Geron Announces Two Imetelstat Poster Presentations at the American Association for Cancer Research Annual Meeting

MENLO PARK, Calif., April 20, 2016 (GLOBE NEWSWIRE) -- Geron Corporation (Nasdaq:GERN) today announced two poster presentations of data from non-clinical studies of the telomerase inhibitor, imetelstat, at the 2016 American Association for Cancer Research (AACR) Annual Meeting held in New Orleans, Louisiana. The first poster presentation described results that treating acute myeloid leukemia (AML) cell lines with imetelstat enhanced the effects of agents currently used for the treatment of AML. These data extend the rationale from prior non-clinical studies for the potential use of imetelstat in hematologic myeloid malignancies, such as AML, including in combination with standard therapies. The second poster presentation described results from non-clinical studies that provide further evidence of potential on-target mechanisms of telomerase inhibition by imetelstat underlying the reduction in platelets observed in previously conducted imetelstat clinical trials.

The non-clinical studies were conducted by scientists at Janssen Research & Development, LLC and academic collaborators under the terms of the exclusive worldwide imetelstat license and collaboration agreement between Geron and Janssen Biotech, Inc. The poster presentations are available on Geron’s website at

Impact of hypomethylating agents on hTERT expression and synergistic effect in combination with imetelstat, a telomerase inhibitor, in AML cell lines

AML cells express high levels of the telomerase catalytic subunit (hTERT). The expression of hTERT may be regulated through chemical changes to DNA, known as epigenetic modifications, such as the addition of a methyl group (methylation). Non-clinical studies by various cancer biologists have suggested a correlation between hTERT overexpression and hypermethylation in some cancers. Two compounds that are currently used for the treatment of AML, decitabine and 5-azacitidine, act as hypomethylating agents by inhibiting DNA methylating enzymes. Furthermore, these compounds have been reported to also reduce hTERT expression in AML cells in addition to inhibiting cell growth.

The aim of the non-clinical study in the AACR poster was to determine whether combining hypomethylating agents and imetelstat can further inhibit AML cell viability in vitro compared with either agent alone. Combination treatment of the AML cell lines with either decitabine or 5-azacitidine followed by imetelstat, resulted in a greater reduction in cell viability or slower recovery of growth, respectively, than when a hypomethylating agent was administered alone. Similarly, when AML cell lines were treated with decitabine or 5-azacitidine followed by imetelstat, apoptosis, or cell death, increased in a dose-dependent manner.

Rusbuldt J, et al. 2016 AACR

Myelosuppression in patients treated with the telomerase inhibitor imetelstat is not mediated through activation of toll-like receptors

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns to trigger innate immune responses. For example, synthetic, single-stranded oligonucleotides with certain properties characteristic of bacteria and virus genomes activate the innate immune response through TLR9 signaling. In addition, TLR activation has been associated with lipopolysaccharide-induced thrombocytopenia in animal models.

The aim of the non-clinical study in the AACR poster was to test a recent hypothesis that the thrombocytopenia observed in patients with myeloproliferative neoplasms (MPN) treated with imetelstat might occur through off-target effects by binding to and activating TLRs, such as TLR9. Results from the study suggest that the thrombocytopenia associated with imetelstat is not likely to be driven via interactions with TLRs. First, the oligonucleotide imetelstat is shorter and lacks certain features in its sequence required to activate TLR9. Second, in an assay for TLR activity, treatment with imetelstat at clinically relevant concentrations had no stimulatory effect on the majority of TLRs tested, including TLR9. Although a small induction of TLR8 was observed in the assay, such activity was not believed to be relevant because the induction was substantially lower than the positive control used in the experiment, and TLR8 has not been reported to be associated with thrombocytopenia.

The poster also cites results from previous non-clinical studies which suggest potential on-target mechanisms of telomerase inhibition for the observed thrombocytopenia in patients treated with imetelstat. Since telomerase activity is required for the differentiation of megakaryocyte progenitors into mature platelet-producing cells, previous ex vivo studies used cells taken from MPN patients and healthy individuals to show that treatment with imetelstat decreases hTERT expression and inhibits telomerase activity, which is concurrent with blocking the terminal maturation of normal megakaryocyte precursors, reducing the number of mature megakaryocytes available to produce platelets. Other prior ex vivo studies also included in the poster showed that imetelstat selectively inhibits the proliferation of malignant megakaryocyte progenitors from patients with essential thrombocythemia compared to normal progenitors from healthy individuals, suggesting that imetelstat may regulate telomerase differently in malignant versus normal cells.

Baerlocher GM, et al. 2016 AACR

About Imetelstat

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 myeloid malignancies in a relatively select manner. Most commonly reported adverse events in imetelstat clinical studies conducted previously by Geron included fatigue, gastrointestinal symptoms and cytopenias. Patients in those studies also experienced elevated liver enzymes, which resolved to normal or baseline in the majority of patients after imetelstat treatment was withdrawn. Imetelstat has not been approved for marketing by any regulatory authority.

About the Collaboration with Janssen

On November 13, 2014, Geron entered into an exclusive worldwide license and collaboration agreement with Janssen 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. Certain regulatory, development, manufacturing and promotional activities are being managed through a joint governance structure, with Janssen responsible for these activities.

Janssen is conducting two imetelstat clinical trials: a Phase 2 clinical trial in patients with intermediate-2 and high risk myelofibrosis (MF) and a Phase 2/3 clinical trial in patients with low and intermediate-1 risk myelodysplastic syndromes (MDS). For more information about these clinical trials, please visit

About Geron

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 about Geron, visit

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 statements in this press release regarding: (i) the conduct and continuation of the current Phase 2 clinical trial in MF and Phase 2/3 clinical trial in MDS, and other potential activities under the collaboration agreement with Janssen; (ii) the safety and efficacy of imetelstat; (iii) the potential receipt by Geron of additional payments up to a potential total of $900 million for the achievement of development, regulatory and commercial milestones, and royalties from net sales of imetelstat; 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) the uncertain, time-consuming and expensive product development and regulatory process, including whether Geron and Janssen will succeed in overcoming all of the clinical safety and efficacy, technical, scientific, manufacturing and regulatory challenges in the development and commercialization of imetelstat; (ii) regulatory authorities permitting the current clinical trials to continue to proceed and potential clinical trials to begin or continue to proceed; (iii) Janssen’s ability to enroll patients in the current or any of the planned or potential clinical trials of imetelstat; (iv) the fact that Janssen may terminate the collaboration agreement for any reason; (v) whether imetelstat is safe and efficacious, and whether any future efficacy or safety results may cause the benefit-risk profile of imetelstat to become unacceptable; (vi) the fact that Geron may not receive any milestone, royalty or other payments from Janssen; (vii) the ability of Geron and Janssen to protect and maintain intellectual property rights for imetelstat; (viii) Geron’s dependence on Janssen, including the risks that if Janssen were to breach or terminate the collaboration agreement or otherwise fail to successfully develop and commercialize imetelstat and in a timely manner, Geron would not obtain the anticipated financial and other benefits of the collaboration agreement and the clinical development or commercialization of imetelstat could be delayed or terminated; and (ix) whether imetelstat can be applied to any or to multiple hematologic malignancies. Additional information on the above risks and uncertainties and other 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 annual report on Form 10-K for the year ended December 31, 2015. 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.

CONTACT: Anna Krassowska, Ph.D. Investor and Media Relations 650-473-7765

Source:Geron Corporation