There are many ways to think about partnering

Forum rules
- Comments must be civil and on topic
- Back up claims with evidence/reasoning/sources (posting links is allowed)
- No commercials/harassment/spam
LWS
Posts: 130
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Fri Apr 08, 2022 1:37 am

Keep in mind for Imetelstat:

1. The Cancer Moonshot now a high priority
2. MHRA (UK) approvals based upon rolling-data
3. TELOMERE (AML) combination trails
4. Disease modification and the death of cancer stem-cells
5. MD Anderson inputs

New partners, including NIH, have to be interested.
Last edited by LWS on Fri Apr 08, 2022 3:31 pm, edited 2 times in total.

LWS
Posts: 130
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Fri Apr 08, 2022 1:39 am

Since the JNJ 'walk', Imetelstat has gone from a possible successful cancer medicine to a proven cancer medicine that causes disease modification, and apparently has the ability to kill cancer stem-cells. In addition, many JNJ people, in the know medically, are now at Geron. JNJ, at the time of the 'walk', said that they believed Imetelstat would get approved. That seems a given now.

JNJ has maintained a long-term interest, and certainly has very deep pockets. Imetelstat, on the famous list of JNJ likely hits at the time of the 'walk', was near #1. JS's price was too high then, but certainly more in-line now with the phase 2 successes, ongoing & confirming phase 3s and inputs from MD Anderson.

It appears that Geron and JNJ have been cooperating with each other for many years. No one knows more about Imetelstat than JNJ. It seems to me, that in one way or the other, Geron will be associated with or part of JNJ. JNJ, I believe, gave JS & Dr. Rizo full reign to improve Imetelstat, which they have done, with combination trials now in formation (TELOMERE, AML, AbbVie).

The question of the day: What is Imetelstat worth as a single-agent in confirming phase 3s, and in combination as a disease modifier and killer of cancer stem-cells?

huntingonthebluffs
Posts: 206
Joined: Wed Feb 24, 2016 12:00 am

Re: There are many ways to think about partnering

Post by huntingonthebluffs » Sat Apr 09, 2022 10:38 pm

VIVO Capital steps up with an aggregate number of shares equaling a 5.9% position (22,857,143) in Geron. The aggregate per the Schedule 13G consists of 15,238,095 common stock shares and 7,619,048 shares of common stock shares issuable upon exercise of certain warrants.

https://d18rn0p25nwr6d.cloudfront.net/C ... 56ea79.pdf

From the VIVO Capital website “About” tab: VIVO Capital helps its portfolio companies develop corporate strategy, facilitate strategic alliances including cross-border partnerships, recruit management, and acquire new products and technologies to accelerate growth.

https://vivocapital.com/about/

FWIW, I also found the background of several of the partners, etc. at VIVO Capital to be very deep and varied including the person signing the Schedule 13G for VIVO Capital. Which was Gaurav Aggarwal and from the website team tab his bio-summary stated the following:

Gaurav Aggarwal, M.D, Managing Director. comes to Vivo with prior experience investing in private and public biopharmaceutical and medical device companies across the spectrum of development. He previously served as Managing Director with Investor Growth Capital, Partner with Panorama Capital and Associate at JPMorgan Partners. He was an investor and previously served on the boards of Auspex Pharmaceuticals (acquired by Teva), Hyperion Therapeutics (acquired by Horizon), NextWave Pharmaceuticals (acquired by Pfizer), Piramed (acquired by Roche) and Flowcardia (acquired by CR Bard). Other successful investments include Amarin, ISTA Pharmaceuticals and Spinal Concepts. In addition to his role as an investor, Gaurav was the Chief Business Officer of Ocera Therapeutics, a publicly traded clinical stage company developing therapies for orphan liver conditions.

Gaurav received his M.D. from Columbia University, College of Physicians & Surgeons, and his B.S. in Agricultural Economics from Cornell University.

https://vivocapital.com/Team/gaurav-aggarwal/

IMHO it is undeniable that the companies investing in Geron, such as VIVO Capital, are expanding and extending the Geron team in exciting and immeasurable ways. So regardless of the size of the employee directory, JS and company are adding and developing scope rapidly as this snowball continues to roll downhill. It’s been a long time coming but the patients and investors alike are starting to take front row seats as curtain time approaches. Best of luck to all that are able to hang in here, especially the patients in need with unmet needs.

LWS
Posts: 130
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Thu Apr 14, 2022 3:02 am

Geron is in a powerful negotiating position to find partners with deep pockets on their terms. I see no reason for them to go it alone since there are 'so many mountains to climb' beyond single-agent blood cancers starting with TELOMERE (AML, combination, with AbbVie).

The recent news that Imetelstat can kill cancer stem-cells is revolutionary. Imetelstat is beginning to appear to be something beyond a good cancer medicine (miracle-medicine?). Imetelstat is a proven medicine now, with research opportunities that will continue for decades.
-----------------------------------
From YMB

Needham Interview:
- Drug results to-date have exceeded expectations
- Overall survival and infusion dependence are massive markers
- Regrowth of bone marrow and death of LSC's not seen in any other treatment but Imetelstat
- Positive January 2023 results expected to be in-line with phase 2 results
- Enough cash in hand to make it through 2023 results
- Self commercialization seems to be main interest with projected peak revenue of 3 Billion in 2030 based
on patient population
-Open to other "value enhancing options" 24:20 marker in the presentation video
- and a partridge in a pear tree

It's not if but when. The approval of Imetelstat will be life changing in multiple ways.
---------------------------------------
Planned Milestone From Needham:

LR MDS
Top-line results (TLR) for IMerge Phase 3 trial in early January 2023; assuming positive TLR, potential:
– NDA submission in 1H 2023
– MAA submission in 2H 2023
– U.S. regulatory approval and commercialization as early as 1H 2024

Refractory MF
Open the rest of selected IMpactMF clinical sites in 2022 to enable planned interim analysis in 2024

Pipeline Expansion
Expand pipeline into additional indications and treatment combinations:
– Start of IMproveMF Phase 1 study of imetelstat + ruxolitinib in frontline MF in 1H
2022
– Start of IMpress Phase 2 study of single-agent imetelstat in R/R AML and HR MDS in 2H 2022
– Start of TELOMERE Phase 1/2 study of imetelstat + HMAs or venetoclax in R/R AML in 2H 202

LWS
Posts: 130
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Sun Apr 17, 2022 12:49 am

Combination Cures and Important Partners (also posted on YMB, and in danger of being deleted)

AbbVie is already a partner (Looks like an outstanding combination, preclinical). The Geron and AbbVie partnership (forming TELOMERE clinical trial now for AML) will be closely observed. This promises to be a closely watched, major event for both companies, and for the Cancer Moonshot.

In combinations Imetelstat may be part of a cure (see preclinical results). We may be cutting a fine line between, "Tantamount to a cure--from Mayo Clinic" and a complete-cure.

***Results (preclinical): A dose-dependent synergistic activity in inducing apoptosis was observed in multiple AML cell lines when combining imetelstat with venetoclax. In the MOLM-13 cell line, single-agent imetelstat and venetoclax had modest apoptotic activity after 48 hours (22% and 30% respectively), but the combination achieved 88% at 48 hours and nearly 100% at 96 hours. **

This potential combination cure is made more likely by the recent AML evidence that Imetelstat kills cancer-stem-cells.
-------------------------
Imetelstat is a medicine of immense value for research, treatments and potential cures. "Tantamount to a cure" and miracle status is the hope and the promise.

JS and Dr. Rizo can continue to negotiate with several prominent major pharma-oncology companies. We know AbbVie and JNJ are on the list, and we suspect Novartis is on the list. There are likely others.

