LENZ (lenzilumab) / Humanigen, Telcon, Taran Therapeutics - LARVOL DELTA

Unravelling the epigenetic drivers of chip – MDS/CMML – AML progression through novel methylation-sensitive regulatory elements (ASH 2025) - P2 | "Patients with RAS-pathwaymutations (NRAS, KRAS, CBL) received 24 cycles of Azacitidine (Aza; 75 mg/m² SC, d1–7) and Lenzilumab(Lenz; 552 mg IV; d1 & d15 of cycle 1, then d1 per cycle). These signatures could pinpoint epigenetic events necessary for effective therapy.Similarly, in MDS and AML, identification of Mesa elements could identify functional DNA methylationsensitive elements accounting for induction of disease as well as a potential therapeutic approach. Suchresearch aims to uncover functional elements and epigenetic biomarker signatures that are directlylinked to disease stage, progression, and responsiveness to treatment"

Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • ASXL1 • CSF1 • DNMT3A • FOSL1 • GLI2 • KRAS • NRAS • TET2 • TP53 • TP63 • TP73

Durable efficacy of lenzilumab plus azacitidine in newly diagnosed proliferative CMML patients: Interim analysis after four years of study commencement (ASH 2025) - P2 | "Interim analysis of the PREACH-M trial shows promising results with LENZ/AZA resulting indurable complete responses beyond 12 months with 86% of subjects achieving a complete remission ormarrow complete remission without significant LENZ related toxicity."

Clinical • Chronic Myelomonocytic Leukemia • Febrile Neutropenia • Hematological Malignancies • Leukemia • Neutropenia • Thrombocytopenia • ASXL1 • BRAF • CSF2 • KRAS • NF1 • NRAS • PTPN11 • TET2

High dose ascorbate downregulates innate immune cytokines in the bone marrow of TET2 mutant chronic myelomonocytic leukemia (ASH 2025) - "As of 1st August 2025, 8 patients hadcompleted at least 3 cycles of ascorbate and azacitidine treatment (27 enrolled in the total; 20 subjects inLenzilumab arm). Our preliminary data demonstrates a role for high dose ascorbate in down regulatingmultiple innate immune cytokines including IL-1β and GM-CSF but not IFNγ in the bone marrow of TET2mutant CMML patients. This is consistent with our in vitro data showing engineered human TET2-mutated monocytes exhibit hyper-activated innate immune responses through CD14-NLRP3-IL-1β axisreversible with high dose ascorbate. Ascorbate deficiency (< 11 µmol/L) was detected in 27% of CMMLpatients, a higher rate than reported for the general population (8.7%)."

Chronic Myelomonocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • CD14 • CSF2 • CXCL8 • IFNG • IL13 • IL15 • IL1B • IL1R1 • NLRP3 • STING • TET1 • TET2

Secondary Acute Myeloid Leukemia transformed from chronic myelomonocytic leukemia is strongly resistant to venetoclax but demonstrates sensitivity to anti-GM-CSF lenzilumab immunotherapy (ASH 2025) - "Published reports and our South AustralianRegistry revealed poorer median overall survival of sAML (3.5-3.7 months) and CR/CRi rates (0-33%)compared to newly-diagnosed previously untreated AML receiving azacitidine and venetoclax therapy(median OS 14.7 months, CR/CRi 66.4%)...Colony suppression by LENZ was significantly greater than VEN or AZA aloneor in combination (52.7±7.0 colonies vs. VEN 120.0±23.6; P=0.0004 or AZA 126.0±23.1; P=0.0002, VEN/AZA98.7±17.2; P=0.007), but comparable to VEN/AZA/LENZ triple therapy... The ability of secondary AML to form colonies may be driven by an autocrine source of pro-inflammatory cytokine production, revealing a vulnerability that can be targeted by precisionimmunotherapy. We report for the first time that venetoclax resistant secondary AML transformed fromCMML show sensitivity to antibody-directed GM-CSF blockade. Indeed, encouraging real-world clinicaldata of a patient with secondary AML safely receiving..."

IO biomarker • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • ANXA5 • CD33 • CSF2 • NPM1 • PTPRC

Suppression of KRAS and CBL Mutations and Hematological Improvement By Lenzilumab and Azacitidine Treatment in Proliferative Chronic Myelomonocytic Leukemia (ASH 2023) - "In 11 evaluable subjects with proliferative CMML and RAS-pathway mutations, GM-CSF neutralization with LENZ in addition to AZA standard of care, resulted in significant decreases in the proportion of KRAS and CBL mutant leukemic cells, accompanied by clinically significant hematologic improvements and a reduction in splenomegaly. Lenzilumab may have efficacy in preventing outgrowth of RAS-pathway mutations, specifically KRAS and CBL, in the context of CMML and other myeloid malignancies."

Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CSF2 • KRAS • NRAS

Lenzilumab in Addition to Azacitidine Improves Complete Response Rates in Chronic Myelomonocytic Leukemia (ASH 2023) - P2 | "Interim analysis of the PREACH-M trial demonstrated that GM-CSF neutralization with LENZ/AZA, for the treatment of CMML with RAS-pathway mutations resulted in 55% CR, achieved early in treatment, durability up to 18 months, thus far, and no unexpected serious adverse events. These data suggest CMML is driven by a non-redundant cytokine that responds to immunotherapy. Xu Y, Guo R, Miao M, Zhang G, Lan J, Jin J. Real-world data on efficacy and safety of azacitidine therapy in chronic myelomonocytic leukemia in China: results from a multicenter, retrospective study."

Clinical • IO biomarker • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CSF2 • KRAS • NRAS • TET2

Cytokine and Mutation Profiling Reveal Patterns of Complete Remission Rates with Lenzilumab Combination Therapy in Chronic Myelomonocytic Leukemia (ASH 2023) - P2 | "Introduction: Chronic myelomonocytic leukemia (CMML) is characterized by accumulation of classical CD14+CD16- inflammatory monocytes driven in part by hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), a pro-inflammatory cytokine. CMML is a disorder of profound innate immune activation, driven by GM-CSF and other pro-inflammatory cytokines. Early treatment with LENZ/AZA, a precision immunotherapeutic approach, leads to a) efficacy in INNATE-1 that exceeds historical CR rates for hypomethylating agents1,2; and b) evolving efficacy in INNATE-2, in which pro-inflammatory activity is more robust. Xu Y, Guo R, Miao M, Zhang G, Lan J, Jin J. Real-world data on efficacy and safety of azacitidine therapy in chronic myelomonocytic leukemia in China: results from a multicenter, retrospective study."

Clinical • Combination therapy • IO biomarker • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Oncology • CD14 • CRP • CSF2 • CX3CL1 • IFNG • IL17A • IL1B • KRAS • NRAS • PHF6 • SRSF2 • TNFA • WT1

CBL Variants in Chronic Myelomonocytic Leukemia Exhibit a Complex Sub-Clone Architecture with a High Frequency of RING Domain Mutations Sufficient to Induce GM-CSF Hypersensitivity (ASH 2024) - P2 | "Here we examined the clinical, molecular and immunophenotypic features of CMML patients with CBL mutations enrolled in the ongoing PREcision Approach to Chronic Myelomonocytic Leukaemia (ACTRN12621000223831) trial which assesses the efficacy of Lenzilumab (LENZ; Taran Therapeutics, NJ) with azacytidine (AZA) in CMML patients harbouring RAS pathway mutations (KRAS, NRAS, CBL) at a variant allele frequency (VAF) > 3%. A high proportion of CD116-expressing progenitors, rather than CD115, indicates they may be targetable by anti-GM-CSF neutralization. The sensitivity of CBL mutants to GM-CSF blockade has implications for the treatment of CMML and JMML."

Chronic Myelomonocytic Leukemia • Hematological Malignancies • Immunology • Juvenile Myelomonocytic Leukemia • Leukemia • Oncology • CD34 • CSF2 • KRAS • NRAS • PTPRC

High Dose Ascorbate Reduces Interleukin-1 Beta Secretion in TET2 Mutant Monocytes and Demonstrates Excellent Safety and Tolerability in CMML Patients in Combination with Azacitidine (ASH 2024) - "As of 1st August 2024, 7 patients had completed at least 3 cycles of ascorbate and azacitidine treatment (27 enrolled in the total; 20 subjects in Lenzilumab arm). Ascorbate deficiency (< 11 umol/L) was detected in 27% of CMML patients, a higher rate than reported for the general population (8.7%), which warrants further investigation. In CMML patients, high dose ascorbate, given with azacitidine, demonstrates adequate safety and tolerability and restores vitamin C blood levels."

Clinical • Combination therapy • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Oncology • CD14 • CD68 • CD80 • IL1B • ITGAM • MRC1 • NLRP3 • TET1 • TET2

Durable Responses Observed in Chronic Myelomonocytic Leukemia Treated with Lenzilumab and Azacitidine (ASH 2024) - P2 | "Conclusion : Interim analysis of the PREACH-M trial shows promising results with LENZ/AZA resulting in durable complete responses beyond 12 months with 85% of subjects achieving a complete remission or marrow complete remission without significant LENZ related toxicity. Significantly, 90% of patients with major clone CBL mutations achieved complete remission or marrow complete remission."

