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Exelixis, Inc. Message Board

wilderguide 248 posts  |  Last Activity: 6 hours ago Member since: Jan 13, 2011
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  • Reply to

    Muted AH action

    by roger5147 May 13, 2015 6:06 PM
    wilderguide wilderguide May 13, 2015 6:21 PM Flag

    $$$$
    "Not ...much in the way of a response..."
    There is a lot of data to assimilate in a lot of indications...
    Give it a few days to soak n before you make any decisions. There'll be more at ASCO once the doors open and embargoes are lifted. I really like what we are seeing thus far, particularly the HR values in NSCLC and the updated CRs out of BRIM7. So far so good...

  • wilderguide wilderguide May 13, 2015 6:10 PM Flag

    $$$$
    Thanks for posting, Bif. A 1 in 6 CR rate and further evidence of higher efficacy in BRAF-inhibitor naive patient pops might be enough to qualify for breakthrough status. I can't help but wonder if it's been applied for...
    Think MMM's holding out on us...timing such an announcement with an offering?

  • $$$$
    Cancer Res 4/2/15... Cohen NA, et al...
    "Finally, cabozantinib, a dual MET and KIT small-molecule inhibitor, was markedly more effective than imatinib in multiple preclinical models of imatinib-sensitive and imatinib-resistant GIST. Collectively, our findings showed that activation of compensatory MET signaling by KIT inhibition may contribute to tumor resistance. Furthermore, our work offered a preclinical proof of concept for MET inhibition by cabozantinib as an effective strategy for GIST treatment."
    ...and the hits just keep on a'comin'... GLTA

  • $$$$
    I'm fairly certain I heard MMM say "...we've had some good discussions..."
    After the independent investigators and the NCI log in with new data, post-ASCO could be very interesting...
    I'm beginning to suspect we've graduated beyond SNAFU...my take is we've got some superior data...
    And I say "Bring it, Bagdad Bob." Seymour, are you still with us...??
    I'd love to hear your take at this point, Mr Zero Shareholder Equity...Mr VooDoo medicine...
    What's changed - other than your Dydees - Big Boy?
    GLTA

  • Reply to

    MM speaking today...

    by chiraag_19 May 12, 2015 1:27 PM
    wilderguide wilderguide May 12, 2015 1:47 PM Flag

    $$$$
    "He cannot do much damage."
    I'm really bad at SP predictions, but will agree that we appear to be in a continued uptrend. With three oral presentations pending at ASCO, I think it possible this trend could continue into the convention. These analyst events have seldom been productive wrt SP. I'm hopeful to hear assurances of a non-dilutive nature...
    I'm also hopeful to hear news of continued research affiliation with Roche. At this juncture, Cobi has the potential to become a true clinical rock star. MMM should be barely able to contain his excitement. I think we'll be OK if he doesn't babble...

  • Reply to

    Prostate cancer trial

    by trufflesdrive May 11, 2015 3:35 PM
    wilderguide wilderguide May 11, 2015 10:31 PM Flag

    $$$$
    "Could you expand your thoughts on "As it stands..."
    What I really should've stated is that - for unequivocally successful and truly differentiated commercialization in the competitive realm of TKIs - Cabo needs to display an unquestioned survival signal in at least one indication. This is particularly important in the absence of a CDX. A lot of TKIs have been approved in the past few years within the regulatory framework that have not played well to the gold standard of prolonged OS. I'm not necessarily saying that surrogate endpoints for OS are not important, only that optimal commercial success is realized when that survival benefit is beyond question. Cabo is not alone in this dilemma, and the entire movement within the industry is toward best-defined patient pops. JMO - Targeting large, non-secular patient groups in disease indications known to be highly heterogenous is behind us, and the best laid plans for future oncodrug approvals will best achieve clinical acceptance thru mechanisms of CDX, biomarker-driven prescription, or documented trial successes in treatment-refractory disease...particularly in scenarios where those mechanisms of resistance are minimally understood. Cabo has achieved some small notoriety in this regard, and has proven itself as somewhat of a "darling" of the research community - which makes for great clinical speculation...creating unique hopes of efficacy...
    But - at the end of the day - only the most predictable mechanisms of treatment will be those most sought, and all others will remain in the shadows of end stage salvage use.

