- Updated imetelstat data from IMerge Phase 2 describe
significant continuous durable transfusion independence, meaningful
reduction in mutational burden and progression-free survival, which
indicate disease-modifying activity
- Ongoing Phase 3 IMerge clinical trial of imetelstat designed to
confirm Phase 2 data; top-line results expected in early January
2023
- Additional ASH abstracts support the broad potential of
imetelstat in hematologic malignancies
Geron Corporation (Nasdaq: GERN), a late-stage clinical
biopharmaceutical company, today announced that four abstracts
related to imetelstat, a first-in-class telomerase inhibitor, have
been accepted for presentation at the 64th American Society of
Hematology (ASH) Annual Meeting taking place from December 10-13 in
New Orleans, Louisiana. A fifth abstract has been published on the
ASH website and will be available in Blood. These abstracts assess
the potential of imetelstat in various blood cancers, or
hematologic malignancies, including lower risk myelodysplastic
syndromes (MDS), acute myeloid leukemia (AML), myelofibrosis (MF)
and lymphoid malignancies.
“The upcoming presentation at ASH of the longer-term follow-up
data from our Phase 2 IMerge trial showing unprecedented greater
than one-year continuous transfusion independence in approximately
one-third of the 38 lower risk MDS patients in the study highlights
the differentiating qualities of imetelstat that could address
significant unmet needs in this indication,” said Faye Feller,
M.D., Executive Vice President, Chief Medical Officer of Geron. “We
look forward to reporting top-line results from the Phase 3 IMerge
trial shortly after ASH, in early January 2023.”
Dr. Feller continued: “Further, I am pleased to see other
abstracts representing our imetelstat pipeline at ASH,
demonstrating broad potential for the drug in hematologic
malignancies.”
Clinical Data – Lower Risk Myelodysplastic Syndromes
(MDS)
Abstract #459: “Imetelstat Achieved Prolonged, Continuous
Transfusion Independence in Patients With Heavily Transfused
Non-Del(5q) Lower Risk MDS (LR-MDS) Relapsed/Refractory to
Erythropoiesis Stimulating Agents Within the IMerge Phase 2
Study”
Oral Presentation on December 11, 2022, at
5pm CT
The abstract describes the 29% (11/38) of patients in Phase 2
IMerge who achieved a greater than one-year sustained transfusion
independence (TI). These transfusion dependent patients were
treated with imetelstat for a median of 126.1 weeks (range:
70.1-168.1), and their median duration of TI was 92.4 weeks (95%
CI: 69.6, 92.4). After a median follow-up of 51.5 months, median
progression-free survival (PFS) was 34.2 months (95% CI: 25.1,
39.2), median overall survival (OS) was 57.0 months (95% CI: 29.4,
NE), and none of these patients progressed to AML.
Mutation data was available for the majority of the patients who
achieved greater than 1-year sustained TI, and 89% had any
reduction in SF3B1 variant allele frequency (VAF) while 56%
achieved greater than or equal to 50% VAF reduction. Reduction in
VAF correlated with longer TI duration and shorter time to onset of
TI.
Safety findings for these patients were consistent with the
overall population, and the most frequent adverse events were
reversible thrombocytopenia and neutropenia.
The abstract concludes that the greater than one-year periods of
transfusion independence observed in these patients represents
relief from iron overload and other transfusion associated
complications, and decreased demand on healthcare resources.
Furthermore, durable TI, meaningful reduction in mutational burden,
and good survival post-ESA suggest imetelstat may have
disease-modifying activity.
Non-Clinical Data – Acute Myeloid Leukemia
Abstract #201: “Imetelstat-Mediated Alterations in Lipid
Metabolism to Induce Ferroptosis As Therapeutic Strategy for Acute
Myeloid Leukemia”
Oral Presentation on December 10, 2022, at
2:30pm CT
This abstract describes results from non-clinical in vitro and
animal in vivo experiments of imetelstat using AML cell lines and
AML patient samples. Conducted by Geron collaborators in Australia,
Germany and the U.S., the experiments found that imetelstat
promotes the formation of polyunsaturated fatty acids-containing
phospholipids which cause excessive levels of lipid peroxidation
and oxidative stress in AML cells, potentially leading to
programmed cell death. The abstract concludes that this mechanistic
insight could be leveraged to develop an optimized therapeutic
strategy using oxidative stress-inducing chemotherapy to sensitize
patient samples to imetelstat causing significant delay of relapse
in AML.
Trials in Progress Poster Presentations –
Myelofibrosis
Abstract #3037: “MYF3001: A Randomized Open Label, Phase 3 Study
to Evaluate Imetelstat Versus Best Available Therapy in Patients
with Intermediate-2 or High-Risk Myelofibrosis Relapsed/Refractory
to Janus Kinase Inhibitor”
Poster Presentation on December 11, 2022,
6-8pm CT
MYF3001, or IMpactMF (NCT04576156), is a Phase 3, randomized
(2:1), open label multicenter study of imetelstat compared with
best available therapy (BAT) in approximately 320 adult patients
with Intermediate-2 or High-Risk MF whose disease has relapsed
after or is refractory to janus associated kinase inhibitor, or
JAKi, treatment. The primary endpoint is overall survival and
secondary endpoints include symptom and spleen response rates at
Week 24, progression-free survival, clinical response assessments,
time to and duration of response, reduction in degree of bone
marrow fibrosis, safety, pharmacokinetics and patient-reported
outcomes. Biomarkers and mutation analyses will be performed to
evaluate the impact of imetelstat on reduction/depletion of
malignant clones. Approximately 180 sites are planned in North and
South America, Europe, Middle East, Australia and Asia. The study
is actively enrolling.