Anemia • Chronic Myelomonocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • ASXL1 • CSF2 • KRAS • NRAS • TET2

Abstract number abs25-9821, titled ‘Durable efficacy of lenzilumab plus azacitidine in newly diagnosed proliferative CMML patients: Interim analysis after four years of study commencement’... (ACCESS Newswire) - "Taran Therapeutics reports publication of ASH abstract....The abstract describes updates from the PREACH-M Phase 2/3 study in 54 treatment-naive CMML adults, stratified according to mutation status....As of May 30, 2025, 40 subjects were enrolled overall...81% (26) of subjects had not progressed, two (2) went to allogeneic transplant (of which one had progressive disease), 9% (three subjects) had progressive disease (of which one was transplanted), one discontinued and one deceased. 22 subjects had evaluable responses within the first 12 months."

P2 data • Chronic Myelomonocytic Leukemia

Pharmacokinetics, Safety and Tolerability of Intravenous Lenzilumab, an Anti-GM-CSF Monoclonal Antibody Drug, in Healthy Korean Subjects. (PubMed, Drug Des Devel Ther) - "The systemic exposure of lenzilumab was dose-proportional across 1 to 10 mg/kg in healthy Korean subjects. A single IV administration of lenzilumab was safe and well tolerated in the dose range between 1 and 10 mg/kg."

Clinical • Journal • PK/PD data • Infectious Disease • Inflammation • Novel Coronavirus Disease • CSF2

The Role of Inflammation in CMML Pathobiology and Progression. (PubMed, Curr Hematol Malig Rep) - "On the therapeutic front, drugs targeting cytokine pathways, such as ruxolitinib (a JAK inhibitor) and lenzilumab (an anti-GM-CSF antibody), have shown early promise in modifying disease activity and improving symptoms. Understanding and targeting these inflammatory circuits may not only help slow disease progression but also improve quality of life for patients. As our knowledge grows, incorporating inflammation into both our diagnostic frameworks and treatment approaches will likely become standard in the care of CMML."

Journal • Review • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Immunology • Inflammation • Leukemia • Oncology • CSF2 • CXCL8 • IL6 • SRSF2 • TET2 • TNFA

New Therapies and Targeted Treatments: MDS/ MPN Overlap Syndromes (SOHO 2025) - "This has led to the use of parenteral azanucleosides — decitabine and azacitidine — and, perhaps most successfully in the United States, the oral agent decitabine/ cedazuridine (Dec-C)...While decitabine led to improved response rates, it failed to show benefit in event-free survival (EFS) or overall survival (OS) over the hydroxyurea arm, 5 raising questions about the role of azanucleosides — at least in MP-CMML — and underscoring the urgent need for disease-specific therapies for patients with MPCMML and other MDS/MPNs...This yielded promising responses, 8 but the arm was closed, as itacitinib was discontinued by the manufacturer...9 Given these findings, in the phase 2 PREACH study in Australia comparing lenzilumab plus azacitidine in untreated, high-risk RAS- mutated CMML, investigators reported a 55% complete response (CR) rate, found to be durable at 18 months...STX-0712 is a cytotoxicity targeting antibody (CyTAC) that links an antibody designed to induce..."

IO biomarker • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • ABL1 • BCR • CCL2 • CCR2 • CSF2 • LILRB4 • SF3B1

Publication of Provisional Patent Application for Lenzilumab in Chronic Myelomonocytic Leukemia (CMML) (ACCESS Newswire) - "The publication number is US-2025-0154243-A1....The Notice of Publication confirms this patent application has been published by the United States Patent and Trademark Office and covers the treatment of chronic myelomonocytic leukemia with RAS-pathway mutations using Lenzilumab in combination with current standard of care agents."

Patent • Chronic Myelomonocytic Leukemia

Contemporary CMML Risk Stratification and Management. (PubMed, Curr Hematol Malig Rep) - "These include lenzilumab (anti-GM-CSF) and IO-202 (anti-LILRB4), which have demonstrated promising early efficacy signals but require further study. Established treatments, which include hypomethylating agents and hydroxyurea as well as the JAK1/2 inhibitor ruxolitinib, provide limited survival benefits in CMML, underscoring the urgent need for novel therapeutic development. Coordinated dedicated research efforts have started to evaluate new agents in CMML. Along with further diagnostic and prognostic refinement, these advances are welcomed for this rare and heterogenous disease."

