Geron Reports Ten Imetelstat Presentations at American Society of Hematology Annual Meeting - Seite 2

Relapsed/Refractory Myelofibrosis (MF) – Three Oral Presentations

Title: Potential Disease-Modifying Activity of Imetelstat Demonstrated By Reduction in Cytogenetically Abnormal Clones and Mutation Burden Leads to Clinical Benefits in Relapsed/Refractory Myelofibrosis Patients (Abstract #346)

This oral presentation reported significant dose-dependent reduction of mutation burden by imetelstat, including complete elimination of mutations in MF driver and non-driver genes. A greater than 20% reduction in variant allele frequency by imetelstat treatment correlated with improved clinical benefits, including higher rates of spleen and symptom responses, bone marrow fibrosis improvement and longer overall survival (OS). As concluded in the presentation, imetelstat demonstrated disease-modifying activity by targeting malignant clones, improvement in bone marrow fibrosis and OS.

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 #347)

This oral presentation reported dose-dependent inhibition of telomerase, as evaluated by reductions in telomerase activity, human reverse transcriptase (hTERT) levels and telomere length in patients treated with imetelstat in the IMbark Phase 2 clinical trial. Analyses of these biomarker data correlated with clinical responses and longer OS. In addition, dose-dependent reduction in variant allele frequency of driver mutations was noted, indicating that imetelstat has disease-modifying activity by targeting the underlying MF malignant clones. As expected for a telomerase inhibitor, treatment with imetelstat at 9.4 mg/kg improved clinical outcomes in patients with shorter telomeres and higher hTERT expression at baseline. These data are consistent with telomere biology in cancer cells and provide evidence for on-target mechanism of action of imetelstat through telomerase inhibition. These results were previously reported as a poster presentation at the EHA Annual Congress in June.

Title: Favorable Overall Survival with Imetelstat Treatment Correlates with Other Clinical Benefits in Intermediate-2 or High-Risk Myelofibrosis Relapsed/Refractory to Janus Kinase Inhibitor (Abstract #53)

This oral presentation reported the correlation of overall survival results from the IMbark Phase 2 with clinical benefits observed with imetelstat treatment. The correlation analyses showed a trend of longer OS in patients who achieved symptom response, spleen volume reductions ranging from > 10% to > 35%, and statistically significant improvement in OS in patients with improved bone marrow fibrosis, in a dose-dependent manner. These results were previously reported as a poster presentation at the EHA Annual Congress in June.