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Exelixis, Inc. Message Board

wilderguide 4373 posts  |  Last Activity: May 21, 2016 11:46 AM Member since: Jan 13, 2011
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  • Reply to

    Mismatch repair demistified

    by erniewerner May 20, 2016 9:59 PM
    wilderguide wilderguide May 21, 2016 11:46 AM Flag

    $$$$
    This concept makes me laugh...
    "Mismatch repair" sounds like a warranty offering from MatchDOTcom...
    "If your romantic match-up leads to spiteful, costly, heart-breaking divorce...
    We'll cheerfully refund your subscription fee..."

  • $$$$
    "Everyone knows why no one wants to be in the room with us." - Daniel Weiner, Turing lawyer...
    Most punchable face in America? Halitosis? B.O.? Sphincter stench?
    More on the Shkrelification of America from Reuters, 5/13/2016...

  • $$$$
    Taken from the research article,"Inhibition of the angiopoietin/Tie2 axis induces immunogenic modulation, which sensitizes human tumor cells to immune attack" Dec, 2015 - free at Research Gate...
    Grenga.. et al, in differentiating amongst sunitinib, sorafenib, and Cabo in modifying immune response:
    "Only one of these agents, cabozantinib, which is an inhibitor of multiple receptor tyrosine kinases, including RET, MET, and VEGRF2 has been reported to induce immunogenic modulation, altering tumor-cell phenotype and sensitizing tumor cells to immune-mediated attack." Very informative...
    Apparently, one of the Anna Kwilas NCI studies...Note that co-author Farsaci is employed by BMY...

  • Reply to

    clinical trial RCC

    by timesensitive May 7, 2016 5:46 AM
    wilderguide wilderguide May 19, 2016 1:07 PM Flag

    $$$$
    "clinical trials exclude the sickest people..."
    Ernie, I think we discussed this editorial several months ago...(unless I dis-remember this study as a product of the Dan George Duke team). A "sicker" real world population does outwardly suggest that there may be more patients that might be interested in Cabo, if only for Cabo's gaining rep as salvage treatment - perhaps immediately following exposure to Nivo...or sunitinib re challenge. No doubt, the market has responded well to the abstract release, and I suspect there may be a lot of juice in Choueiri's presentation and the ensuing investors conference - especially if we get clarity on further development.

  • Reply to

    ASCO data outstanding

    by hum14jbird May 18, 2016 9:41 PM
    wilderguide wilderguide May 19, 2016 8:08 AM Flag

    $$$$
    A small Italian study is being published in conjunction with ASCO 2016 that I won't let slip by w/o comment, as it directly addresses the Cabo bone phenom:
    "Conclusions: Overall, this is the first evidence in human of the “direct” effect of CBZ on OCLs and “indirect” osteoblast-mediated through a modulation of RANKL/OPG balance. These multiple effects of CBZ on the cells of bone microenvironment are consistent with its effectiveness in reducing lesions from prostate cancer metastases."
    Previous research has described Cabo effect in terms of RANKL inhibition, but this is the first reference I have found suggesting a corresponding upregulation of osteoprotegerin production. This is more than an interesting side note to Cabo benefit, as it further differentiates Cabo from any other existing MKI currently approved.

  • Reply to

    Digital Pong

    by wilderguide May 18, 2016 12:11 PM
    wilderguide wilderguide May 18, 2016 2:58 PM Flag

    $$$$
    "...my intention was not to play one upmanship..."
    Heck, I didn't take it thataway at all. Thin skin is not in my nature...
    The dynamics of greed vs ethics on Wall Street should be open to discussion, regardless of who gets exposed, who gets caught, or who's the next SEC target. I might be a bit naive, but in still believe #$%$ sapiens are elementally honest.
    Those that work on Wall Street appear to be a derivative of #$%$ indomitus...

  • Reply to

    Digital Pong

    by wilderguide May 18, 2016 12:11 PM
    wilderguide wilderguide May 18, 2016 1:38 PM Flag

    $$$$
    "Now driven by..."
    Knowing the identity of the puppeteer isn't necessarily inclusive of any gainful knowledge regarding the actual timing of the stage show...or the pulling of the strings. It's a bit like attempting to guess the content of the next chapter to a book that's still being written - or charting the course of a ship with an uncalibrated compass. Ya just can't figure out where yer going till you get there...

