UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
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Current Report Pursuant to
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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instructions A.2. below):
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Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
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Securities registered pursuant to Section 12(b) of the Act:
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
Item 7.01. Regulation FD Disclosure.
On January 9, 2025, Mural Oncology plc (the “Company”) issued a press release titled “Mural Oncology Highlights Pipeline Progress and Anticipated 2025 Catalysts”. The Company also made available a copy of an updated corporate presentation, which can be accessed on the Company’s website at https://ir.muraloncology.com/events-and-presentations. A copy of the press release is attached hereto as Exhibit 99.1 and a copy of the corporate presentation is attached hereto as Exhibit 99.2, both of which are incorporated by reference herein. The information contained in, or that can be accessed through, the Company’s website is not a part of this filing.
The information contained under this Item 7.01 in this Current Report on Form 8-K, including Exhibit 99.1 and Exhibit 99.2, is being furnished herewith and shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall such information be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Item 9.01 Financial Statements and Exhibits
(d) Exhibits
Exhibit |
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Description |
99.1 |
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Press release issued by Mural Oncology plc on January 9, 2025. |
99.2 |
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Mural Oncology plc Corporate Presentation, dated January 2025. |
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Cover Page Interactive Data File (embedded within the Inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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Mural Oncology plc |
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Dated: January 10, 2025 |
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/s/ Maiken Keson-Brookes |
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Maiken Keson-Brookes |
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Chief Legal Officer |
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Exhibit 99.1 |
Mural Oncology Highlights Pipeline Progress and Anticipated 2025 Catalysts
Readouts for two late-stage, potentially registrational trials of nemvaleukin alfa expected in late Q1/early Q2 2025 for platinum-resistant ovarian cancer and Q2 2025 for mucosal melanoma
Preliminary data readouts for less-frequent intravenous dosing of nemvaleukin in patients with cutaneous melanoma expected in 1H 2025 for monotherapy, with patient enrollment now complete, and 2H 2025 for combination therapy
Mural nominated two new development candidates, MURA-8518 a novel binding protein-resistant IL-18 with half-life extension, and MURA-7012, targeted split sub-units of IL-12; Mural anticipates an IND submission for MURA-8518 in Q4 2025
Company extends cash runway projection into Q1 2026 through operational efficiencies
WALTHAM, Mass and DUBLIN – January 9, 2025 – Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company developing novel, investigational engineered therapies targeting cytokine pathways designed to address areas of unmet need for patients with a variety of cancers, today announced it has reached the 75% of overall survival (OS) events necessary for the planned interim analysis of ARTISTRY-7, its potentially registrational trial of nemvaleukin in combination with pembrolizumab in platinum resistant ovarian cancer (PROC), and that it has extended its cash runway projection into Q1 2026 beyond key upcoming catalysts.
The company expanded its pipeline in Q4 2024, by nominating two development candidates, one for its interleukin-18 (IL-18) program and one for its IL-12 program. MURA-8518 is designed to be a half-life extended, binding protein-resistant IL-18 in order to overcome the native cytokine’s limitations as a therapeutic. Mural expects to submit an Investigational New Drug (IND) Application or Clinical Trial Application (CTA) for a phase 1 trial of MURA-8518 in Q4 2025. MURA-7012 is comprised of targeted split IL-12 sub-units that preferentially self-assemble at the tumor site and are designed to limit systemic exposure.
“In just over a year since becoming an independent company, we have transformed Mural from a biotech with a binary readout in 2025 into a robust organization with multiple expected data catalysts. Not only have we stayed on track with our milestones as planned, we have also extended our cash runway into the first quarter of 2026 through operational efficiency,” said Caroline Loew, Ph.D., CEO of Mural Oncology. “With two readouts in our late-stage trials on the horizon, nemvaleukin has the potential to become a new treatment option for patients with high unmet need in platinum-resistant ovarian cancer and mucosal melanoma. 2025 will be a pivotal year for Mural, and we look forward to advancing our clinical programs to bring value to patients and shareholders alike."
Upcoming catalysts:
Mural has also made available a copy of an updated corporate presentation, which can be accessed on its website at https://ir.muraloncology.com/events-and-presentations.
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 in potentially registrational trials in platinum-resistant ovarian cancer and mucosal melanoma reading out in the first half of 2025. 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 and X.
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 two potentially registrational late-stage trials: ARTISTRY-7 in platinum-resistant ovarian cancer, with an interim data readout expected in late Q1/early Q2 2025 and final OS results projected in Q2 2026, and ARTISTRY-6, Cohort 2 in mucosal melanoma, with a topline readout in Q2 2025.
