Hi

[KTArsenal]

Can someone with a deeper skillset of these issues please explain these things that are deeply concerning to me?

1. The absence of Dr. Feller

2. In any way has OS somehow been corrupted or compromised?

3. I’ve been here since ‘19. Unsure if 2027 is worth hanging around for.

Thanks.

Kevin

[biopearl123]

KT, the best I can do is this. Dr. Faye had a prominent position as Chief Medical Officer. Then she disappeared off the masthead and the position was solely Dr. Eid’s. If she left the company the company was obligated to make an announcement, they did not. So it was thought that she just changed to a less visible position within the company. Shortly after, a lecture slide showed her as Director of Development, certainly not an unimportant position. I can’t do better than that. As to OS, yes by intention for ethical reasons apparently, the design of the PIII MF longevity study allows for crossover from the BAT group to treatment which would “dilute” the primary end point but its better for patients in the study if they continue to progress and can’t be offered anything else. The statisticians plan to project what it “would have been like” if they had stayed in the BAT arm but yes it will probably make the end point less strong but it is by design and ethically stronger. As to your third question, that’s up to you.

[Ryan]

KT, the best I can do is this. Dr. Faye had a prominent position as Chief Medical Officer. Then she disappeared off the masthead and the position was solely Dr. Eid’s. If she left the company the company was obligated to make an announcement, they did not. So it was thought that she just changed to a less visible position within the company. Shortly after, a lecture slide showed her as Director of Development, certainly not an unimportant position. I can’t do better than that. As to OS, yes by intention for ethical reasons apparently, the design of the PIII MF longevity study allows for crossover from the BAT group to treatment which would “dilute” the primary end point but its better for patients in the study if they continue to progress and can’t be offered anything else. The statisticians plan to project what it “would have been like” if they had stayed in the BAT arm but yes it will probably make the end point less strong but it is by design and ethically stronger. As to your third question, that’s up to you.

Dr. Feller is no longer w Geron as of Dec 2025, per her own LinkedIn.

[biopearl123]

Ryan, wouldn't the company have had to share publicly that a major office holder had changed? (Like within a constrained time period). Maybe they did and I missed it.

[Ryan]

Ryan, wouldn't the company have had to share publicly that a major office holder had changed? (Like within a constrained time period). Maybe they did and I missed it.

They definitely did not announce her departure… perhaps because of the title change and thus she wasn’t a chief executive when she departed, or perhaps she was part of the mass layoff, which was announced. No idea of the semantics just know for sure she is no longer with the company.

[lacour_98]

BP,
In your reply to KT, "......the design of the PIII MF longevity study allows for crossover from the BAT group to treatment which would “dilute” the primary end point....", in addition to projecting what it would have been like had the patient(s) not crossed-over, it would seem the converse could be demontsrtated, at least in the early patients, the clear OS benefit.

[biopearl123]

Lacour, I think i understand you proposition, that if early crossover occurs the patients would live longer and that hopefully would be true. The problem I see and it may not be correct is that for a meaningful statistically valid conclusion to be drawn the two arms of the Kaplan Meir curve have to diverge, the farther apart they are the bigger difference in validity in the working design namely untreated patients die sooner. If they cross over early as you suggest, then it is reasonable to assume they will live longer and arms move closer together and might even show similar results. Since one arm is the control arm if the study were pure and no crossover were allowed the BAT group would show shorter longevity and the study could conclude sooner. Allowing crossover no matter how early just brings the two arms closer together, prolongs the study and makes the difference between the two arm less profound, it emphasizes sameness not differences. So yes early crossover may show a longevity effect but in this case it is the role of the control arm to show patients do not benefit nearly as much as the treatment arm. Once BAT crosses over that benefit is lessened. Good for the patient bad for the study. I think you are saying we should look for longevity in both groups but the study looks for death in the control group and by prolonging death in the control group by allowing crossover the time to death may be extended and the control group start to look more like the treatment group. Now that is a rambling stab at trying to answer your question. If I didn’t get it right ask me again in a different way.

[biopearl123]

Ryan thanks for the clarification. I don’t know what the rules are for leaving. Maybe they gave her a lesser position for some defined period that then allowed them to part without an announcement. It’s troubling she left, I thought she was great. I hope it was for some wonderful reason and not because she lost faith in the company. We may never know if she had to sigh an NDA.

[lacour_98]

BP, You were able make sense of my question and clarified my understanding of the trial analysis protocols. Nonetheless, I think the results will speak for themselves and across-over patients OS will stand out.

[biopearl123]

lacour, to expand a little on my last comments, in addition to the “actual” statistics there will likely be some analysis of the cross over arm that includes a projection of death that looks at “what the arm would have looked like” had there not been cross over. This is the statistical magic I have referred to previously that has to take into account that the cross over patients may start to live longer had they not crossed over. There has been reference to this in the past discussions. The fact is that the interim analysis can not take place until 112 patients have died, not projected to die but actually die. So even if the statisticians can make an accurate projection of when the control group patients would have died (which they will), the trigger for the interim analysis requires actual deaths. This is a long winded way of saying that the study is necessarily prolonged by allowing crossover (if the drug is working), which I think is the point you were making in the first place. So I think the control arm will have two plots, actual deaths and projected deaths if they had not crossed over (even though they did) but it won’t happen until there are the requisite number of actual deaths to trigger the interim analysis.