Geron Provides Update on Imetelstat Trials Being Conducted by Janssen

Geron Corporation recently provided updates on the clinical trials being conducted by Janssen Research & Development, LLC, of the telomerase inhibitor imetelstat. Planned internal reviews of initial data from both trials have been completed by Janssen, and both trials are continuing in order to evaluate additional and more mature data.

IMbark (NCT02426086) was originally designed as a Phase II clinical trial to evaluate two dose levels of imetelstat (either 4.7 mg/kg or 9.4 mg/kg administered every 3 weeks) in approximately 200 patients (approximately 100 patients per dosing arm) with Intermediate-2 or High risk myelofibrosis (MF) who have relapsed after or are refractory to prior treatment with a JAK inhibitor. The co-primary efficacy endpoints for the trial are spleen response rate and symptom response rate at 24 weeks. To date, over 90 patients have been enrolled in the trial across both dosing arms.

To inform an assessment of the appropriate dose and schedule for relapsed or refractory MF patients in IMbark, Janssen conducted a planned internal interim review of safety, efficacy, and pharmacokinetic data from 20 patients from each dosing arm who have been followed on the trial for at least 12 weeks. Based on this first internal review at the early 12-week time point, the following has been determined by Janssen:

-The safety profile was consistent with previous imetelstat clinical trials in hematologic myeloid malignancies. No new safety signals were identified.

-Activity in the 4.7 mg/kg dosing arm does not warrant further investigation of that dose and this arm will be closed to new patient enrollment. An amendment to the trial protocol is planned to allow eligible patients in this arm to increase their dose to 9.4 mg/kg per investigator discretion.

-In the 9.4 mg/kg dosing arm, even though at the week 12 data assessment an insufficient number of patients met the protocol defined interim criteria, this arm warrants further investigation because encouraging trends in the efficacy data were observed. Patients already enrolled in this arm may continue to receive imetelstat. New enrollment in this arm will be suspended while the trial continues in order to obtain additional and more mature data that includes a longer follow-up of patients at 24 weeks, consistent with the co-primary efficacy endpoints. The number of patients enrolled to date is expected to be sufficient to inform potential future development of this dose.

-Janssen plans to conduct an additional internal data review in the second quarter of 2017 to include a longer follow-up of patients at 24 weeks. Potential outcomes of the second internal review at the 24-week time point could include resuming enrollment in the 9.4 mg/kg dosing arm, with or without changes to the dosing regimen; adding a new dosing arm; or closing the trial.

-Any protocol amendments will be subject to review by health authorities around the world.

IMerge (NCT02598661) is a Phase II/III clinical trial evaluating imetelstat in transfusion dependent patients with Low or Intermediate-1 risk myelodysplastic syndromes (MDS) who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). The clinical trial is in two parts: Part 1 is a Phase II, open-label, single-arm design in approximately 30 patients and Part 2 is a Phase III, randomized, double-blind, placebo-controlled design in approximately 170 patients. The primary efficacy endpoint is the rate of red blood cell transfusion-independence lasting at least 8 weeks. Part 1 of the trial is fully enrolled.

Janssen has conducted an initial internal review of efficacy, safety, and pharmacokinetic data from a subset of patients from Part 1 of IMerge, and this review indicated that emerging safety and efficacy in IMerge is consistent with data reported from the pilot study conducted at Mayo Clinic in MDS patients. IMerge will continue unmodified at this time.

Further assessment of data from IMerge is expected to occur in the second quarter of 2017 to include longer follow-up of all patients enrolled in Part 1. A decision on whether to move forward to Part 2 of IMerge will be based on an assessment of the benefit/risk profile of imetelstat in these patients. If Janssen decides to move forward with Part 2, the Phase III clinical trial is expected to be open for patient enrollment in mid-2017. Janssen expects to submit data from Part 1 of IMerge to be considered for presentation at a medical conference in the future.

Imetelstat (GRN163L; JNJ-63935937) is a potent and specific inhibitor of telomerase that is administered by intravenous infusion. This first-in-class compound, discovered by Geron, is a specially designed and modified short oligonucleotide, which targets and binds directly with high affinity to the active site of telomerase. Preliminary clinical data suggest imetelstat has disease-modifying activity by inhibiting the progenitor cells of the malignant clones associated with hematologic malignancies in a relatively select manner. Most commonly reported adverse events in imetelstat clinical studies include fatigue, gastrointestinal symptoms, and cytopenias. Patients in these studies also experienced elevated liver enzymes, which resolved to normal or baseline in the majority of patients followed after imetelstat treatment was withdrawn. Imetelstat has not been approved for marketing by any regulatory authority.

On November 13, 2014, Geron entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc., to develop and commercialize imetelstat for oncology, including hematologic myeloid malignancies, and all other human therapeutics uses. Under the terms of the agreement, Geron received an upfront payment of $35 million and is eligible to receive additional payments up to a potential total of $900 million for the achievement of development, regulatory, and commercial milestones, as well as royalties on worldwide net sales. All regulatory, development, manufacturing, and promotional activities related to imetelstat are being managed through a joint governance structure, with Janssen responsible for these activities.

Geron is a clinical-stage biopharmaceutical company focused on the collaborative development of a first-in-class telomerase inhibitor, imetelstat, in hematologic myeloid malignancies. For more information, visit www.geron.com.