About MURA-8518
IL-18 is a potent immune-stimulating cytokine, but its activity is blunted by IL-18 binding protein (IL-18BP), a high affinity decoy protein that neutralizes IL-18, thereby rendering it ineffective. Native IL-18’s potency is also limited by its short half-life. MURA-8518 aims to address the shortcomings of native IL-18 in two ways. First, through the introduction of mutations designed to minimally impact the native structure while eliminating binding to IL-18BP. Secondly, half-life extension via fusion to a protein scaffold increases the cytokine’s exposure, allowing for sustained immune stimulation. Together, these have demonstrated more durable immunological effects in preclinical studies. Mural expects to submit an IND or a Clinical Trial Application for a phase 1 trial of MURA-8518 in Q4 2025.
About MURA-7012
Native IL-12 is a highly potent pro-inflammatory cytokine that has a narrow therapeutic index when administered systemically. To mitigate this toxicity, Mural, through its novel approach to protein engineering, split the IL-12p70 heterodimer into two inactive monomers: IL12p35 and IL-12p40. These individual subunits are then separately fused to antibody fragments and sequentially injected, which deliver and concentrate IL-12 preferentially in the tumor microenvironment to limit systemic exposure. In preclinical studies, MURA-7012, Mural’s engineered IL-12, achieved the desired reduction in serum while maintaining tumor concentrations providing the potential to reduce systemic toxicities.
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 and ARTISTRY-7 trials, the expected timing of a BLA submission for nemvaleukin in combination with pembrolizumab for the treatment of PROC, the potential regulatory pathways for nemvaleukin, the expected timing of preclinical updates and IND submission, including with respect to MURA-8515 and MURA-7012, 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 Quarterly Report on Form 10-Q for the quarterly period ended September 30, 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
INVESTOR PRESENTATION January 2025 Exhibit 99.2
Forward-Looking Statements Certain statements set forth in this presentation constitute “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. The words “anticipate,” “believe,” “expect,” “may,” “will” and similar expressions are intended to identify forward-looking statements. Forward-looking statements made in this presentation include, but are not limited to, statements concerning: the protein engineering capabilities of Mural Oncology plc (the “Company”); the potential therapeutic and commercial value, and anticipated safety profile, of the Company’s engineered IL-2, IL-12, and IL-18 cytokine programs and product candidates, including nemvaleukin alfa (“nemvaleukin”) as a cancer immunotherapy when used as monotherapy or in combination, and its broad potential utility across a wide array of tumor types and indications and its potential dosing optionality; the Company’s expectations regarding timelines and plans for the development of its engineered IL-2, IL-12, and IL-18 cytokines, including, for nemvaleukin, expectations related to ongoing clinical studies in the ARTISTRY development program, the ability of ongoing studies to support potential registration, and potential for expansion of the development program, including to explore novel combinations with other cancer treatments; and the sufficiency of the Company’s existing cash resources for the period anticipated. You are cautioned that forward-looking statements are inherently uncertain. Although the Company believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, the forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. Actual results may differ materially from those expressed or implied in the forward-looking statements due to various risks, assumptions and uncertainties. These risks, assumptions and uncertainties 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; 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 (“FDA”) may make adverse decisions regarding the Company’s product candidates; the separation may adversely impact the Company’s ability to attract or retain key personnel that support the Company’s oncology business; and those risks, assumptions and uncertainties described under the heading “Risk Factors” in the Company’s filings with the Securities and Exchange Commission (“SEC”), including its Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2024, and as may be updated in subsequent filings the Company may make with the SEC, which are available on the SEC’s website at www.sec.gov. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Except as required by law, the Company disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this presentation.
