- Of 34 CMML treatment-naïve participants enrolled and treated with lenzilumab plus azacitidine, 22 have evaluable responses in the first twelve months of follow-up
- Of the 10 subjects with dominant CBL mutations, 90% achieved a CR or marrow complete remission in the first 12 months with durable suppression of CBL clones.
- Building upon previously reported positive clinical responses, these data in CMML demonstrate statistically significant and clinically relevant improvements in hematologic outcomes, along with improvements in inflammatory markers, that occur in the early months after treatment initiation and appear durable and notably in CBL as well as other RAS mutations
- Additional data in other conditions adjacent to CMML, may lead to development of treatment for multiple myeloid conditions and a lenzilumab revenue franchise, if approved and commercialized
BURLINGAME, CA / ACCESS Newswire / July 28, 2025 / Taran Therapeutics ("Taran") a privately held company focused on hematology/oncology, announced the publication of a paper entitled ‘Durable Responses to Lenzilumab: Azacitidine Combination Therapy in High Risk Proliferative Chronic Myelomonocytic Leukaemia with Suppression of CBL and RAS Mutant Subclones' in the July 2025 edition of the European Medical Journal, Hematology edition.
The paper reports on the PREACH-M study assessment to date with a specific focus on the CBL sub-class of RAS-pathway mutations in CMML, a particularly challenging subclass. Link to the paper:
EMJ Hematology 13.1 2025 - European Medical Journal
PREACH-M is a Phase 2/3 non-randomized, uncontrolled, open-label trial involving 54 adults aged at least 18 years, newly diagnosed with the WHO 2016 criteria for CMML and stratified according to mutation status. Subjects exhibiting RAS pathway mutations (NRAS, KRAS, CBL) receive 24 cycles (every 28 days) of azacitidine (AZA) and Lenzilumab (LENZ). Those with only TET2 mutations receive the same AZA regimen along with sodium ascorbate. Subjects who complete 24 cycles of treatment are followed every 6 months for an additional 24 months. The primary endpoint is the frequency of CR or partial response during the first 12 cycles according to Savona Criteria. To date, and unreported in the paper due to cut-off timings of the database, 34 subjects are receiving LENZ plus AZA, with a per protocol target of 36 of that arm of the study.
Overall, subjects had completed a median number of 13.5 cycles of LENZ/AZA at the time of reporting. Of the patients, 85% attained a complete remission or a marrow complete remission within the first 12 months on study, according to International Working Group (IWG) 2006 criteria. According to Savona criteria, 85% of patients achieved a CR or an optimal marrow response within the first 12 months on treatment. Importantly, 64% of patients achieving a CR or a marrow CR had detectable CBL mutations at baseline. Of the 10 subjects with dominant CBL mutations (variant allele frequency >10%), 90% achieved a CR or marrow complete remission in the first 12 months with durable suppression of CBL clones.
Almost all participants with a RAS mutation, regardless of whether it was a CBL mutation or a different RAS mutation, had a rapid clinical response.
15 subjects have been on therapy for more than 12 months, five for two years or more, and three for three years or more with one subject at four years of therapy with no clinical relapse.
CMML is a rare, aggressive cancer in which levels of monocytes, blast cells, and pro-monocytes are significantly elevated from normal levels. These pathologic changes are accompanied by significantly elevated pro-inflammatory markers, including C-reactive protein. Current treatment options for CMML patients are limited to blood transfusions, hydroxyurea, and supportive care alongside the current standard of care, which includes hypomethylating agents such as azacitidine and decitabine, which have limited response rates of 7% to 18%1, 2, 3 with no proven increase in overall survival.
In the last 30 years, no new medicines with a novel mechanism of action have been approved for CMML patients who are at high risk of death or disease progression.4 Only about 20% of patients diagnosed with CMML survive for three years.5
The authors conclude that this interim analysis shows promising results: LENZ/AZA resulted in durable CRs beyond 12 months, with 85% of subjects achieving a complete remission or a marrow complete remission without significant LENZ related toxicity. "The PREACH-M trial findings to date, indicate that lenzilumab may improve treatment response in CMML," said Taran Therapeutics Founder Cameron Durrant, MD, MBA. "The study is now almost 95% enrolled and we are seeing clinical responses that mirror those previously reported as earlier stages of the study. These results and those previously presented in secondary AML, may create the possibility for lenzilumab development in a range of myelodysplastic leukemias. We are also seeing encouraging data in RAS MDS and various other conditions, suggesting the possibility that lenzilumab may play a valuable role across the spectrum of myeloid disorders and offer a revenue franchise opportunity if approved and commercialized."
"Patients with CMML are normally treated with hypomethylating agents such as azacitidine, with reported response rates of just 7% to 18%, usually of limited duration," continued Dr. Durrant. "Treating patients with lenzilumab appears to be improving clinical parameters, quality of life and systemic inflammation in the patients studied so far, and patients appear to be tolerating lenzilumab well. Critically, clinical responses appear to occur early, prior to the fourth monthly treatment cycle. We also hope to be able to demonstrate that treatment with lenzilumab will increase overall survival, which existing agents do not appear to."
Lenzilumab, a granulocyte-macrophage colony-stimulating factor (GM-CSF) neutralizing antibody, prevents GM-CSF from binding to receptors on hematologic progenitor cells. When GM-CSF binds to those receptors, it triggers normal myelocyte proliferation and maturation. In the presence of RAS-pathway mutations, GM-CSF contributes to the proliferation of myelocytes in myelodysplastic leukemias such as CMML, juvenile myelomonocytic leukemia (JMML), and acute myeloid leukemia (AML).6,7,8 Therefore, lenzilumab's ability to prevent GM-CSF binding to its receptor may inhibit the proliferation in these conditions.
PREACH-M (PREcision Approach to CHronic Myelomonocytic Leukemia), a non-randomized, open-label trial, is being conducted at multiple sites in Australia in treatment-naïve patients. It is sponsored by the South Australian Health and Medical Research Institute (SAHMRI), with grant funding from the Australian government and the study drug supplied by Taran.
About the PREACH-M Trial
PREACH-M (PREcision Approach to CHronic Myelomonocytic Leukemia) is a Phase 2/3, non-randomized, open-label clinical trial investigating precision medicine for treatment-naïve adults with CMML.9 This trial investigates treatment response rates determined by the Savona Criteria for patients with CMML after administration of lenzilumab alongside azacitidine in patients with RAS pathway mutations. The study also measures the patients' quality of life, using the MPN Symptoms Assessment Form: Total Symptom Score.
During the active treatment phase of the study, participants are required to attend clinic visits on Days 1 & 15 of the first cycle, and then on Day 1 of each subsequent 28-day cycle to assess how the participant is tolerating the therapy and ensure ongoing safety.10 In addition to regular safety blood tests throughout each cycle, participants' disease response assessments are scheduled after 3, 6, 12 and 24 cycles of therapy to measure their disease response.10 Such assessments include blood tests, bone marrow aspirate and trephine, ultrasound of the spleen, physical exam and assessment of transfusion requirements and clinical symptoms.10
Participants who complete 24 cycles of active treatment enter the follow-up phase of the study where they are followed up every 6 months for 24 months for survival, disease status and further CMML-related treatment.9 For patients with confirmed progressive disease or relapse during the active treatment phase of the study, further study treatment will cease. Patients remain on study and are followed up for disease status, survival, and further CMML-related treatment every 6 months until 48 months from Cycle 1, Day 1.9 During the follow-up period, participants no longer receive any investigational drugs but are permitted to receive any CMML treatment at the discretion of the treating clinician.
As part of the screening process, participants are required to have a bone marrow aspirate and trephine to test for certain acquired mutations that can be present in CMML.9 The study is seeking participants with TET2 and/or RAS pathway mutations. Participants with RAS pathway mutations or both TET2 and RAS mutations, receive azacitidine (administered subcutaneously at a dose of 75mg/m2 on Days 1-5, 8-9 or Days 1-7 for a total of 7 doses per 28-day cycle) in combination with lenzilumab (administered intravenously at a dose of 552mg on Days 1 & 15 of Cycle 1. Day 1 only for all subsequent cycles).9
The trial is sponsored by the South Australian Health and Medical Research Institute ("SAHMRI") and funded by a Medical Research Future Fund grant from the National Health and Medical Research Council of the Australian government to the University of Adelaide. Taran provides lenzilumab for use in the study through its Australian subsidiary.
Enrollment is open to newly diagnosed CMML patients who haven't received any treatment and people interested in learning more about the study, or obtaining additional information could visit the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au).