1. Only GERN's drug kills the cancer stem cells.
2. Only GERN's drug returns cancerous bone marrow to normal.
3. Only GERN's drug gives years of extra life to these terminal blood cancer patients.
4. TELOMERE new clinic combination trial (based upon near 100% effective combination in preclinic trials) for AML with AbbVie's approved cancer medicines.
5. MD Anderson fully endorses Imetelstat.
-------------------------------------------------------------
From MD Anderson Cancer Center

Srdan Verstovsek, MD, PhD, United Energy Resources, Inc. Professor of Medicine, director, Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms, chief, Section for Myeloproliferative Neoplasms, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the key objective of the phase 3 IMpactMF trial (NCT04576156) examining imetelstat in patients with myelofibrosis.

The trial is comparing the use of intravenous imetelstat vs best available therapy in the second-line setting, Verstovsek says. To be eligible for enrollment, patients must be nonresponsive or refractory to JAK inhibitors. The key objective of the study is to improve overall survival (OS) in this patient population, according to Verstovsek.

This trial marks the first time that investigators have had the ability to consider prolonging life for patients with myelofibrosis within the context of a clinical study, Verstovsek adds. Using OS as a primary end point has raised the bar for the field in that the focus has moved beyond the spleen or symptoms such as anemia, Verstovsek explains. Imetelstat is an exciting new approach in development for patients with myeloproliferative neoplasms, Verstovsek concludes.

LWS
Posts: 130
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Fri Apr 22, 2022 6:12 pm

Imetelstat (current successes and future potential)

Approvals certain (timeline not known) with decades of use and research. Perhaps, the 'holy grail' for big pharma potential partners.

1. The Past--Various blood cancers as a single-agent in several modes (phase 2s done, phase 3s ongoing and confirming---a very good cancer medicine that modifies damaged bone marrow and can kill cancer-stem -cells).

2. The Present-- TELOMERE AML combination clinical trials forming with AbbVie (brings forth IMET by enhancing existing approved blood cancer medicines). Also, MD Anderson inputs.

3. The Future--The ultimate big prize (solid cancer tumors in combinations with IMET). The main problem, as I understand it, is a suitable delivery system. There have been some papers recently that look hopeful.
----------------------------------
Imetelstat, a 13-base oligonucleotide (5'-TAGGGTTAGACAA-3'), is a potent, investigational telomerase inhibitor in clinical development for the treatment of hematologic myeloid malignancies.
----------------------------------
Delivery Systems Research---Nano Delivery Systems

Mol Pharm. 2021 Apr 5; 18(4): 1491–1506.
Published online 2021 Mar 18. doi: 10.1021/acs.molpharmaceut.0c01238

Advances in the Design of (Nano)Formulations for Delivery of Antisense Oligonucleotides and Small Interfering RNA: Focus on the Central Nervous System
Monique C. P. Mendonça,† Ayse Kont,† Maria Rodriguez Aburto,‡§ John F. Cryan,‡§ and Caitriona M. O’Driscoll*†

Abstract

RNA-based therapeutics have emerged as one of the most powerful therapeutic options used for the modulation of gene/protein expression and gene editing with the potential to treat neurodegenerative diseases. However, the delivery of nucleic acids to the central nervous system (CNS), in particular by the systemic route, remains a major hurdle. This review will focus on the strategies for systemic delivery of therapeutic nucleic acids designed to overcome these barriers. Pathways and mechanisms of transport across the blood–brain barrier which could be exploited for delivery are described, focusing in particular on smaller nucleic acids including antisense oligonucleotides (ASOs) and small interfering RNA (siRNA). Approaches used to enhance delivery including chemical modifications, nanocarrier systems, and target selection (cell-specific delivery) are critically analyzed. Learnings achieved from a comparison of the successes and failures reported for CNS delivery of ASOs versus siRNA will help identify opportunities for a wider range of nucleic acids and accelerate the clinical translation of these innovative therapies.