Section 1: Executive Summary
Mural Oncology: Building a New Class of Cytokine Therapies Abbrev.: CM: cutaneous melanoma; IL-12: interleukin-12; IL-18: interleukin-18; MM: mucosal melanoma; OS: overall survival; PDR: preliminary data readout; PROC: platinum resistant ovarian cancer; RP2D: recommended phase 2 dose; TLR: topline results; IND: investigational new drug; CTA: clinical trial application Subject to event accrual Subject to patient enrollment Phase 2 & 3 Late-Stage Trials: Cash Projection: Runway into Q1 2026 2 indications with limited available therapies and planned indication expansion Commercial Opportunity: Pipeline Expansion: Late-Stage Trials: 2 potentially registrational trials reading out 1H 2025 IND submission for MURA-8518 (IL-18 candidate) expected in Q4 2025 Key Anticipated Catalysts Late Q1/Early Q2: Interim analysis for ARTISTRY-7 (potentially registrational), with final OS projected in Q2 20261 Q2: TLR Cohort 2 of ARTISTRY-6 (potentially registrational) 1H: PDR Cohort 3-mono of ARTISTRY-6 (Phase 2, CM) 1H 2025 2H: PDR Cohort 4-combo of ARTISTRY-6 (Phase 2, CM)2 Q4: MURA-8518 (IL-18) IND or CTA submission 2H 2025
Highly Experienced Late-Stage Oncology Team Executive Team Caroline Loew, PhD CEO Vicki Goodman, MD CMO Maiken Keson-Brookes CLO Adam Cutler CFO Board of Directors Francis Cuss MB, BChir, FRCP Scott Jackson MBA – Chairman Caroline Loew PhD George Golumbeski PhD Sachiyo Minegishi MBA Benjamin Hickey MBA
Pipeline Overview: 2024-2025 Milestones Discovery Preclinical Phase 1 Phase 2 Phase 3 Indication Dosing Nemvaleukin (IV) Combination with Pembrolizumab (Potentially Registrational) Platinum Resistant Ovarian Cancer (PROC) (ARTISTRY-7) Nemvaleukin (IV) Monotherapy (Potentially Registrational) Mucosal Melanoma (ARTISTRY-6, Cohort 2) Program 2025 Milestones Interim readout projected in late 1Q/ early 2Q 2025 IND or CTA submission expected in 4Q 2025 Top-line data readout projected in 2Q 2025 Mechanism MURA-7012 MURA-8518 Tumor-targeted self-assembling split IL-12 Engineered IL-18 Abbrev.: IL: interleukin; IV: intravenous; LFIV: less frequent IV dosing; OS: overall survival; IND: Investigational New Drug; CTA: clinical trial application Cutaneous Melanoma (ARTISTRY-6, Cohort 3) Nemvaleukin (LFIV) Monotherapy Preliminary data readout projected in 1H 2025 Doses per 3-week cycle Subject to patient enrollment Nemvaleukin (LFIV) Combination with Pembrolizumab Cutaneous Melanoma (ARTISTRY-6, Cohort 4) Preliminary data readout projected in 2H 20251 5x 5x 2x 5x 2x 2x
Section 2: Nemvaleukin ALFA
Nemvaleukin: Engineered to Unlock the Efficacy Potential of the IL-2 Pathway for More Patients PROLEUKIN©(aldesleukin): proven curative potential in melanoma and RCC Extremely durable complete responses Toxic AE profile requires administration in an acute care setting, severely limits use to the fittest patients Nemvaleukin: a novel, stable, immediately active fusion protein Engineered to selectively expand CD8+ T cells and NK cells while mitigating toxicity Fusion of alpha sub-unit preferentially binds to beta and gamma receptor complex, hinders binding to trimeric high-affinity receptor Deep and durable responses in Ph1/2 trial (ARTISTRY 1) Durable responses seen with monotherapy in post PD-1 cutaneous and mucosal melanoma Durable responses, including complete responses, seen in combination therapy with pembrolizumab in heavily pre-treated PROC patients1 Manageable AE profile for outpatient administration Currently in two registrational studies – mono and combination therapy Data available on slide 13 of this presentation ARTISTRY-7 (combination therapy), ARTISTRY-6, cohort 2 (monotherapy) Target with Validated Efficacy: A New Class of Cytokine Therapy: Nemvaleukin’s Comprehensive Clinical Dataset:
