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

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

Rytelo: Expiry of patents related to methods of treatment in US in Mar 2033 and EU in Nov 2033 (Geron Corporation) - Annual Report 2025

Patent • Hematological Malignancies • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology

A MASS OF UNCERTAINTY: CANDIDA TROPICALIS ENDOCARDITIS PRESENTING AS A LEFT VENTRICULAR MASS (ACC 2026) - "Case: A 77-year-old man with Myelodysplastic Syndrome (MDS) on Imetelstat and an indwelling chemoport presented with bilateral pedal edema...Micafungin was initiated and filgrastim was started for neutropenia... Fungal endocarditis may extend beyond valves and present as an intracavitary or wall-adherent mass in immunocompromised patients with indwelling catheters, requiring high suspicion for diagnosis and management."

Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Myelodysplastic Syndrome • Neutropenia • Pneumonia • Respiratory Diseases • Thrombosis

Clinical Approach to Relapsed or Refractory Lower-Risk Myelodysplastic Syndromes (ICKSH 2026) - "In the phase 3 COMMANDS trial (ESA -naïve TD LR -MDS; IPSS -R very low/low/intermediate; sEPO <500 U/L; <5% blasts; del(5q) excluded), luspatercept significantly improved the primary endpoint (RBC -TI for ≥12 weeks with concurrent mean hemoglobin [Hb] increase ≥1.5 g/dL during weeks 1–24) versus epoetin alfa (60.4% vs 34.8%; p<0.0001). Evidence -based sequencing begins with early ESA use when appropriate, transitions to luspatercept when response is lost, but consider this agent not only in R/R cases, but also as an effective and durable first -line option (with subgroup -consistent benefit), for TD ESA -naïve LR -MDS who do not have probability to respond to ESAs and incorporates imetelstat as a potentially disease -modifying therapy in ESA -failed/ESA -ineligible and lus patercept -failed TD LR - MDS , especially if with high transfusion burden . Molecularly targeted agents and cytogenetically defined approaches (e.g., lenalidomide in del(5q) ,..."

Clinical • Cardiovascular • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Neutropenia • Thrombocytopenia • ACVR2A • IDH1 • IDH2 • SF3B1

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

Geron at TD Cowen: Strategic Growth and Market Expansion (Investing.com) - "Geron projects revenue growth for RYTELO from $184 million to $220 million-$240 million next year....Interim analysis of the phase 3 myelofibrosis trial is expected in the second half of the year."

P3 data • Sales projection • Myelofibrosis

HSP90 inhibition disrupts telomere maintenance and promotes chromosomal instability (CIN) in cancer cells. (PubMed, Res Sq) - "Methods Four HSP90 inhibitors (TAS-116, XL-888, SNX-2112, 17-AAG) were tested at each compound's cell-specific LC50 in HT1080 (linear and circular HACs) and HEK293 (linear HAC) cells, with GRN163L as a positive control. Conclusions TAS-116 consistently disrupts telomere maintenance-driving linear HAC loss, telomere shortening, reduced FISH signal, elevated TIFs, and increased MNi-thereby validating the HAC-based framework for discriminating telomere-directed activity. These findings support the therapeutic promise of HSP90 inhibition against telomere maintenance in cancer."

Journal • Oncology • CDC37 • HSP90AA1 • TERF2

The patient voice: measuring what matters in lower-risk myelodysplastic syndromes treated with imetelstat. (PubMed, Haematologica) - "Not available."

Journal • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Geron Corporation Reports Fourth Quarter and Full Year 2025 Financial Results and Recent Business Highlights (GlobeNewswire) - "Achieved RYTELO net product revenue of $48.0 million in the fourth quarter of 2025, and $183.6 million in full year 2025. Grew RYTELO demand by 9% in the fourth quarter 2025 compared to the third quarter 2025. Increased ordering accounts by 150 in the fourth quarter 2025 to approximately 1,300."

Commercial • Sales • Myelodysplastic Syndrome

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

A prospective, single-center, single-arm study to evaluate the efficacy and safety of imetelstat in adults with severe alopecia areata refractory to systemic therapy. (ChiCTR) - P=N/A | N=32 | Not yet recruiting | Sponsor: Affiliated Hospital of Guilin Medical University; Affiliated Hospital of Guilin Medical University

New trial • Alopecia • Dermatology • Immunology

Sequential treatment with ruxolitinib and imetelstat effectively depletes myelofibrosis hematopoietic stem and progenitor cells. (PubMed, Leukemia) - No abstract available

Journal • Myelofibrosis

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

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

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

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

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

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

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

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

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

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

Geron Corporation Provides 2026 Financial Guidance (GlobeNewswire) - "RYTELO net product revenue expected in the range of $220 million to $240 million; Total operating expenses expected in the range of $230 million to $240 million."

Sales projection • Myelodysplastic Syndrome

Efficacy of novel agents in the treatment of acute myeloid leukemia and myelodysplastic syndrome: A systematic review and meta-analysis (ASH 2025) - "Newer agents included for AML were Guadectiabine, Magrolimab, Alvocidib, Enasidenib, Flotetuzumab, Vadastuximab, Mitoxantrone, Pevonedistat, Entospletinib, Eprenetapopt, Belinostat, Onvansertib, Panobinostat, Cediranib Maleate, Nilotinib, Emavusertib, and anti-CD45 antibody (DOTA-BC8). The newer agents investigated for MDS included Rigosertib, Imetelstat, Pembrolizumab, Enasidenib, Sabatolimab, Ivosidenib, Elitercept, Pevonedistat, Emavusertib, Atezolizumab, and Olutasidenib...All patients were treated concomitantly with either azacitidine (77%) or decitabine (23%)... This meta-analysis and systematic review demonstrate promising efficacy for novel agents in AML and MDS patients. There is a need for prospective trials with larger patient populations to investigate these agents further."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • TP53