INVESTOR PRESENTATION January 2024 Exhibit 99.1
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 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 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, 2023, and 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 is a new, independent publicly traded company with $275M in cash1, providing runway into 4Q 2025. Highly experienced senior leadership team with deep immuno-oncology experience Nemvaleukin is an intrinsically active, stable fusion protein which does not degrade into native-IL-2 and is designed to selectively bind to the intermediate-affinity IL-2 receptor, enabling a potentially enhanced therapeutic window Mural Oncology - Building a Novel Engineered Cytokine Company Nemvaleukin has generated compelling clinical data to date, with durable responses2 in monotherapy and in PD-1 combination across a range of tumor types. ARTISTRY-6 and ARTISTRY-7 readouts both expected in 1H 20253 Portfolio of novel, investigational cytokines engineered to optimize the “known knowns” of native interleukins (IL) – retain their high potency while potentially overcoming their low tolerability IL-18 and IL-12 programs in development with potentially differentiated therapeutic properties and leveraging advanced protein engineering capabilities. Candidate nominations expected in 2024 1 2 4 3 Mural Oncology Abbrev.: IL-2: interleukin-2: IL-12: interleukin-12; IL-18: interleukin-18 5 Cash balance as of Nov 15, 2023 Durable response defined as a response with a duration that exceeds the response generally observed with standard of care treatment; in the context of high unmet disease states such as mucosal melanoma and platinum-resistant ovarian cancer (“PROC”), a response that exceeds six months is considered durable Subject to patient enrollment
Industry Leading Management Team and Board of Directors Executive Team Caroline Loew, Ph.D. CEO Vicki Goodman, M.D. CMO Maiken Keson-Brookes CLO Adam Cutler CFO Board of Directors Caroline Loew, Ph.D. Susan Altschuller, Ph.D., MBA Francis Cuss, M.B., B.Chir., FRCP Scott Jackson, MBA - Chairman Benjamin Hickey, MBA
Pipeline Overview – Near-Term Milestones Discovery Preclinical Phase 1 Phase 2 Phase 3 Indication Dosing Nemvaleukin (IV) Monotherapy and Combination with Pembrolizumab (Potentially Registrational) Platinum Resistant Ovarian Cancer (PROC) (ARTISTRY-7) Nemvaleukin (IV) Monotherapy (Potentially Registrational) Mucosal Melanoma (ARTISTRY-6) Nemvaleukin (LFIV) Monotherapy and Combination with Pembrolizumab Subject to patient enrollment Program Advanced Solid Tumors (ARTISTRY-3) Anticipated Program Milestones Interim OS readout projected in 1Q 20251 Recommended Phase 2 dose selection expected in 1Q 20241 Candidate nomination projected in 2024 Top-line data readout projected in 1H 20251 Candidate nomination projected in 2024 Mechanism IL-12 IL-18 Tumor-targeted self-assembling split IL-12 Engineered IL-18 Abbrev.: IV: intravenous; LFIV: less frequent IV dosing Nemvaleukin
Mural’s Novel Approach to Cytokine Design Seeks to Elevate Immunotherapy Treatment for Cancer Patients Extracted from Lei Q, et al. Front. Cell Dev. Biol. 2020;8:00672 GlobalData Thematic Research: Immuno-Oncology Minority of patients respond to anti-PD-(L)1 therapy Responders often experience disease progression Immunotherapy (IO) has transformed oncology over the last few decades and continues to generate staggering sales $88 B Projected by 20271 Despite the progress of IO treatment, most patients fail to benefit from current treatments Developing elegantly engineered cytokines to unlock the promise of IO for broader cancer populations Foundational Approach: Proprietary "Picasso" Technology Introduces new termini to aid design of novel fusion proteins Deep Biologic Understanding Sophisticated Fit-for-purpose Protein Engineering Protein X Circular Permutation Picasso X Elegantly Designed Cytokines Developed to meaningfully enhance utility of selected protein