Nemvaleukin’s Design Differentiates It from Other IL-2 Pathway Approaches with the Potential to be First-in-Class Nemvaleukin Abbrev: CPI: checkpoint inhibitor; IL-2: interleukin-2 Other IL-2 Variant Approaches: Shielding Prodrug Require activation upon dosing Degrade to native IL-2 Include non-native components Masking Pegylation Maintain Known Efficacy Clear expansion and activation of CD8 T cells Immediately active Mitigate Pathway Toxicity Fusion of alpha sub-unit leads to minimal activation of immune-suppressive Tregs Manageable adverse event profile for outpatient administration Novel Fusion Protein Designed to:
ARTISTRY-1: First-In-Human Trial of IV Nemvaleukin Global, Multicenter, Open-Label Phase 1/2 Trial Dose Expansion NCTO2799095 1. Patients from Parts A and B could roll over to Part C upon progression or stable disease (after > 4 cycles) on monotherapy 2. Nemvaleukin daily Q5D, then off treatment for 9 days (cycle 1) or 16 days (cycle 2+) 3. ORR assessed by investigator (RECIST v1.1) 4. Nemvaleukin 3 µg/kg/d in C1-C4, 6 µg/kg/d in C5-C7. PD-(L)1 approved/unapproved indication based on FDA prescribing information and may have changed over time Selection of RP2D, 6 µg/kg Part A: Dose Escalation1 Median Prior lines of therapy Part B Monotherapy Melanoma: 3 Part B Monotherapy RCC: 2 Part C Combination therapy: 3 Nemvaleukin 3 or 6 µg/kg IV2 + pembrolizumab 200 mg IV Part C: Combination Therapy RP2D: Nemvaleukin 6 µg/kg IV2 Part B: Monotherapy2 Advanced melanoma (n=47): CPI pretreated Advanced RCC (n=27): CPI naive or pretreated Objectives: safety and anti-tumor activity3 Objectives: safety and anti-tumor activity3 Select advanced tumor cohorts (N=166): Safety run-in, nemvaleukin 1 µg/kg + pembro (n=3) C4: Monotherapy rollover (n=43) C1: PD-(L)1 unapproved4: pretreated (n=42) C5: Melanoma: treatment naive (n=3) C2: PD-(L)1 approved4: CPI pretreated (n=26) C6: NSCLC: CPI relapsed (n=21) C3: PD-(L)1 approved4: CPI naive (n=26) C7: HNSCC: CPI naive (n=2) Abbrev.: C1-7: Cohorts 1-7; CPI: checkpoint inhibitor; HNSCC: head & neck squamous cell carcinoma; IV: intravenous; NSCLC: non-small cell lung cancer; ORR: overall response rate; PD-(L)1: programmed death (ligand) 1; RCC: renal cell carcinoma; RECIST: Response Evaluation Criteria In Solid Tumors; RP2D: recommended phase 2 dose
ARTISTRY-1 Proof of Mechanism: Nemvaleukin Preferentially Expands Cytotoxic CD8+ T Cells and NK Cells While Minimally Expanding Tregs Data are from the 6 μg/kg cohort in Part A of ARTISTRY-1. Data are mean + SD (N=12). Vaishampayan et al. Oral Abstract 2500 presented at ASCO 2022. Abbrev: NK: natural killer; Tregs: regulatory T cells
Nemvaleukin’s Adverse Event Profile in ARTISTRY-1 Was Consistent with Our Expectations Based on its Mechanism of Action Dose expansion: monotherapy (Part B) and combination therapy (Part C) Data as of March 27, 2023 Administered on outpatient basis; most frequent AEs were manageable with supportive care AE profile consistent with nemvaleukin mechanism of action Monotherapy safety profile was similar to combination, with no additive toxicity Most frequently observed grade 3-4 TRAE: neutropenia1 Not associated with risk of serious infections or febrile neutropenia No capillary leak events reported in ART-1 TRAEs leading to discontinuation: 4% (monotherapy)2, 4% (combination)3 Includes neutropenia and neutrophil count decreased TRAEs leading to discontinuation in monotherapy were Gr3 failure to thrive, Gr3 bronchospasm, Gr2 ECG T wave abnormal, and Gr1 cardiac troponin increase TRAEs leading to discontinuation in combination were Gr5 starvation, Gr3 arthralgia, Gr3 fatigue, Gr3 pneumonia, and Gr2 cytokine release syndrome Part C includes patients who received nemvaleukin at 1, 3, or 6 µg/kg IV in combination with pembrolizumab 200 mg IV. Data as of Mar 27, 2023 . Data on file.
ARTISTRY-1: Nemvaleukin Combination Treatment with Pembrolizumab Demonstrated Durable Responses Data cut off Mar 27, 2023 1. DOR data cut off Sept 27, 2023 Abbrev.: BEV: bevacizumab; CBP: carboplatin; CDDP: cisplatin; CR: complete response; DOC: docetaxel; FDA: Food and Drug Administration; GEM: gemcitabine; mo: month; NIR: niraparib; PAC: paclitaxel; PCA: paclitaxel albumin; PD: progressive disease; PD-(L)1: programmed death (ligand) 1; PLD: pegylated liposomal doxorubicin hydrochloride; PR: partial response; PROC: platinum-resistant ovarian cancer; SD: stable disease; TAM: tamoxifen; TOP: topotecan; uPR: unconfirmed PR. Data on file. Best overall response n (%) PROC (n=14) CR 2 (14.3%) PR 2 (14.3)* ORR, n (%) 4 (28.6)* DOR in weeks 27.6-130.41 Cohort 1 * Includes 1 confirmed PR, 1 unconfirmed PR Of the 14 evaluable, investigator reported PROC patients, the median prior lines of ovarian cancer therapy was 5
