Geron Corporation (Nasdaq: GERN) today announced that two posters related to imetelstat, the Company’s first-in-class telomerase inhibitor, were presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida on December 8 and 9. Both posters are available on Geron’s website at www.geron.com/r-d/publications.
Trials in Progress Poster Presentation
Title: IMerge: A Study to Evaluate Imetelstat (GRN163L) in Transfusion-Dependent Subjects with IPSS Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) That Is Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment (Abstract #4248)
The poster described key aspects of the IMerge Phase 2/3 clinical trial, including: the trial design; patient eligibility criteria; primary, secondary and exploratory endpoints; and the status of the trial. The poster also included a summary of previously presented data from the Phase 2 portion of the IMerge trial.
IMerge is an ongoing global two-part Phase 2/3 clinical trial of imetelstat in red blood cell (RBC) transfusion dependent patients with Low or Intermediate-1 risk, or lower risk myelodysplastic syndromes (MDS), who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). The primary endpoint for the IMerge Phase 2/3 clinical trial is 8-week RBC transfusion independence (TI), which is defined as the proportion of patients achieving transfusion independence during any consecutive eight weeks since entry into the trial. Key secondary endpoints include the rate of transfusion independence lasting at least 24 weeks, or 24-week TI rate, durability of transfusion independence and the amount and relative change in transfusions.
IMerge Phase 3 Trial Now Enrolling
The IMerge Phase 3 is planned to enroll approximately 170 patients in a randomized, double-blind, placebo-controlled clinical trial. The trial will enroll non-del(5q) lower risk MDS patients who are naïve to treatment with hypomethylating agents (HMAs) and lenalidomide. The primary and secondary endpoints remain the same as the Phase 2 portion of the trial. Approximately 90 sites are planned to participate in 12 countries across North America, Europe, Middle East and Asia. Enrollment opened in August 2019, and the first patient was dosed in October 2019.
To learn more about the IMerge Phase 3 clinical trial and whether the study is enrolling patients in your area, please visit www.clinicaltrials.gov (NCT02598661).
IMerge Phase 2 Data Summary
- Imetelstat treatment showed meaningful and durable transfusion independence in 38 non-del(5q) lower risk MDS patients who were naïve to HMAs and lenalidomide.
- 42% (16/38) of patients achieved ≥8-week RBC-TI
- 29% (11/38) of patients achieved ≥24-week RBC-TI
- Median duration of TI was 85.9 weeks (range: 8.0-140.9)
- 68% (26/38) of patients achieved HI-E, or improvement in red blood cell count, as measured by either transfusion reduction or a rise in hemoglobin:
- All 26 patients had a reduction of at least four RBC units over eight weeks compared with prior transfusion burden
- 12 patients had a hemoglobin increase of at least 1.5 g/dL lasting at least eight weeks
- Mean relative reduction in transfusion burden from baseline was 68%
- Transfusion independence was observed across different MDS patient subgroups.
- Biomarker data suggested potential impact on malignant clone and disease modification by imetelstat treatment.
- No new safety signals were identified. Reversible cytopenias were the most frequent adverse events.
Non-Clinical Data Poster Presentation
Title: Combination Treatment with Imetelstat, a Telomerase Inhibitor, and Ruxolitinib Depletes Myelofibrosis Hematopoietic Stem Cells and Progenitor Cells (Abstract #2963)
This poster presentation described results from early, nonclinical experiments on the potential effect of combining imetelstat and ruxolitinib on malignant myelofibrosis (MF) cells. The experiments explored the hypothesis that, due to different mechanisms of action, a combination of imetelstat and ruxolitinib might create a treatment regimen for MF that could be more efficacious than using either drug alone in reducing both malignant progenitor and stem cells. Ruxolitinib is a janus kinase (JAK) inhibitor that inhibits proliferation of malignant progenitor cells without eliminating malignant stem cells. Imetelstat is a telomerase inhibitor that selectively depletes malignant progenitor and stem cells.
In the experiments, the sequential treatment of ruxolitinib followed by imetelstat had additive inhibitory activity resulting in greater reductions in both malignant progenitor and stem cells when compared to simultaneous treatment or either drug alone. Furthermore, the sequential treatment regimen did not affect normal hematopoietic progenitor and stem cells. As stated in the poster, these non-clinical findings suggest that sequential treatment of ruxolitinib followed by imetelstat represents a potentially effective treatment that may eliminate both malignant MF progenitor and stem cells.
Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Early clinical data suggest imetelstat may have disease-modifying activity through the suppression of malignant progenitor cell clone proliferation, which allows potential recovery of normal hematopoiesis. Ongoing clinical studies of imetelstat consist of IMerge, a Phase 2/3 trial in lower risk myelodysplastic syndromes (MDS), and IMbark, a Phase 2 trial in Intermediate-2 or High-risk myelofibrosis (MF). Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis-stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus kinase (JAK) inhibitor treatment.
Geron is a late-stage clinical biopharmaceutical company focused on the development and potential commercialization of a first-in-class telomerase inhibitor, imetelstat, in hematologic myeloid malignancies. For more information about Geron, visit www.geron.com.
Use of Forward-Looking Statements
Except for the historical information contained herein, this press release contains forward-looking statements made pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such statements, include, without limitation, those regarding: (i) that the IMerge Phase 3 clinical trial is planned to enroll approximately 170 patients and is planned to be conducted at multiple medical centers globally; (ii) that recently reported Phase 2 IMerge data suggested meaningful and durable transfusion independence, potential disease-modifying activity, and transfusion independence across different MDS patient subgroups potentially achievable with imetelstat treatment; (iii) that imetelstat may have disease-modifying activity; and (iv) other statements that are not historical facts, constitute forward looking statements. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. These risks and uncertainties, include, without limitation, risks and uncertainties related to: (i) whether regulatory authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (ii) whether imetelstat is demonstrated to be safe and efficacious in clinical trials; (iii) whether any future efficacy or safety results may cause the benefit-risk profile of imetelstat to become unacceptable; (iv) whether imetelstat actually demonstrates disease-modifying activity in patients; and (v) whether imetelstat has adequate patent protection and freedom to operate. Additional information on the above risks and uncertainties and additional risks, uncertainties and factors that could cause actual results to differ materially from those in the forward-looking statements are contained in Geron’s periodic reports filed with the Securities and Exchange Commission under the heading "Risk Factors," including Geron’s quarterly report on Form 10-Q for the quarter ended September 30, 2019. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made, and the facts and assumptions underlying the forward-looking statements may change. Except as required by law, Geron disclaims any obligation to update these forward-looking statements to reflect future information, events or circumstances.