4 abstracts on imetelstat at ASH2017


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Fishermangents
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4 abstracts on imetelstat at ASH2017

Postby Fishermangents » Thu Nov 02, 2017 11:58 am

Geron Announces Presentations at American Society of Hematology Annual Meeting
Imetelstat Clinical Data from Part 1 of IMerge in Myelodysplastic Syndromes to be Presented


MENLO PARK, Calif., Nov. 01, 2017 (GLOBE NEWSWIRE) -- Geron Corporation (Nasdaq:GERN) today announced that four abstracts related to the telomerase inhibitor imetelstat have been accepted for presentation at the 59th American Society of Hematology (ASH) Annual Meeting and Exposition to be held in Atlanta, Georgia from December 9-12, 2017. The abstracts were published today on the ASH website at www.hematology.org.

Clinical Data Presentation
An abstract containing data from the first 32 patients enrolled in Part 1 of IMerge, the ongoing Phase 2/3 clinical trial of imetelstat in patients with lower risk myelodysplastic syndromes (MDS) being conducted by Janssen Research & Development, LLC., was accepted for a poster presentation.

Title: Efficacy and Safety of Imetelstat in RBC Transfusion-Dependent (TD) IPSS Low/Int-1 MDS Relapsed/Refractory to Erythropoiesis-Stimulating Agents (ESA) (IMerge) (Abstract #4256)
Date: Monday, December 11, 2017
Time: 6:00 p.m. – 8:00 p.m. ET

Pre-Clinical Data Presentations
Three abstracts by academic collaborators were selected for presentation that build on previous studies investigating imetelstat’s effects and mechanism of action in pre-clinical models of hematologic myeloid malignancies.

Title: Imetelstat, a Telomerase Inhibitor, Is Capable of Depleting Myelofibrosis Hematopoietic Stem Cells and Progenitor Cells (Abstract #1654)
Date: Saturday, December 9, 2017
Time: 5:30 p.m. - 7:30 p.m. ET

Title: Telomerase Inhibition Impairs Self-Renewal of b-Catenin Activated Myeloproliferative Neoplasm Progenitors (Abstract #2860)
Date: Sunday, December 10, 2017
Time: 6:00 p.m. – 8:00 p.m. ET

Title: Integrated Molecular Analysis Identifies Replicative Stress as Sensitizer to Imetelstat Therapy in AML (Abstract #798)
Date: Monday, December 11, 2017
Time: 5:45 p.m. ET

link: http://ir.geron.com/phoenix.zhtml?c=673 ... ID=2313299

Fishermangents
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Re: 4 abstracts on imetelstat at ASH2017

Postby Fishermangents » Thu Nov 02, 2017 2:50 pm

And here are the links and conclusions for each abstract:

4256 Efficacy and Safety of Imetelstat in RBC Transfusion-Dependent (TD) IPSS Low/Int-1 MDS Relapsed/Refractory to Erythropoiesis-Stimulating Agents (ESA) (IMerge)

Conclusions:
In IPSS Low/Int-1 RBC transfusion dependent MDS patients relapsed/refractory to ESA, TI was observed in 34% and erythroid HI in 63% with imetelstat therapy. TI response appeared to be independent of sEPO level. Reversible cytopenias were the most frequent adverse events, which were generally manageable with dose reduction or delays. Elevated LFTS were reversible. Patients who were naïve to lenalidomide and HMAs and who lacked del(5q) had a higher rate of durable TI (54%) than other groups, which should be further explored.
link: https://ash.confex.com/ash/2017/webprog ... 05028.html

798 Integrated Molecular Analysis Identifies Replicative Stress As Sensitizer to Imetelstat Therapy in AML

Conclusions:
In summary, imetelstat prolonged overall survival in a large cohort of AML PDX. In 57% (17 out of 30 individual AML patient samples), sustained responses to imetelstat were associated with marked improvements in survival and a baseline replicative stress-annotated transcriptional signature. The rational sequencing of standard induction chemotherapy to induce replicative stress provides proof-of-concept to sensitize imetelstat-resistant AML patient samples and suppress expansion and prevent relapse in AML.
link: https://ash.confex.com/ash/2017/webprog ... 08269.html

1654 Imetelstat, a Telomerase Inhibitor, Is Capable of Depleting Myelofibrosis Hematopoietic Stem Cells and Progenitor Cells

Conclusions:
These findings suggest that Imet is capable of selectively promoting apoptosis and inhibiting the proliferation of phenotypically and functionally defined MF but not normal HSCs/HPCs. Imet, therefore, represents a potentially promising drug for the treatment of MF which appears to affect primitive MF HSCs.
link: https://ash.confex.com/ash/2017/webprog ... 04157.html

2860 Telomerase Inhibition Impairs Self-Renewal of ß-Catenin Activated Myeloproliferative Neoplasm Progenitors

Conclusions:
Niche responsive interactions between the telomerase complex and the Wnt/b-catenin self-renewal pathway sensitize b-catenin activated MPN progenitors to imetelstat in both in vitro and in vivo humanized pre-clinical MPN mouse models thereby providing a strong rationale for studies assessing eradication of malignant progenitors using imetelstat.
link: https://ash.confex.com/ash/2017/webprog ... 05993.html

Fishermangents
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Re: 4 abstracts on imetelstat at ASH2017

Postby Fishermangents » Thu Nov 02, 2017 3:07 pm

Some of my observations regarding the 4 abstracts:
- impact of imet on MDS disease has been refined, while positive effect on TI and HI is confirmed;
- the IMerge paper has been co-authored by 5 JnJ employees and 10 researchers/doctors from various hospitals, of which 7 from Europe and 3 from US (incl. Mayo Clinic and Dana-Farber);
- evidence of imet being capable of selectively targeting the malignant hematopoietic and progenitor cells in MF is strengthened;
- the scope of imet selectively targeting malignant progenitor cells is now broadened to the whole set of MPN's (ET, PV, MF, MDS)
- AML seems to be a logical target for another clinical trial;
- The AML paper has been co-authored by Steven Lane and Claudia Bruedigam, both known for being involved in imetelstat/AML studies for a relative long time.

Other observations are welcome.

biopearl
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Re: 4 abstracts on imetelstat at ASH2017

Postby biopearl » Fri Nov 03, 2017 12:48 am

Nicely done, thank you Fish. bp

biopearl
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Re: 4 abstracts on imetelstat at ASH2017

Postby biopearl » Fri Nov 03, 2017 1:21 am

Fish two of your abstract links take you to the same article. The link to selective depletion of clonal precursors is not correct. Just a housekeeping issue. Thanks for keep this site current and relevant. bp

Fishermangents
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Re: 4 abstracts on imetelstat at ASH2017

Postby Fishermangents » Fri Nov 03, 2017 7:58 pm

Thanks, bio. Should work now.


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