Mural's Core Competency: Fit-For-Purpose Engineered Cytokines Abbrev.: Tregs: regulatory T cells; rhIL: recombinant human IL; IL-2R: IL-2 receptor; IL-2Rα: IL-2R alpha, IL-18BP: IL-18 binding protein Intrinsically active stable, not degraded fusion protein, sterically occluded from binding to the high-affinity IL-2R Program Technical challenge Protein engineering solution Nemvaleukin1 (IL-2 fusion protein) Systemic toxicities due to preferential binding to immunosuppressive high-affinity IL-2R Fusion of circularly permuted IL-2 with IL-2Rα subunit resulting in only activating immunostimulatory intermediate-affinity IL-2R Engineered IL-18 Limited clinical efficacy due to IL-18BP tightly binding to IL-18, neutralizing IL-18 receptor activation Engineered IL-18 designed with a half-life extension and resistant to IL-18BP neutralization, while retaining native IL-18 activity Tumor-targeted split IL-12 Clinical utility limited by severe toxicities at efficacious doses Separate inactive tumor-targeted IL-12 subunits that preferentially assemble and activate in the tumor IL-12R IL-12R STAT4 IL-18R IL-18R MYD88 IL-2Rg IL-2R STAT5
Section 2: Nemvaleukin Alfa
Nemvaleukin is Meaningfully Differentiated from Native IL-2 Source: Lopes J, et al. J Immunother Cancer. 2020;8:e000673. Abbrev.: IL-2R: IL-2 receptor; hdIL-2: high dose IL-2 b a High-Affinity Receptor-Bearing Cell b Intermediate-Affinity Receptor-Bearing Cell CD8+ T cell NK cell Treg cell CD25 CD122 CD132 Nemvaleukin CD122 CD132 b Treg cell a High-Affinity Receptor-Bearing Cell b Intermediate-Affinity Receptor-Bearing Cell CD8+ T cell NK cell CD25 CD122 CD132 IL-2 CD122 CD132 Nemvaleukin Sterically occluded from binding to the high-affinity IL-2R Activity focused on immunostimulation Immunosuppression Immunostimulation Immunostimulation IL-2 a Nemvaleukin Native IL-2 Preferential binding to high-affinity IL-2R Immunosuppressive activity outweighs immunostimulant activity Our Design Objective Fuse IL-2 to α subunit to block activation of high-affinity IL-2R
Nemvaleukin Design Detail Abbrev.: IL-2R: IL-2 receptor; IL-2Rα: IL-2R alfa Results in stable fusion protein Sterically occluded from high-affinity IL-2R Minimizes immunogenicity risk Intrinsically active No metabolic or proteolytic conversion Rigorous Selection of α Subunit for Fusion to IL-2 Application of PICASSO™ Technology Nemvaleukin Elegantly-designed fusion protein harnessing IL-2 immunostimulant biology Circular permutation & fusion to α subunit Minimal alteration to IL-2 sequence Allows appropriate placement of α subunit Maintains IL-2 structure Preserves confirmation and activity at intermediate affinity IL-2R Directly blocks α component of high affinity IL-2R Native component of IL-2 receptor immune system IL-2Ra
Clinical Pharmacodynamic Effects of Nemvaleukin: More NK Cells and Fewer Tregs than High-Dose IL-21,2 Nemvaleukin data are from the 6 μg/kg cohort in Part A of ARTISTRY-1. For fold change plots, data are mean + SE (N=10). For time course plot, data are mean + SD (N=12). 1. Vaishampayan et al. Oral Abstract 2500 presented at ASCO 2022. 2. Bhatt et al. Poster P123 presented at SITC 2018. HD, high-dose; IL-2, interleukin-2; IV, intravenous; NK, natural killer; SD: Standard deviation; SE: Standard Error; TID, 3 times daily; Treg, regulatory T cell Nemvaleukin: CD8 T and NK cells preferentially activated while Tregs remained suppressed Nemvaleukin1 High-Dose IL-22 High-dose IL-2 33 µg/kg IV TIDx5 Cycle 1 (14 days) Cycle 2 (21 days) 0 5 10 15 Day 25 30 35 40 0 500 1000 1500 2000 Absolute count (cells/L blood) 20 Total NK cells Total CD8+ T cells FOXP3+ Treg Immune cell expansion Cycles 1 – 2