Rationale Underpinning Use of Nemvaleukin in PROC Abbrev.: CII: Cancer Immunology, Immunotherapy; CR: complete response; IL-2: interleukin-2; JCO: Journal of Clinical Oncology; ORR: overall response rate; OS: overall survival; PR: partial response; PROC: platinum resistant ovarian cancer In two peer-reviewed, intraperitoneal trials of recombinant IL-2 in ovarian cancer: 1997 JCO paper 26% ORR (6 CRs, 3 PRs in 35 evaluable patients) Median survival time of responders was not reached at time of publication (range, 27 to 90+ mos) 2010 CII paper 25% ORR (4 CRs, 2 PRs in 24 evaluable patients) OS of 2.1 years with one responder surviving for 10 years
ARTISTRY-7: Phase 3 / Potentially Registrational Study for Platinum-Resistant Ovarian Cancer Pembrolizumab may be administered up to 35 cycles. Investigational Nemvaleukin IV + Pembrolizumab versus Chemotherapy Key eligibility criteria Platinum-resistant/refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer At least 1L of systemic platinum therapy and ≤5L of systemic platinum-resistant therapy Prior bevacizumab treatment Measurable disease by RECIST v1.1 Randomization 3:1:1:3 Futility analysis completed for monotherapy arms Key Endpoints Primary outcome measure: Overall survival (OS) Secondary outcome measures: PFS, ORR, DCR, DOR, and TTR CA-125 response TEAEs Clinical trial and supply agreement with MSD (a tradename of Merck & Co., Inc. Rahway, NJ, USA) Conduct of trial is in association with The GOG Foundation, Inc. (GOG), the European Network of Gynaecological Oncological Trial groups (ENGOT), and the Asia-Pacific Gynecologic Oncology Trials Group (APGOT) Pembrolizumab dosing Nemvaleukin dosing a Alternative topotecan regimen: 1.25 mg/m2 on Days 1-5 of 21-d cycles b Response per RECIST v1.1 c Response per GCIG Arm 4 Investigator's Choice Single-Agent Chemotherapy PLD IV, 40 mg/m2 (Day 1 of 28-day cycle) Paclitaxel IV, 80 mg/m2 (Days 1, 8, 15, and 22 of 28-day cycle) Topotecan IV, 4 mg/m2 (Days 1, 8, and 15 of 28-day cycle) Gemcitabine IV, 1000 mg/m2 (Days 1 and 8 of 21-day cycle) 16 days nontreatment period 20 days nontreatment period Abbrev.: CA-125: cancer antigen-125; DCR: disease control rate; DOR: duration of response; GCIG: Gynecologic Cancer InterGroup; IV: intravenous; ORR: objective response rate; PFS: progression-free survival; PLD: pegylated liposomal doxorubicin; RECIST: Response Evaluation Criteria in Solid Tumors; TEAE: treatment-emergent adverse event; TTR: time to response Final Enrollment: 456 patients (vs 448 planned) Arm 1 Nemvaleukin IV 6 µg/kg + Pembrolizumab1 IV 200 mg Daily IV 21-day cycle Arm 2 Pembrolizumab1 IV 200 mg 21-day cycle Arm 3 Nemvaleukin IV 6 µg/kg Daily IV 16-day nontreatment period 21-day cycle 16-day nontreatment period 20-day nontreatment period
ARTISTRY-7 Interim Analysis Readout Expected Late Q1 or Early Q2 2025 Events: ~215 events for planned interim analysis occurred in early Q1 2025 Data Readout: OS IA readout in late Q1 or early Q2 2025 EVENTS AND STATISTICS # of Events: Protocol specified interim analysis (IA) for overall survival (OS) will occur at 75% of events (~215 of 286 total events) Alpha Spend: Cumulative alpha spend at IA is 1-sided, 0.0096 Protocol assumptions: median OS of 10 months for chemotherapy arm and median OS of 14.3 months for Arm 1 (nemvaleukin + pembrolizumab) Hazard Ratio: Maximum hazard ratio for success is 0.727 (a 27.3% reduction in the risk of death1) TIMING 1. Assuming exactly 215 events
ARTISTRY-7 Interim Analysis (IA): Potential Outcomes 1 2a 2b IA Readout Q1 or early Q2 2025 Next Steps Interim Analysis Meets Bar for Success Study Declared Positive File BLA for PROC in 2025 Decision to Continue to Final Analysis Decision to Terminate Study Interim Analysis Not Statistically Significant Final Analysis Expected Q2 2026 Hazard Ratio Meets Bar for Success File BLA for PROC in 2026 Final analysis at ~286 events 85% power to demonstrate a 30% reduction in the risk of death, or target hazard ratio of 0.7 with cumulative alpha spend (1-sided, 0.025)1 Maximum hazard ratio for success at final OS: 0.7881 1. Assuming exactly 286 events
