Rytelo (imetelstat) / Geron - LARVOL DELTA

Outcomes with imetelstat in myelofibrosis: A systematic review and meta-analysis. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Retrospective data • Review • Myelofibrosis

Efficacy and safety of imetelstat in transfusion-dependent lower-risk myelodysplastic syndromes: A systematic review and meta-analysis. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Retrospective data • Review • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

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 | "Clinical Trial Registration Number: NCT05371964 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • P1 data • Myelofibrosis

IMpactMF, randomized, open-label, phase 3 trial of imetelstat (IME) versus best available therapy (BAT) in patients (pts) with intermediate-2 (INT-2) or high-risk (HR) myelofibrosis (MF) relapsed or refractory (R/R) to Janus kinase inhibitors (JAKi). (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT04576156 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • P3 data • Myelofibrosis

Effect of prior treatment (tx) on the clinical activity of imetelstat (IME) in transfusion-dependent (TD) patients (pts) with erythropoiesis-stimulating agent (ESA), relapsed or refractory (R/R)/ineligible lower-risk myelodysplastic syndromes (LR-MDS). (ASCO 2025) - P2/3 | "Clinical Trial Registration Number: NCT02598661 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Infusion-Related Reactions (IRR) and Management in Patients With Red Blood Cell (RBC) Transfusion-Dependent (TD) Relapsed or Refractory Lower-Risk Myelodysplastic Syndromes (LR-MDS) Treated With Imetelstat From the IMerge Phase 3 Trial (ONS 2025) - P2/3 | "The most common premedication antihistamines and corticosteroids were dexchlorpheniramine, diphenhydramine, and chlorphenamine and hydrocortisone, dexamethasone, and methylprednisolone, respectively. Any-gr IRRs occurred in 9 (7.6%) imetelstat-treated patients and 2 (3.4%) placebo recipients (both gr1). Majority of IRRs with imetelstat were gr1-2 (77.8%) without any gr4 IRR observed."

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

Accurate prediction of clinical immunotoxicity of oligonucleotide therapeutics using ex vivo circulating fresh human whole blood test system (AACR 2025) - "Additionally, imetelstat caused a decreasing trend with platelet counts, which correlates with its clinical manifestations of thrombocytopenia. Taken together, the data show that our ex vivo circulating whole blood test system has the potential to predict human immunotoxicity responses to ONDs before FIH trials."

IO biomarker • Preclinical • Oncology • CXCL8 • IL6 • TNFA

Discovery and preclinical characterization of novel TCR-mimetic T-cell engagers targeting TERT peptide-HLA complex for the treatment of solid and hematologic malignancies (AACR 2025) - "Although several TERT-targeting approaches are being investigated in clinical trials, only one therapeutic (RYTELO®, imetelstat) has received FDA approval for the treatment of low-risk myelodysplastic syndrome...Here we report the preclinical characterization of potent and specific TCRm-based TCEs targeting TERT540 pHLA...Comprehensive analytical and biophysical assessments revealed favorable developability profiles for both TCEs. In summary, these data provide strong preclinical evidence of potency, specificity, safety, and developability of novel, TCRm-based TCEs for TERT-targeted cancer therapy."

Preclinical • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Ovarian Cancer • Solid Tumor • CD34 • HLA-A • IFNG • TERT

Rytelo: Expiry of patents related to methods of treatment in US in Mar 2033 and EU in Nov 2033 (Geron Corporation) - Annual Report 2024: Expiry of patents related to composition-of-matter in US in Dec 2025

Patent • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Managing Myelofibrosis: Matching Advances in Treatments With Clinical Unmet Needs. (PubMed, Hematol Oncol) - "The janus kinase inhibitor (JAKi) ruxolitinib has been the mainstay of treatment for over a decade...Other JAKi (pacritinib, momelotinib, jaktinib) address treatment-related cytopenia, expanding the therapeutic utility of this class of agents to patients with baseline anemia or thrombocytopenia. Novel candidates exploit multiple molecular pathways, and offer the potential to improve the management of MF-associated cytopenia (imetelstat, pelabresib, navitoclax, selinexor, luspatercept, sotatercept, elritercept, LCL161, bomedemstat) and recover bone marrow fibrosis (imetelstat, pelabresib, navitoclax and bomedemstat). It remains to be seen if these newer agents can induce any remission in MF and enable patients to come off therapy, but the future is beginning to look much brighter."

