Geron Reports Presentations at American Society of Hematology Annual Meeting
“The posters for this year’s ASH Meeting highlight our ongoing Phase 3 development of imetelstat in lower risk MDS and refractory MF, as well as exploratory work in new indications to maximize the potential value of imetelstat,” said Aleksandra Rizo, M.D., Ph.D., Geron’s Chief Medical Officer. “We believe the unique telomerase inhibition MOA of imetelstat has the potential to transform the standard of care in hematologic malignancies.”
Lower Risk Myelodysplastic Syndromes (MDS)
Abstract Title: On-Target Activity of Imetelstat Correlates with Clinical Benefits, Including Overall Survival (OS), in Heavily Transfused Non-Del(5q) Lower Risk MDS (LR-MDS) Relapsed/Refractory (R/R) to Erythropoiesis Stimulating Agents (ESAs) Abstract #2598
The poster reports new analyses to assess the correlation between imetelstat’s inhibition of telomerase with the efficacy and safety data from the IMerge Phase 2 clinical trial. These correlative analyses indicating that patients who achieved optimal pharmacodynamic (PD) effect achieved higher rates of red blood cell transfusion independence (RBC-TI), longer RBC-TI and a trend toward improved overall survival. Importantly, these patients did not have higher rates of Grade 3+ neutropenia, thrombocytopenia or liver function elevations compared to patients who did not achieve optimal PD effect.
These data provide further evidence for the on-target mechanism of action (MOA) of imetelstat through telomerase inhibition and links imetelstat’s on-target activity with clinical benefits.
To confirm these and other results from IMerge Phase 2, the Company is conducting a double-blind, randomized, placebo-controlled Phase 3 clinical trial with registrational intent. The trial is designed to enroll approximately 170 transfusion dependent patients with Low or Intermediate-1 risk myelodysplastic syndromes (MDS), also referred to as lower risk MDS, who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). The primary endpoint is the rate of RBC-TI for any consecutive period of eight weeks or longer, or 8-week RBC-TI rate. Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks, or 24-week RBC-TI rate, and the rate of hematologic improvement-erythroid (HI-E), defined as a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden.
IMerge Phase 3 is fully enrolled and patient enrollment has been closed. Based on current planning assumptions, the Company expects top-line results from IMerge Phase 3 in early January 2023.
Refractory Myelofibrosis (MF)
Abstract Title: A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat Versus Best Available Therapy (BAT) in Patients with Intermediate-2 (Int-2) or High-risk Myelofibrosis (MF) Refractory to Janus Kinase Inhibitor (JAKi) Abstract #1503 Trials in Progress
IMpactMF is an open label, randomized, controlled Phase 3 clinical trial with registrational intent. The trial is planned to enroll approximately 320 patients with Intermediate-2 or High-risk myelofibrosis who are refractory to prior treatment with a JAK inhibitor, also referred to as refractory MF. Patients will be randomized to receive either imetelstat or best available therapy. The primary endpoint is overall survival (OS). Key secondary endpoints include symptom response, spleen response, progression free survival, complete response, partial response, clinical improvement, duration of response, safety, pharmacokinetics, and patient reported outcomes.
IMpactMF is currently enrolling patients. For further information about IMpactMF, including enrollment criteria, locations and current status, visit ClinicalTrials.gov/NCT04576156.
Pre-Clinical Poster – Pediatric Acute Myeloid Leukemia
Abstract Title: Imetelstat Significantly Reduces Leukemia Stem Cells in Patient-Derived Xenograft Models of Pediatric AML Abstract #3352
Acute myeloid leukemia (AML) is the deadliest malignancy in children. To improve survival in pediatric AML, novel targeted therapies and other alternative treatment methods are needed. Due to the significant unmet medical need in this disease, the use of imetelstat was evaluated to determine whether the drug 1) has anti-leukemia activity and 2) could be used as a therapeutic for pediatric AML.
The poster describes results from pre-clinical studies of imetelstat in pediatric AML cell lines (in vitro studies) and patient derived (PDX) mouse models (in vivo studies). The efficacy of imetelstat either as a single agent or in combination with chemotherapy or azacitidine was also evaluated. In cell line experiments, imetelstat treatment resulted in cell apoptosis/death of leukemia stem cells (LSCs) in a time- and dose-dependent manner and with minimal effect on normal bone marrow samples. In the in vivo studies, imetelstat treatment reduced LSC numbers and prolonged survival in mice. Observations of prolonged survival in mice were also seen when combining imetelstat with chemotherapy or azacitidine.
These data suggest imetelstat may represent an effective therapeutic strategy to target the LSC population in pediatric AML patients.
Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from Phase 2 clinical trials provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. 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 associated 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 myeloid hematologic malignancies. The Company currently is conducting two Phase 3 clinical trials: IMerge in lower risk myelodysplastic syndromes and IMpactMF in refractory myelofibrosis. 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 Company believes the unique telomerase inhibition MOA of imetelstat has the potential to transform the standard of care in hematologic malignancies; (ii) that there may be a potential link between imetelstat activity and clinical efficacy in lower risk MDS; (iii) that there is strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity; (iv) that the IMerge Phase 3 and IMpactMF clinical trials have registrational intent; (v) that the Company expects top-line results from IMerge Phase 3 in early January 2023; (vi) that there may be additional potential applications for imetelstat in hematologic malignancies; and (vii) other statements that are not historical facts, constitute forward-looking statements. These forward-looking 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 whether: (i) imetelstat demonstrates disease-modifying activity in clinical trials; (ii) regulatory authorities permit the further development of imetelstat; (iii) imetelstat demonstrates to regular authorities that it is safe and efficacious in Phase 3 clinical trials; (iv) Geron is able to expeditiously manage the delivery of the results of IMerge Phase 3 by early January 2023; and (v) any future efficacy or safety results cause the benefit-risk profile of imetelstat to become unacceptable. 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, 2021. 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.
Source: Geron Corporation