AACR abstracts

[biopearl]

AACR abstracts are up. I can't copy them for some reason or I would. Impressive synergy in AML therapy reducing viable AML cell line in one instance to 1 percent after only four weeks (what happened after that???) Check it out and let us know what you think. Regards, bp

[Fishermangents]

Here they are:

Abstract Number: 2731
Presentation Title: Impact of hypomethylating agents on hTERT expression and synergistic effect in combination with imetelstat, a telomerase inhibitor, in AML cell lines
Link: http://www.abstractsonline.com/Plan/Vie ... 0fb1922267

Abstract Number: 2732
Presentation Title: Myelosuppression in patients treated with the telomerase inhibitor imetelstat is not mediated through activation of toll-like receptors
Link: http://www.abstractsonline.com/Plan/Vie ... 0fb1922267

I will add them to imetelstat.info soon.

Both presentations are very interesting (although rather technical for me...). The AML one, because it seems that the imet + DAC/AZA combo may make standard treatment significantly more effective, rather then just using imetelstat to prevent relapse after BM-transplant. The toll-like receptors presentation shines some light on how imetelstat causes thrombocytopenia. If this mechanism is understood, it may become possible to prevent this adverse side effect, thus making imetelstat even better to tolerate.

[Fishermangents]

Here are some remarks from (our) Phil on the AACR abstracts, MoA etc.:

"I have mentioned a few times that the reason I was so excited to have Geron partner with Janssen was that to me, while imetelstat and telomerase inhibition has massive potential, the drug has always needed better understanding, and now, this AACR abstract starts to lead us directly down that path of enlightenment. We know that some MF patients obtained complete remission, others got a good, but lesser response, but Why? Imetelstat has shown efficacy on virtually every cancer cell line, but some better than others...Why? Dr. Lane's study in AML using combo therapy worked wonders with Zero relapses, but Why??? What is the mechanism of Action?
Those are the questions many of us have asked, and it looks like Janssen has wasted no time at all getting their world-class research department looking into imetelstat and how to make it a blockbuster. In order to do that, they are collecting data, data, data and trying to get a better understanding. AML cell viability knocked down to 1% using imet in combo??? That's remarkable. While this data would be better if seen in patients, it still shows Janssen cares and is putting serious resources and efforts into figuring out the drug.
One the second abstract: Remember the editorial in NEJM on imet's mechanism of action? A few editors hypothesized that the MoA was more related to the drug being an oligonucleotide than being a telomerase inhibitor, and that raised concern. However, now we see the other AACR abstract debunks that theory, making it fairly certain that telomerase inhibition is in fact why the drug works and that is its MoA- very important. This abstract is critical for a few reasons: It shows Janssen's commitment to making this partnership go full speed by throwing the weight of their research team behind the study, it shows that they are moving forward swiftly, it shows the MofA is not oligo related (a good thing), and most importantly, the abstract demonstrates that the drug WORKS! A nominal 1% viability in AML cell."

[scottmayhew]

So how long before Janssen starts recruiting for an AML stage one combo trial? Any chance something like that is given light at AACR?

[biopearl]

I would say no chance. It might happen independently of the AACR meetings and could be coincidental timing only. ASCO in the summer might be a bigger splash. I am hope to get some read on the pediatric consortium study then. Geron has implied AML study by mid year I think. bp