Journal • Review • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia

AMLM27/ IMpress_001: A phase II study evaluating the efficacy and safety of Imetelstat in Patients with high-risk (HR) myelodysplastic syndromes (MDS) or Acute Myeloid Leukaemia (AML) failing HMA-based therapy. (ANZCTR) - P2 | N=6 | Active, not recruiting | Sponsor: Australasian Leukaemia & Lymphoma Group

New P2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • FLT3 • IDH1

2024 FDA TIDES (Peptides and Oligonucleotides) Harvest. (PubMed, Pharmaceuticals (Basel)) - "Interestingly, among the strategies employed in recent approvals to enhance stability and/or delivery, the prodrug approach, exemplified by palopegteriparatide and pegulicianine, is emerging as a more targeted and precise therapeutic strategy. Additionally, the Enhanced Stabilization Chemistry (ESC)-GalNAc platform has been expanded for hepatic delivery of a new oligonucleotide drug, olezarsen. Furthermore, novel modifications to the ribose moiety in oligonucleotides, such as the 3'-amino substitution in imetelstat, enhance their stability. This review examines the TIDES approved in 2024 based on their chemical structure, medical targets, modes of action, administration routes, and common adverse effects. In addition, it highlights how the prodrug strategy has improved targeting efficiency and extended the half-lives of the active drugs."

Journal • Review • Developmental Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Movement Disorders

Low-risk MDS-A spotlight on precision medicine for SF3B1-mutated patients. (PubMed, Hemasphere) - "Novel agents such as Luspatercept and Imetelstat have shown promise, but their availability remains restricted and their long-term efficacy is to be investigated. Emerging strategies targeting metabolic mis-splicing (e.g., COASY) with vitamin B5, pyruvate kinase activators, and inhibitors of oncogenic pathways like MYC and BCL-2 represent potential future avenues for treatment, but their clinical utility remains to be fully explored. The current limitations in treatment underscore the urgency of developing novel, more effective therapies for patients with SF3B1-mutated MDS."

IO biomarker • Journal • Review • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • BCL2 • SF3B1

205: Updates in the Management of Myelodysplastic Syndrome (HOPA 2025) - "Describe the pathophysiology, diagnosis, and risk stratification of MDS2. Summarize the management strategies for low-, intermediate-, and high-risk MDS and review the safety profile and monitoring for ivosidenib and imetelstat"

Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • IDH1

Imetelstat in myeloid malignancies: current data and future directions. (PubMed, Expert Rev Anticancer Ther) - "Monitoring real-world outcomes will offer valuable insights into imetelstat's safety and efficacy in patient populations underrepresented in clinical trials. Imetelstat's role in other malignancies, especially myelofibrosis, is being explored."

Journal • Review • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Leukopenia • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia • Thrombocytosis

Rytelo: Initial data from Part 2 of P1 IMproveMF trial (NCT02598661) for myelofibrosis in 2026 (Geron Corporation) - Q4 & FY2024 Results

P1 data • Hematological Malignancies • Myelofibrosis • Oncology

IMpress: Study to Evaluate Imetelstat in Patients With High-Risk MDS or AML Failing HMA-based Therapy (clinicaltrials.gov) - P2 | N=46 | Active, not recruiting | Sponsor: GCP-Service International West GmbH | Trial primary completion date: Feb 2025 ➔ Sep 2025

Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

IMpactMF: A Study Comparing Imetelstat Versus Best Available Therapy for the Treatment of Intermediate-2 or High-risk Myelofibrosis (MF) Who Have Not Responded to Janus Kinase (JAK)-Inhibitor Treatment (clinicaltrials.gov) - P3 | N=320 | Recruiting | Sponsor: Geron Corporation | Trial completion date: Nov 2026 ➔ Jun 2028 | Trial primary completion date: Nov 2026 ➔ Jun 2028

Trial completion date • Trial primary completion date • Myelofibrosis

Imetelstat: “The committee was reminded of the status of this application and its remaining outstanding issues. The committee adopted a list of outstanding issues with a specific timetable”; Myelodysplastic syndrome (European Medicines Agency) - CHMP Final Minutes of the meeting on 14- 17 Oct 2024

CHMP • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Geron Announces European Commission Approval of RYTELO (imetelstat), a First-in-Class Telomerase Inhibitor, for the Treatment of Adults With Transfusion-Dependent Anemia Due to Lower-Risk MDS (Businesswire) - "Geron Corporation...announced that the European Commission (EC) has granted marketing authorization for RYTELO (imetelstat) as a monotherapy for the treatment of adult patients with transfusion-dependent (TD) anemia due to very low, low or intermediate risk myelodysplastic syndromes (lower-risk MDS or LR-MDS) without an isolated deletion 5q cytogenetic (non-del 5q) abnormality and who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy (ESAs)....The marketing authorization of RYTELO approved by the EC is supported by data from the IMerge Phase 3 clinical trial, which demonstrated the significant clinical benefit of RYTELO in patients with transfusion-dependent anemia due to LR-MDS....Patent exclusivity in the EU for LR-MDS is anticipated into 2038, subject to approval of patent term extension by the European Patent Office."

