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Updated Results from Geron's Imetelstat Phase 2 Proof-of-Concept Trial in Essential Thrombocythemia Presented at the European Hematology Association Congress


Data from an Additional Six Months of Imetelstat Treatment and Follow-Up since ASH 2012

Imetelstat Continues to be Well Tolerated with No New Safety Signals Reported; No Patients Have Discontinued Treatment Due to Drug-Related Adverse Events

Hematologic and Molecular Responses are Maintained

MENLO PARK, Calif., June 16, 2013 - Geron Corporation (Nasdaq: GERN) today announced that updated clinical results from the company's Phase 2 trial of imetelstat in essential thrombocytopenia (ET) were presented in an oral session at the 18th Congress of the European Hematology Association (EHA) in Stockholm by a principal investigator of the trial, Prof. Dr. med. Gabriela M. Baerlocher, of the University Hospital and University of Bern, Switzerland. ET is a chronic blood disorder that is representative of a group of diseases known as myeloproliferative neoplasms (MPNs). The initial trial results from 14 patients with ET were presented at the American Society of Hematology (ASH) annual meeting in December 2012. The updated results, which showed robust hematologic and molecular responses in patients treated with imetelstat, included data for an additional six months of treatment and follow-up for the original 14 patients, as well as data from four additional patients enrolled in the trial after the data cut-off for the ASH presentation. To view the presentation slides, please visit

"The observed 100% hematologic response rate in the updated data set, accompanied by a molecular response rate of 88% among the patients who had a JAK2 V617F mutation, are consistent with the data reported at ASH last year," said Prof. Baerlocher. "Imetelstat continues to be well tolerated in this trial. With no patients on treatment losing hematologic response, and molecular responses maintained in 86% of the patients, the drug also appears to have good durability of its effects on the disease."

Trial Rationale and Design
Geron's multi-center, single arm, open-label Phase 2 trial of imetelstat in patients with ET was designed to provide proof-of-concept for the potential use of the drug as a treatment for hematologic myeloid malignancies, including myelofibrosis (MF), myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML). The trial leveraged clinical observations from Phase 1; i.e., that imetelstat reduces platelet counts, as well as non-clinical observations that imetelstat distributes well to bone marrow in rodent models and selectively inhibits the proliferation of malignant progenitors ex vivo from patients with ET. Published non-clinical data also suggest elevated telomerase activity in malignant progenitors and shorter telomeres in granulocytes from patients with MPNs compared to healthy controls.

The primary endpoint of the trial was hematologic response and the secondary endpoints included molecular response and safety. Hematologic responses were measured by reductions in platelet counts, which are elevated in patients with ET. Molecular mutations, such as JAK2 V617F, which occur in 50% of patients with ET and are believed to be acquired in malignant clonal progenitor cells, can be used as molecular markers of disease burden. Therefore, molecular responses were measured by reductions in JAK2 V617F allelic burden compared to the normal, or wild type, JAK2 gene in circulating granulocytes. A decrease in the proportion of JAK2 V617F relative to wild type JAK2 is consistent with selective inhibition of the neoplastic progenitor cells responsible for the disease. Hematologic and molecular responses were graded using adapted European LeukemiaNet criteria, as defined by Barosi, et al, in the journal Blood (2009).

The trial was closed to enrollment in December 2012, with a total of 20 patients enrolled: 18 with ET and two with polycythemia vera (PV). Results for efficacy were presented from all 18 ET patients enrolled in the trial, with a median time on imetelstat treatment of 14 months (range 3 months to 2.5 years), as of a May 2013 data cut-off date. At this data cut-off date, there was insufficient efficacy follow-up data available from the two patients with PV, but follow-up data for safety were included. The presentation at the ASH annual meeting in December 2012 reported data as of an October 2012 cut-off date from the first 14 ET patients, with a median time on imetelstat treatment of eight months.

Efficacy Results
All 18 ET patients were refractory to, intolerant of or had refused conventional therapies (hydroxyurea, anagrelide and/or interferon-alpha). Platelet counts were reduced in all patients (a 100% hematologic response rate) and normalized in 16 out of 18 patients (an 89% complete response (CR) rate). The JAK2 V617F gene mutation was detected in eight patients. Seven out of the eight (88%) patients achieved 72% to 96% reductions in JAK2 V617F allele burden that qualified as partial molecular responses (PRs) within three to 12 months of treatment with imetelstat. Molecular PRs were maintained in six of the seven (86%) patients, with a median follow-up of 9.5 months (range 0 to 19 months) after first achieving a response. The median durations of hematologic and molecular response have not yet been reached.

