Another nice summary from Sdraw

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biopearl
Posts: 367
Joined: Wed Dec 09, 2015 12:12 am

Another nice summary from Sdraw

Post by biopearl » Tue Mar 27, 2018 5:05 pm

Repost from YMB, Sdraw:

sdrawkcabeman12 minutes ago
Here’s a micro-brief on some of the publications:

From the Huff, et al, paper on MM:
“Over the course of treatment, the frequency of MM CSCs decreased significantly, on average 2 fold every 30 days.”

100% hematologic response in ET, with 89% CR, drastic reduction of neoplastic clones with selectivity, correlated with drastic reduction in JAK2 V617F allelic burden, as well as CALR mutant allele.

Unprecedented CRs in the MF pilot study, even including the actual reversal of fibrosis in the bone marrow. Histologists said the pts’ bone marrow was indistinguishable from completely healthy individuals. This included 21% CR/PR, 36% ORR, and 64% stable disease! In a pilot! The myelosuppression, in fact, was an indication of Imet’s on-target activity!

As was seen in the ET study, the pilot RARS group saw reductions in JAK2 V617F and CALR mutant allelic burden. 50% of these pts were highly pretreated by other drugs, and carried multiple mutations, indicating genomic instability; here is the idea, again, that these diseases must be treated to eradicate CSCs (which is precisely Imet’s target) before they unravel into the clonal diaspora. The pts with higher clonal mutations responded more poorly. It will indeed be an important trial for Imet in frontline therapies across the board with an eye towards destroying clones early on. You can see how well these pts responded, reaching “rapid and sustained hematologic and molecular responses within 3-6 cycles of treatment”(Tefferi).

The Haubitz, et al, ASH presentation in 2016 yet again demonstrates Imet’s target is, in fact, cancer stem cells by measuring the ET patients’ allelic burden correlated to telomere length. The diseased cells have very short telomeres and, as the clones are destroyed, telomere length actually rebounds, indicating Imet’s on-target activity.

And lastly, the Fenaux, et al, AHS presentation in 2017 on Imerge. For the primary endpoint, 38% achieved transfusion independence greater than 8 weeks, 16% reached greater than 24 weeks. What’s more, the non-del5q pts who were naive to lenalidomide and HMAs responded even more favorably, at 54% and 31% for 8wk and 24wk transfusion independence, respectively. 13% achieved CR and marrow CR.

All adverse events are reversible by simple dose and schedule modifications.

The much-anticipated AML trial will be the next development in blood.

Imet is unquestionably efficacious across the myeloid group, and this is just as a single agent. And this is just in the blood indications. I think it’s a no-brainer that Imet will approved for use in treatments across these diseases, even in ET, if you consider the case for disease progression and genomic instability. And even more significantly, we’re already seeing groundbreaking results in preclinicals for Imet’s forays into diseases beyond blood.
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