6 years ago

Throughout 2017, ongoing treatment and follow up of patients in IMbark and IMerge, the two clinical trials of imetelstat being conducted by our partner Janssen Biotech, have added to our understanding of the potential treatment settings for the drug, setting the stage for important events to occur in 2018. In IMbark, the patient population in which imetelstat is being tested clearly needs new therapies. The Phase 2 trial is evaluating imetelstat in intermediate-2 or high-risk myelofibrosis (MF) patients who are refractory to or have relapsed after treatment with a JAK inhibitor. Only one drug, a JAK inhibitor, is currently approved for MF, and once patients fail or discontinue this treatment, median overall survival is approximately seven to 16 months. Thus, imetelstat could potentially address a significant unmet medical need if its use is associated with meaningfully longer survival. Patients who remain in the treatment phase of IMbark may continue to receive imetelstat, and to the extent possible, are being followed until death to enable an assessment of overall survival. As of the latest January 2018 data cut in which patients in both imetelstat treatment arms of the study had been followed for approximately 19 months, the median overall survival has not been reached for patients in either arm of the study. In March 2018, IMbark was officially closed to new patient enrollment and an extension phase of the trial is being established to allow continued treatment and follow-up of patients who are benefitting from imetelstat, including for survival. Based on the rate of deaths occurring in IMbark, our partner Janssen will begin the protocol-specified primary analysis of the trial, which includes an assessment of overall survival, by the end of the second quarter of 2018. After this analysis is completed, Janssen must decide whether to continue development of imetelstat (Continuation Decision). We expect Janssen to make its Continuation Decision by the end of the third quarter of 2018. Although completing the protocol-specified primary analysis of IMbark is the trigger for the Continuation Decision by Janssen, we expect data from Part 1 of IMerge, the two-part Phase 2/3 trial of imetelstat in patients with lower risk myelodysplastic syndromes (MDS) to contribute important information about imetelstat. Notably, preliminary data from the first 32 patients in the Phase 2 component of IMerge, presented in December at the American Society of Hematology annual meeting, support our hypothesis from previous clinical trials that imetelstat may have the potential to suppress the proliferation of malignant progenitor cell clones to allow the recovery of normal hematopoiesis in patients with hematologic malignancies. These preliminary data from IMerge showed that treatment with imetelstat reduced the frequency and number of transfusions needed by most lower risk MDS patients in the trial. Because the MDS patients enrolled in IMerge suffered from anemia and were heavily dependent on red blood cell transfusions, being able to become independent of transfusions for as long as possible, or reducing the frequency of their transfusions, significantly improves their quality of life. In particular, a subset of 13 patients in IMerge, who had not received prior treatment with either a hypomethylating agent or the immunomodulatory agent lenalidomide, and who did not have a chromosomal abnormality known as del(5q), exhibited an increased rate and durability of transfusion independence in comparison to the overall trial population. For example, the proportion of patients with transfusion-free periods lasting at least 8-weeks for the overall trial population of 32 patients in IMerge was 38% and for the 13-patient subset it was 54%. The proportion of patients with transfusion-free periods lasting at least 24-weeks for the overall trial population was 16% and for the 13-patient subset it was 31%. These were impressive efficacy outcomes. Based on these preliminary data, Janssen has now enrolled approximately 20 additional patients who were naïve to treatment with lenalidomide and hypomethylating agents and were not del(5q) to increase the experience and confirm the preliminary efficacy and safety of imetelstat in this refined target population of lower risk MDS patients. Enrollment of these additional patients occurred faster than anticipated, highlighting both the unmet need in this patient population and the keen interest in imetelstat among clinical investigators. We believe Janssen will need the results from these new patients before deciding whether to make a positive Continuation Decision and start the Phase 3 component of IMerge. I would like to thank our stockholders for supporting Geron over the years. We look forward to the outcomes in this important upcoming year.