EMA approval • Patent • Anemia • Myelodysplastic Syndrome

Emerging Pathogenetic Mechanisms and New Drugs for Anemia in Myelofibrosis and Myelodysplastic Syndromes. (PubMed, Am J Hematol) - "These include TGF-β ligand traps (luspatercept, elritercept), activin A receptor type 1 (ACVR1)/activin receptor-like kinase 2 (ALK2) inhibitors (momelotinib, zilurgisertib), and anti-hemojuvelin antibody-based therapies (DISC-0974). Luspatercept and momelotinib are approved for anemia related to lower-risk MDS and MF, respectively, and represent an important addition to the treatment armamentarium, along with imetelstat, a telomerase inhibitor, recently ratified for anemia in lower-risk MDS. A promising strategy to overcome the limitations of existing anemia-directed therapies includes the use of drug combinations with complementary mechanisms (luspatercept + erythropoiesis stimulating agents, luspatercept + momelotinib, DISC-0974 + momelotinib), and harnessing the erythropoietic potential of sodium-glucose co-transporter-2 inhibitors (SGLT-2I). Future research should address the complex pathophysiology of anemia, standardize definitions for anemia with gender-specified..."

Journal • Review • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Oncology • ACVR1 • SMAD2 • SMAD4 • TGFB1

Geron stock plunges 30% amid Rytelo sales concerns (update) (MSN News) - "Shares of Geron...plunged 30% Wednesday after management reportedly indicated on the company's Q4 earnings call that sales of its lead drug Rytelo appear to be slowing. For Q4, Geron...reported a non-GAAP loss of $0.04 per share on revenue of $47.5M. Analysts, on average, were expecting a non-GAAP loss of $0.02 per share on revenue of $45.3....Sales of Rytelo, which was approved by the FDA in June 2024, rose to $47.5M in Q4 from $28.2M in Q3. The drug is used to treat myelodysplastic syndromes. During the company's earnings call early Wednesday, management reportedly said they had observed flattening revenue trends for Rytelo."

Sales • Stock price • Myelodysplastic Syndrome

Novel drugs approved by the EMA, the FDA and the MHRA in 2024: A year in review. (PubMed, Br J Pharmacol) - "Some notable examples are the first drug successfully using a 'dock-and-block' mechanism of inhibition (zenocutuzumab), the first approved drug for schizophrenia designed as an agonist of M1/M4 muscarinic receptors (xanomeline), the first biparatopic antibody (zanidatamab), binding two distinct epitopes of the same molecule, the first haemophilia therapy that instead of relying on external supplementation of clotting factors, restores Factor Xa activity by inhibiting TFPI (marstacimab), or the first ever authorised direct telomerase inhibitor (imetelstat) that reprogrammes the oncogenic drive of tumour cells. In addition, an impressive percentage of novel drugs were first in class (28 out of 53 or 53% of the total) and a substantial number can be considered disease agnostic, indicating the possibility of future approved extensions of their use for additional indications. The 2024 harvest demonstrates the therapeutic potential of innovative pharmacological design,..."

European regulatory • FDA event • Journal • Review • CNS Disorders • Hematological Disorders • Hemophilia • Oncology • Psychiatry • Rare Diseases • Schizophrenia

Geron Corporation Reports Fourth Quarter and Full Year 2024 Financial Results and Recent Business Highlights (Businesswire) - "Recent Business Highlights: Continued execution on U.S. commercial launch, with net product revenue for RYTELO (imetelstat) of $47.5 million in the fourth quarter of 2024 and $76.5 million since launch at the end of June 2024, following approval by the U.S. Food and Drug Administration (FDA). Received positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) in December 2024 recommending approval of RYTELO for the treatment of certain adult patients with transfusion-dependent anemia due to lower-risk MDS. Subject to receiving regulatory approval, which is expected in the first half of 2025, Geron is preparing to commercialize RYTELO in select EU countries in 2026."

EMA approval • Launch Europe • Sales • Myelodysplastic Syndrome

Geron Corporation Reports Fourth Quarter and Full Year 2024 Financial Results and Recent Business Highlights (Businesswire) - "Achieved approximately 80% enrollment in the Phase 3 IMpactMF trial evaluating imetelstat in patients with relapsed/refractory myelofibrosis (R/R MF). Based on our current planning assumptions for enrollment and event (death) rates in the trial, we now expect the interim analysis for overall survival may occur in the second half of 2026 (when approximately 35% of planned enrolled patients have died) and the final analysis may occur in the second half of 2028 (when approximately 50% of planned enrolled patients have died)."

Enrollment status • P3 data • Myelodysplastic Syndrome