Fellow Board Members

[biopearl123]

Fellow Board Members, Geron has kindly responded to my query regarding the sub study. They have confirmed that the study was not triggered by any particular safety concern but is a necessary part of the approval process and that it is anticipated that the study will be of short duration. bp

[FC4364]

Excellent News. Thank you BP.

[ashah]

Andrew,
Excellent news and information. Thank you.
I will repost a hypothesis postulated a few weeks ago.
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Andrew
Thank you as always for wonderful analysis.
Quick question or rather feedback on an hypothesis.

Any possibility that ventricular repolarization is mandated for ILAP? Drug Candidate effectiveness can be acceptable when considering - RWD and phase 2 days. P3 days cannot be unblinded early for obvious reasons. Likely mortality among trial patients is disease or cardiovascular events... and this arm COULD answer the Cardiovascular Safety sufficiently to green light conditional approval per ILAP.

[bucbeard]

As always, thank you BP!!

[biopearl123]

Ashah, I think the intent is pretty universal, e.g. EU, FDA as well as ILAP.

[ashah]

Andrew, Wasn't this study one which proceeded after discussions with the FDA?
If so, then the new additional analysis, in the middle of the P3 trial proceeding seems unusual.
However, if there is "new" player who wants additional data - which prior FDA discussions did not particularly pre-specify...
What might be the missing link/new entity to request new analysis...

[biopearl123]

Hi Ashah, I have to think it was always the intention to do the sub study and that this was telegraphed in 2017, they just couldn’t do it properly with the existing main protocol which has to be completed first. The new study allows for multiple exclusions and a more pure look at the QT interval, as well as the allowance of crossover which is also not part of the main protocol. Crossover of course means all 45 patients end up on Imetelstat (if the drug works (!!) ), with a low risk of mortality from other reasons since the study to just look at the QT is short. The main study did not allow for crossover and did not have all the other exclusions so mortality might be clouded by co existent conditions. In a non cancer world, QT might be studied in normal healthy individuals and be done with the issue. In the world of cancer agents that attack something as basic to cell function as the telomere, it seems unlikely the FDA and other regulatory agencies would allow testing in normal healthy individuals (unlike say an anti-inflammatory agent or an antibiotic). So I (just my opinion here) have to believe the study was planned since there really was no other way to assess “just” the QT and they couldn’t do it in normal “volunteers”. Given the stringency of the FDA and its blood relation, the EU, its really hard for me to think this was just a requirement for ILAP. But I love your theory! Especially given the timing. But the timing also coincided with the conclusion of enrollment in the main study and the planning and execution for the sub study had to be in the cooker for a while. bp

[Hoosier Investor]

BP,

I echo everyone else's appreciation for your efforts & update. Good news that it isn't being done in response to a safety observation (or concern), and good news that it won't take long to complete the study. However, I did notice the expected trial enrollment is now listed at 278.....up from a prior estimate of 220???? Thus, it does appear they'll need to reopen the trial in the coming months. Agree?

[biopearl123]

HI well yes I don’t see how they can’t. CKTC probably has a better sense as to how this would go. I can envision a scenario where top line data is released as planned January 2023 whether the sub study is completed or not, particularly since the goal of the substudy and the primary and secondary endpoints of the main study are different. It may be that since QT measurement is simple and immediate that it is not unreasonable to envision the substudy completed by the time top line data released. It’s pure speculation on my part.

[biopearl123]

HI, an additional thought is that there are two date for study completion, the familiar Jan 2023 for top line data and the final completion date of October 2023. It is possible that this additional time would allow for the substudy to be completed sometime after the January top line date but I gave up trying to second guess the Geron team a long time ago. Best Wishes, bp