Nemvaleukin Characteristics Significance Designed to include IL-2Rα and minimize non-native sequences Potentially reduced immunogenicity and more native-like-IL-2 signaling potential Does not require activation by tumor intrinsic factors Immediately active upon delivery Limited binding to high affinity IL-2R Potentially enhances therapeutic window Observed expansion of CD8/NK cells with minimal effect on regulatory T cells in humans Potentially greater therapeutic window and reduced immune suppression Observed monotherapy responses in multiple tumor types Validation of our design and approach Demonstrated clinical activity post-CPI progression and in CPI-unapproved tumor types Clinical activity in patients who no longer respond to CPI therapies Product candidate is in Phase 2/3, potentially registrational, trials Potentially first IL-2 variant to market Nemvaleukin: Potential First-in-Class, Differentiated Immunotherapy Design PK/PD Clinical Abbrev.: CPI: checkpoint inhibitor
Nemvaleukin: Deliberate and Focused Development Program Abbrev.: IV: Intravenous; SC: Subcutaneous Type of Clinical Trial Trial Name / Phase Tumor Types Dosing Mono or Combo? Status Foundational ARTISTRY-1 Phase 1/2 Advanced solid tumors Daily IVx5 Multiple responses in mono and combo Trial complete Potentially Registrational Enabling ARTISTRY-6* Phase 2 Mucosal melanoma Daily IVx5 Monotherapy Enrollment ongoing ARTISTRY-7 Phase 3 Platinum-resistant ovarian cancer Daily IVx5 Pembro combo Enrollment ongoing Alternative Dosing ARTISTRY-2 Phase 1/2 Advanced solid tumors SC Q1W Combo with pembro Data maturing ARTISTRY-3 Phase 1/2 Select advanced solid tumors Less frequent IV Monotherapy RP2D expected 1Q 2024 * Cohort 2 of Artistry-6 is registrational enabling and explores daily IVx5 dosing in mucosal melanoma. Cohort 1 and Cohort 3 explore SC Q1W and less frequent IV dosing, respectively, in cutaneous melanoma.
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, 6µg/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=162): Safety run-in, nemvaleukin 1 µg/kg + pembro (n=3) C4: Monotherapy rollover (n=39) 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.: 1-7: Cohort 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
Nemvaleukin’s Adverse Event Profile in ARTISTRY-1 Was Consistent with Our Expectations Based on its Mechanism of Action 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 Median duration 4 days; not associated with risk of serious infections or febrile neutropenia 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
ARTISTRY-1: Nemvaleukin Combination Treatment with Pembrolizumab Demonstrated Durable Responses Data cut off Mar 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 Best overall response n (%) PROC (n=14) CR 2 (14.3%) PR 2 (14.3)* SD 6 (42.9) PD 2 (33.3) ORR, n (%) 4 (28.6)* DCR, n (%) 10 (71.4)* Median DOR in weeks 65.5 Cohort 1 * Includes 1 confirmed PR, 1 unconfirmed PR
ARTISTRY-7: Phase 3 / Potentially Registrational Study for Platinum-Resistant Ovarian Cancer Herzog T et al. Poster presented at the Society for Gynecologic Cancers Annual Meeting (SGO), Phoenix, AZ, March 18-21, 2022 Investigational Nemvaleukin IV ± Pembrolizumab Versus Pembrolizumab Monotherapy or 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 planned for monotherapy arms 1 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 Estimated 448 participants Arm 1 Nemvaleukin IV 6 µg/kg + Pembrolizumab IV 200 mg Daily IV 21-day cycles Arm 2 Pembrolizumab IV 200 mg 21-day cycles Arm 3 Nemvaleukin IV 6 µg/kg Daily IV 16-day nontreatment period 21-day cycles 16-day nontreatment period 20-day nontreatment period
