| To: tuck who wrote (3149) | 9/9/2017 4:09:26 PM | | From: tuck | | | | IDO/PD1 . . . Here's is INCY's presentation, which dose give demographic data. This was a dose escalation trial, whereas, NLNK's was at single dose. So apparent disadvantage of Epacadostat I noted in the prior post may be due to that.
Incyte ESMO presentation
I can't quite read through the patient baseline characteristics. It seems ECHO had a slightly higher % of M1c patients: 55 versus 50. Further, every patient was M stage (stage IV), whereas in the NewLink trial, 13% were stage III. ECHO also had substantially fewer treatment naive patients.
So now, having seen all the available data, I would call this approximately even. NLNK had better numbers, but population was less sick.
Cheers, Tuck |
| | Incyte (INCY) | Stock Discussion ForumsShare | RecommendKeepReplyMark as Last ReadRead Replies (1) |
|
| To: tuck who wrote (3153) | 1/4/2018 1:08:22 PM | | From: Miljenko Zuanic | | | | I do not think that it is kynurenine level (as biomarker) that describe path for cancer IDO-1 activity, it was biopsy of resected brain tumors. So, my guess is that regardless long t1/2 and high dose (in addition to preclinical model), PFE candidate did not penetrate tymor mass...results was inactivity.
In general, this guy from SA favorise NLNK Inoximod:
seekingalpha.com
but, I was sceptical about Inoximod MOA early and still am. Wish, PGS can stop by and drop few words on topic (I do not like conversation @ twitter).
PS: IF INCY drop further (due to luck of data at JPM), I am considering position. |
| | Incyte (INCY) | Stock Discussion ForumsShare | RecommendKeepReplyMark as Last ReadRead Replies (1) |
|
| To: Miljenko Zuanic who wrote (3154) | 1/4/2018 2:39:23 PM | | From: former_pgs | | | | I don't really understand the PFE decision. Based on IDO's role, it's not expected to have single agent activity, so it's bizarre to see them drop this drug after <20 patients and without even trying a combo. Regardless of whether or not IDO is a good target, I don't think this trial is an indictment as it seems strangely limited in scope. PFE clearly got spooked by something. My suspicion is given their trailing status, they had a very high internal bar for what this drug had to do to make it seem worthwhile.
>I was sceptical about Inoximod MOA early and still am<
A couple of excerpts below from a recent review paper. I'm relatively convinced that indoximod is not an IDO inhibitor. This doesn't validate the IDO inhibitors out there, but does suggest one would make a mistake by extrapolating heavily based on the indoximod data.
"By far, the IDO probe most employed in the preclinical liter- ature is the simple racemic compound 1-methyl-D,L-tryptophan (1MT) with a reported Ki for IDO1 of 34 mmol/L (65, 66). The L isomer acts as a weak substrate for IDO1 and is ascribed the weak inhibitory activity observed with the racemate, as the D isomer neither binds nor inhibits the purified IDO1 enzyme (4)." - note, indoximod is the D isomer of 1MT
"A number of studies have addressed the mechanism of action of indoximod. However, in considering an evaluation of human pharmacokinetics where clinical responses have been noted (69), only one study has provided an explanative mechanism consis- tent with blood serum levels achieved in clinical trials (70). Specifically, this study revealed that indoximod can resuscitate cellular mTORC1 activity inhibited by tryptophan depletion with an IC50 of approximately 70 nmol/L (70). Thus, indoximod acts as a high-potency tryptophan mimetic in reversing mTORC1 inhibition and the accompanying autophagy that is induced by tryptophan depletion in cells." |
| | Incyte (INCY) | Stock Discussion ForumsShare | RecommendKeepReplyMark as Last ReadRead Replies (3) |
|
| To: former_pgs who wrote (3155) | 1/4/2018 7:13:53 PM | | From: Miljenko Zuanic | | | | Thanks, we agree Indo is not an INDO-1 inhibitor.
<Thus, indoximod acts as a high-potency tryptophan mimetic in reversing mTORC1 inhibition and the accompanying autophagy that is induced by tryptophan depletion in cells.>
Can this explain synergy with IO path and added activity, seen for other INDO-1 inhibitor? Should re-activation of the mTORC1 bring "survival" benefit to cancer cells? |
| | Incyte (INCY) | Stock Discussion ForumsShare | RecommendKeepReplyMark as Last Read |
|
| From: scaram(o)uche | 1/7/2018 7:32:20 PM | | | | | | Celgene buying fedratinib for what?????
PGS and friends discussing it at twitter, no need to digest here. "Incremental" has become CELG-important, a shame. |
| | Incyte (INCY) | Stock Discussion ForumsShare | RecommendKeepReplyMark as Last Read |
|
| To: former_pgs who wrote (3155) | 1/9/2018 1:59:18 PM | | From: Miljenko Zuanic | | | | At JPM, INCY was cautious on IDO1, so...PFE exiting IDO-target may (after hearing their and BMY presentation) sound as diversification from BMY-overlapping programs. IF PFE can afford (at least) 40% premium to current BMY MC, they would go after it.
Sorry to pollute INCY tread with PFE/BMY thoughts! |
| | Incyte (INCY) | Stock Discussion ForumsShare | RecommendKeepReplyMark as Last ReadRead Replies (2) |
|
| To: Miljenko Zuanic who wrote (3158) | 1/9/2018 2:47:15 PM | | From: scaram(o)uche | | | | >> At JPM, INCY was cautious on IDO1 <<
With all of the commentary about duration and deepening of the response, and with the slide showing data vs. historical for PD-1 alone? Emphasizing that nivo/epa results were as strong as pembro/epa? I got the opposite feel, that they were very strong re. IDO1. |
| | Incyte (INCY) | Stock Discussion ForumsShare | RecommendKeepReplyMark as Last ReadRead Replies (1) |
|
| |
