MRX2843 / Meryx, Betta Pharma - LARVOL DELTA

MERTK inhibition cooperates with immunomodulatory cyclophosphamide to induce CXCL9⁺ monocyte-macrophage programming and durable antitumor immunity in triple negative breast cancer. (PubMed, Cancer Immunol Res) - "Triple-negative breast cancer (TNBC) has high rates of recurrence despite chemotherapy and immune checkpoint blockade (ICB). PD-1 blockade further increases durability, preventing recurrence in most treated basal-like tumors. Together, these findings define an IFN licensed, MERTK regulated myeloid checkpoint that can be therapeutically targeted to convert suppressive TNBC microenvironments into durable adaptive immunity, supporting clinical translation of CTX + MRX-2843 based combinations in basal-like TNBC."

Journal • Breast Cancer • Hematological Disorders • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD4 • CXCL9 • CXCR3 • MERTK • SOCS1

MerTK Inhibition Aggravates Pancreatic Inflammation and Structural Damage via the NF-κB Pathway in an in vivo Type 2 Diabetic Rat Model. (PubMed, Diabetes Metab Syndr Obes) - "Seventy male Sprague-Dawley rats were randomized into five groups: normal control (CON), CON+MRX-2843 (MerTK inhibitor), T2DM 2-week (T2DM-2; assessed 2 weeks after diabetes induction), T2DM 12-week (T2DM-12; assessed 12 weeks after diabetes induction), and T2DM-12+MRX-2843...MerTK expression is dynamically upregulated in T2DM and exerts a compensatory protective effect by limiting NF-κB-driven inflammation and preserving pancreatic integrity. Pharmacological inhibition of MerTK exacerbates cytokine release, metabolic disturbances, and pancreatic injury, suggesting that MerTK may represent a promising candidate for further therapeutic investigation in T2DM."

Journal • Preclinical • Diabetes • Inflammation • Metabolic Disorders • Type 2 Diabetes Mellitus • IL1B • MERTK • TNFA

MEK inhibition overcomes stromal-mediated resistance to a MERTK targeted therapy in AML co-cultures and vascularized mesenchymal organoids (AACR 2026) - "In preliminary dose-finding studies, concurrent treatment with MRX-2843 and pimasertib was well-tolerated in mice. Collectively, these data identify MEK/ERK signaling as a mechanism of stromal-mediated resistance to MERTK inhibition and establish combined treatment with MRX-2843 and a MEK inhibitor as a promising strategy for effective treatment of AML."

Stroma • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • MERTK

MERTK inhibitor MRX-2843 sensitizes AML to venetoclax and azacitidine in preclinical models (AACR 2026) - "Moreover, mouse survival was significantly prolonged by the triple combination (median survival > 150 days, 59.1% survival after 150 days of treatment) compared to MRX-2843 (median survival = 76.5 days, 0% survival at 150 days, p<0.0001) or venetoclax/azacitidine (median survival = 104.5 days, 4.6% survival at 150 days, p<0.001). Together these findings (i) implicate co-administration of MRX-2843, venetoclax and azacitidine as an effective strategy to treat AML, (ii) reveal a potential mechanistic basis for this strategy, and (iii) support evaluation of this novel 3-drug combination in future clinical trials."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • MERTK • MYC • PTPRC

Combination treatment of mertki and immunomodulatory chemotherapy results in cxcl9 positive macrophage reprogramming and anti tumor adaptive memory in triple negative breast cancer (AACR 2026) - "Reprogramming of the bone marrow, with immunomodulatory cyclophosphamide drives myeloid cells into the monocytic lineage resulting in increased activated monocyte production. Furthermore, TAM RTK receptors regulate IFN signaling in monocytic derived cells and when inhibited can synergize with chemotherapy to drive long term durable responses in TNBC pre-clinical models. TAM reprogramming with MRX-2843 + CTX + ICB, therefore, may represent a novel therapeutic approach for patients with basal TNBC."

Immunomodulating • IO biomarker • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AXL • CD4 • CD8 • CXCL9 • MERTK • PD-L1 • STAT1

PIM kinase inhibition synergizes with a MERTK inhibitor to treat osimertinib resistant EGFR-mutant non-small cell lung cancer (AACR 2024) - "Further, two structurally distinct PIM kinase inhibitors, SGI-1776 and PIM447, provided synergistic inhibition of cell expansion and colony formation in osimertinib-resistant cell line cultures when combined with MRX-2843 treatment. Furthermore, knockdown of PIM kinases (PIM1, 2, 3) using nine sets of siRNAs led to various changes in expression of TAM receptor family members (TYRO3, AXL, MERTK), indicating a role for PIM kinases in regulation of TAM kinase expression. These studies suggest a novel treatment strategy for osimertinib-resistant EGFR-mutant NSCLC using a first-in-class MERTK kinase inhibitor that is currently under evaluation in multiple Phase I clinical trials."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL • EGFR • MERTK • PIM1