Keywords: antisense oligonucleotide, small interfering RNA, blood−brain barrier, systemic delivery, neurological diseases

LWS
Posts: 130
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Sat Apr 30, 2022 6:41 pm

The Approval Timeline and Partners (or Buyout)

There seems to be near 100% agreement that Imetelstat has passed all completed trials (phase 2) with 'flying colors', and that phase 3 trials are confirming those trials. Approvals (single-agent) are a foregone conclusion. TELOMERE (AML) combination trials, with AbbVie, are underway.

There also have been separate discussions about Geron's leadership (primarily John Scarlett and Dr. Rizo) and why, if Imetelstat is so good, it has not been sold for a huge sum, and why the PPS is still under $1.50.

My take on that is that potential partners are being vetted, Geron is in a very strong negotiating position, and they have enough cash on hand for a considerable time. With Imetelstat, Geron cannot be pressured into 'a deal' that they do not find very attractive. The PPS is unrealistically extremely low from various market forces (another topic).
Last edited by LWS on Fri May 06, 2022 7:51 pm, edited 2 times in total.

Bridge to Sell
Posts: 26
Joined: Sat Mar 19, 2022 11:33 pm

Re: There are many ways to think about partnering

Post by Bridge to Sell » Mon May 02, 2022 11:18 pm

Good luck everyone. I'm not going to stick around and get harassed by guys like Kmall.
Last edited by Bridge to Sell on Thu Jun 16, 2022 2:00 pm, edited 1 time in total.

biopearl123
Posts: 918
Joined: Fri Jul 20, 2018 5:13 pm

Re: There are many ways to think about partnering

Post by biopearl123 » Tue May 03, 2022 2:34 am

I think its reasonable to assume the AML study will be short.

LWS
Posts: 130
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Fri May 06, 2022 3:55 pm

(Previous)--"There seems to be near 100% agreement that Imetelstat has passed all completed trials (phase 2) with 'flying colors', and that phase 3 trials are confirming those trials. Approvals (single-agent) are a foregone conclusion. TELOMERE (AML) combination trials, with AbbVie, are underway."
--------------------------------------------------------------------
AbbVie has an obvious interest in Imetelstat. From early on, it has been known that IMET's greatest potential was in combinations. The preclinical AML combination results have been outstanding. I suspect that there has been some under-the-radar clinical work, and both AbbVie & Geron have very high hopes of success. New information about the death of cancer-stem-cells with IMET, adds to the hopes.
-----------------------------------------------------------------------------
More details (from John---YMB)

Programs to Explore New Indications and Combinations for Imetelstat Expand Telomerase Inhibition Potential

● The Company unveiled three new clinical programs and one preclinical program for imetelstat. The clinical programs explore the use of imetelstat as a single agent and in combination with current standard of care treatments to expand the potential application of imetelstat.

● The first new clinical program will evaluate imetelstat in combination with ruxolitinib in frontline MF patients. Named IMproveMF, the Geron- sponsored Phase 1 trial will begin as a dose-finding study in approximately 20 patients with a primary endpoint of safety. Upon finding a recommended dose of the combination therapy, the next portion of the trial will confirm the safety of the recommended dose and evaluate the efficacy of the combination therapy. Approximately 20 patients will be enrolled into the second part of the trial and the endpoints include safety, symptom response, spleen response and change in fibrosis. The Company expects the first clinical site for IMproveMF to be open in the first half of 2022.

● The second new clinical program will evaluate imetelstat as a single agent in higher risk MDS and acute myeloid leukemia (AML) patients after failing hypomethylating agent (HMA) treatment. Named IMpress, this investigator-sponsored trial has been designed to enroll approximately 45 patients with overall response rate as the primary endpoint. The Company expects IMpress to begin in the first half of 2022.