Responses per RECIST v1.1 ARTISTRY-1: Nemvaleukin Demonstrated Durable Monotherapy Responses in Melanoma (Part B) 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 Alla,b (n=46) Mucosal (n=6) Best overall response, n (%) CR 0 0 PR 6 (13.0)c 2 (33.3)d SD 30 (65.2) 2 (33.3) PD 10 (21.7) 2 (33.3) ORR, n (%) [95% CI] 6 (13.0) [4.9-26.3]c 2 (33.3) [4.3-77.8]d DCR, n (%) [95% CI] 36 (78.3) [63.6-89.1] c 4 (66.7) [22.3-95.7] 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
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 were 21 days3 Cohort 2 Mucosal melanoma (N=90) Nemvaleukin IV 6 µg/kg QDx5 Monotherapy 21-day cyclesa 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 and 3, which are designed to explore alternative dosing regimens of nemvaleukin in cutaneous melanoma Nemvaleukin dosing
Focused on Initial, Potentially Registrational Indications with Compelling Expansion Opportunities Clarivate Epidemiology; Estimated number of patients in the U.S. and Europe Represents 3rd line PROC patients Abbrev.: CPI: Checkpoint Inhibitor; MOA: Mechanism of Action; RCC: Renal Cell Carcinoma; NSCLC: Non-small cell lung cancer Initial Development Two indications with unmet need Planned Expansion Into Broader Cancer Indications Evolution of a proven cytokine provides opportunity to expand utility Platinum-Resistant Ovarian Cancer 13K Patients1,2 FDA Fast Track Designation In combination with pembrolizumab Potential to provide an immunotherapy option to an indication where CPIs have failed Mucosal Melanoma 2K Patients1 FDA Fast Track and Orphan Drug Designation Opportunity to further establish monotherapy efficacy in a larger patient cohort Potential to be first approval specific to mucosal melanoma Earlier Lines of Therapy in Ovarian and Cutaneous Melanoma 40K+ First line patients in each indication1 Multiple complete and partial responses Observed in both cutaneous melanoma and ovarian cancer in combination with an anti-PD-(L)1 therapy Other Mechanistic Combinations Scientific rationale for many combinations to advance cancer treatment across a range of tumor types Apply design and development approach to advance additional immunotherapy applications
Exploration of Alternative Dose Administration and Schedule Underway to Further Optimize Nemvaleukin Profile 5x 2x ARTISTRY-3 Phase 1 Monotherapy 5x daily Q3W Future Nemvaleukin Clinical Trials ARTISTRY-1 Phase 1/2 Monotherapy / Dose Escalation / Expansion / Combination ARTISTRY-6 Phase 2 Mucosal Melanoma ARTISTRY-7 Phase 3 PROC 5x daily Q3W Dosing modeled after approved high-dose IL-2 2x (day 1,4 or day 1,8) Q3W Improved patient-friendly dosing schedule RP2D expected 1Q 2024 Abbrev.: PROC: Platinum-resistant ovarian cancer; RP2D: Recommended Phase 2 Dose
Section 3: Additional Pipeline Programs
IL-18 Engineering: Resist IL-18BP Checkpoint to Unleash the Therapeutic Potential of IL-18 Challenge to IL-18 Internal expertise in protein engineering Mural Solution: Engineer IL-18 variants resistant to IL-18BP Resist IL-18 neutralization by immune checkpoint IL-18BP Retain and optimize IL-18 activity Increase exposure via half-life extension 1 2 Design Approach via Mutation(s): NK / CD8+ T / DCs IL-18R IL-18R IL-18v IL-18BP IL-18BP-rich TME Re-invigorates dysfunctional T-cells ↑Anti-tumor immunity IL-18R IL-18R IL-18 IL-18BP IL-18BP-rich TME IL-18BP Minimal IL-18 Signaling Lack of anti-tumor immunity 3
