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wilderguide 344 posts  |  Last Activity: 18 hours ago Member since: Jan 13, 2011
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  • $$$$
    Pubmed March 2014, Knubel, et al. Foretinib in preclinical glioblastoma with some interesting results.
    "We have found that Foretinib, a RTK inhibitor currently in clinical trial, inhibited phosphorylation of TAM receptors, with highest efficacy against MerTK, and blocked downstream activation of Akt and Erk in adult and pediatric glioblastoma cell lines, findings that are previously unreported."
    GLTA

  • $$$$
    Just a heads up...as I firmly believe longs need to maintain perspective.
    Dr Mark Kris - as an invited guest speaker - will be presenting at 10:15am Swiss time. His invited commentary will be directed toward abstract 940 on RET fusion NSCLC - which includes updates on Cabo.
    I wouldn't undermine the potential for a good word on behalf of Cabo from the pre-eminent oncodoc from MSKCC. After all, he is one oft he most highly regarded and heavily published thoracic oncologists in the world. I'm relatively certain he wouldn't show up just to undermine the program, and the embodiment of abstract 940 mentions a pending global initiative to enlist a RET - fusion NSCLC trial involving cabozantinib.
    GLTA

  • Reply to

    Comet -1 results

    by anitdua Apr 4, 2014 3:43 PM
    wilderguide wilderguide Apr 4, 2014 3:57 PM Flag

    $$$$
    Current guidance from IR is sometime in 2014 for both Comet trials.
    That info is per Susan Hubbard, and is current as of yesterday's e-mail per my query.
    Personally, I think we'll see a peer-reviewed presentation on each in Sept's ESMO...with initial reporting sometime in July...perhaps August, if OS results prove to be superior. Initial reporting will constitute only essential pass/fail endpoint info. Updated details will be at ESMO...Patience is a requirement here.
    GLTA

  • $$$$
    Published 9/13 by Michael Evans, et al...Dr Charles Sawyers is listed as a co-author.
    "...strongly suggesting that inhibition of VEGFR2 in host tissues is (at least in part) responsible for the dramatic bone scan resolution by cabozantinib. Further studies with comparatively more selective VEGFR2 inhibitors (axitinib, sunitinib) are underway to support this conclusion. In summary, these results implicate a VEGFR2-driven mechanism in host tissues to account for the dramatic bone scan resolutions observed in clinical trials, and promote the immediate use of VEGFR-directed therapies to suppress bone pain and improve quality of life for patients with CRPC (and other malignancies that propagate well in the bone microenvironment)."

    "(and other malignancies that propagate well in the bone microenvironment)"
    If this paper published at ESMO 2013...I missed it. I like the mention of this expanded research into VEFGR-directed therapeutics as it may pertain to the significance of VEGFR-related BSR, but feel these studies are likely dramatically underfunded - their importance under-recognized. I think this will change spectacularly if we get statsig OS from Cabo. It seems a lot of future research may hinge on Comet results. I have this feeling we're about to open Pandora's Box, and perhaps get a glimpse beyond the iceberg's tip.
    GLTA

  • wilderguide by wilderguide Feb 24, 2014 4:01 PM Flag

    $$$$
    We are right in the proximity of typical Euro Commision response as follow-up to CHMP positive opinion.
    If not this week, I think next week. JMHO
    GLTA

  • $$$$
    $$$$
    Lots going on here, beginning tomorrow...
    I count 11 abstracts pertinent to Cabo...
    Amongst the ones I like best:
    4/7 Targeting cMET & VEGFR2 in the Stromal Compartment of Prostate Cancer Bone Mets
    4/6 - Evaluation of Cabozantinib in Combo with Abiraterone, Enzalutamide, or Docetaxel in a CRPC xenograft in Vivo
    4/6 - Effects of cabozantinib in Breast cancer metastasis, overall survival, and bone mass in a mouse model
    Lots of clinical and preclinical reporting this week...
    This oughta give ol' Jonesy Dingle-Berry lots to be thankful for...
    GLTA

