The IMpactMF Trial: A Comprehensive Analysis of Potential Outcomes

[biopearl123]

MG, STA and Ryan correct me if I am wrong but we have covered the specific studies that support the idea that patients enrolled in formal studies have an advantage over their counterparts. Moffett is certainly first class and these findings would apply to patients enrolled in most academic centers. Also we have looked at MF registries from IMPact overlapping non US and non European centers for exactly the reasons under consideration. I do think these exercises help refine the data going into the AIs. MG thank you for doing exactly that.

[lacour_98]

As I have stated before, much of the discussion has been difficult to digest and understand, but still very interesting. It seems the board has explained Geron has gone to great lengths to design the trial for undisputable results and have set a high bar for an interim analysis that halts the trial. Where I am confused is as to the recent discussions on the latest RWD comparisons with the P2 results and how they relate to the P3 trial. Also confusing is the discussion related to patients that leave the trial and are censored or not censored and Rux patients (failed) that have entered the trial and the potential impact to the trial analysis.

[biopearl123]

Lacour, back in civilization for a few hours for 4th celebrations so I have internet. You are not alone. You have the support of the board to help address the areas of confusion. When I return next week, we can walk together through those areas and see if that helps. bp

[Ryan]

Interesting commentary from the ceo of SLS regarding similar chatter about their study. More effective means of public communication than a fireside chat, imo , making it relatively clear the audience that Geron is seeking. SLS also uo about 3x in 2026 …

Found it on Reddit and easily findable on x I am sure ::: https://www.reddit.com/r/biotech_stocks ... etty_sure/

[Secret Third Arm]

Great find Ryan. I agree, we need this kind of investor engagement!

[biopearl123]

STA, I have to respectfully disagree. The less the CEO and management have to say about the study at this point with interim analysis looming, the better. Let the data speak for itself. Anything else begs for litigation.

[biopearl123]

lacour, just back tonight. Will try to post in the next few days.

[biopearl123]

lacour_98, Let me take a shot at trying to address the questions you raised on July 2nd. I will just tell you how I am thinking about the very issues you raised and freely admit to being very far from any kind of authority in this regard. Regarding your first issue, that being the relationship between the latest RWD comparison with the P2 results and how they relate to the Impact trial. First off, I found it useful to think of Dr. K's poster in two separate parts. The first deals with an up date the matched comparison approach to trying to deal with the fact that IMbark for all intents and purposes had no real placebo arm. As you know it had a low dose (as a comparator) with a high dose arm. There was a definite survival signal but no real idea as to how this finding would apply to patients who only were real BAT. patients. That study concluded in 2018. Dr. K has gone back and found age matched controls from a bucket of Rux failure patients to try to recreate a true placebo arm. There are lots of potential problems with this approach but it was the best anyone could do. This showed roughly a doubling of survival in the imet arm as you know. The recent abstract (the first part) now expanded the bucket of post Rux failures to use matched controls to include an expanded time period up to 2025. This showed a longer BAT as expected since the use of Rux was changing in ways we discussed. OK so that's part one. If the BAT stayed the same over the time from onset of IMbark to the cessation of Impact (still ongoing) I think we would have a slam dunk, but we don't. Enter part 2. Dr. K looked at 27 patients post 2019 to 2025 to see if they were living longer (also noted in the 2016 to 2019 group) and they were. His point is that maybe the old BATs no longer apply. This post 2019 group is very small and hard to apply statistics to for that reason. So to your second question. If we want to know how long a patient on BAT will live they can be followed once they fail Rux. So far ok but what happens if they are taken out of the post rux bucket and offered a different therapy for example a bone marrow transplant. Can you put them back in the same bucket and follow them for survival? Clearly not otherwise the survival numbers are suddenly prolonged and it's no longer a "fair" look. But the bucket shrinks, so you have to subtract these patients from the original 27. That is what censoring does. They are no longer in the bucket but probably alive. If they die it is not reflected in the original 27. Patients taken out of the original bucket for bone marrow transplant or another reason (Impact?) reduce the numbers listed at the bottom of the KM curve. These are "number of patients at risk". You can see that this number gets to about half pretty quickly and toward the end (the tail) gets to something like 4 patients. So the numbers at the bottom include patients who have died (reflected in the little drops in the plateau of the KM curve) plus the censored patients (tick marks). Nothing you would think could have statistical validity at that point. Who are these patients left as time passes? Maybe the low risk or Intermediate 1 patients or the healthier MF patients. Not sure. But I think that's what the curves show. I think the message is that for these reasons we can't think of the recent KM curves as reflecting what Impact BAT is likely to show in the Impact study, with the caveat that not just BAT alone is likely showing prolongation. Since the Impact study is taking so very long and has had interim and final analysis extended a few times, as we have discussed it is likely that both arms are living longer. MG's analysis has looked carefully at all the reasons we can discern as to why. So to summarize we can't party like it's 2016, the times they are a changing', but maybe in a good way since bone marrows are probably healthier as patients enter Impact and if Imetelstat is to shine as we hope then the drug should have more to work with but the comparator arm bar is also raised.

[lacour_98]

BP, thank you for addressing my questions. I continue to digest your summary, and I think I’m getting there. The shear length of the trial in completing enrollment coupled with extension in the interim and final analysis dates throwing a few curve balls suggests the BAT has improved and helped both CT Arms. I hope the IMET patients prevail.