A very basic note on other telomerase inhibitors

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cheng_ho
Posts: 202
Joined: Sun Apr 03, 2016 11:27 pm

A very basic note on other telomerase inhibitors

Post by cheng_ho » Fri Apr 19, 2019 3:51 pm

Imet is not the only telomerase inhibitor. As everyone with any familiarity with this field should know, AZT was the first telomerase inhibitor, followed by its other anti-retrotranscriptase cousins (e.g. ddI).

Those who keep saying that "imetelstat is the only telomerase inhibitor tested in humans" need to read a few 1990s papers ;)

https://www.researchgate.net/profile/St ... 000000.pdf

Now, I'm all about combinations... but the FDA, not so much. The fewer drugs in a combo, the better for approval and testing. There might be a theoretical advantage to using imet AND AZT together... but we don't know. And JNJ does know.

Notice that JNJ dropped GERN and immediately picked up ARGX. It's possible that JNJ thinks that they only need one telomerase inhibitor in an anti-cancer cocktail... or at least, they're likely to only be allowed to use one. This in spite of the public data on combinations (see paper linked below).

If GERN's patent on "any telomerase inhibitor" in AML, MDS, or MF holds up, then GERN could prevent the use of AZT in those patients. Personally I don't see that patent as valid (it's well established that you can patent specific chemicals, but not vague concepts), but it's a possible threat to the ARGX patients... hopefully JNJ's lawyers will be able to claim that the AZT MOA is "apoptosis induction" instead of "telomerase inhibition", and keep GERN from shutting down the trial.

Public information indicates that it's generally more effective (and safer) to use smaller doses of more drugs in combination. That said, I don't have the data from Janssen's brute-force screening labs... they can generate data that is far more extensive and statistically significant than any starving postdoc can do with a few thousand dollars in an academic lab.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281941/

cheng_ho
Posts: 202
Joined: Sun Apr 03, 2016 11:27 pm

Re: A very basic note on other telomerase inhibitors

Post by cheng_ho » Mon Apr 22, 2019 9:09 pm

Correction, the ARGX trial used AZA. The basic point stands, there are many TI drugs already in use for other purposes, and JNJ may not feel that they have to own one.

rinconj
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Re: A very basic note on other telomerase inhibitors

Post by rinconj » Tue Apr 23, 2019 4:14 am

I appreciate your effort to identify all potential competitors. We all need to do our DD. It's interesting to know that during Dr. Sekeres and Dr. Steensma's recent online conference call about future treatments of MDS they never mentioned Argenx or its AML and MDS drug cusatuzumab (ARGX-110). Cusatuzumab is about to enter P3 too for high risk MDS. Do you know why they ignore it?

biopearl123
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Re: A very basic note on other telomerase inhibitors

Post by biopearl123 » Tue Apr 23, 2019 4:35 am

Rinconj, I think it’s pretty clear that imetelstat is trying to carve out “low risk (for aml ), high tx requirement niche. High risk pts you allude to are different, carry a poorer prognosis, and are clearly closer to aml. Since the discussion did not cover that pt population, your answer may lie there. bp

cheng_ho
Posts: 202
Joined: Sun Apr 03, 2016 11:27 pm

Re: A very basic note on other telomerase inhibitors

Post by cheng_ho » Tue Apr 23, 2019 2:52 pm

JNJ may think that these older, better-tested drugs are "competitors"... but I see them as potential combos.

The FDA hates anything that doesn't fit the mono or at best duo therapy model... but if you throw three selected drugs at each MOA, you can use each one at a less toxic level AND keep the cancer from evolving around them.

Imet isn't the only telomerase inhibitor... but it sure looks like the MOA isn't exactly the same as the others'. 20 years from now, every cancer will be genetically tested and treated with a customized combo treatment. Let's just hope we're not all flying to Shanghai for it ;)

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