Abstract #1713: “An Open Label, Dose Escalation and Expansion,
Phase 1/1b Study to Evaluate the Safety, Pharmacokinetics,
Pharmacodynamics and Clinical Activity of Imetelstat in Combination
with Ruxolitinib in Patients with Intermediate-1, Intermediate-2 or
High-Risk Myelofibrosis”
Poster Presentation on December 10,
5:30-7:30pm CT
MYF1001, or IMproveMF (NCT05371964), is a single arm, open
label, two-part Phase 1 study to evaluate the safety,
pharmacokinetics, pharmacodynamics and clinical activity of
imetelstat in combination with ruxolitinib as a frontline treatment
in patients with Intermediate-1 or -2 or High-risk MF (frontline
MF). In both parts, patients will receive ruxolitinib followed by
imetelstat. Part 1 will enroll up to 20 frontline MF patients who,
at the time of enrollment, have received an optimized dose of
ruxolitinib, to which imetelstat treatment will be added at
increasing dose levels based on safety and tolerability. The
primary purpose of Part 1 is to identify a safe dose for treating
frontline MF patients with a combination of imetelstat and
ruxolitinib. If a safe dose is identified in Part 1, participants
in Part 2 will be JAK inhibitor naïve and will receive treatment
with ruxolitinib after screening and enrollment at a starting dose
based on standard-of-care or local prescribing information.
Treatment with single-agent ruxolitinib will continue for at least
12 weeks, including four consecutive weeks at a stable dose prior
to the addition of imetelstat. Part 2 is designed to confirm the
safety profile of imetelstat in combination with ruxolitinib and to
evaluate for preliminary clinical activity of the combination. Part
1 is open for enrollment, with approximately three sites planned in
North America.
Non-Clinical Data – Lymphoid Malignancies
Published online in Blood: “Pharmacological Inhibitory Effect of
Imetelstat, A Novel Human Telomerase Inhibitor in Diffuse Large
B-cell Lymphoma and Peripheral T-Cell Lymphoma”
This abstract describes the characterization of telomerase
activity and telomere length, as well as results from in vitro
experiments of imetelstat, on a panel of diffuse large B-cell
lymphoma (DLBCL) and peripheral T-cell lymphomas (PTCL) cell lines.
This work was conducted by Geron collaborators at MD Anderson
Cancer Center. These in vitro experiments found that imetelstat
reduced cell viability and increased apoptosis in DLBCL cell lines.
In contrast, imetelstat single-agent activity on cell viability was
limited in PTCL cell lines, even though a time and dose-dependent
reduction of telomerase activity were noted. The greater inhibitory
effect of imetelstat in DLBCL, compared to PTCL cell lines, may be
attributed to higher telomerase activity observed in DLBCL compared
to PTCL cells. Furthermore, the PTCL cell lines had a ~7.3 fold
longer telomere length than DLBCL cell lines, which potentially
also influenced the lower response to imetelstat.
The abstracts are available on the ASH website at
www.hematology.org.
In accordance with ASH policies, abstracts submitted to the ASH
Annual Meeting are embargoed from the time of submission. To be
eligible for presentation at the ASH Annual Meeting, any additional
data or information to be presented at the Annual Meeting may not
be made public before the presentation. The presentations and
posters will be available at www.geron.com/r-d/publications
following the ASH Annual Meeting presentations.
About Imetelstat
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.
About Geron
Geron is a late-stage biopharmaceutical company pursuing
therapies with the potential to extend and enrich the lives of
patients living with hematologic malignancies. Our first-in-class
telomerase inhibitor, imetelstat, harnesses Nobel Prize-winning
science in a treatment that may alter the underlying drivers of
disease. Geron currently has two Phase 3 pivotal clinical trials
underway evaluating imetelstat in lower risk myelodysplastic
syndromes (LR MDS), and in relapsed/refractory myelofibrosis (MF).
To learn more, visit www.geron.com or follow us on LinkedIn.
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) the potential
link between imetelstat activity and clinical efficacy in lower
risk MDS; (ii) that imetelstat may have potential disease-modifying
activity; (iii) that there may be additional potential applications
for imetelstat in hematologic malignancies; (iv) that IMerge Phase
3 results will be reported in early January 2023; (v) that
imetelstat could address significant unmet patient need in lower
risk MDS; and (vi) 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 is safe and efficacious in clinical
trials; and (iv) 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 June 30, 2022. 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20221103005211/en/
Aron Feingold Investor and Media Relations investor@geron.com
media@geron.com
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