Imetelstat was initially administered weekly by intravenous infusion during an induction phase. After achieving a hematologic CR, which occurred in a median time of six weeks, a maintenance treatment phase was begun in which dosing frequency was modified based on a patient's individual response profile. As of the May 2013 data cut-off date, follow-up data for the maintenance phase were available for 15 out of 16 patients who attained a hematologic CR. In all 15 patients the frequency with which imetelstat was administered to maintain the response was reduced to every two weeks or less (up to every seven weeks), generally decreasing over time. 13 of the 16 patients (81%) who attained a hematologic CR remain on study as of May 2013, with the median duration of treatment of 14.5 months. As of May 2013, a total of four ET patients have discontinued study treatment. The reasons cited for discontinuation include frequency of imetelstat treatment that was required to maintain a response (n=1), co-morbid conditions/social issues (n=2) and convenience issues (n=1).

Safety Results
In the trial, long-term administration of imetelstat was generally well tolerated. There were no new safety signals observed in the six-month update, and no patients discontinued the trial due to drug-related adverse events. The majority of the non-hematologic adverse events were mild-to-moderate in severity, the most frequent assessed as imetelstat-related by investigators being gastrointestinal events and fatigue. No drug-related Grade 4 non-hematologic adverse events were reported.

Three patients had Grade 4 neutropenia, but no cases of febrile neutropenia were reported. No thromboembolic events or bleeding events associated with thrombocytopenia were reported.

At least one abnormal liver function test (LFT) was observed in laboratory findings in all patients. The majority were Grade 1 elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST); two Grade 3 increases in ALT/AST were reversible on dose reduction. With longer dosing, Grade 1 increases in alkaline phosphatase were observed, associated with mostly Grade 1 to some Grade 2 unconjugated hyperbilirubinemia. LFT abnormalities do not appear to progressively worsen over time. No liver injury symptoms were reported and no patients discontinued study treatment due to enzyme elevations.

Further Development of Imetelstat in Hematologic Malignancies
"The molecular responses observed in the ET trial suggest that imetelstat had a relatively selective inhibition of the malignant progenitor cells, which are believed to be responsible for the underlying disease," said John A. Scarlett, M.D., Geron's President and Chief Executive Officer. "As a consequence, we believe that imetelstat may have potential as a treatment for other hematologic myeloid malignancies, including myelofibrosis."

Based on data from the trial of imetelstat in patients with ET, in November 2012, Dr. Ayalew Tefferi at Mayo Clinic initiated an investigator-sponsored trial to evaluate the safety and efficacy of imetelstat in patients with MF and to determine an appropriate dose and schedule for further evaluation. For more information about this trial, please refer to Dr. Tefferi has communicated to Geron that enrollment of the first cohort of 11 patients in the study was completed at the end of March 2013 and that the pre-specified criteria in the clinical protocol of at least two responders with a clinical improvement (CI), partial remission (PR) or complete remission (CR) according to the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria in the first 11 patients was met to enable expanded enrollment. In the first cohort of 11 patients with MF, imetelstat was administered once every three weeks. In the second cohort of an additional 11 patients with MF, imetelstat initially will be administered weekly during a four week induction phase, followed by a maintenance regimen in which imetelstat is given once every three weeks. Geron expects data from the investigator-sponsored trial, if positive, to inform the design of a company-sponsored multi-center trial in MF.

Geron also intends to expand its directed program of investigator-sponsored trials in 2013 to other hematologic myeloid indications, including AML and MDS.

About Imetelstat

Imetelstat (GRN163L) is a potent and specific inhibitor of telomerase. This first-in-class compound is a specially designed and modified short oligonucleotide, which targets and binds directly with high affinity to the active site of telomerase. Unique and proprietary oligonucleotide chemistry improves binding affinity and stability in plasma and tissues. A lipid modification enables cellular and tissue penetration and biodistribution.

About Geron

Geron is a clinical stage biopharmaceutical company developing 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 Geron's plans or expectations for or of: (a) the receipt of or dates to obtain or present data or other results from any clinical trials, including the investigator-sponsored trial in myelofibrosis; and (b) clinical development plans or success of imetelstat, including imetelstat possibly having applicability for the treatment of any other hematologic myeloid malignancies, including myelofibrosis, 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: (a) regarding the receipt of or dates for the availability of data or other results - delays in enrollment, delays caused by institutional review boards or regulatory agencies, shortage of supply, dependence on clinical trial collaborators and safety issues; and (b) regarding clinical development plans or success of imetelstat, including imetelstat possibly having applicability for the treatment of other hematologic myeloid malignancies, including myelofibrosis and positive safety and efficacy data from the investigator-sponsored trial in myelofibrosis and other clinical trials, including the ET clinical trial - those risks and uncertainties inherent in the development of potential therapeutic products, including without limitation, results from the ET trial may not mean that imetelstat has applicability for the treatment of any other hematologic myeloid malignancies, including myelofibrosis, technical and scientific challenges, limitations on freedom to operate arising from intellectual property of others and the protection of Geron's intellectual property rights. Additional information on the above risks and uncertainties (a) and (b) and other 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 March 31, 2013. 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.


Anna Krassowska, Ph.D.
Investor and Media Relations


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