Journal • Review • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • Transplantation • CSF2 • LILRB4

DURABLE RESPONSES TO LENZILUMAB - AZACITIDINE COMBINATION THERAPY IN HIGH RISK PROLIFERATIVE CMML WITH SUPPRESSION OF CBL AND RAS MUTANT SUBCLONES (EHA 2025) - P2 | "Interim analysis of the PREACH-M trial shows promising results with LENZ/AZA resulting in durable complete responses beyond 12 months with 85% ofsubjects achieving a complete remission or marrow complete remission without significant LENZ related toxicity."

Combination therapy • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ASXL1 • CSF2 • KRAS • NRAS • TET2

Efficacy of assigning treatment for participants with VEXAS syndrome with lenzilumab plus azacitidine (ANZCTR) - P2 | N=10 | Not yet recruiting | Sponsor: South Australian Health & Medical Research Institute Ltd

New P2 trial • Inflammation • Targeted Protein Degradation • CSF2

A Glimpse for the subsistence from pandemic SARS-CoV-2 infection. (PubMed, Bioorg Chem) - "Although some drug regimens and vaccines have shown safety in trials, none have been entirely successful yet. This review highlights, some of the potential antibodies (tocilizumab, Sarilumab, Avdoralimab, Lenzilumab, Interferon (alfa /beta /gamma)) screened against SARS-CoV-2 and the most promising drugs (Favipiravir, Hydroxychloroquine, Niclosamide, Ribavirin, Baricitinib, Remdesivir, Arbidol Losartan, Ritonavir, Lopinavir, Baloxavir, Nitazoxanide, Camostat) in various stages of development with their synthetic protocol and their clinical projects are discussed to counter COVID -19."

Journal • Review • Cardiovascular • Gastrointestinal Disorder • Infectious Disease • Nephrology • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Pythium and Globisporangium species associated with cucumber rhizosphere causing damping-off and their effects on cucumber seed decay in Oman. (PubMed, Arch Microbiol) - "Pythium aphanidermatum, P. myriotylum, Globisporangium spinosum, Globisporangium sp.1 (isolates Kb003/PySyCu-1 and Kb004/PySyCu-2), and Globisporangium sp.2 (isolate Ib002R) were identified. This study showed that P. aphanidermatum is the most prevalent species in greenhouses in Oman and exhibited a moderate level of genetic diversity. Most of the isolates exhibited differences in tolerance to hymexazol but showed no resistance."

Journal

ZUMA-19: Study of Lenzilumab and Axicabtagene Ciloleucel in Participants With Relapsed or Refractory Large B-Cell Lymphoma (clinicaltrials.gov) - P1 | N=6 | Terminated | Sponsor: Kite, A Gilead Company | Phase classification: P1/2 ➔ P1

Phase classification • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Suppression of KRAS and CBL mutations and hematological improvement by Lenzilumab and Azacitidine treatment in proliferative chronic myelomonocytic leukemia (NDLR 2024) - No abstract available

Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • KRAS

C-SMART.nCOVID-19 Prevention and Treatment in CancernArm 4: treatment among cancer patients with severe COVID-19 infection. (ANZCTR) - P3 | N=72 | Withdrawn | Sponsor: Peter MacCallum Cancer Centre | Not yet recruiting ➔ Withdrawn

Trial withdrawal • Infectious Disease • Novel Coronavirus Disease • Oncology

C-SMART: COVID-19 Prevention and Treatment in Cancer; a Sequential Multiple Assignment Randomised Trial; (clinicaltrials.gov) - P3 | N=441 | Completed | Sponsor: Peter MacCallum Cancer Centre, Australia | Recruiting ➔ Completed | N=2282 ➔ 441 | Trial completion date: Dec 2021 ➔ Apr 2023 | Trial primary completion date: Dec 2021 ➔ Nov 2022

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Oncology • Solid Tumor • CRP

Humanigen Announces First Participant Dosed in RATinG Trial of Lenzilumab for Early Treatment of Acute Graft Versus Host Disease Following Allogeneic Stem Cell Transplantation (Yahoo Finance) - "Planned interim assessment expected in 2024 following treatment of first 20 participants....Humanigen...today announced successful dosing of the first participant in the RATinG trial of lenzilumab for the early treatment of acute Graft versus Host Disease (aGvHD)....The RATinG trial, a Phase 2/3 study, aims to evaluate the efficacy of lenzilumab as an early treatment to improve non-relapse mortality in patients with high risk aGvHD following allogeneic stem cell transplant (HSCT)."

P2/3 data • Trial status • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology