Rytelo (imetelstat) / Geron - LARVOL DELTA

IMproveMF update: Phase 1/1B trial of imetelstat (IME)+ruxolitinib (RUX) in patients (pts) with intermediate (INT)-1, INT-2, or high-risk (HR) myelofibrosis (MF). (ASCO 2025) - P1, P2 | "In part 1 of IMproveMF, no DLTs were observed and the RP2D dose of 9.4 mg/kg IME was determined. AEs were consistent with those observed in other IME clinical trials, and preliminary efficacy was positive, demonstrating the potential of IME+RUX in this pt population with high unmet needs. Part 2 of this trial is ongoing across the US at 6 sites."

Clinical • P1 data • Anemia • Fatigue • Hematological Disorders • Infectious Disease • Leukopenia • Myelofibrosis • Neutropenia • Pain • Pneumonia • Respiratory Diseases

TERT Reactivation in Thyroid Cancer: Mechanisms, Clinical Implications, and Therapeutic Opportunities. (PubMed, Eur Thyroid J) - "However, isolated TERT promoter mutations are more often associated with intermediate risk tumours and comparatively better outcomes, underscoring the importance of molecular context. The recent approval of the telomerase inhibitor Imetelstat and the preclinical success of the rRNA transcription inhibitor CX5461 in restoring differentiation and iodine uptake support telomerase- and ribosome-targeted strategies as emerging therapeutic avenues for TERT-driven thyroid cancers."

Journal • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • TERT

Updated Analysis of Overall Survival With Imetelstat in Relapsed or Refractory Myelofibrosis From IMbark Versus Real-World Data and Assessment of Real-World Treatment Patterns: Updated Post Hoc Analysis With Extended Follow-Up (SOHO 2026) - P2 | "RW treatment patterns, baseline/disease characteristics, and mOS of patients diagnosed before/after 2016 (cut point selected to match diagnosis period of IMbark population) and 2019 (fedratinib US approval) were compared. A more favorable OS benefit with imetelstat versus BAT in RW patients with R/R myelofibrosis and poor prognosis was observed. The significant improvement in OS in RW patients over the last decade was independent of transplant status, potentially due to shorter time from diagnosis to ruxolitinib start and earlier switch to next-line JAKi or clinical trial. Evolving treatment patterns are key considerations for interpreting future clinical trial outcomes."

Clinical • HEOR • Real-world • Real-world evidence • Retrospective data • Myelofibrosis • Oncology

DISEASE MODIFYING ACTIVITY OF IMETELSTAT IN PATIENTS WITH HEAVILY TRANSFUSED NON-DEL(5Q) LOWER-RISK MYELODYSPLASTIC SYNDROMES RELAPSED/REFRACTORY TO ERYTHROPOIESIS STIMULATING AGENTS IN IMERGE PHASE 3 (EHA 2023) - P2/3 | " Patients with heavily red blood cell (RBC) transfusion-dependent (TD) erythropoiesis stimulating agent (ESA) relapsed/refractory (R/R) or ineligible non-del(5q) LR-MDS naive to lenalidomide and hypomethylating agents (len/HMA) received 2-hr infusions of imetelstat 7.5 mg/kg or placebo every 4 weeks. In the phase 3 IMerge study, heavily RBC TD ESA R/R/ineligible non-del(5q) LR-MDS patients naive to len/HMA treated with imetelstat experienced more cytogenetic response and reduction in SF3B1 , TET2 , DNMT3A, and ASXL1 mutational burden compared with placebo. Furthermore, SF3B1 VAF reduction correlated with clinically meaningful endpoints of increased hemoglobin and TI duration. These data, taken together with robust rates of TI that are continuous and durable, may indicate improvement of the ineffectiveerythropoiesis characteristic of LR-MDS and suggest imetelstat may alter the underlying biology of disease in these patients."

Clinical • P3 data • Tumor mutational burden • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • ASXL1 • DNMT3A • SF3B1 • TET2 • TMB

OVERALL SURVIVAL, CLINICAL BENEFIT, AND DURABLE TRANSFUSION INDEPENDENCE WITH IMETELSTAT IN THE IMERGE PHASE 3 TRIAL OF RED BLOOD CELL-TRANSFUSION DEPENDENT LOWER-RISK MYELODYSPLASTIC SYNDROMES (EHA 2024) - P2/3 | "7%) in patients with non-del(5q) lower risk-myelodysplastic syndromes (LR-MDS)that were red blood cell (RBC)-transfusion dependent (TD), relapsed/refractory to or ineligible forerythropoiesis-stimulating agents, and naïve to lenalidomide or hypomethylating agents (Platzbecker U, etal. Results from these updated analyses confirm that achievement of RBC-TI with imetelstat was durable andassociated with improvement in Hb level. Additionally, preliminary OS analysis suggests no detriment withimetelstat vs placebo. VS/RSK and AMZ/UP contributed equally."

Clinical • P3 data • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Imetelstat Achieved Prolonged, Continuous Transfusion Independence (TI) in Patients with Heavily Transfused Non-Del(5q) Lower-Risk Myelodysplastic Syndrome (LR-MDS) Relapsed/Refractory (R/R) to Erythropoiesis Stimulating Agents (ESAs) within the IMerge Phase 2 Study (ASH 2022) - P2/3 | "Treatment with imetelstat achieved >1 year sustained, continuous TI in 29% of RBC TD, ESA-R/R LR-MDS patients who were non-del(5q) and lenalidomide/HMA-naïve and was safe and well tolerated. Of the overall population, attainment of 24-week TI was indicative of a likelihood to achieve TI >1 year. In this ESA-R/R population with a high transfusion burden prior to treatment, a decrease to zero RBC transfusions for a period >1 year represents relief from iron overload and other transfusion-associated complications, and decreased demand on health care resources."

Clinical • P2 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • SF3B1 • TERT • TMB

Real-World Outcomes of Imetelstat: Interrogating Safety, Efficacy, and Predictors of Response in Heavily Pretreated Lower-Risk Patients With MDS (SOHO 2026) - "Imetelstat was used as later line of therapy (median, third line); 35 patients (87.5%) had prior luspatercept, 28 patients (70%) had prior ESA, 15 patients (37.5%) had prior HMA, and 17 patients (42.5%) had prior lenalidomide. Real-world experience confirms safety and clinical efficacy of imetelstat in LR-MDS, including patients with extensive prior therapies and luspatercept failure. We report novel predictors of response, including baseline platelet count and ASXL1 mutation. ASXL1: ASXL transcriptional regulator 1, AUC: area under the curve, EPO: erythropoietin, ESA: erythropoiesis-stimulating agent, G-CSF: granulocyte-colony stimulating factor, Hb: hemoglobin, HMA: hypomethylating agent, IPSS-M: International Prognostic Scoring System-Molecular, IPSS-R: International Prognostic Scoring System-Revised, MDS: myelodysplastic syndromes, OR: odds ratio, OS: overall survival, RBC: red blood cell, RBC-TI: red blood cell–transfusion independence, SF3B1: splicing factor 3b..."

Clinical • Real-world • Real-world evidence • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • ASXL1 • SF3B1 • TET2

Preliminary safety and efficacy of oral azacitidine (Oral-AZA) in patients (pts) with low-/Intermediate (Int)-risk myelodysplastic syndromes (MDS): Phase 2 results from the ASTREON trial. (ASCO 2024) - P2/3 | "Most pts (42/47 [89.4%]) had prior MDS tx, including but not limited to erythropoiesis-stimulating agents, lenalidomide, luspatercept, and imetelstat. The safety of Oral-AZA 200 mg and 300 mg was consistent with the known Oral-AZA safety profile. Preliminary efficacy data support continued evaluation of Oral-AZA in LR-MDS."

Clinical • P2 data • Acute Myelogenous Leukemia • Anemia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

From Pancytopenia to Remission: Successful IL-23 Inhibition for Crohn's Disease Associated With Myelodysplastic Syndrome After Vedolizumab Failure and Anti-TNF Immunogenicity (ACG 2026) - "We present a case of newly diagnosed CD in a patient with MDS who demonstrated vedolizumab failure, secondary loss of response to infliximab due to immunogenicity, and subsequent clinical improvement with risankizumab. Case Description/ An 80-year-old male with MDS previously on imetelstat and a history of small bowel obstruction presented with diarrhea, fevers, and abdominal pain...Figure: Fig 1. Mural thickening of the distal sigmoid colon/rectum with concern for proctocolitis in an acute flare of active Crohn's Disease despite biologic therapy."

Clinical • Colorectal Cancer • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immunology • Inflammation • Inflammatory Bowel Disease • Myelodysplastic Syndrome • IL23A

Effect of Prior Treatments on the Clinical Activity of Imetelstat in Transfusion-Dependent Patients with Erythropoiesis-Stimulating Agent, Relapsed or Refractory/Ineligible Lower-Risk Myelodysplastic Syndromes (ASH 2024) - P2/3 | "Prior lenalidomide (LEN) and prior hypomethylating agent (HMA) use were exclusion criteria in phase 3 only. In this analysis, IME-treated patients (N=226) were pooled from phase 2, phase 3, and the QTc study of IMerge and analyzed on the basis of prior treatment as follows : ± ESA, luspatercept (LUSP), LEN, and HMA...Conclusions : Patients who were ESA-ineligible or who had prior treatment with LUSP, LEN, or HMA in IMerge experienced clinical benefit from IME treatment, though the number of patients was small. Given the evolving therapeutic landscape for LR-MDS and the limited data available on outcomes in later lines of treatment, these results have important clinical implications, suggesting that IME demonstrates clinical activity regardless of prior therapies."

Clinical • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

CONTINUOUS TRANFUSION INDEPENDENCE WITH IMETELSTAT IN HEAVILY TRANSFUSED NON-DEL(5Q) LOWER-RISK MYELODYSPLASTIC SYNDROMES RELAPSED/REFRACTORY TO ERYTHROPOIESIS STIMULATING AGENTS IN IMERGE PHASE 3 (EHA 2023) - P2/3 | "In IMerge Phase 2 (NCT02598661), treatment with imetelstat, a telomerase inhibitor, resulted in prolonged, durable transfusion independence (TI) across a broad range of heavily RBC TD ESA relapsed/refractory non-del(5q) LR-MDS patients (pts) naive to lenalidomide and hypomethylating agents (len/HMA). Imetelstat demonstrated statistically significant and clinically meaningful efficacy with robust 8-wk, 24-wk, and 1-yr TI rates and durable continuous TI. For this LR-MDS patient population, almost one fifth of imetelstat-treated pts achieved continuous TI for ≥1 yr, representing substantial relief from transfusion- associated complications. VAF reduction and its correlation to clinical endpoints, including durable TI, supportimetelstat's disease-modifying potential."

P3 data • Tumor mutational burden • Hematological Disorders • Hematological Malignancies • Infectious Disease • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • ASXL1 • DNMT3A • SF3B1 • TET2 • TMB

Closing the disease modification gap: Emerging therapies in myelofibrosis beyond JAK inhibition. (PubMed, Semin Hematol) - "We discuss BET inhibitors (pelabresib), PIM kinase inhibitors (TP-3654), telomerase inhibition (imetelstat), nuclear export inhibition (selinexor), LSD1 inhibition (bomedemstat), MDM2 antagonism (navtemadlin), mutant CALR-directed immunotherapies, and activin receptor ligand traps (elritercept). Strategies such as high-molecular-risk mutation profiling and variant allele frequency monitoring to assess disease progression and clonal burden will also be discussed. As the focus of MPN management shifts towards curative nontransplant options, a combination of improved access to clinical trials and accounting for patient-reported outcomes will be vital if we are to realize the promise of these next-generation therapies."

IO biomarker • Journal • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Transplantation • CALR

Improvement of Patient‑Reported Fatigue in IMerge Phase 3 Trial of Imetelstat vs Placebo in Heavily Transfused Non‑Del(5q) Lower‑Risk Myelodysplastic Syndromes Relapsed/Refractory/Ineligible for Erythropoiesis‑Stimulating Agents (SOHO 2023) - P2/3 | "Patients: Consenting patients with heavily red blood cell transfusion-dependent (TD) non-del(5q) LR-MDS ineligible for or relapsed/refractory to erythropoiesis- stimulating agents and naïve to lenalidomide/hypomethylating agents. Unlike other available treatments, imetelstat did not worsen fatigue in a heavily TD non-del(5q) LR- MDS population but showed an improvement in fatigue in patients with a transfusion burden of ≥4 units. Author Contributions: MAS/VS and AMZ/UP contributed equally."

Clinical • P3 data • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

IMerge: Results from a phase 3, randomized, double-blind, placebo-controlled study of imetelstat in patients (pts) with heavily transfusion dependent (TD) non-del(5q) lower-risk myelodysplastic syndromes (LR-MDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESA). (ASCO 2023) - P2/3 | "In P2 of the IMerge study (NCT02598661), heavily RBC TD ESA R/R non-del(5q) LR-MDS pts naive to lenalidomide and hypomethylating agents (len/HMA) treated with imetelstat, a telomerase inhibitor, achieved durable and continuous transfusion independence (TI). For this LR-MDS pt population, imetelstat demonstrated statistically significant and clinically meaningful efficacy with high 8- and 24-wk TI rates, prolonged TI duration and increased hemoglobin. VAF reduction and its correlation to clinical endpoints support imetelstat’s disease-modifying potential. Safety results were consistent with prior reported experience."

Clinical • P3 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • ASXL1 • DNMT3A • SF3B1 • TET2

Correlation between treatment-emergent cytopenias and clinical response with imetelstat (IME) in patients (Pts) with lower-risk myelodysplastic syndromes (LR-MDS): Analysis from the imerge Trial (ASH 2025) - P2/3 | "Introduction: IME is a first-in-class, direct, and competitive telomerase inhibitor approved for thetreatment (tx) of certain adult pts with LR-MDS with red blood cell (RBC) transfusion-dependent anemiawho are relapsed or refractory to/ineligible for erythropoiesis-stimulating agents. In this post hoc analysis, pts with ≥75% NEUT or ≥50% PLT reductions in the first 2 cycles ofIME tx were more likely to have greater Hb increases from pre-tx or to achieve an HI-E response. Thegreater Hb increase from pre-tx emerged as a main driver for achieving ≥8-wk and ≥24-wk RBC-TIresponses. Collectively, these data suggest that tx-emergent cytopenias with IME may be associated withpotential for clinical benefit, similar to lenalidomide in del5q MDS."

Clinical • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Neutropenia • Thrombocytopenia

Efficacy of Imetelstat in Achieving Red Blood Cell Transfusion Independence (RBC-TI) across Different Risk Subgroups in Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory (R/R) to Erythropoiesis-Stimulating Agents (ESAs) in IMerge Phase 3 Study (ASH 2023) - P2/3 | "Improvement in RBC-TI rates was observed in patients treated with imetelstat vs placebo across different risk subgroups as defined by IPSS, IPSS-R, IPSS-R cytogenetic, or IPSS-M risk profiles. Notably, placebo had not achieved durable (≥24-week and ≥1-year) TI response in the higher-risk groups irrespective of the risk classification assessment model used, while TI response rates with imetelstat in higher-risk subgroups with poor prognosis were similar to TI response rates in lower-risk subgroups of heavily transfused R/R ESA LR-MDS, indicating that clinical efficacy of imetelstat is independent of risk categories."

Clinical • P3 data • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Modulation of the clonal burden in patients with lower-risk myelodysplastic neoplasms treated with imetelstat. (PubMed, Leukemia) - P2/3 | "Lastly, 60% of patients with ≥1-year RBC-TI had ≥50% reduction in telomerase activity/human telomerase reverse transcriptase RNA. These results suggest that imetelstat targets clonal progenitor cells and may modify LR-MDS biology."

Journal • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • ASXL1 • DNMT3A • SF3B1 • TERT • TET2

Myelodysplastic Syndrome With SF3B1 Mutation Hidden Behind Anemia of Chronic Kidney Disease: A Diagnostic Odyssey in a Transfusion-Dependent Patient (SOHO 2026) - "Timely molecular characterization is essential to connect patients with disease-modifying therapies when you consider that luspatercept achieved 59% transfusion independence in the COMMANDS trial (vs 31% epoetin alfa), imetelstat demonstrated clonal burden reduction in the IMerge trial, and IPSSM enables precision risk stratification. This case advocates for incorporating bone marrow biopsy with next-generation sequencing into the diagnostic algorithm for ESRD patients with unexplained transfusion dependence in the era of precision hematology. CABG/PCI: coronary artery bypass grafting/percutaneous coronary intervention, CAD: coronary artery disease, COPD: chronic obstructive pulmonary disease, DNMT3A: DNA methyltransferase 3 alpha, ESRD: end-stage renal disease, FFP: fresh frozen plasma, GI: gastrointestinal, HFmrEF: heart failure with mildly reduced ejection fraction, IPSS-M: International Prognostic Scoring System-Molecular, IWG-PM: International Working Group for..."

Clinical • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • DNMT3A • PPM1D • SF3B1

Correlation Among IL-8, TNF-α, and Overall Survival in Imetelstat-Treated Patients With Myelofibrosis Relapsed or Refractory to a Janus Kinase Inhibitor in the IMbark Trial (SOHO 2026) - P2 | "Imetelstat induced dose-dependent reductions from IL-8 and TNF-α baseline levels, corresponding with TSS reduction and SVR. Furthermore, 8.9 versus 4.4 mg/kg imetelstat showed longer OS in patients with higher baseline IL-8 and TNF-α levels, although numbers were small. Collectively, these data suggest potential disease-modifying activity in myelofibrosis."

Clinical • Myelofibrosis • Oncology • CXCL8 • TNFA

Clinical outcomes and safety in patients with lower-risk myelodysplastic syndromes treated with imetelstat: Substudy of the phase 3 IMerge trial. (PubMed, Br J Haematol) - No abstract available

Clinical data • Journal • P3 data • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Real-World Outcomes With Early Adoption of Imetelstat in Patients With Transfusion-Dependent Myelodysplastic Syndromes: Insights From a United States Community Oncology Chart Review (SOHO 2026) - "Imetelstat demonstrated clinically meaningful hemoglobin improvements despite short treatment duration and later-line use during the initial adoption period. Findings support a treatment effect while highlighting implementation gaps, including suboptimal LOT selection, inconsistent transfusion documentation, and limited familiarity with proactive cytopenia management. Earlier use and optimized cytopenia management may improve real-world outcomes."

Clinical • Real-world • Real-world evidence • Review • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Overall survival and long-term outcomes from the randomized, double-blind, placebo-controlled, phase III IMerge trial of imetelstat for lower-risk myelodysplastic syndromes. (PubMed, Haematologica) - "Not available."

Clinical • Journal • P3 data • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Imetelstat improves patient-reported outcomes and quality of life in lower-risk myelodysplastic syndromes: results from the phase III IMerge study. (PubMed, Haematologica) - P2/3 | "Fewer imetelstat-treated patients experienced deterioration in fatigue and more imetelstat-treated patients experienced sustained improvement in fatigue and QOL versus placebo. In the imetelstat group, 8-week, 24-week, and 1-year RBC-TI responders had sustained improvements in predefined significance thresholds versus nonresponders for fatigue (70%, 73%, and 88%, respectively, vs. 37%, 41%, and 44%, respectively; P."

HEOR • Journal • P3 data • Fatigue • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

IMproveMF: A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of Imetelstat in Combination With Ruxolitinib in Participants With Myelofibrosis (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Geron Corporation | Recruiting ➔ Active, not recruiting

Enrollment closed • Myelofibrosis

Geron Corporation Reports Second Quarter 2026 Financial Results and Recent Business Highlights (GlobeNewswire) - "Reported RYTELO net product revenue of $57.5 million in the second quarter of 2026: Grew RYTELO demand by 5% in the second quarter 2026, compared to the first quarter 2026; Increased ordering accounts by roughly 8% in the second quarter 2026 to approximately 1,575."

Sales • Myelodysplastic Syndrome