Geron Reports Four Imetelstat Data Presentations at Virtual Edition of the European Hematology Association (EHA) Annual Congress - Seite 3

IMbark was designed as a Phase 2 clinical trial to evaluate two dosing regimens of imetelstat (either 4.7 mg/kg or 9.4 mg/kg administered by intravenous infusion every three weeks) in patients with Intermediate-2 or High-risk myelofibrosis (MF) who have relapsed after or are refractory to prior treatment with a janus kinase inhibitor (JAKi). The co-primary efficacy endpoints for IMbark were spleen response rate, defined as the proportion of patients who achieve a reduction of at least 35% in spleen volume as assessed by imaging, and symptom response rate, defined as the proportion of patients who achieve a reduction of at least 50% in Total Symptom Score (TSS), at 24 weeks. Key secondary endpoints were overall survival (OS) and safety.

Title: Telomerase Activity, Telomere Length and hTERT Expression Correlate with Clinical Outcomes in Higher-Risk Myelofibrosis (MF) Relapsed/Refractory (R/R) to Janus Kinase Inhibitor Treated with Imetelstat (Abstract #EP1098)

The conclusions of the poster are as follows:

• Imetelstat achieved dose- and exposure-dependent reduction of telomerase activity and human reverse transcriptase (hTERT) expression level, demonstrating on-target mechanism of action.
• Achieving optimal pharmacodynamic (PD) effect in patients treated with imetelstat is correlated with longer OS, as well spleen and symptom response.
• Significant dose-dependent reduction in VAF of JAK2, CALR and MPL mutations were observed, indicating that imetelstat has disease-modifying activity by targeting the underlying MF malignant clones.
• Treatment with 9.4mg/kg of imetelstat improved clinical outcomes in patients with short telomeres or high hTERT expression level at baseline. The results are consistent with telomere biology in cancer cells and provide evidence for on-target mechanism of action of imetelstat through telomerase inhibition. 
• This is the first clinical report to systematically evaluate the mechanism of action based PD effect of imetelstat, and its relationship to exposure and clinical benefits.

The poster presentation is available on Geron’s website at www.geron.com/r-d/publications.

Title: Imetelstat Treatment Results in Clinical Benefits, Including Improved Overall Survival, in Patients with Higher-Risk Triple Negative Myelofibrosis Relapsed/Refractory to Janus Kinase Inhibitors (JAKI) (Abstract #1101)

The overall conclusion of the poster is that triple negative (TN) patients who are relapsed/refractory to JAKi and treated with 9.4 mg/kg of imetelstat had better clinical outcomes and prolonged overall survival (OS) compared to non-TN patients, suggesting that imetelstat may improve the poor outcomes expected for TN patients. Additional highlights from the poster include: