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Exelixis, Inc. Message Board

wilderguide 181 posts  |  Last Activity: 1 hour 4 minutes ago Member since: Jan 13, 2011
  • Reply to

    Poster: have people seen this?

    by socialidiocies 18 hours ago
    wilderguide wilderguide 1 hour 4 minutes ago Flag

    $$$$
    Also of value is the accompanying roundtable with Figlin, Choureiri, and Schwab. The evolution of understanding in disease biology witnessed by those following the development of Cabo has proven instructional, to say the least. At first noted as a "dual inhibitor", Cabo has grown into its entitlement as a multi-kinase inhibitor with noteworthy clinical responses resulting from co-targeting RET, Axl, and FLT3.
    In the roundtable, Dr Schwab comments that Cabo inhibits VEGFRs (plural), perhaps suggesting that a previously unrecognized VEZgF target has been identified.
    Interesting...

  • Reply to

    Practice Update.

    by commonwealthinc 22 hours ago
    wilderguide wilderguide 22 hours ago Flag

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    Good find. Pay attention as KOLs weigh in. The CMEs produced by Practice Update, PERS, etc are viewed by a large audience of practitioners, and KOL- opined expectations seem in-line with results to date. I suspect the application of Cabo in RCC will be revealed through such disclosures long before earnings reflect actual sales, and the positivity we are seeing seems a solid bellwether of pending clinical adoption. Have a good weekend...

  • wilderguide by wilderguide Feb 11, 2016 6:05 AM Flag

    $$$$
    "We Asked Scientists: Just How Punchable Is Martin Shkreli’s Face?
    BY JESSICA GOLDSTEIN

    Smarmy bastages everywhere beware: this reporter has science providing the rationale for your undoing...
    With this sort of media coverage, jail time is out of the question for Shkreli. What greater punishment could justice administer than scientifically identifying a guy as having "the most punchable face in America"...with the research analysis to prove it? I say Free Marty,. Turn him loose - let his victims sort him out.

  • Reply to

    DNA subset analysis has recently proven...

    by wilderguide Feb 10, 2016 1:10 PM
    wilderguide wilderguide Feb 10, 2016 2:25 PM Flag

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    My apologies to all the silly little yellow fellwas to which my statements may not apply...
    MB commentary lends itself to a target-rich environment for sarcasm, scorn, and abuse...and humor.
    My advice to you is... Don't make a target of yourself by virtue of over-righteousness...
    Nothing worse than moral snobbery in the face of a little harmless humor.
    Yer probly a democrat, too...

  • $$$$
    ...that the silly little yellow man is directly descended of...
    ...little-peckered gelatinous ooze, primordial chaos...
    ...and limited capacity for achieving cranial prowess.
    Regardless of how many Mercedes he portends to own...

  • wilderguide wilderguide Feb 10, 2016 10:43 AM Flag

    $$$$
    "Je crois qu'il a également dit qu'il peut prendre une chirurgie pour enlever le pénis de Homeslice de la bonde de Ulingt "

  • wilderguide by wilderguide Feb 8, 2016 11:36 PM Flag

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    "Clinical Cancer Advances 2016: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology" published in the JCO 2/4/16. Cabo grabs some good coverage here for thyroid, RET-mutated NSCLC, and RCC. Lots of good overview...

  • Reply to

    EXEL..Up through the atmosphere

    by db2_man Feb 8, 2016 12:42 PM
    wilderguide wilderguide Feb 8, 2016 1:31 PM Flag

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    "Perhaps we need a little of that Mary Poppins Magic..."
    If a Snickers Bar can transform Danny Trejo into Marcia Brady...
    ... and Willem Dafoe into Marilyn Monroe...
    I'm guessing a single bite into that nutty coco bar would transform Seymour...
    Into either Mary Poppins or Hillary Clinton - or perhaps both, simultaneously...
    In a changing world, even Seymour wants to be more...