Preclinical Studies Demonstrated Improved Potency with Maximal Resistance to IL-18BP Inhibition No Detectable Binding of Variants to IL-18BP Note: No detectable binding of IL18 Variants to hIL-18BP WT-IL18 IL18 Variant 1 IL18 Variant 2 Variants with Broad Range of Potency vs WT IL-18 with Resistance to IL-18BP Suppression *Mural internal data
IL-12 Engineering: Tumor Site-Specific Assembly of Functional IL-12 Designed to Limit Systemic IL-12 Exposure IL-12 subunits are fused to Mural’s antibody fragments Tumor-targeted IL-12 subunits Non-targeted engineered inactive subunits Tumor-targeting Antibody fragments p35 Treat with targeted p35 subunit Clearance of systemic p35 subunits from circulation Results in active IL-12 in the tumor Treat with targeted p40 subunit *IL-12 subunits could be both cis- and trans-acting Active IL-12 assembly in situ Cancer Cancer cells expressing tumor antigen Cancer IL-12R Activated T Cell Active IL-12* Tumor-killing toxins Assemble functional IL-12 in the tumor with goals of avoiding toxicity associated with systemic exposure and maximizing the IL-12 therapeutic window p35 p40 p40
Preclinical Studies Provide Proof of Mechanism with a Clear Pharmacodynamic Response Source: Company internal data on file Abbrev: rhIL-12: recombinant human IL-12; GLP: good laboratory practice PBMC Humanized NCG Mouse Model In general, IL-12 anti-tumor activity observed in preclinical studies has been driven by activation of innate and adaptive immune compartments and production of IFN-γ1,2 Clinical utility has been limited by severe toxicities from systemic exposure leading to a narrow therapeutic index1,2,3 Mural’s sequential administration of tumor-targeted IL-12 subunits resulted in a dose-dependent increase in serum IFN-γ levels Nguyen KG et. al. Cancer Immunotherapy. Front. Immunol. October 15 2020 11:575597 Vecchio MD et. al. Clin Cancer Res August 15 2007 (13) (16) 4677-4685 Strauss J et. al. Clin Cancer Res January 1 2019 (25) (1) 99-109
Mural Oncology is a new, independent publicly traded company with $275M in cash1, providing runway into 4Q 2025. Highly experienced senior leadership team with deep immuno-oncology experience Nemvaleukin is an intrinsically active, stable fusion protein which does not degrade into native-IL-2 and is designed to selectively bind to the intermediate-affinity IL-2 receptor, enabling a potentially enhanced therapeutic window Mural Oncology - Building a Novel Engineered Cytokine Company Nemvaleukin has generated compelling clinical data to date, with durable responses2 in monotherapy and in PD-1 combination across a range of tumor types. ARTISTRY-6 and ARTISTRY-7 readouts both expected in 1H 20253 Portfolio of novel, investigational cytokines engineered to optimize the “known knowns” of native interleukins – retain their high potency while potentially overcoming their low tolerability IL-18 and IL-12 programs in development with potentially differentiated therapeutic properties and leveraging advanced protein engineering capabilities. Candidate nominations expected in 2024 1 2 4 3 Mural Oncology Abbrev.: IL-2: interleukin-2: IL-12: interleukin-12; IL-18: interleukin-18 5 Cash balance as of Nov 15, 2023 Durable response defined as a response with a duration that exceeds the response generally observed with standard of care treatment; in the context of high unmet disease states such as mucosal melanoma and platinum-resistant ovarian cancer (“PROC”), a response that exceeds six months is considered durable Subject to patient enrollment
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