In support of Cheng Ho’s arguments

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huntingonthebluffs
Posts: 246
Joined: Wed Feb 24, 2016 12:00 am

Re: In support of Cheng Ho’s arguments

Post by huntingonthebluffs » Fri May 07, 2021 9:09 pm

Thanks again biopearl for posting these insightful links. This research paper, published in November 2018 and to date has not been updated. One has to wonder if JNJ incorrectly interpreted this information prior to the negative CD.

Certainly an interesting paper, however, IMHO the goal seems to be ranking by speed how each telomerase inhibitor destabilizes specific human artificial chromosome (HAC) cell lines. Obviously, this study is above my pay grade and I am probably overlooking its finest merits so using this methodology is likely legitimate on certain levels. I just suspect that one should not conclude that speed of destabilizing chromosomes is the primary attribute to assess and probably only scratches the surface of “identification of compounds that selectively inactivate telomere replication and interfere with cell proliferation” and ultimately lead to desired patient safety/efficacy outcomes.

From a hunting perspective, (my way of relating) ranking how fast one can discharge a firearm does not determine the efficacy of a hunter, there is so much more to it than the ammo or just using a semi-automatic versus a bolt action versus a pump versus a single shot, etc. Maybe comparing this analysis to a study of which hand grenade is most effective is appropriate. In any event, we will live with these uncertainties until Imetelstat is approved and commercially available. But I would say, again in my opinion, that the road ahead for all entrants to the telomerase inhibitor commercialization race is long, winding, expensive and complex with Geron’s Imetelstat clearly ahead.

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

Re: In support of Cheng Ho’s arguments

Post by biopearl123 » Sat May 08, 2021 2:13 am

What an interesting observation, Hunt, that this study was published right around the time of the Janssen disaster. As you suggest, one has to wonder if that data played into the final (dis)continuation decision. After all Janssen waited until the last second to make the announcement. Had they simply done it even a week earlier, the late run up and subsequent crash in stock price, as we all were schnookered into thinking an agreement was imminent, could have been avoided. It looked bad and it smelled bad. Anyway, this current study looks at G quadraplex drugs but to my knowledge none are currently being tested in hematologic malignancies including MAIA's agent. That the two companies could have synergisms is inescapable. That the two companies could find themselves in a patent wrangle may also be inescapable (not all shotgun weddings are bad). Dr. Scarlett will probably address the patent question I posed in my previous post so maybe we will get clarity. As far as your weapons analogy, well all I can say is that the laws of astrophysics may not always apply to the world of micro particles. Since one of the drawbacks to Imetelstat is that multiple cell divisions seem to be required for the telomere effect (but we also have the non canonical effects as well), it may be that the earlier a malignant cell is destroyed the better. We get our yearly one shot to ask management questions in a public forum on Tuesday. I think you should ask the question, (I have already made a large withdrawal from the "bank of goodwill" with my submissions), and find a way to phrase it in a way that relates to Imetelstat. Clearly the shareholders meeting will be the forum where management and scientific officers will take pains to differentiate Imetelstat from competitors. Best Wishes and thanks for posting. bp

huntingonthebluffs
Posts: 246
Joined: Wed Feb 24, 2016 12:00 am

Re: In support of Cheng Ho’s arguments

Post by huntingonthebluffs » Sun May 09, 2021 2:04 am

Ha! So granted my hunting analogy was crude at best, but I think both hunting and aiming in the right location is usually far more advantageous than speed to indiscriminate senescence or generalized coverage possibly excessively exacerbating cytopenias. Which I don’t believe was or could be fairly analyzed in the subject paper but again my eyes glazed over frequently while trying to read through it. And to your point, I do think there is significant merit in what happens in the “non canonical” pathways even though that is not yet widely factual, just my intuition.

I do think we can say Imetelstat is safe and efficacious and in some vernaculars the tortoise wins the race while still having access to combination synergisms to win any race entered measuring whatever clinical benefit one may value including OS.

Still, of course, I do not hope to ever have a grip on the G-quadruplex drugs but understand that while very promising, unexpected effects could derail drug development processes. Uncertainties that will take possibly years to vet or not. I will, as always, lean on you for your continued wisdom regarding what is occurring in the trenches of competition or desired synergisms! And as always, warm wishes and thanks for being in our space and on our side of the fence.

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