● The third new clinical program will evaluate imetelstat in combination with venetoclax or azacitidine in relapsed/refractory AML patients. Named TELOMERE, this investigator-sponsored trial has been designed to be conducted in two parts. The first part will be a dose finding study in approximately 20 patients with a primary endpoint of safety. Upon finding a recommended dose of the combination therapy, the next portion of the trial will confirm the safety of the recommended dose and evaluate the efficacy of the combination therapy. Approximately 50 patients will be enrolled into the second part of the trial and the primary endpoint is overall response rate. The Company expects TELOMERE to begin in the first half of 2022.

● The preclinical program is being conducted at MD Anderson Cancer Center to define the role of imetelstat in lymphoid malignancies. In vitro and in vivo experiments are planned, and the Company expects preliminary results to be available by the end of 2022.

*********************************************

LWS
Posts: 130
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Tue May 10, 2022 11:02 pm

Focus on TELOMERE & AbbVie.

Combinations are the principle targets now. The AML preclinical work has been outstanding "---the combination achieved 88% at 48 hours and nearly 100% at 96 hours----". This information (preclinical with AbbVie) has been known for a long time. We do not know how much under-the-radar clinical work has been done (somewhere). The probability of success looks very high.

-------------------------------

Previous #1 (Preclinical)


***Results (preclinical): A dose-dependent synergistic activity in inducing apoptosis was observed in multiple AML cell lines when combining imetelstat with venetoclax. In the MOLM-13 cell line, single-agent imetelstat and venetoclax had modest apoptotic activity after 48 hours (22% and 30% respectively), but the combination achieved 88% at 48 hours and nearly 100% at 96 hours. **

This potential combination cure is made more likely by the recent AML evidence that Imetelstat kills cancer-stem-cells.

Previous #2 (Clinical)

● The third new clinical program will evaluate imetelstat in combination with venetoclax or azacitidine in relapsed/refractory AML patients. Named TELOMERE, this investigator-sponsored trial has been designed to be conducted in two parts. The first part will be a dose finding study in approximately 20 patients with a primary endpoint of safety. Upon finding a recommended dose of the combination therapy, the next portion of the trial will confirm the safety of the recommended dose and evaluate the efficacy of the combination therapy. Approximately 50 patients will be enrolled into the second part of the trial and the primary endpoint is overall response rate. The Company expects TELOMERE to begin in the first half of 2022.

LWS
Posts: 130
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Thu May 19, 2022 1:33 am

Imetelstat's medical single-agent successes + new combination trials with partners+ MD Anderson's support ---> insuring approvals.

1. Single-agent phase 2 trials have been very successful. Ongoing phase 3 are fully confirming the earlier trails

2. There are two combinations trials underway, with partners (AbbVie & Incyte) approved blood cancer medicines.

3. MD Anderson has been using Imetelstat for both treatment and research, with very positive comments.
---------------------------------------------
How does ruxolitinib work in myelofibrosis?

Ruxolitinib is a janus kinase inhibitor ( JAK inhibitor) with selectivity for subtypes JAK1 and JAK2. Ruxolitinib inhibits dysregulated JAK signaling associated with myelofibrosis. JAK1 and JAK2 recruit signal transducers and activators of transcription (STATs) to cytokine receptors leading to modulation of gene expression

What type of cancer is Ruxolitinib used to treat?


Ruxolitinib (Jakavi ®) is used to treat some types of myeloproliferative neoplasms (MPNs). MPNs are types of cancer that affect how blood cells are made.

The Official Patient Website To Learn More About Jakafi. Register For IncyteCARES.

Zhears
Posts: 50
Joined: Mon Oct 08, 2018 12:19 pm

Re: There are many ways to think about partnering

Post by Zhears » Thu May 19, 2022 11:36 am

Just for clarity - "Ongoing phase 3 are fully confirming the earlier trails"

As far as I am aware there is no public evidence for this statement? It may be, hopefully, a safe assumption, but if you could back this up it would be appreciated.

biopearl123
Posts: 918
Joined: Fri Jul 20, 2018 5:13 pm

Re: There are many ways to think about partnering

Post by biopearl123 » Thu May 19, 2022 4:10 pm

To my knowledge there is no partnership with Abbie or Incyte.