MERTK inhibition regulates tumor-associated myeloid cell phenotypes and potentiates host-versus-lung cancer immunity (AACR 2025) - "MRX-2843 is a novel first-in-class MERTK-selective inhibitor that is currently being tested in phase 1/1b clinical trials...Furthermore, tumors from Mertk KO mice had evidence of increased antigen-presenting capacity with significantly increased numbers of tumor-associated macrophages expressing high levels of MHC-II and increased incidence of dendritic cells. Together these findings suggest that MERTK inhibits anti-tumor immunity by regulating myeloid cell functions and implicate MERTK as an immunotherapeutic target in Kras-mutant non-small cell lung cancer."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL • KRAS • MERTK

MRX-2843 and Osimertinib for the Treatment of Advanced EGFR Mutant Non-small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=69 | Recruiting | Sponsor: Emory University | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Defective Single-Site Nanozymes with Exposed Unsaturated Cu-N2 Sites for Antitumor Immunotherapy via Innate Immune-Checkpoint Blockade. (PubMed, J Am Chem Soc) - "Herein, we develop an MRX-2843 (MerTK inhibitor) and Mn2+ codelivered defective metal-organic framework (copper-2,3,6,7,10,11-hexaiminotriphenylene (Cu-HITP))-based single-site nanozyme (Ir@D-Cu-HITP-MMP) for antitumor immunotherapy via innate immune-checkpoint blockade...This synergizes with Mn2+ to enhance the stimulator of interferon genes (STING) activation, triggering robust immune responses. Overall, Ir@D-Cu-HITP-MMP demonstrates potent antitumor effects by activating powerful innate and adaptive immune responses."

Checkpoint inhibition • IO biomarker • Journal • Oncology • MERTK • STING

MERTK inhibition cooperates with immunomodulatory cyclophosphamide to induce CXCL9⁺ monocyte-macrophage programming and durable anti-tumor immunity in triple negative breast cancer. (PubMed, bioRxiv) - "Combining CTX with the next generation MERTK-selective inhibitor UNC2371 (MRX-2843) drives complete remissions in both models, but durable long-term responses occurred selectively in the basal-like subtype model. Suppressive myeloid programing limits effective adaptive immune engagement in TNBC usually resulting in ICB treatment resistance and tumor recurrence. This study identifies a therapeutically actionable myeloid interferon checkpoint in which MERTK inhibition stabilizes CXCL9⁺ monocyte-macrophage programming to promote CD4⁺ T cell dependent immune memory and durable tumor control in basal-like TNBC."

Journal • Breast Cancer • Hematological Disorders • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD4 • CXCL9 • CXCR3 • IRF1 • IRF7 • MERTK • SOCS1 • STAT1

Pharmacokinetic and Safety Study of MRX-2843 in Adults With Relapsed/Refractory Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=42 | Completed | Sponsor: Meryx, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Apr 2025 ➔ Dec 2025 | Trial primary completion date: Feb 2025 ➔ Dec 2025

First-in-human • Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Pharmacokinetic and Safety Study of MRX-2843 in Adolescents and Adults With Relapsed/Refractory AML, ALL, or MPAL (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Meryx, Inc. | Trial completion date: Mar 2026 ➔ Sep 2026 | Trial primary completion date: Dec 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Combining mertk inhibitor mrx-2843 with venetoclax and 5-azacitidine in AML (ASH 2025) - "Treatment with MRX-2843 sensitized AML cells to standard-of-care venetoclax/azacitidine, leading to increased AML cell death, more effective targeting of AML cells in the bone marrow, and prolonged survival in mouse models. These findings implicate combined treatment with MRX-2843, venetoclax and azacitidine as an effective therapeutic strategy with potential to improve outcomes for patients with AML."

Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • ANXA5 • FLT3 • MERTK • PTPRC

Pharmacokinetic and Safety Study of MRX-2843 in Adults with Relapsed/Refractory Advanced And/or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=42 | Active, not recruiting | Sponsor: Meryx, Inc. | Trial completion date: Jul 2024 ➔ Apr 2025 | Trial primary completion date: Dec 2023 ➔ Feb 2025

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Pharmacokinetic and Safety Study of MRX-2843 in Adolescents and Adults with Relapsed/Refractory AML, ALL, or MPAL (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Meryx, Inc. | Trial completion date: Dec 2024 ➔ Mar 2026 | Trial primary completion date: Jul 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

MERTK inhibition selectively activates a DC - T-cell axis to provide anti-leukemia immunity. (PubMed, Leukemia) - "Host Mertk knock-out or MERTK inhibitor MRX-2843 increased CD8α+ dendritic cells (DCs) with enhanced antigen-presentation capacity in the leukemia microenvironment and inhibited leukemogenesis...Axl-/- did not impact leukemogenesis. These data demonstrate differential TAM kinase roles in the leukemia microenvironment and provide rationale for development of MERTK and/or TYRO3-targeted immunotherapies."

