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ARQL / MET
I have to admit I was operating under the premise that the majority of oncogenic mutations to c-met were not yet known - either from a percentage of all oncogenic c-met mutations or from a percentage of of humans with a c-met mutated cancer. But your sentence above implies that the significant majority of mutations are known and listed - which is/would-be a surprise to me given how difficult it is to find something when you don't know what it looks like?
ARQL / MET:
I looked at both papers, the one Iwfal cited and the one you cited. I didn't see anything in supplemental data to exclude what Iwfal stated, or what I postulated. Rather than making a general dismissal, why don't you cite the specific part of supplemental data where the author's claims can be unambiguously shown.
That may well be true, but we aren't looking at by and large, Iwfal asked about the specific cell line TOV-112D, not the general mutations found in tumors.
I was postulating very c-terminal deletion that would eliminate the short terminal part of MET shown in Fig 1A as the CT domain, which is c-terminal to the kinase domain
I already explained how it was possible to miss the protein by Western blot AND the mRNA by PCR using a single primer. If you have other papers which more precisely characterize the TOV-112D tumor cell line, then do so rather come back with than some snide comment.
Quite frankly, I am surprised at your comments. You need a better attitude if you ever want to go from being a poorgradstudent to a poorpostdoc.
ARLQ / MET
Sorry poorgradstudent but I disagree with you.
ARQL:
But my question is whether looking for the c-Met unmutated mRNA will find heavily mutated c-Met (as many consitutively active c-Mets are). I.e. I believe that the two assays they did would miss a high fraction of constitutively actived c-Met. But that said, the reason I asked for vin (or you) to look is that I don't know the precise limits of the two assays they used - so I was looking for someone to comment on that.
c-MET:
They claim Tiv was effective against the TOV112D cell line which "doesn't express c-Met". But the source paper for the claim that it doesn't express c-Met is far from conclusive since (in a quick look) they appear to have looked only for full, unaltered c-Met
Well, as jq noted, they seem to be pursuing similar strategy as ARQL (monotherapy in HCC) and they are well behind in it.
Way behind ARQL's tivantinib. How is INCY's MET inhibitor differentiated?
ONXX:
What do you think this means?
I think the stock is close to fully valued right now and they probably think so as well.
Thanks.
I guess I'll wait until the relevant data are posted.
FAERS data is significantly different than that reported in the Favus survey.
Any comment?
OT:
The whole tenor of the articles and commentary are towards the idea that there is systemic fraud rampant in all of science, and I don't buy it.
OT:
I guess I wasn't asking for a list of what you do. It's a matter of what ALL researchers do. So I find most of your response to be besides the point.
Nor do I find this a pharma versus academic science thing. I'm just worried about what I contribute to, and that's the academic side. I think we owe it to ourselves as a community to do the most reliable / reproducible science possible, and let history sort out what was important and what was incremental.
Also, I do not agree with this concept that airing basic science's dirty laundry somehow helps those who are against it. Silly senators who are going to complain about 1.5 MILLION DOLLARS SPENT ON FRUIT FLY RESEARCH!!!! are going to complain regardless. Their supposed "ammunition" is science's strength, and they'll never realize that.
That's all I got on this topic.
OT:
The 50% comment is a likely a major over-estimate. Are you saying the 50% figure in a particular small area, or as a general view. It also depends on what you mean by not being able to be reproduced.
The unspoken rule is that at least 50% of the studies published even in top tier academic journals – Science, Nature, Cell, PNAS, etc… – can’t be repeated with the same conclusions by an industrial lab.
ARIA:
Thanks.
ARIA:
If they sold it would be very bearish right? Can you talk about why you think they have a bearish stance?
ARIA:
Blackrock adds aria over 3 million
ONXX:
Yes, but only marginally; however, many investors probably think the breakthrough therapy designation is a very big deal.
ONXX:
Their likelihood of 8% palbociclib royalties just went up.
AARY:
Yes, they've talked about that as a possibility for the high AAG group specifically.
ARIA:
This is a ludicrous and unprofessional thing for a CEO to say when he just established a 10b5-1 selling plan.
ARIA:
My last point on this, mostly because your obtuse responses are annoying.
Poorgradstudent, you are making this way too easy.. I'm confident that the results will speak for themselves over time. It will not matter what some lame brain individual or firm has to say.
ARIA:
Harvey did tell you if you listened carefully to the CC.
ARIA:
Poor grad, Ariad data will be delivered in 30 days, May 7th, so hang in there..
ARIA:
Harvey refuted the claims regarding Iclusig safety, gave updates on everything, and answered every question.
ARIA:
Brutal, meandering call. It was so long and disjointed that it's hard to know why they even had it.
i had to stop listening around 50 minutes.
Boring or not, if it was a competitor that sponsored this report, how could it be considered unbiased?
I have no idea who sponsored it, but I will wait for a clearer picture before I decide if Pona has safety issues. Not AF's buddy and this obviously tainted opinion.
ARIA:
You guys do realize that this Elliot Favus report was a competition sponsored survey, don't you?
This was a smear campaign and a successful one for the time being.
ARIA
My question is isn't the main risk here the cardio risk?
My bet is that they added lipase elevations to pancreatitis and reported both as pancreatitis.
ARIA:
I wonder if they should try dose titration similar to Jakafi
PYMX:
There's bad management. And then there's bad management.
But that's life when you take a flier on one of these super speculative companies. I wonder if someone will try to move the IP forward or has everyone taken a look under the hood and run away screaming?
For AF to allow the hedge fund guy to label Iclusig a "dirty drug" was irresponsible at best. If he as informed as he claims to be on the space he covers, he knows the data the FDA used included all the AE's and not just the ones attributed to the drug. Why allow some hedge fund guy with an obvious agenda to talk trash?
ARIA:
The slope of the sales ramp
INCY:
A reliable poster on twitter said that the patient has been on drug for 1 month.
I've not been able to independently confirm this, so make of it what you will.
GERN:
Are you fairly confident that the ET results will be more likely to translate to MF than to MM?
I am also curious how PV fits into all of this and why GERN has apparently never reported data on the 2 PV patients enrolled in the ET/PV trial. Should we take the lack of disclosure of specific details on the 2 PV patients as a negative and how closely does PV correspond to MF?
GERN:
Are you still holding on in belief that MF data, or perhaps AML/MDS in due time, will be positive?
It’s apparently going to mean little more than the old Fast Track designation.
So O'Karma's gone and you figure, what...That all his hencemen were not aware of the shenanigans? That GERN has turned over a new leaf? OK so forgetabout the mirkyness...Things are different now I guess.
Gern
Disagree - the cancellation of the PV trial without explanation adds murk IMO, and when added to the paucity of data out of the ET trial (there are at least 3 important aspects of ET, two of which overlap with PV. And the ET paper was silent on the PV-overlap data (spleen size and symptoms).) I think it is a very good bet that the PV trial had some significant issues.
The real problem with that is that, if anything, MF has more in common with PV than with ET. So if PV was a bust... .