  • wilderguide wilderguide Feb 7, 2016 1:38 PM Flag

    $$$$
    Just for the record, IR also reaffirmed guidance for CABOSUN top line results in first half 2016. Ms Hubbard has proven to be the most responsive of correspondents, and I encourage those that have not utilized that resource to do so.

  • wilderguide wilderguide Feb 7, 2016 1:24 PM Flag

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    I queried IR for info, the reply below:
    "As we said at the time of the OS topline
    announcement, we are targeting presenting the OS data at an upcoming major
    medical meeting, so no, we won't be discussing the specific results at the
    Leerink conference. But certainly Mike will be talking about them
    qualitatively and how they complete the full clinical profile of cabo and
    position cabo in the marketplace. Just so you know, the format for
    Leerink is actually a Q&A session between the analyst, Michael Schmidt,
    and the company CEO's, which is of course Mike Morrissey in our case. Not
    a formal presentation. Michael Schmidt will lead the discussion."

    JMO, but I don't expect much revelation from the LEERINK Q&A w/ Scmidt as Q4 & FY 2015 reporting is likely before end of Feb. MMM won't give up much before that time...

  • Reply to

    HSP90

    by socialidiocies Feb 5, 2016 11:48 AM
    wilderguide wilderguide Feb 6, 2016 12:39 PM Flag

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    "...do you know data for AUY922...?"
    High incidence of visual disturbances - and additional side effects - have convinced me to look toward the next generation of HSP90 inhibitors. FWIW - I don't think luminespib has yet generated enough convincing data to move the drug into pivotal analysis. Another FWIW - the FDA.gov site has a lengthy presentation providing overview analysis on the promise of ganetespib (dated Dec 2015) suggesting they see value in the future prospect of HSP90i, despite Synta's dismissal of further development.

  • Reply to

    HSP90

    by socialidiocies Feb 5, 2016 11:48 AM
    wilderguide wilderguide Feb 6, 2016 12:35 AM Flag

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    I'd be very, very careful wrt investing in any HSP90 technology till there is is a reliable predictive assay. Novartis gave AUY922 back to Vernalis in Dec 2014, and that program has completely stalled. Development of Ganetespib has practically BK'ed Synta. A serendipitous synergy might play for XL-888 in melanoma, but to date - no one has stepped up to the plate. I don't doubt the hypothesized efficacy - there have been some dramatic, notable responses in lung & breast cancers. However, those limited successes have proven ill- defined at best, and -at worst - non-reproducible in clinical practice. Too elusive a science for me... All well-rationalized therapeutics will have their share of non-responders, limited responders, and exceptional responders - but successful commercialization must embrace an unwavering predictability of response...and I've yet to see that in any HSP90i...

  • wilderguide by wilderguide Feb 4, 2016 4:09 PM Flag

    $$$$
    See "9 most punchable Shkreli faces (just from today)...
    Huffington Post...hilarious...

  • Reply to

    OS question

    by ulingt Feb 3, 2016 7:31 AM
    wilderguide wilderguide Feb 3, 2016 5:00 PM Flag

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    "...I think they will shoot for the March NCCN meeting."
    It is a very appropriate venue, their agenda being "Advancing the Standard of Care". To the best of my knowledge, the abstracts at NCCN have never been availed public viewing. It's a closed affair. That said - they've only had poster presentations a couple years now, and all that may be subject to change. Again, it is a most appropriate venue, and NCCN expertise will undoubtedly be called upon to satisfy the treatment algorithm. Looking forward, it makes great sense to address prescribed sequencing prior to approval, and I expect to see an upsurge of KOLs lending advice on how best to proceed as the new algorithm evolves.

  • Reply to

    30% of float is short

    by patriot901 Feb 3, 2016 3:50 PM
    wilderguide wilderguide Feb 3, 2016 4:15 PM Flag

    "...did you know that I know an employee of Exel....?"
    Yessirree Beijing Bob...
    There's more than a few of us that have seen him doing you in the patootie in the men's washroom at Cecilia's Pizzaria on Grand Ave. Might be best to keep it private, you silly little yellow man....
    But it sure is funny how you smile each time he grunts...
    Do you enjoy the marinara too...??