Responses per RECIST v1.1 ARTISTRY-1: Nemvaleukin Demonstrated Durable Monotherapy Responses in Melanoma (Part B) Alla,b (n=46) Mucosal (n=6) Best overall response, n (%) CR 0 0 PR 6 (13.0)c 2 (33.3)d ORR, n (%) [95% CI] 6 (13.0) [4.9-26.3]c 2 (33.3) [4.3-77.8]d DOR in weeksd, Mean (SD) Median (range) 40.77 (55.6) c 16.75 (6.1-150.3) 78.2 (101.9)d 78.2 (6.1-150.3) a Excludes 1 patient who did not meet tumor-evaluable criteria. b Patients with mucosal, cutaneous, uveal, acral included in ‘All’. C Includes 4 confirmed PRs, 2 unconfirmed PRs, d 1 confirmed PR. e DOR for Part B only and does not include patients who rolled over to Part C; some patients may still be on treatment Data cut off Mar 27, 2023 Abbrev.: adj: adjuvant; ATEZO: atezolizumab; BIN: binimetinib; CBP: carboplatin; CI: confidence interval; COB: cobimetinib; CPI: checkpoint inhibitor; CR: complete response; DAB: dabrafenib; DCR: disease control rate (CR+PR+SD); DOR: duration of response; ENCO: encorafenib; FDA: US Food and Drug Administration; IPI: ipilimumab; MHRA: Medicines and Healthcare products Regulatory Agency; MV: melanoma vaccine; NA: not applicable; NIVO: nivolumab; ORR: overall response rate; PAC: paclitaxel; PD: progressive disease; PEMBRO: pembrolizumab; PR: partial response; SD: stable disease; TRAM: trametinib; TVEC: talimogene laherparepvec; VEM: vemurafenib. Data on file. All responders had been on prior CPI therapy and progressed FDA Orphan Drug and Fast Track designations, as well as MHRA’s ILAP Innovation Passport, granted in mucosal melanoma Data supported design of ARTISTRY-6 study
Cohort 2 of ARTISTRY-6: Phase 2 - Potentially Registrational Trial of Nemvaleukin in Mucosal Melanoma https://clinicaltrials.gov, NCT04830124 Key eligibility criteria 1 Unresectable and/or metastatic mucosal melanoma Patient has received anti–PD(L)-1 ± anti–CTLA-4 therapy No more than 1 prior systemic therapy Measurable disease per RECIST v1.1 ECOG PS 0-1 Key endpoints Primary: ORR per RECIST v1.1 (by independent central review) Key secondary: DOR, PFS, DCR, TTR per RECIST v1.1 (by independent central review) a With the exception of Cycle 1, which is 14 days (daily IV for 5 days + 9 days nontreatment), all cycles are 21 days3 Cohort 2 Mucosal melanoma (N=90) Nemvaleukin IV 6 µg/kg QDx5 Monotherapy 21-day cyclea 16-day nontreatment period Daily IV Abbrev.: CTLA-4: cytotoxic T-lymphocyte–associated antigen 4; DCR: disease control rate; DOR: duration of response; ECOG PS: Eastern Cooperative Oncology Group performance status; IV: intravenous; ORR: objective response rate; PD-(L)1: programmed death (ligand) 1; PFS: progression-free survival; RECIST: Response Evaluation Criteria in Solid Tumors; TTR: time to response ARTISTRY-6 also includes Cohorts 1, 3, and 4 which are designed to explore alternative dosing regimens of nemvaleukin, both as a monotherapy and in combination with pembrolizumab, in cutaneous melanoma Nemvaleukin dosing Final Enrollment: 92 patients
ARTISTRY-6 Cohort 2: Data Readout Expected in Q2 2025 Cohort 2 of ARTISTRY-6 study expected to provide the most robust clinical dataset in advanced mucosal melanoma to date Primary analysis will occur when all patients have a minimum follow up of at least 6 months Target response rate: 25% We believe a response rate of 20-25% would be meaningful for patients and would support discussion with FDA around Biologics License Application (BLA) submission Trial designed so that at 25% response rate, lower bound of 95% confidence interval will exceed a 15% response rate Intend to discuss data with FDA in advance of BLA submission Potential accelerated approval with confirmatory evidence to be later submitted for conversion to regular approval Regulatory filing may be deferred if ARTISTRY-7 study continues to final analysis, pending the final outcome Abbrev.: BLA: Biologics License Application
Exploration of Alternative Dose Administration and Schedule Underway to Further Optimize Nemvaleukin Profile 5x 2x ARTISTRY-3 Phase 1 Monotherapy - explored 1X and 2X Q3W ARTISTRY-1 Phase 1/2 Monotherapy / Dose Escalation / Expansion / Combination Cohort 2 of ARTISTRY-6 Phase 2 Mucosal Melanoma ARTISTRY-7 Phase 3 PROC 6 µg/kg; Days 1-5 Q3W Dosing modeled after approved high-dose IL-2 30 µg/kg; Days 1 and 8 Q3W Improved patient-friendly dosing schedule RP2D selected 1Q 2024 Abbrev.: PROC: platinum-resistant ovarian cancer; RP2D: recommended phase 2 dose Cohorts 3 & 4 of ARTISTRY-6 Phase 2 Cutaneous Melanoma Future Nemvaleukin Clinical Trials