LWS
Posts: 130
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Thu May 19, 2022 8:23 pm

biopearl123----It depends what you mean by partner. I am talking about combination trial partners (AbbVie & Incyte so far). I am not talking about deep-pocket partners, but they could end up being the same people.

Zhears---Just for clarity - "Ongoing phase 3 are fully confirming the earlier trails"

This has been discussed. These are double-blind studies so the state of each patient is unknown. However, Geron (probably JS & Dr. Rizo) would be able to see the trends (survival rates and times mostly) and patterns (comparing with phase 2s). This seems logical.

LWS
Posts: 130
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Tue May 24, 2022 6:55 pm

At some point, I believe that Geron will choose to have close partners. That will be to Geron's advantage.

MD Anderson is a collaborator. Names that have been mentioned for one reason or another (combinations, deep-pockets, past history, oncology interest, Europe, etc.) are:

1. AbbVie
2. Incyte
3. JNJ
4. BMY
5. Novartis

Imetelstat can go in many directions from single-agent to a variety of combinations, with numerous patents now in place. Disease modification, the good safety profile, and the ability to kill cancer-stem-cells (normal cells not affected), all are unique and very positive factors. Single-agent approvals are close, with the UK (MHRA) likely first.

Note -- Combinations studies in progress, with more to come:


(With Incyte)-- IMproveMF Phase 1 study of imetelstat + ruxolitinib in frontline MF in May 2022
(With AbbVie) -- TELOMERE Phase 1/2 study of imetelstat + HMAs or venetoclax in R/R
AML in 2H 2022

LWS
Posts: 130
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Sat May 28, 2022 7:31 pm

Abbvie in Combinations and as a Partner

In terms of combinations and partners, no company has received more attention than AbbVie, with clinical trials forming for some very promising combinations, based upon extraordinary pre-clinical results. Imetelstat's most important potential has always been in combinations, enhancing an already approved cancer medicine. The opportunities for research are almost unlimited.

I wonder if there have been some under-the-radar studies in humans (somewhere), and both Geron and AbbVie already know the results. Considerable time has passed since the very promising pre-clinical results were known.

This new clinical program will evaluate imetelstat in combination with venetoclax or azacitidine in relapsed/refractory AML patients. Named TELOMERE, this investigator-sponsored trial has been designed to be conducted in two parts.

Correction:
Imetelstat AML preclinical (in Delaware), pediatric studies show that IMET kills cancer-stem-cells, while leaving normal cells alone.

This may turn out to be the medical find of this decade, especially if the TELOMERE combination works out (combinations with AbbVie medicines for AML). IMET will likely be a key factor in the reformed Cancer Moonshot.

Previous #1 (Preclinical)


***Results (preclinical): A dose-dependent synergistic activity in inducing apoptosis was observed in multiple AML cell lines when combining imetelstat with venetoclax. In the MOLM-13 cell line, single-agent imetelstat and venetoclax had modest apoptotic activity after 48 hours (22% and 30% respectively), but the combination achieved 88% at 48 hours and nearly 100% at 96 hours. ***

This potential combination cure is made more likely by the recent AML evidence that Imetelstat kills cancer-stem-cells.
Last edited by LWS on Sun May 29, 2022 5:05 pm, edited 1 time in total.

biopearl123
Posts: 918
Joined: Fri Jul 20, 2018 5:13 pm

Re: There are many ways to think about partnering

Post by biopearl123 » Sun May 29, 2022 6:22 am

LWS, help us understand why you think the NIH performed this study:

https://www.geron.com/file.cfm/53/docs/ ... models.pdf

It was performed in Delaware. Maybe I missed something.

