I always wondered…

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biopearl123
Posts: 1004
Joined: Fri Jul 20, 2018 5:13 pm

I always wondered…

Post by biopearl123 » Sun Sep 25, 2022 5:44 pm

I always wondered what the basic scientists meant by “non canonical” imetelstat effects. They seemed to imply that there were effects that went beyond just telomere shortening. And so there are. For the non oncologist such as myself, sorting through the jungle of beta catenins, ADARs as well as the hTERC’s etc has certainly made post retirement interesting for me. The canonical and the non canonical. Sounds like a pitched battle between the theists and the atheists. The theocrats and the apocryphal. But its not. They cooperate. At ASH poster presentations seem to be buried by the spoken word (the oral abstracts) but the very elegant poster presentations by Dr. Ma from the world famous labs of Dr. Jamieson, seem to suggest that understanding these essential pathways and the canonical and non canonical effects of Imetelstat can possibly prevent CML blast crisis, transformation of MPNs to acute leukemia and treat AML when it does occur not to mention reverse bone marrow fibrosis in MF. Also we are seeing preliminary suggestions of utility in lymphoma and look to MD Anderson for more research. Geron has certainly allied with strong research labs. I am so disappointed to know that the FDA in its “wisdom” has delayed Imetelstat AML combination studies. With a life expectancy of 9 or so months, this seems unduly conservative. Well at least some patients will be allowed mono therapy and perhaps the delay will provide additional useful clinical information. Regards, to all and happy New Year to those who celebrate it now. bp

kmall
Posts: 297
Joined: Thu Mar 21, 2019 3:57 pm

Re: I always wondered…

Post by kmall » Sun Sep 25, 2022 7:24 pm

Speaking of research labs. I have often wondered where (what research facility - Janssen pre-discontinuation?) and who (besides Geron scientists?) have initiated and identified the "Next Generation Telomerase Inhibitor"?

"Next Generation Telomerase Inhibitor Discovery Program

We have initiated a discovery program to identify a lead compound as a potential next generation telomerase inhibitor. If such a compound is identified, we plan to conduct preclinical experiments which may serve as a basis for potential future clinical testing. If we select a lead compound from this discovery program, we expect to provide an update on our efforts at that time."

https://www.geron.com/pipeline/overview/

Is it possible that this was discovered at Janssen while Dr. Rizo was the Senior Director, Compound Development Team Leader at Janssen Research and Development, LLC (Janssen) for all Phase 1 myeloid assets, and Global Clinical Leader for all late-stage myeloid assets, including imetelstat from 2014-2018.??

Could there possibly be a link between JNJ-74856665 and Imetelstat (JNJ-63935937)???

I have often wondered.........???? -Kmall

LWS
Posts: 142
Joined: Thu Jul 14, 2016 2:00 am

Re: I always wondered…

Post by LWS » Wed Sep 28, 2022 12:26 am

The evidence is compelling. JNJ, AbbVie and Geron have been working on combinations of Imetelstat (Telomerase inhibitor) and Venetroclax (BCL-2 protein inhibitor) for a very long time, with amazing preclinical results that are now becoming clinical results (TELOMERE AML trial and JNJ successes for example). JS, Dr. Rizo and the ever-building Geron staff know that they have a winner and time is on their side. The key words are "enhances apoptosis" (kills cancer cells by two difference methods in combination).

Note: Aleksandra Rizo's name (2017)
----------------------------------------------------------------------------------------
Abstract 1101: Telomerase inhibitor imetelstat in combination with the BCL-2 inhibitor
venetoclax enhances apoptosis in vitro and increases survival in vivo in acute myeloid leukemia

Joshua J. Rusbuldt, Leopoldo Luistro, Diana Chin, Melissa Smith, Amy Wong, Margarita Romero, Aleksandra Rizo, Jacqueline Bussolari, Fei Huang and Amy (Kate) Sasser
DOI: 10.1158/1538-7445.AM2017-1101 Published July 2017

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