Cohorts 3 and 4 of ARTISTRY-6: Phase 2 Trial in Melanoma https://clinicaltrials.gov, NCT04830124 Nemvaleukin starting dose will be 30 µg/kg but will allow for de-escalation as necessary per safety data review Key endpoints Primary: ORR per RECIST v1.1 Key secondary: DOR, PFS, DCR, TTR per RECIST v1.1 6 Days 21-day cycle Abbrev.: CTLA-4: cytotoxic T-lymphocyte–associated antigen 4; D1/4: days 1 and 4; DCR: disease control rate; DOR: duration of response; ECOG PS: Eastern Cooperative Oncology Group performance status; IV: intravenous; LFIV: less frequent IV; ORR: objective response rate; PD-(L)1: programmed death (ligand) 1; PFS: progression-free survival; Q3W: 3-week cycle; QDX2: two doses, one each day ; RECIST: Response Evaluation Criteria in Solid Tumors; TTR: time to response. 13-day nontreatment period Pembrolizumab dosing Nemvaleukin dosing Cohort 4 Cutaneous Melanoma – Combination with Pembro (N=20) Nemvaleukin LFIV 30 µg/kg d1, 8 Q3W2 + Pembrolizumab IV 200 mg Key eligibility criteria1 Unresectable and/or metastatic cutaneous melanoma ECOG PS 0-1 Measurable disease per RECIST v1.1 Cohort 3 only Patient has received anti–PD(L)-1 ± anti–CTLA-4 or anti-LAG-3 therapy No more than 1 other prior systemic therapy Cohort 4 only Prior adjuvant/neo-adjuvant therapy with anti–PD(L)-1 therapy if ≥ 6 mos have elapsed between date of last dose and date of recurrence No prior systemic therapy for unresectable or metastatic disease Cohort 3 Cutaneous Melanoma – Monotherapy (N=30) 21-day cycle 6 Days 13-day nontreatment period Nemvaleukin LFIV 30 µg/kg d1, 8 Q3W
Focused on Near Term Expansion With Vision Towards Next-Generation IO Opportunity Source: Clarivate Epidemiology; 1) US and EU Patient Populations. Ba Platinum-Resistant Ovarian Cancer 13K Patients1 FDA Fast Track Designation Potential to be the first immunotherapy option for ovarian patients Mucosal Melanoma 2K Patients1 FDA Fast Track and Orphan Drug Designation Potential to be first and only approved therapy specific to mucosal melanoma Clinical Validation Initial indications with high unmet need Expansion Larger populations with established clinical rationale Next-Gen IO Backbone Elevating outcomes / broadening IO patient population (PROLEUKIN© (aldesleukin)) approved indications Positive ARTISTRY-7 & ARTISTRY-6 readouts would support development in earlier lines Nemvaleukin Cell therapies Chemo PARP Inhibitors TKI Therapy ADCs Biologic rationale for augmenting existing treatment options Mucosal Melanoma 3.2 0.3 1.7 1.3
Section 3: PIPELINE EXPANSION
Activates NK cells and antigen-experienced CD8+ T cells Restores activity in dysfunctional T cells Matures dendritic cells (DCs) IL-18R IL-18R MYD88 IL-18 Suppressed activity IL-18R IL-18R IL-18 IL-18BP IL-18BP IL-18BP overexpressed in the TME IL-18BP binds strongly to IL-18 minimizing signaling IL-18 rapidly cleared from circulation Limited Application IL-18 is a Potent Stimulator of Innate and Adaptive Immunity, but with Key Limitations IL-18 Attractive Biology IL-18 Challenges
Mural Solution: Engineer an IL-18 with Optimized Characteristics NK / CD8+ T / DCs IL-18R IL-18R IL-18v IL-18BP IL-18BP-rich TME Engineer an active IL-18 molecule unaffected by IL-18BP presence Engineer an IL-18 with an extended half-life Optimize the IL-18 potency to fit its newly engineered profile Enhanced Anti-Tumor Activity MURA-8518: Engineered to Deliver a More Sustained Immune Response
--No Binding-- IL-18 huMOv1 IL-18 huMOv2 No Binding of Mural Oncology Variants to IL-18BP Broad Range of Potency Enhanced Pharmacokinetics Native HuIL-18 tight binding to IL18-BP No binding of MOV to IL18-BP huMOv1/2/3- human Mural Oncology variants IL18BP-resistant, half-life enhanced Preclinical Studies Demonstrated Enhanced Pharmacokinetics with an Optimized Potency and Maximal Resistance to IL-18BP Inhibition
Enhanced Pharmacokinetic Extended Pharmacodynamic muMOv1-mouse Mural Oncology variant IL18BP-resistant, half-life enhanced Mural’s Approach Achieves Intended Half-Life and Associated Pharmacodynamics Effects
Complete Responses and Survival Improvement Seen in Mural’s IL-18 Mouse Ortholog Variant Agent Dose (mg/kg) % TGI* Day 21 Complete Response Day 50 Probability of Survival Day 50 muMOv1 2.56 86% 2/10 40% muMOv1 5.12 93% 4/10 50% muMOv1 7.68 92% 5/10 50% *%TGI = % tumor growth inhibition, calculated before 1st animal in vehicle reached endpoint muMOv1- IL18BP-resistant, half-life enhanced mouse ortholog of Mural human variant The combination of IL-18BP resistance and half-life enhancement achieved desired effect