LWS
Posts: 130
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Sun May 29, 2022 3:18 pm

biopearl123--- It looks like this research was not done at NIH, but NIH was involved. I will have to go back and see why I thought NIH was involved. I believe I saw something that pointed to NIH.
----------------------
Journal of Clinical Medicine

Imetelstat Induces Leukemia Stem Cell Death in Pediatric
Acute Myeloid Leukemia Patient-Derived Xenografts


Simple Summary:
About 20% of children with acute myeloid leukemia (AML) experience refractory disease or relapse, despite receiving intensive therapy. Leukemia stem cells (LSC) have the ability to evade chemotherapy and propagate the disease leading to chemoresistance and relapse. Therefore, treatment options that are able to eliminate LSCs are likely to be more effective in prolonging disease free survival. We have tested the effect of imetelstat, a potent inhibitor of telomerase activity that specifically kills LSCs, on pediatric AML cells in culture and in mouse models. Imetelstat was effective in specifically killing LSCs and extended animal survival when used as a single agent or in combination with chemotherapy or epigenetic drug azacitidine.

Sonali P. Barwe 1
, Fei Huang 2
, Edward Anders Kolb 1 and Anilkumar Gopalakrishnapillai 1,*
1 Nemours Centers for Childhood Cancer Research and Cancer & Blood Disorders, Nemours Children’s Health,
Wilmington, DE 19803, USA; sbarwe@nemours.org (S.P.B.); eakolb@nemours.org (E.A.K.)
2 Geron Corporation, Parsippany, NJ 07054, USA; fhuang@geron.com
* Correspondence: anil.g@nemours.org; Tel.: +1-302-651-4833
Last edited by LWS on Mon May 30, 2022 7:08 pm, edited 3 times in total.

LWS
Posts: 130
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Sun May 29, 2022 4:47 pm

Welcome to NCBI
The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information.


https://www.ncbi.nlm.nih.gov/home/about/


Grant support

unnumbered/Geron (United States)
unnumbered/Lisa Dean Moseley Foundation
unnumbered/Leukemia Research Foundation of Delaware
P20GM103446/GM/NIGMS NIH HHS/United States
unnumbered/Andrew McDonough B+ Foundation
unnumbered/Nemours Foundation

. 2022 Mar 30;11(7):1923.
doi: 10.3390/jcm11071923.

Imetelstat Induces Leukemia Stem Cell Death in Pediatric Acute Myeloid Leukemia Patient-Derived Xenografts


Sonali P Barwe 1, Fei Huang 2, Edward Anders Kolb 1, Anilkumar Gopalakrishnapillai 1

Abstract
Acute myeloid leukemia (AML) in children remains deadly, despite the use of maximally intensive therapy. Because leukemia stem cells (LSCs) significantly contribute to chemoresistance and relapse, therapies that specifically target the LSCs are likely to be more beneficial in improving outcome. LSCs are known to have high telomerase activity and telomerase activity is negatively correlated with survival in pediatric AML. We evaluated the preclinical efficacy of imetelstat, an oligonucleotide inhibitor of telomerase activity in patient-derived xenograft (PDX) lines of pediatric AML. Imetelstat treatment significantly increased apoptosis/death of the LSC population in a dose-dependent manner in six pediatric AML PDX lines ex vivo, while it had limited activity on the stem cell population in normal bone marrow specimens. These results were validated in vivo in two distinct PDX models wherein imetelstat as single agent or in combination with chemotherapy greatly reduced the LSC percentage and prolonged median survival. Imetelstat combination with DNA hypomethylating agent azacitidine was also beneficial in extending survival. Secondary transplantation experiments showed delayed engraftment and improved survival of mice receiving imetelstat-treated cells, confirming the diminished LSC population. Thus, our data suggest that imetelstat represents an effective therapeutic strategy for pediatric AML.

Keywords: imetelstat; leukemia stem cells; patient-derived xenograft models; pediatric acute myeloid leukemia; telomerase.

Post Reply