  • Reply to

    Foretinib as a MerTK inhibitor in GB

    by wilderguide Mar 31, 2014 3:55 PM
    wilderguide wilderguide Apr 1, 2014 8:17 AM Flag

    $$$$
    Doing further read-up on XL-880, and found this posted in European Urology Nov 2013...
    "Dual Met/VEGFR-2 inhibitor foretinib overcomes acquired resistance to sunitinib in metastatic renal cell carcinoma (mRCC)"
    Potent ROS 1 inhibitor, MerTK inhibitor that mitigates resistance to sunitinib in mRCC...seems like EXEL's other METi is showing some real potential...getting some attention. Small wonder GSK is interested. Glaxo sponsored P2 NSCLC trial should begin recruitment this month.
    EXEL could become the "go-to" guy for MET inhibition. There are research notes at researchgate claiming foretinib may be effective in Crizotinib refractory ALK-rearranged ROS1 driven LADC.
    GLTA

  • wilderguide by wilderguide Apr 10, 2014 12:56 PM Flag

    $$$$
    Mdpidotcom...Brian Hu, et al. ISSN 2072 6694. Published 12/4/13...
    Well written update on CTC enumeration and characterization in all stages of PCa progression.The portion of this document that addresses advanced disease elicits a very compelling argument for a successful OS outcome of Comet 1, and speaks directly to CTC reduction in discordance with PSA observations. Multidisciplinary CTC platforms discussed at length, in addition to Veridex. Good read...
    GLTA

  • wilderguide by wilderguide Apr 17, 2014 8:37 PM Flag

    $$$$
    Health-related quality of life improvements improve survival in European lung cancer study, BJC today. As patient-reported outcome data mature in Cabo trials, I expect to see strong interaction of these subjective prognostic factors with clinically quantifiable biometrics...resulting in improved OS.
    "results: After controlling for covariates, every 10-point increase in baseline pain and dysphagia was associated with 11% and 12% increased risk of death with hazard ratios (HRs) of 1.11 and 1.12, respectively. Every 10-point improvement of physical function at baseline (HR=0.93) was associated with 7% lower risk of death. Every 10-point increase in pain (HR=1.08) was associated with 8% increased risk of death at cycle 1. Every 10-point increase in social function (HR=0.91) at cycle 2 was associated with 9% lower risk of death."
    GLTA

  • Reply to

    Capital Research Advisors

    by ddaly8585 Apr 10, 2014 6:02 PM
    wilderguide wilderguide Apr 10, 2014 11:43 PM Flag

    $$$$
    I won't pretend to speak for anyone else. I have a lot of respect for Ernie, and hold him in the highest regard, particularly when it comes to objectively interpreting the subtleties of trial results and theoretic analysis. Oncodoc has made many valid contributions, though I must profess I harbor a reluctant suspicion toward anyone claiming to be a doctor in the midst of the crowd you encounter on a YMB. It simply doesn't ring quite right w/ me, though I realize this may be a fault of my own prejudiced fabrication. Just never had no use for docs of any kind...lucky, I guess.
    As for me, I liken this decline to the market bust-cycle that followed the Japanese Fukushima earthquake/nuclear facility meltdown a couple years ago. I played the odds to the Max - sold off everything - including my gold positions - and got behind EXEL 100% at $3.96...and actually did pretty good. I must admit, the temptation is great to go that route again.
    I'm rebalancing my portfolio continually, and have traded EXEL often enough to have a relatively low ACB. I suspect the same of many that have regularly posted here since the Cabo bone phenom was first published.
    Personally, I think most are still holding..taking their spankings as I am...
    YMB politics have become tedious & tiresome...and the posers are driving out the long-term players...yet another cubicle-contrived manipulation. This is not a time to lose focus...EXEL will likely report on 4 pivotal trials this year, at least 3 of which I have very high hopes for... I'll let you figure out which three.
    Your guess is as good as mine...and as for you - Sigmond "Drizzle-britches" McDingleberry - you can certainly quote me on that, smarmy boy.
    GLTA

  • $$$$
    When these guys - including Uncle Margin - start showing up...
    My bullishness is restored. Especially when their posts are unecessarily obnoxious, accusatory, and contradictory. The more pointless, rude, and annoying their commentary...the better.
    We're on track here...stay tough, stay tuned.
    GLTA