IO biomarker • Journal • Hematological Malignancies • Leukemia • Oncology • Pediatrics • AXL • CD8 • MERTK

A Phase 1b Study of the MER Tyrosine Kinase Inhibitor, MRX-2843, in Combination with Osimertinib in Advanced EGFR Mutant Non-Small Cell Lung Cancer (IASLC-WCLC 2024) - "Based on suggestion of preliminary evidence of efficacy, expansion cohorts to include both treatment-naïve and osimertinib-resistant patients is currently underway. (NCT # 04762199)"

Combination therapy • Metastases • P1 data • Cardiovascular • Heart Failure • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor • AXL • EGFR • MERTK

MERTK Is a Potential Therapeutic Target in Ewing Sarcoma. (PubMed, Cancers (Basel)) - "Combined treatment with MRX-2843 and BCL-2 inhibitors venetoclax or navitoclax provided enhanced therapeutic activity compared to single agents. These data highlight MERTK as a promising therapeutic target in EWS and provide rationale for the development of MRX-2843 for the treatment of EWS, especially in combination with BCL-2 inhibitors."

Journal • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • MERTK

Combining the novel FLT3 and MERTK dual inhibitor MRX-2843 with venetoclax results in promising antileukemic activity against FLT3-ITD AML. (PubMed, Leuk Res) - "Gilteritinib is a FLT3 inhibitor that is US FDA approved for treating adult patients with relapsed/refractory AML and a FLT3 mutation...Importantly, we found that VEN synergistically enhances cell death induced by MRX-2843 in FLT3-ITD AML cells with acquired resistance to cytarabine (AraC) or VEN+AraC...Mechanistic studies show that MRX-2843 decreases Mcl-1 and c-Myc protein levels via transcriptional regulation and combined MRX-2843 and VEN significantly decreases oxidative phosphorylation in FLT3-ITD AML cells. Our findings highlight a promising combination therapy against FLT3-ITD AML, supporting further in vitro and in vivo testing."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • MCL1 • MERTK • MYC

Combining the Novel FLT3 and MERTK Dual Inhibitor MRX-2843 with Venetoclax Results in Promising Antileukemic Activity Against FLT3-ITD AML (Leuk Res, ScienceDirect) - "We found that VEN synergistically enhances cell death induced by MRX-2843 in FLT3-mutated AML cell lines and primary patient samples. Importantly, we found that VEN synergistically enhances cell death induced by MRX-2843 in FLT3-ITD AML cells with acquired resistance to cytarabine (AraC) or VEN+AraC. VEN and MRX-2843 significantly reduce colony-forming capacity of FLT3-ITD primary AML cells."

Preclinical • Acute Myelogenous Leukemia

Combining the Novel FLT3 and MERTK Dual Inhibitor MRX-2843 with Venetoclax Results in Promising Antileukemic Activity Against FLT3-ITD AML (Leuk Res, ScienceDirect) - "We found that VEN synergistically enhances cell death induced by MRX-2843 in FLT3-mutated AML cell lines and primary patient samples. Importantly, we found that VEN synergistically enhances cell death induced by MRX-2843 in FLT3-ITD AML cells with acquired resistance to cytarabine (AraC) or VEN+AraC. VEN and MRX-2843 significantly reduce colony-forming capacity of FLT3-ITD primary AML cells."

Preclinical • Acute Myelogenous Leukemia

Co-targeting JAK1/STAT6/GAS6/TAM signaling improves chemotherapy efficacy in Ewing sarcoma. (PubMed, Nat Commun) - "Importantly, pharmacological inhibition of either JAK1 by filgotinib or TAM kinases by UNC2025 sensitizes Ewing sarcoma to chemotherapy in vitro and in vivo. Excitingly, the TAM kinase inhibitor MRX-2843 currently in human clinical trials to treat AML and advanced solid tumors, enhances chemotherapy efficacy to further suppress Ewing sarcoma tumor growth in vivo. Our findings reveal an Ewing sarcoma chemoresistance mechanism with an immediate translational value."

Journal • Acute Myelogenous Leukemia • Ewing Sarcoma • Oncology • Pediatrics • Sarcoma • Solid Tumor • AXL • GAS6 • JAK1 • MERTK • STAT6

MRX-2843 and Osimertinib for the Treatment of Advanced EGFR Mutant Non-small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=69 | Recruiting | Sponsor: Emory University | Phase classification: P1b ➔ P1 | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Combination therapy • Metastases • Phase classification • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Pharmacokinetic and Safety Study of MRX-2843 in Adults With Relapsed/Refractory Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=42 | Active, not recruiting | Sponsor: Meryx, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Oncology • Solid Tumor

Constitutively Synergistic Multiagent Drug Formulations Targeting MERTK, FLT3, and BCL-2 for Treatment of AML. (PubMed, Pharm Res) - "We developed a nanoscale combination drug formulation that exploits ectopic expression of MERTK tyrosine kinase and dependency on BCL-2 family proteins for leukemia cell survival in pediatric AML and infant ALL cells. We demonstrate ratiometric drug delivery and synergistic cell killing in AML, a result achieved by a systematic, generalizable approach of combination drug screening and nanoscale formulation that may be extended to other drug pairs or diseases in the future."

IO biomarker • Journal • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • BCL2 • FLT3 • MERTK