  • wilderguide by wilderguide May 18, 2016 12:11 PM Flag

    $$$$
    Share price du jour brought to you...
    ...compliments of Dubin & Swieca....
    Playing the game, setting up the point, eyeing the match...
    To cover or convert? That is the question, my dear Watson...

  • Reply to

    From three little pigs to one big pig

    by snowflakeformationxy May 16, 2016 9:50 PM
    wilderguide wilderguide May 17, 2016 2:29 PM Flag

    $$$$
    $$$$
    I pulled the following excerpt off-line from ValueWalk, posted 9/10/15 by Clayton Browne "CFTC joins investigation into JPMorgan "Client Steering" "

    The CFTC inquiry into JPMorgan’s hedge funds had not been publicly released until today as it is a part of a larger probe by federal and state regulators.
    The sources also noted the investigation includes a closer look at new client activities at Highbridge Capital Management, a hedge fund firm owned by JPMorgan. The CFTC is investigating why such a high percentage of Highbridge’s AUM stems from JPMorgan’s private-bank assets, and, moreover, just how important was the new client cash infusion in stabilizing Highbridge during the financial crisis, according to the WSJ sources."
    Whether yer ticketed for 1st class, cabin, or steerage...
    It appears everybody is somebody's biotch...

  • wilderguide wilderguide May 16, 2016 10:17 PM Flag

    $$$$
    A June 27, 2009 EXEL PR introduces the concept:
    "In January 2005, the GSK agreement was amended to focus on 12 specific programs: XL647, XL999, XL784, XL880, XL820, XL844, XL184, XL281, XL418, XL228 and two earlier-stage programs, from which GSK had the right to make its development elections. Exelixis retains rights to collaboration compounds not selected by GSK, subject to payment to GSK of a low, single-digit royalty on certain Refused Candidates that GSK elects not to choose with its development election which Exelixis thereafter successfully commercializes. "
    XL-184 is one of the "Refused Candidates"... It's mentioned elsewhere, ncluding some of Ernie's past posts. As for your Q wrt XL-880... I feel if it were to have moved into pivotal trial, it needed to happen sooner than later. JMO, it's tardy to the party...

  • wilderguide wilderguide May 16, 2016 5:26 PM Flag

    $$$$
    "It's odd but Wilder is right..."
    I may not be smart, but I sure am ugly...

  • wilderguide wilderguide May 16, 2016 5:04 PM Flag

    $$$$
    "Ten studies under Phase II by GSK; is III coming?"
    Doubtful, as the XL-880 & XL-184 molecules are very similar. I suspect there are overlaps in IP. I also suspect GSK has given up on future development.
    "What would EXEL want to suppress?"
    I don't have a simple answer, though it's possible it's as simple as limiting competition in the MET/VEGFR/RET/AXL/ROS1/MNK inhibitor space. As I mentioned earlier - as far as concerns proprietary molecules - the two really are quite similar. If you look around, you'll find a lot of potential "me too" molecules in development. Mirati has one. Easai has one. I think the space could crowd up in the coming decade... Lucky for you...Cabo got the first solid approval with another P3 reporting - probably in the next 12 months. In the long run, Cabo may not be the best...
    But, it's undeniably the first...

  • wilderguide wilderguide May 16, 2016 3:01 PM Flag

    $$$$
    "Cabo...also targets AXL."
    You may be right. If memory serves, GSK still owns a small piece of Cabo - maybe as much as 3%. I think it was a condition of closing out a prior agreement. Now that Cabo might be worth something, I'm certain GSK will want to exercise its proprietary piece of the action.

  • Reply to

    comparing Cabozantinib and Lenvatinib

    by biotechblood May 14, 2016 6:45 AM
    wilderguide wilderguide May 15, 2016 4:25 PM Flag

    $$$$
    "How often and how many times...
    ...will adjustments be needed ?"
    Your question made me laugh - reminded me of a scene from The Terminator where Arnold takes the hand of Linda Hamilton and says "Come wizs me if you want to live..."
    I suspect the answer to your question is simple -
    "As often as is necessary to produce the optimum effect."
    IAW - it's probably different for each patient, and totally dependent upon lab work-ups, patient education, therapist expertise, and overall patient response. I'd bet a good number of physiologic "tells" have been recognized on the pathway to successful drug titration. Definitely not a bandaid fix, but a derned sight better than the alternative...