  • Reply to

    Prostate cancer trial

    by trufflesdrive May 11, 2015 3:35 PM
    wilderguide wilderguide May 11, 2015 3:58 PM Flag

    $$$$
    I think - by far - the most compelling data to come out of Comet-1 was the OS for the 191 patients with documented baseline visceral mets. If this had been a trial endpoint, this stock would be trading in the teens today. As it stands, we are still riding that slippery slope of justifying an approved drug that has yet to objectively display a survival benefit in a clinically-defined patient group. GLTA

  • wilderguide by wilderguide May 10, 2015 4:19 PM Flag

    $$$$
    This ASCO poster presentation could also prove of value. The following excerpt appears in the Am J Nuc Med Mol Imaging 2015 5(1) 72-82: MGH Cabo PI Chris Sweeney is a co-author...
    "Our data suggest that baseline 18F-FDG-PET/CT may identify men with mCRPC who are likely to benefit from cabozantinib and abiraterone therapy more reliably than standard imaging. Further, 18F-FDG may be superior to 18F-NaF in this patient population. Finally, 18F-FDG-PET/CT has the potential to stratify men with mCRPC into 3 groups (widespread 18F-FDG-avid disease, oligometastaic 18F-FDG-avid disease and non-18F-FDG-avid disease) to tailor therapy. A major unmet clinical need in men with mCRPC is the development of biomarkers to identify those who will benefit from therapy while avoiding futile expensive and toxic treatment."
    In the ASCO 2014 Cabo/Abi update, both lowest dose cohorts (20 & 40mg) had patients on therapy for 22 and 23 months, respectively. The premise of the above study stratifies CRPC by baseline imaging modalities, creating the potential for a biomarker-driven patient pool of best responders to Cabo in combo with Abi. Importantly, this study also contains a data set definitively tying baseline imaging (other than bone scan) to survival benefit.

  • wilderguide wilderguide May 10, 2015 2:20 PM Flag

    $$$$
    There's another possibility here to consider...
    The E1512 study - though chaired by Joel Neal - has been designed and mentored by Heather Wakelee, also of Stanford. Her affiliation in working with Cabo in NSCLC is quite lengthy, and she has documented patient successes dating back to 2010. What I'm suggesting is that there exists an aggregate of data that could conceivably provide the collective level of evidence to file for an sNDA in that indication. At any rate, I would imagine the NCCN will sit up and take notice, should E1512 PFS results ultimately translate into highly statsig overall survival benefit. I am hopeful to see OS data at ASCO. If not, (due to lack of mature OS data) - I feel confidant that benefit will surely be beyond all expectation.

  • wilderguide wilderguide May 10, 2015 11:25 AM Flag

    $$$$
    Of course I am guessing - as are we all. FWIW - here's my take. The excerpt below is from the Nov 2014 EXEL PR announcing positive top line results from the ECOG E1512 study:
    "In the E1512 trial, 125 patients were randomized to one of the three arms: erlotinib, cabozantinib, or the combination. During a pre-planned interim ECOG-ACRIN Data Safety Monitoring Committee analysis for futility, it was found that the trial met its primary endpoint of improving progression-free survival (PFS) with cabozantinib alone and also with the combination of cabozantinib plus erlotinib, as compared to erlotinib alone, and the results were highly statistically significant. Safety data were consistent with those observed in other trials of cabozantinib. At time of analysis, the median follow-up was 5.9 months and overall survival data were immature."
    According to the ECOG-ACRIN website, wild type EGFR NSCLC defines 80% of ALL NSCLC cases. Erlotinib is the current SOC for these patients, and is associated with a modest survival benefit. A "highly statistically
    significant" return on PFS data infers the potential for improved survival benefit as compared to the current SOC. This news is potentially huge for Cabo. If you await the oral presentation of these data, you will have waited too long, and effectively missed the boat. JMO

  • wilderguide wilderguide May 9, 2015 7:27 PM Flag

    $$$$
    "Instead ECOG takes the lead!"
    It really makes good sense to let outside funding pay for the early trial structures. Why not simply sit back and let the CRADA/ CTEP funding agreement pay for the R&D? Let the IST sponsorships mature to the point of unlocking hidden clinical value...and step in strategically as the cards unfold...all the while letting others pay the early development costs. It simply looks like sound risk management to me. To date, nearly half of the clinical development costs for Cabo have been borne by OPM.