Mural Oncology: Building a New Class of Cytokine Therapies Abbrev.: CM: cutaneous melanoma; IL-12: interleukin-12; IL-18: interleukin-18; MM: mucosal melanoma; OS: overall survival; PDR: preliminary data readout; PROC: platinum resistant ovarian cancer; RP2D: recommended phase 2 dose; TLR: topline results; IND: investigational new drug; CTA: clinical trial application Subject to event accrual Subject to patient enrollment Phase 2 & 3 Late-Stage Trials: Cash Projection: Runway into Q1 2026 2 indications with limited available therapies and planned indication expansion Commercial Opportunity: Pipeline Expansion: Late-Stage Trials: 2 potentially registrational trials reading out 1H 2025 IND submission for MURA-8518 (IL-18 candidate) expected in Q4 2025 Key Anticipated Catalysts Late Q1/Early Q2: Interim analysis for ARTISTRY-7 (potentially registrational), with final OS projected in Q2 20261 Q2: TLR Cohort 2 of ARTISTRY-6 (potentially registrational) 1H: PDR Cohort 3-mono of ARTISTRY-6 (Phase 2, CM) 1H 2025 2H: PDR Cohort 4-combo of ARTISTRY-6 (Phase 2, CM)2 Q4: MURA-8518 (IL-18) IND or CTA submission 2H 2025
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APPENDIX
Nemvaleukin Design Details: A New Class of Engineered Fusion Protein Targeting IL-2 Pathway N C IL-2Ra New locations of N and C termini N C Native component of IL-2 receptor complex directly blocks α component of high affinity IL-2R Minimal alteration to IL-2 sequence maintains IL-2’s structure and allows for appropriate placement of α subunit Native IL-2: Nemvaleukin:
ARTISTRY-3 Cohort 2: Nemvaleukin Increased Immune Activation in Patient Tumors Intratumoral Immune Cell Densities Intratumoral Effector:Treg Ratios NK:Treg ratio CD8+:Treg ratio Tot GZB+ CD45RO+ Tot GZB+ CD45RO+ Tot GZB+ CD45RO+ Tot GZB+ CD45RO+ Tot GZB+ CD45RO+ Tot GZB+ CD45RO+ Tot GZB+ CD45RO+ Tot GZB+ CD45RO+ Muc Mel1 Muc Mel2 Muc Mel3 Cut Mel OC1 OC2 OC3 BrCa Tot GZB+ Tot GZB+ Tot GZB+ Tot GZB+ Tot GZB+ Tot GZB+ Tot GZB+ Tot GZB+ Paired biopsy data shown (n=8, all dose schedules combined) SCR C2D8 Key Takeaways: Nemvaleukin led to increased intratumoral effector NK and CD8+ T-cells Accompanied by favorable increase in effector:Treg ratio across tumor types
ARTISTRY-7: Futility Criteria for Monotherapy Arms Smaller Single Agent Arms to Assess Contribution of Components Futility criteria for Arm 2: Based on Keynote-100 trial, where single agent pembro was evaluated in 376 patients with PROC with a response rate of 8% Futility in ARTISTRY-7 trial defined as <2 confirmed complete or partial responses in the first 12 patients enrolled This arm was closed to further enrollment for futility in August 2023 after enrolling 27 patients Arm 4 Investigator's Choice Single-Agent Chemotherapy PLD IV, 40 mg/m2 (Day 1 of 28-day cycle) Paclitaxel IV, 80 mg/m2 (Days 1, 8, 15, and 22 of 28-day cycle) Topotecan IV, 4 mg/m2 (Days 1, 8, and 15 of 28-day cycle) Gemcitabine IV, 1000 mg/m2 (Days 1 and 8 of 21-day cycle) 16 days nontreatment period 20 days nontreatment period Abbrev.: CA-125: cancer antigen-125; DCR: disease control rate; DOR: duration of response; GCIG: Gynecologic Cancer InterGroup; IV: intravenous; ORR: objective response rate; PFS: progression-free survival; PLD: pegylated liposomal doxorubicin; RECIST: Response Evaluation Criteria in Solid Tumors; TEAE: treatment-emergent adverse event; TTR: time to response Arm 1 Nemvaleukin IV 6 µg/kg + Pembrolizumab IV 200 mg Daily IV 21-day cycle Arm 2 Pembrolizumab IV 200 mg 21-day cycle Arm 3 Nemvaleukin IV 6 µg/kg Daily IV 16-day nontreatment period 21-day cycle 16-day nontreatment period 20-day nontreatment period Futility criteria for Arm 3: Based on two phase 2 trials using different doses and schedules of aldesleukin with consistent response rates of approx. 25%, including some patients with durable CRs1 At least 1 patient among first 24 enrolled to achieve ORR or SD for at least 3 months needed to continue enrollment Nemvaleukin single agent arm met the threshold to continue and enrolled a total of 55 patients 1. Edwards et al. “Comparison of toxicity and survival following intraperitoneal recombinant interleukin-2 for persistent ovarian cancer after platinum: twenty-four-hour versus 7-day infusion.” Journal of Clinical Oncology, November 1, 1997; Vlad et al. “A phase II trial of intraperitoneal interleukin-2 in patients with platinum-resistant or platinum-refractory ovarian cancer.” Cancer Immunology and Immunotherapy. February 2010.