  • wilderguide wilderguide Feb 8, 2014 3:08 PM Flag

    $$$$
    I think it very likely that we see the scheduled interim reporting on Comet 1 this quarter. I also agree with the long opinion of this MB that those interim results may prove unremarkable, at best. Advanced, late stage, heavily pretreated, multiple-treatment refractory disease is simply not the best research forum for determining overall survival. Keep on mind, Comet-1 has recruited a very sick patient group that has already run the gamut of existing therapies. They have not only reaped the benefits those therapeutics may confer, but have also suffered all the consequential toxicities that come with the treatment package. If all these prior treatment toxicities prove cumulative, Cabo may have simply been administered too late to favorably impact OS.
    GL

  • Reply to

    Here's my #$%$ take...

    by wilderguide Mar 28, 2014 1:44 PM
    wilderguide wilderguide Mar 28, 2014 2:52 PM Flag

    $$$$
    "Do you know about the talk?"
    I know very little about investing, hedge funds, or anything much to do with practiced medicine. Don't have many doctor acquaintances, don't know any hedge fund managers...and feel fortunate on both those counts. I'm a fan of the science, and have placed my current bet on the preclinical work of Dr Donald McDonald of UCSF...and also upon the preponderance of positive data that has been generated in the wake of Cabo's P2 RDT, as well as the ongoing PCF/CTEP/NCI - sponsored trials.
    Amongst the clinicians whose work I follow in the prostate space are Docs Scher, Higano, PG Corn, Logothetis, E Basch, Dan George, Phil Kantor, and Charles Sawyers. I feel confident I'm in good company with these practicing academics, and the pervasive clinical optimism that has been previously projected has not diminished. I feel the science will find it's way into practice.
    It's actually a fairly simple investment strategy, though the manipulations of the market certainly can frustrate. I've added a few shares down here, but I've bought previously in the sub-$4 range. I've been in EXEL a while, and have also sold over $11/share. I like the risk/reward.
    I'm actually a pretty patient guy. Like horses, I don't assign much importance to time.
    Don't own a watch. Don't need one...
    GLTA

  • Reply to

    CTCs in Prostate Cancer

    by wilderguide Apr 10, 2014 12:56 PM
    wilderguide wilderguide Apr 11, 2014 1:37 PM Flag

    $$$$
    Sometimes this seems a bit silly, posting a positive spin on technonews amidst the pumpers and the gravediggers, but I don't make the news...I just bring it.
    See Dr Scott Tagawa at Onclive today regarding CTCs in NEPC. CTC monitoring as a response to therapy in all phases of PCa treatment is becoming a reality right before our eyes, and - coincidentally - early and durable CTC redux remains one of Cabo's most strikingly consistent markers of therapeutic benefit...correlating with extended PFS and many known biometrics of survival. The news just keeps getting better...
    GLTA

  • wilderguide wilderguide Mar 14, 2014 4:51 PM Flag

    $$$$
    "I understand how it happened. The bone thing is unique..."
    Ernie, you can be a master of understatement.
    Not only did the "bone thing" draw the attention of the investment community, but it got the attention of the best and brightest thought leaders in all of investigative cancer research. After 3 years of observation and analysis, $10's of millions in NIH funding, and thousands of additional trial hours...what more do we know about the Cabo bone phenom since it was first presented?
    The BJC has published that it represents a "favorable therapeutic benefit'...
    Doc deBono has told us the effect suggests "tumor-specific cell death"...
    Doc Vogelzang has told us he expects Cabo's bone effect will change the way CRPC is treated...
    The whole bone effect package fits nice and tidy into Doc Scher's proposed CRPC biomarker assay...
    Doc Higano is recruiting her third round of Cabo research ( can't wait to hear what she says next...)
    Since I first drank the Cabo Koolaid, trials have expanded from a handful to over fifty. Cabo stands to represent one of the most profound impacts on cancer therapy in over a decade, and a great portion of that perspective is based upon the uniqueness of the bone phenom and all that it represents. Cabo's greatest misfortune to date has been that the dosing considerations were lengthy, but the greatest obstacle yet to overcome is the relative naïveté of the regulatory pathways...and the infancy of the requisite biomarker sciences. It'll all fall into place...I'm very optimistic.
    It's simply taking a bit longer than anyone could have anticipated.
    GLTA