  • Reply to

    comparing Cabozantinib and Lenvatinib

    by biotechblood May 14, 2016 6:45 AM
    wilderguide wilderguide May 15, 2016 2:12 PM Flag

    $$$$
    " Eisai's trial compared L/E to Ever, not Cabo or Nivo."
    If I understand your logic correctly - would you expect a successful supplemental filing to be made based on non-inferior CABOSUN results?
    If not, how positive would you expect those results need be to create the basis for a successful filing in frontline RCC?

  • Reply to

    comparing Cabozantinib and Lenvatinib

    by biotechblood May 14, 2016 6:45 AM
    wilderguide wilderguide May 14, 2016 4:57 PM Flag

    $$$$
    A short addendum to these thoughts...just thought to toss it out for feedback.
    I'm actually a bit alarmed by the L/E approval, for all the reasons I've suggested and more...
    Just when you think you've got a handle on the overture of conservatism practiced by the FDA - they grant approval in a crowding indication based upon data from a 50+ patient cohort! when the competition only just recently proved out in very much larger trials.
    Doesn't this sort of defy the CW? ...is this some sort of "gimme..."?
    Or - has Easai bought a few more tickets to the Policeman's Ball this year?

  • Reply to

    comparing Cabozantinib and Lenvatinib

    by biotechblood May 14, 2016 6:45 AM
    wilderguide wilderguide May 14, 2016 11:17 AM Flag

    $$$$
    The May edition of JOP is afloat in expert commentary on RCC treatment. Mallout, Posadas, Rini, and others have contributed. Unfortunately, only the extracts are free. Lots to debate going into ASCO, and the conference may actually raise more questions than provide answers. JMO, but I think updates on Nivo, Cabo, and the two combined will steal the show. I also feel that most Oncos will await CABOSUN data before even thinking to add Lenvatenib to their RCC toolbox. Sparcity of data, toxicity, and insurance coverage will all be issues going forward. No worries...

  • Reply to

    lenvatinib/everolimus combo approved

    by rad.onco May 13, 2016 5:05 PM
    wilderguide wilderguide May 13, 2016 6:14 PM Flag

    $$$$
    "Time will tell how the Oncs view the data..."
    Nivo is great, but there are a high percentage of non-responders. For those who do not respond to PD-1i...and cannot tolerate the toxicity of Cabo...the Lenvima/Everolimus combo provides another treatment option - albeit costly and toxic in its own right.
    I don't see the L/E approval having much impact on the RCC algorithm, except as a salvage agent. It simply doesn't carry the stats for any clinical uptake except w/ dire refractory circumstance. No worries...

  • Reply to

    Bank of America presentation remark

    by hbomb57108 May 10, 2016 5:55 PM
    wilderguide wilderguide May 11, 2016 5:11 PM Flag

    $$$$
    "It was missing a few hours earlier."
    Probly my fault. I got an earlier e-mail from IR suggesting that in the future, I refrain from any reference to MMM as "giddy"...
    "No successful biotech CEO is referred to as "giddy"" ...was the message.
    I think your downtime is that they were in there deleting any potential giddiness...
    Further, Sue Hubbard went on to recommend that - in the future - YMB references to MMM should be preceded by "Oh Captain, my Captain..."
    VE RI TAS

  • Reply to

    Bank of America presentation remark

    by hbomb57108 May 10, 2016 5:55 PM
    wilderguide wilderguide May 10, 2016 10:16 PM Flag

    $$$$
    "At the very least it sounded as if he had seen the abstract Roche will be presenting..."
    Sometimes MMM seems absolutely giddy... And perhaps not w/o justification.
    In the wake of failed SPA negotiation in CRPC, two failed COMETs, and a premature dis-assemblage of the EXEL workforce...MMM has w/o a doubt tied on the glad bag in recent times...
    If you consider that only last year, MMM was a Wall Street biotech toad...
    These recent successes have nearly transformed him into a proverbial Prince...
    All he's gotta do is keep up the clinical momentum, pay off the LT debt, retire the CVs...
    Appease the shareholders, bring back the band, and possibly sell out at a huge premium...
    If there's any dirt, make sure it's all swept under the carpet of zealousness...
    What could possibly be easier?
    It's gotta be nerve wracking...

EXEL
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