...announced that it will host a virtual Investor Day on Thursday, September 26, 2024, beginning at 10 a.m. ET. Mural leadership, including Caroline Loew, Ph.D., CEO, and Vicki Goodman, MD, Chief Medical Officer, will provide new clinical insight into the trial design and assumptions of the company’s late-stage and potentially registrational trials of nemvaleukin, an engineered IL-2. Those trials are on track to deliver topline results in 1H 2025. Mural will also provide an overview and data presentation of its IL-18 program."

Clinical data • Clinical protocol • Preclinical • Oncology

Novel engineered IL-2 Nemvaleukin alfa combined with PD1 checkpoint blockade enhances the systemic anti-tumor responses of radiation therapy. (PubMed, J Exp Clin Cancer Res) - "The addition of Nemvaleukin therapy may enhance responses to RT alone and in combination with anti-PD1."

Checkpoint block • Checkpoint inhibition • IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • CSF2 • IFNG • IL2

Mural Oncology Announces Second Quarter 2024 Financial Results and Provides Update on Pipeline Progress (GlobeNewswire) - "ARTISTRY-7: Patient enrollment in this trial is now complete. Mural continues to expect to report interim overall survival (OS) results based on approximately 75% of events in the first quarter of 2025. The company anticipates reporting final OS results in the second quarter of 2026; Mural expects to report top-line data results from cohort 2 of ARTISTRY-6 in the first half of 2025....The company expects preliminary data readouts in the monotherapy cohort in the first half of 2025, and in the combination cohort with pembrolizumab in the second half of 2025."

Enrollment status • P2 data • P3 data • Gynecologic Cancers • Mucosal Melanoma • Ovarian Cancer • Solid Tumor

Phase 3 Study of Nemvaleukin Alfa in Combination With Pembrolizumab in Patients With Platinum-Resistant Epithelial Ovarian Cancer (ARTISTRY-7) (clinicaltrials.gov) - P3 | N=456 | Active, not recruiting | Sponsor: Mural Oncology, Inc | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Nemvaleukin Alfa Monotherapy and in Combination With Pembrolizumab in Patients With Advanced Cutaneous or Mucosal Melanoma - ARTISTRY-6 (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: Mural Oncology, Inc | Trial completion date: Sep 2025 ➔ Sep 2026 | Trial primary completion date: Mar 2024 ➔ Jun 2025

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • BRAF

Recommended phase 2 dose (RP2D) of nemvaleukin alfa in patients (pts) with advanced solid tumors treated with less frequent intravenous (IV) dosing (ARTISTRY-3). (ASCO 2024) - P1/2 | "In ARTISTRY-1, IV nemvaleukin at 6 μg/kg once daily, days 1-5 (QD×5) in a 21-day (D) cycle showed antitumor activity across multiple tumors alone and in combination with pembrolizumab (1). Nemvaleukin demonstrated PD proof of mechanism in all 3 schedules and was tolerable at all doses tested, with some stabilization of disease. Safety profile was similar across all schedules. Nemvaleukin RP2D for less frequent dosing schedule is expected to be completed in Q1 2024."

Clinical • Metastases • P2 data • Anemia • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • CD4 • CD8