  • wilderguide by wilderguide Apr 16, 2014 10:31 AM Flag

    $$$$
    Check it out: this guy double talks just like ol' please_insert_foot_in_butt:
    "In a report Wednesday, analyst Bart Classen said, "In late March we hosted a conference call to discuss Exelixis’ (EXEL) cabozantinib, which is in the phase III COMET-1 trial for metastatic prostate cancer. EXEL recently announced that the trial would continue, and topline data is expected in 2014. COMET-1 enrolled 960 prostate cancer patients with bone metastases who have failed prior chemotherapy; the trial uses survival as the primary endpoint. There is little evidence that the drug will cause a meaningful improvement in survival. A phase II study demonstrating an improvement in bone scans has been highly criticized for lacking a correlation with clinical outcomes. We believe the product will be expensive, poorly tolerated, and show little benefit. Its benefit over taxanes is dubious. However, we cannot exclude COMET-1 showing a small statistically significant improvement in survival."
    We really don't think it'll work, but can't rule out that it might....
    Lemme get my foot outta my mouth and say that again....

  • $$$$
    I gotta admit, considering the content of yesterday's discussion, I broke a grin when a saw that EXEL hired a new lawyer to assist EXEL's transition to a global concept:
    “Jeff’s appointment comes at an important time for Exelixis, as we strive to fully maximize the opportunity for cabozantinib and further develop cabozantinib into a major oncology product,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. “His broad and successful legal experience, particularly with regard to pharmaceutical marketing and commercialization, makes him well prepared to guide us through the complex issues that arise as we continue our transformation into a global commercial organization.”
    My apologies, but this sorta stuff is funny to me...
    GLTA

  • wilderguide wilderguide Mar 17, 2014 6:18 PM Flag

    $$$$
    There may be an additional important consideration here. The article excerpt below:
    Dr Simon Robinson, leader of the Radioisotope Physics team at The Institute of Cancer Research, London, said: “Until now we haven’t been able to directly measure how effective treatments are for this type of incurable prostate cancer. But together these imaging techniques allow us to watch how the tumour and the surrounding bone are affected by new drugs.
    “This approach can tell us how fast the cancer is growing and the potential impact on a patient’s quality of life. Our work with the drug cabozantinib suggests it may provide pain relief in addition to stopping tumour growth. This method allows us to accelerate development of these promising new prostate cancer drugs from the laboratory to the clinic.”
    ...and that important consideration is this:
    These studies are taking place in London, UK. An EMA decision wrt cabozantinib in MTC is pending final approval. That approval could conceivably enable an NPU is the prostate space based upon Comet results, which are also pending. They are looking at all the angles before they make their call. JMO

  • Reply to

    INHX, HGSI, and now EXEL

    by wilderguide Mar 26, 2014 12:14 PM
    wilderguide wilderguide Mar 26, 2014 12:39 PM Flag

    $$$$
    Hi Frank,
    JMO, but I don't for a moment believe that anyone that follows Cabo thought to see statsig OS results come out of this interim reporting. Street expectations were far in excess of reality, as usual.
    GL

  • $$$$
    From the current edition of the BJC, JJ Ko et al...T Choueiri is a co-author. This article comes up with a site search for Cabo, and Doc Choueiri's affiliation is - of course - well known as a Meteor investigator. The survival numbers below are an excerpt from the abstract, some of which will likely reflect upon Choueiri's take on Cabo as Meteor data comes to maturity. To the best of my knowledge, this publication constitutes the latest posting of survival data relative to RCC trial interpretation. Might be valuable to have around...
    "Results:
    In total, 2705 patients were treated with TT of which 57% received only first-line TT, 27% received two lines of TT, and 16% received 3+ lines of TT. Overall survival of patients who received 1, 2, or 3+ lines of TT were 14.9, 21.0, and 39.2 months, respectively, from first-line TT (P

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