  • $$$$
    In addition to the Cobi-oriented job positions with Genentech, there are a couple of new trials posted at Clinicaltrialsdotgov that have interesting immuno-response endpoints - one of which is an additional small scale P3 trial sponsored by Sid Kimmel CCC. The other is a P2 sponsored by the Netherlands Working Group on Immuno Therapy of Oncology. Both are geared to solicit data correlating AEs with metabolic and immune response in late stage melanoma. Check out NCTs 02427893 & 02414750...

  • Reply to

    Wait just a minute...

    by wilderguide May 8, 2015 12:56 PM
    wilderguide wilderguide May 8, 2015 1:18 PM Flag

    $$$$
    I posted an earlier thread suggesting a run-up to an offering. I know it's not a popular theme, but there is historic precedence for just such a strategy...so I'm expecting some good news along with some not-so-good. At this point, I'd prefer a dilutive partnering to a SO. We'll see soon enough...

  • wilderguide by wilderguide May 8, 2015 12:56 PM Flag

    $$$$
    What about negative shareholder equity, VooDoo medicine, and Bagdad Bob?
    Isn't it just possible that there exists a disconnect between those types of issues...
    ...and biotech market caps in general - making guys like Seymour totally full of bull...???

  • Reply to

    Seymour Butz

    by wilderguide May 4, 2015 5:49 PM
    wilderguide wilderguide May 5, 2015 7:27 PM Flag

    $$$$
    I am in a very busy spot, and will try to RSVP at length later. Treatment acquired resistance resulting in over-expressed cMET is key, and there are a few pubs from ESMO 2014 worthy of note, including a comparison of erlotinib to the combination of cisplatin/ gemcitabine in advanced NSCLC. I'm preparing a roast for a very special lady - my future daughter-in-law! I'm actually a pretty fair cook, but all competency flies when there's a pretty gal on deck... I'll be back...

  • Reply to

    Investopedia article

    by flyer111zz May 4, 2015 9:48 PM
    wilderguide wilderguide May 4, 2015 11:19 PM Flag

    $$$$
    "Did you catch the error...?"
    Does it depend on what your definition of "is"...is...

  • Reply to

    Seymour Butz

    by wilderguide May 4, 2015 5:49 PM
    wilderguide wilderguide May 4, 2015 9:55 PM Flag

    $$$$
    "Cometriq?"
    Absoluta-frickin-mente...
    Dunno if anyone noticed, but today BIOC rallied 12% on news that they had added a cMET biomarker to their genomic assay portfolio. In January, they added a test for the EGFR T790M mutation in NSCLC. JMO - but I believe these tools are in direct alignment with Cabo's need for a companion diagnostic (CDX)...see inclusion criteria and additional outcomes for both E-1512 & Meteor.
    I can't as yet definitively tie the two, but MGH staff is representing the science for BIOC in their assay endeavor in NSCLC and MGH's Toni Choueiri is the Meteor PI. It doesn't take rocket science to connect some dots there...they are likely both utilizing Dan Haber's lab for tissue sampling, serum analysis, and biomarker analytics. I've got a really good feeling about this...

  • wilderguide by wilderguide May 4, 2015 5:49 PM Flag

    $$$$
    Despite your recent success in publishing "Under the Bleachers"...
    You are still inclined to share your advice here? Another of your misanthropic endeavors doomed to failure.
    Do yourself a favor - find a nice gal. Settle down... Spawn little Seymours... Yer job here is done.
    Your short posture is toast. CMETi is about to become an important part of the equation. You've lost.
    Hasta la vista, Seymour...

  • Reply to

    The Real Bottom Line

    by mark_stocket May 3, 2015 9:44 PM
    wilderguide wilderguide May 3, 2015 10:01 PM Flag

    $$$$
    "mark_stocket
    23 posts | Last Activity: 14 minutes ago
    Member since: Apr 17, 2015"
    Yet another 2 week wonder lending advice...
    Is there no end to the madness?

  • Reply to

    Bottom line

    by mheaney12345 May 3, 2015 8:44 PM
    wilderguide wilderguide May 3, 2015 9:06 PM Flag

    $$$$
    "mheaney12345
    22 posts | Last Activity: 17 minutes ago
    Member since: Apr 15, 2015"
    Great...everyone be sure to follow the advice...
    ...of a 2-week wonder with an attitude...
    Get back in yer cubicle!!!

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