ImetelChat

I have not seen mention of the Medalist trial in Gerons materials before. Did I miss it? The trial has similar end points as the Geron/Janssen MDS trial. It looks like luspatercept is a super EPO that treats anemia. It does not appear to target the malignant clone so Imetelstat's uniqueness may favor it but clearly Scarlett is telegraphing that the playing field has other players in MDS. It looks like a race to the finish line with similar timelines for study completion. Just something to watch. Clearly they have positive data in MDS to date or they would not be planning to submit to a future scientific meeting. Submitting is not the same as acceptance but they seem pretty confident of eventual presentation. For now we wait. The mention of AML on Geron's slides to my reading is just a reiteration of the original agreement with J and J. The fact that it hasn't happened yet is disconcerting and makes me wonder if the MF data to date has had some influence on a corporate decision to hold off. bp

bp,

I share your concerns. The fact that they have incorporated another MDS trial in the slides made me concerned and they continue to emphasize that if the safety profile warrants the trial will transition to phase 3. Scarlet seems to emphasize the "if the safety profile warrants" often when it comes to MDS. Also, slide #25 makes it clear that the AML trial won't happen until after a positive continuation decision by Janssen. This is the first that I have seen this.

Bp, anemia is a symptom. If severe, it may not be possible to use imetelstat due to myelosuppression. So if luspatercept is capable of reduce anemia, imetelstat may be administered. You see this now with the combination EPO and interferon in MF. Anemic patients will have problems with interferon due to myelosuppression. If EPO reduces anemia and increase Hb, interferon can be administered.

http://www.bloodjournal.org/content/124 ... ecked=true
(see under 'How I treat anemia')

Luspatercept and imetelstat actually may be a potential combo (imho, because who am I....).

Let's not forget that Dr.S. announced that JnJ was going to present all data of the complete imetelstat program at end of Q2 2017 to the FDA. I presume this will be data from IMbark, IMerge and as much as possible from the Mayo study, as well as data from the 'numerous' pre-clinical studies that JnJ is performing / has performed. The reiteration of AML is good, as I thought it was completely disappeared from the agenda. If imetelstat is disease modifying in MDS (which is what slides 3 (top) and 8 of the Geron presentation are clearly suggesting) we can be pretty sure that an abstract will be accepted by a major conference.

Let's not forget that Dr.S. announced that JnJ was going to present all data of the complete imetelstat program at end of Q2 2017 to the FDA

For sure this is written in stone? All data even from Mayo? And is Friday. June 30th the absolute last day of Q2 2017...so it has to take place by then?

Fisher,

If Imetelstat is relegated to be part of a combo therapy with SOC or luspatercept it seems that would reset the approval clock as a new trial would be needed. I hope this isn't the case. But with Scarlett often using the term "if the safety profile warrants" (or something like that) in reference to the MDS trial and not the MF trial gives me concern.

Scott: it was not written in stone, but mentioned by Dr.S in the latest telco.

Bp: Please let them go straight forward with the current single drug trials. All the comboing after approval... I am not sure I understand your concern.

Fisher,

My concern is that often when I hear him in a webcast discussing the MDS trial moving forward he seems to throw in the caveat "if the safety warrants". He doesn't seem to say this about the MF trial. My paranoid side interprets this to mean that perhaps the Imet side affects outweigh the benefits when compared to Luspatercept or standard of care. Perhaps I'm reading between the tea leaves too much on this.

I think it is a standard disclaimer. For MF we know a lot about potential toxicities and side effects. There has been quite some official reporting about that, e.g. from Dr.T. So no need for Dr.S. to repeat this again. For MDS there is less known/published about toxicities. That could explain the difference in mentioning.

This is what IMET is up against in the present MF trial:

“The long-term outcome of ruxolitinib therapy in MF was recently reported and disclosed a very high treatment discontinuation rate (92% after a median time of 9.2 months) and the occurrence of severe withdrawal symptoms during ruxolitinib treatment discontinuation (“ruxolitinib withdrawal syndrome”) characterized by acute relapse of disease symptoms, accelerated splenomegaly, worsening of cytopenias and occasional hemodynamic decompensation, including a septic shock-like syndrome.”

http://onlinelibrary.wiley.com/doi/10.1 ... 24592/full#

How many of these very sick patients need IMET significantly help in order for the trial to be considered a success? I don’t know. But it seems to me accomplishing that would be no small medical achievement.