About Taran Therapeutics
Taran Therapeutics ("Taran"), is a clinical-stage biopharmaceutical company focused on developing lenzilumab, a first-in-class antibody that binds to and neutralizes granulocyte-macrophage colony-stimulating factor. Taran is developing lenzilumab as a treatment for multiple myeloid disorders and also exploring the use of lenzilumab to prevent toxicities associated with CAR-T therapy through investigator-initiated trials. Taran is also developing several antibody drug conjugates (ADCs) utilizing its EphA-3 targeted monoclonal antibody ifabotuzumab ("IFAB") for solid tumors. For more information, visit www.tarantherapeutics.com.
Forward-Looking Statements about Taran Therapeutics
All statements other than statements of historical facts contained in this press release are forward-looking statements. Forward-looking statements reflect management's current knowledge, assumptions, judgment, and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct, and you should be aware that actual events or results may differ materially from those contained in the forward- looking statements. Words such as "will," "expect," "intend," "plan," "potential," "possible," "goals," "accelerate," "continue," and similar expressions identify forward-looking statements.
Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to, the risks inherent in our lack of profitability and need for additional capital to continue as a going concern; our dependence on partners to further the development of our product candidates; the uncertainties inherent in the development, attainment of the requisite regulatory authorizations and approvals and launch of any new pharmaceutical product; the outcome of pending or future litigation or arbitration; and the various risks and uncertainties described in the "Risk Factors" sections of our latest annual and quarterly reports and other filings with the SEC.
All forward-looking statements are expressly qualified in their entirety by this cautionary notice. You should not rely upon any forward-looking statements as predictions of future events. We undertake no obligation to revise or update any forward-looking statements made in this press release to reflect events or circumstances after the date hereof, to reflect new information or the occurrence of unanticipated events, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, in each case, except as required by law.
Taran Therapeutics Contact
Cameron Durrant
Founder
cdurrant@tarantherapeutics.com
References
Costa, R., et. al. (2010). Activity of azacitidine in chronic myelomonocytic leukemia. Cancer, 117(12), 2690-2696. https://doi.org/10.1002/cncr.25759.
South Australian Registry data, South Australian Health and Medical Research Institute, April 14, 2021
Pleyer, L., et. al. (2014). Azacitidine in CMML: Matched-pair analyses of daily-life patients reveal modest effects on clinical course and survival. Leukemia Research, 38(4), 475-483. https://doi.org/10.1016/j.leukres.2014.01.006
Aim of first-ever CMML study - to improve survival. Leukaemia Foundation. (2023, January 3). Retrieved January 3, 2023, from https://www.leukaemia.org.au/stories/aim-of-first-ever-cmml-study-to-improve-survival/
Ma, L., Jiang, L., Yang, W., Luo, Y., Mei, C., Zhou, X., Xu, G., Xu, W., Ye, L., Ren, Y., Lu, C., Lin, P., Jin, J., & Tong, H. (2021). Real-world data of chronic myelomonocytic leukemia: A Chinese single-center retrospective study. Cancer medicine, 10(5), 1715-1725. https://doi.org/10.1002/cam4.3774
Gupta, A. et al. (2021). Juvenile myelomonocytic leukemia-A comprehensive review and recent advances in management. American Journal of Blood Research, 11(1), 1-21. Retrieved July 21, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010610/pdf/ajbr0011-0001.pdf
Padron, E., et al. (2013). GM-CSF-dependent PSTAT5 sensitivity is a feature with therapeutic potential in chronic myelomonocytic leukemia. Blood, 121(25), 5068-5077. https://doi.org/10.1182/blood-2012-10-460170
Emanuel, P. D., et al. (1991). Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors. Blood, 77(5), 925-929. https://doi.org/10.1182/blood.v77.5.925.925
Australian New Zealand Clinical Trials Registry. Retrieved March 20, 2023, from https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12621000223831
PREACH-M: Precision medicine for chronic myelomonocytic leukaemia in adults: A phase II trial studying the efficacy of lenzilumab and high dose ascorbate with azacitidine based on molecular profiling. PREACH-M - Victorian Cancer Trials Link. (n.d.). Retrieved January 3, 2023, from https://trials.cancervic.org.au/details.aspx?ID=vctl_actrn12621000223831
SOURCE: Taran Therapeutics
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