John Scarlett
Analyst · Piper Jaffray. Your line is now open
Thanks Olivia. Good morning, everyone and thank you for joining. This morning I’ll start my remarks with a summary of the results from the latest internal data review conducted by Janssen on the IMbark, and an update on the projected timing of the protocol specified primary analysis for IMbark and the subsequent potential continuation decision from Janssen. I’ll then conclude with the status of the IMerge trial including a recap of the data that was recently presented at the American Society for Hematology or ASH Annual Meeting that was in last December. As a reminder, IMbark is a Phase 2 clinical trial designed to test two doses of imetelstat 9.4 milligrams per kilogram or 4.7 milligrams per kilogram administered every three weeks in intermediate-2 two or high-risk MF patients who are refractory-2 or have relapsed after treatment with the JAK inhibitor. The planned March 2018 data review was primarily conducted to enable a protocol amendment that will allow the long-term treatment and follow up of patients in the trial including for survival. And reviewing the data which was based on January 2018 data cut, the Collaboration’s Joint Steering Committee or JSC made the following observations. First, the safety profile was consistent with prior clinical trials of imetelstat in hematologic malignancies, and no new safety signals were identified. Second, outcome measures for efficacy including spleen volume responses and reductions in total symptom score remain consistent with the prior data reviews. Third, with a median follow up of approximately 19 months as of the January 2018 data cut, the median overall survival has not been reached in either dosing arm. Following the state of review, the JSC implemented a number of actions. First the trial is being officially closed to new patient enrollment. From the first enrolled patient in September of 2015 to last patient enrolled in October of 2016, more than 100 patients have been enrolled in IMbark. This number is expected to be adequate to assess overall survival. Patients who remain in the treatment phase may continue to receive imetelstat and until the primary analysis all safety and efficacy assessments are being conducted as planned in the protocol including following patients to the extent possible until death to enable an assessment of overall survival. Second, based on the rate of deaths occurring in the trial, the JSC determined that the IMbark protocol specified primary analysis which includes an assessment of overall survival will begin by the end of the second quarter of 2018. Upon the completion of the protocol specified primary analysis, the main trial will be completed. As a third action, the JSC determined that Janssen will amend the IMbark protocol to establish an extension phase of the trial to enable patients remaining in the treatment phase to continue to receive imetelstat per investigator discretion. During the extension phase, standard data collection will primarily consist of safety information. Patients will be continued to be followed for survival. The assessment of survival is important because we believe that in new treatment that could confirm improved would represent a meaningful clinical outcome for patients who are relapsed or refractory to the only approved MF treatment today. As experience with JAK inhibitors increases both in the real world and clinical trials settings, we know that the majority of MF patients fail or stop JAK inhibitor treatment and data from recent literature and other sources suggest that the survival of these patients is limited. For example, an analysis of real world data conducted by Janssen and presented at ASH in 2016 reviewed treatment patterns and outcomes of MF patients from two U.S. medical claims data basis. This analysis suggested that once patients fail or discontinue ruxolitinib mean overall survival is approximately seven months. Three other recently published an independent papers describing outcomes of MF patients after discontinuing JAK inhibitor treatment either in the context of a clinical trial or through commercial supply estimated median overall survival of approximately 14, 15 or 16 months respectively. That imetelstat potentially could address a significant unmet medical need if its uses associated with survival that is meaningfully longer than 14 to 16 months. Moving to Janssen’s decision again, as we’ve commented previously the completion of the protocol specified primary analysis for IMbark is the trigger for the continuation decision by Janssen. Following completion of that analysis, Janssen must notify us of their decision whether to maintain the license rights and continue the development of imetelstat or the continuation decision. With the protocol specified primary analysis for IMbark expected to begin in the second quarter of 2018, we expect Janssen to make its continuation decision by the end of the third quarter of 2018. Although the completion of the protocol specified primary analysis for IMbark is the trigger for the continuation decision by Janssen, we expect data from MDS - MDS from IMerge to contribute important information about imetelstat. So let me review that data that was recently presented at ASH in December. These data support our hypothesis that imetelstat may have the potential to suppress the proliferation of malignant progenitor cell clones to allow the recovery as a normal hematopoiesis in patients with hematologic malignancies. As we’ve described previously, IMerge is the ongoing trial with imetelstat in patients with lower risk MDS syndromes being conducted by Janssen. IMerge is in two parts, Part 1 is a Phase 2 open label single arm trial administering imetelstat intravenously every four weeks at a dose of 7.5 milligrams per kilogram. Part 2 not yet initiated is designed to be a Phase 3 study that will be conducted after Part 1 is completed and is designed to confirm in a randomizing control trial the efficacy and safety of imetelstat in the patient population as well as dosing used in Part 1. To be enrolled in IMerge, all patients must have relapsed after or be refractory to treatment within ESA. In addition, patients must be dependent on red blood cell transfusions requiring at least four units of red cells during an eight week period prior to entry to trial. Among the 32 patients enrolled in IMerge, red blood cell transfusions dependency was high, the median red blood cell transfusion burdened at entry to the trial with six units per eight weeks ranging from 4 to 14 units. In lower risk MDS patients chronic anemia is a predominant clinical problem. Treatment within erythropoiesis stimulating agent or ESA such as EPO can provide an improvement in anemia but the effect is transient. As a result, many patients become dependent on frequent red blood cell transfusions to manage symptoms of anemia and fatigue. Transfusion dependency is associated with poor survival because of toxicity associated with an overloaded, as well as potential infections and allergic reactions. The ultimate goal for most trials of investigational agents and lower risk MDS is to enable patients to become transfusion independent for as long as possible. Therefore the primary endpoint for both parts of IMerge is the rate or percentage of patients who achieve red blood cell transfusion independence for at least a consecutive 8 week period. This has been a key regulatory endpoint in many disorders associated with anemia and transfusion requirements. Secondary endpoint in IMerge includes the rate of 24 week transfusion independence and the rate of hematologic improvement. Hematologic improvement is the degree to which the frequency of transfusions is reduced and increases in serum hemoglobin levels observed. In addition, various measures have the durability of these transfusion in hematologic responses to imetelstat treatment are also being assessed for IMerge. Data presented at ASH were from the first 32 patients enrolled in Part 1 of IMerge using in October 2017 data cut with a median follow-up of 66 weeks. I’ll give the results of the whole 32 patient cohorts first. 