  • Reply to

    OS question

    by ulingt Feb 3, 2016 7:31 AM
    wilderguide wilderguide Feb 3, 2016 2:46 PM Flag

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    "I don't think the prior Nivo treated subset from Meteor gets much notice, the sample size is too small (n=32 split between the cabo and ever arms)"
    If it weren't for the rationale that the NCI is pursuing with Nivo/Ipi/Cabo, I'd agree. But - these compelling numbers fully support the PD-1i/ Cabo combo rationale, particularly with consideration to Nivo's recognized delayed response and lengthy half-life. The trigger will be a move toward a P2 trial. If P2 is decisively skipped (AKA V/C in melanoma) - the fuse would be lit. I see breakthrough status as a distinct possibility spinning out of the Apolo studies. A favorable impact on SP could easily be predicted if a move to P3 is made in 2016...
    To my thinking, that would be the ultimate catalyst toward a favorable JV...

  • Reply to

    OS question

    by ulingt Feb 3, 2016 7:31 AM
    wilderguide wilderguide Feb 3, 2016 1:53 PM Flag

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    "Any idea when the full data set will be presented?"
    June's ASCO annual meeting is the most likely venue, though I wouldn't omit the possibility of an NCCN presentation in March. The AACR-JCA is only weeks away, and is doubtful - even for an LBA. Inopportune timing. I remain watchful, but there aren't too many possibilities that would have the peer impact of those first two... the NCCN annual meeting is still accepting abstracts.
    I expect to see a pre-ASCO approval, so we may see the market labeling prior to the PDUFA date of 6/22. Leaves lots of time to bet your horse...
    Or cover your short...depending upon in which camp you reside...

  • Reply to

    OS question

    by ulingt Feb 3, 2016 7:31 AM
    wilderguide wilderguide Feb 3, 2016 12:22 PM Flag

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    "...also agree that HR is a better indicator of benefit than mOS comparisons."
    I think it's also important to attempt to understand how the algorithm will realign to accommodate these new approvals. What treatments will be displaced? What treatments will be reinforced?
    Your statement regarding the marketing importance of HR makes me consider that Cabo will capture ALL those previously treated with anti-PD-1i - non-responders, those that progress, and those that can no longer tolerate the regimen. The Meteor subgroup HR of .22 should carry the weight of clinical reasoning. How large is that patient pool, and how many of those patients will not consider any other therapeutic other than Cabo per that .22HR. I suspect most of them...perhaps all of them.
    As the algorithm continues it's shake out, and Nivo displaces sunitinib, Cabo stands to stay in line to advance to maintain a post-PD-1 response rate, failing a similar post-PD-1 response from Sutent.
    What be left over for L/E, pazopanib, axitinib, etc. Which will simply "lose out" in this game of musical chairs?

  • Reply to

    Cowen weighs in

    by wilderguide Feb 2, 2016 1:19 PM
    wilderguide wilderguide Feb 2, 2016 2:38 PM Flag

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    Hi Clem,
    Despite COMET failure and EXEL's deprioritizing of Cabo in the prostate space, cabozantinib is still the subject of many currently ongoing studies in ProsCa... As gains are made in understanding the underlying disease biology, I figure to see Cabo tried in combination with both immuno and AR treatments - if only for the research benefit. Time'll tell. Cabo desperately needs a predictive biomarker of patient response. All JMO...

  • Reply to

    p value

    by erniewerner Feb 2, 2016 8:40 AM
    wilderguide wilderguide Feb 2, 2016 1:47 PM Flag

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    Thanks for all the inputs this morning. It's difficult enough to wrap your head around today's marketplace - let alone trying to over-interpret a biotech PR. Let's hope MMM's choice of optimistic verbiage doesn't grossly displace the reality of how Cabo fits into real-world clinical usage. JMO, but I suspect he's as excited as many of us to see first quarter revenue numbers post-approval. His crystal ball is no better than ours...

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