38% of these patients achieved red blood cell transfusion independence lasting for at least 8 weeks. 16% of patients did not require a transfusions for at least 24 weeks with the median duration of transfusion independence exceeding one year and sustained rises in hemoglobin by at least 1.5 grams per deciliter from pretreatment levels. These efficacy results represent clinically meaningful outcomes with a profound impact on a patient’s quality of life and provide further support of data that imetelstat exhibits potential disease modifying activity by suppressing the malignant progenitor cell clones that drive the underlying disease. It’s also worth noting that almost all patients experienced some reduction in transfusion burdened with the average relative transfusion burdened being reduced by approximately two-thirds compared to baseline levels. Also the rate of greater than eight week red blood cell transfusion independence did not differ based on the presence of ring sideroblasts indicating activity of imetelstat across different subtypes of MDS. Now in addition to the analysis of all 32 patients in Part 1, Janssen also evaluated the results of imetelstat treatment in a subset of patients would receive certain prior treatments which I would like to comment on next. So to set the stage for evaluating the results of imetelstat treatment in this subset of patients, let me first comment that in the U.S. hypomethylating agents or HMAs are approved for the treatment of both lower risk and high risk MDS patients. And the immunomodulatory agent lenalidomide is approved for the approximately 15% of lower risk MDS patients, they have a deletion the short arm of chromosome 5, the so-called del(5q) abnormality. Physicians in the U.S. particularly outside of the main academic centers use both HMAs and lenalidomide broadly in lower risk MDS because there are limited alternative treatment options available. In contrast, in Europe HMAs are not approved for lower risk MDS nor is lenalidomide approved for non- del(5q) patients. As a consequence very few if any lower risk European patients are treated with either lenalidomide or an HMA at least until other disease progresses and they can be characterized as higher risk MDS patients. The original inclusion and exclusion criteria in IMerge did not restrict the number or type of other prior MDS patients but the treatments of patient was allowed to have received before entering the trial. Among the 32 patients enrolled in Part 1 we subsequently observed that a subset of 13 patients had not received prior treatment with either in HMA or lenalidomide and also did not have a del(5q) chromosome abnormality. This 13 patient subset showed remarkably increased durability and rate of transfusion independence compared to the overall trial population. 54% of these patients achieved red blood cell transfusion independence lasting for at least eight weeks while 31% achieved an RBC transfusion independence lasting for at least 24 weeks compared to 38% and 16% respectively in the overall trial population. These were very impressive efficacy outcomes. From a safety perspective, imetelstat’s profile in Part 1 was consistent with prior clinical trials of imetelstat in hematologic malignancies and no new safety signals were identified. The adverse events were similar between the overall trial population in the 13 patient subset. The most frequently reported adverse events were cytopenias which were predictable, manageable with those reduction or delays and reversible in most cases. Cytopenias included Grade 3 and Grade 4 neutropenia and thrombocytopenia. Dose reductions or cycle delays due to adverse events were required for 59% of patients. In addition to the posted ASH in which these results were reported, these data were also discussed in detail by Dr. Azra Raza, an MDS Expert in one of the clinical investigators to IMerge during an event for investors that we hosted at the end of last year. The webcast of that event is still available on our website and if you haven’t already listened to it, I would encourage you to do so. We and Janssen believe that the results from the 13 patient subset who were naïve to lenalidomide and HMAs and who lacked the del(5q) chromosomal abnormality suggested imetelstat could offer lower risk MDS patients a much needed alternative prior to preceding to HMAs and lenalidomide treatment. Lower rates of eight week transfusion independence have been reported previously for both HMAs and lenalidomide in similar lower risk MDS patient populations. In comparison to the 54% eight week transfusion independence rate observed for imetelstat, the rate observed for HMAs was 17% and 27% was observed for lenalidomide with no better safety profiles at imetelstat. As such we expect of targeting this lower risk MDS population would not reduce the population of patients potentially eligible for imetelstat but instead sequence imetelstat ahead of HMAs and lenalidomide in the treatment paradigm. As we announced in July last year, Part 1 of IMerge was reopened to enroll approximately 20 additional patients who are non-del(5q) and naïve to HMA and lenalidomide treatment. This is intended to increase the experience and confirm the benefit risk profile of imetelstat in this refined target population. With the approximately 20 additional patients, the total number of patients in Part 1 who are representative of the refined target patient population will be approximately 30 which was the sample size originally proposed in the protocol for Part 1 on which a decision to move to Part 2 would be based. Enrollment of Roman of patients to the expanded Part 1 began in November of last year and was completed in November of this year which was faster than anticipated highlighting both the unmet need in this patient population, and interest in imetelstat among clinical investigators. So we look forward to this very important year for imetelstat and Geron. Before we open the call to questions, I will mention that our search and evaluation process to identify and evaluate oncology products programs or companies for potential acquisition continues. So with that Operator, let’s open the call to questions please.