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Inergy, L.P. Message Board

wilderguide 385 posts  |  Last Activity: Jul 23, 2014 10:08 PM Member since: Jan 13, 2011
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  • wilderguide by wilderguide May 1, 2014 9:36 PM Flag

    Not long ago, I considered this MB to be one of the best informed, best mannered, and well-reasoned of all YMB's. No wonder most of the long element has opted out of the ongoing discussion. 80% of you newcomers are rude and distasteful types whose imperative manner is an assault to intelligent thought.
    Hate to do it, but gonna have to tune up the ignore button - it's become mostly Bozoes on this bus.
    Life is too short...
    Treating cancer is serious business. For those of you that are impatient with the duration of the Comet 1 trial, take a few moments to understand the most important aspect of an OS trial. The required statistical events that determine whether or not a survival benefit is available with cabozantinib are human deaths. Each event is a patient death, whether from the treatment arm or from the control arm. At least display the common decency to respect the bravery that is imperative to the clinical trial process.
    Exploring the wonders of human cancer biology is a passion for some...not so for others. Please leave the name-calling and nose-thumbing where it the second grade classroom. I expect to see this post get it's share of "thumbs down"...and I have but one reply to that:
    What a remarkably juvenile waste of endeavor.
    Your mom must be very proud...

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    Posted at cancercommonsdotorg 27 June 2014 by Emma Shtivelman, PhD...
    "A small clinical trial conducted at Dana-Farber Cancer Institute, tested whether adding a new drug called cabozantinib to abiraterone might improve patient responses. Cabozantinib may inhibit metastasis, particularly metastasis to the bone. Patients in the study received three different doses of cabozantinib, along with a standard dose of abiraterone, and across all doses tested there was a marked improvement seen as a deeper drop of PSA levels and reduction in tumor size."
    Between now and ASCO 2015, I expect to find this trial gets a lot of attention, as duration of response to this combination has displayed wonderful potential. Cabo dosing at 20mg/day w/ Abi might just eliminate DLTs and paint a prettier AE profile than we have seen. Solid synergy with pronounced BSR might just make JNJ take notice. In addition, I expect a combo DFT with Enzalutamide to begin by ESMO.

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    Posted 6 days ago in the DovePress journal "Core EvIdence"... Dr Ulka Vaishampayan, titled as above.
    One of the best and most complete discussions of Cabo in PC I have seen to date, with unbiased discussion of efficacy, clinical application, competitive pricing, FDA approval challenges, and the possibilities of Cabo prescription in biomarker-guided application. This piece positively wowed me...
    I applaud her most capable efforts. Great, most complete read I have seen in a great long while.

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    I simply wanted to isolate this particular quote for future commentary.
    Presentations come and go...but very darn few show response rates that we are witnessing in the V&C combo in advanced refractory metastatic melanoma.
    My long-term sentiment: usernames is a dipshizzle

  • wilderguide by wilderguide Jun 18, 2014 4:22 PM Flag

    Solely to judge the measure of corporate response, earlier today I dropped an e-mail to Sue Hubbard at EXEL IR to inquire of the possibility that the 6-year old Aussie youngster with RMS be included (somehow) in the pediatric cabozantinib trial. I really have no idea if she meets the trial inclusion criteria, but thought I'd let the management team at EXEL sort through the details. Poor kid...

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    I hadn't been aware of this prior to today, but this extension should take some heat off the repayment program.
    "In January 2014, we entered into an amendment to our financing arrangement with Deerfield Private Design Fund, L.P. and Deerfield Private Design International, L.P. to provide us with an option to extend to July 1, 2018 from July 1, 2015 the maturity date of the indebtedness incurred by us under the financing arrangement. See "Certain Factors Important to Understanding Our Financial Condition and Results of Operations - Deerfield Facility" below for additional information on this financing arrangement"
    Other than that, Cabo sales are upward with comm ramp-up in Europe...R&D expenses are up...optimism for Cobi intact - with a couple opportunities near-term for updates...
    FYI-Drs (Dror) Michaelson & R Motzer recently co-authored a sunitinib study in mRCC that presents a strong argument for utilization of PFS as a surrogate for OS. Results are based upon survival comparisons of PFS to PPS (post-progression survival) Just in time for Meteor...90% of sites are active! That's moving!!

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    Abdel O, et al...Cancer Discovery 4/17/14 ePub ahead of print...
    "We demonstrate that intermittent administration of vemurafenib led to a near-complete remission of the melanoma, and the addition of the MEK inhibitor cobimetinib (GDC-0973) caused suppression of vemurafenib-induced leukemic proliferation and ERK activation. Antimelanoma and antileukemia responses have been maintained for nearly 20 months, as documented by serial measurements of tumor-derived DNA in plasma in addition to conventional radiographic and clinical assessments of response. "
    I suspect this is what we will see presented at EADO next week, and is likely the basis for the oral ASCO abstract mentioned in yesterday's CC. This could represent a breakthrough therapeutic combination.
    I encourage everyone to do your own DD.

  • wilderguide by wilderguide May 31, 2014 2:45 PM Flag

    "For lung cancer patients whose tumors are resistant to a class of chemotherapy called tyrosine kinase inhibitors (TKI), a drug called cabozantinib may be able to undo that resistance, according to a new City of Hope study. A new City of Hope study shows that the drug cabozantinib could help undo lung cancer's resistance to chemotherapy. The results will be presented at the American Society of Clinical Oncology's annual meeting on June 3."
    Posted on the City of Hope website 5/21/14 by H Chung So

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    Published in the AACR Journal Clin Can Res June 1, 2014 Q Xiang, et al....
    "...effects of cabozantinib were examined. Results: High level of p-MET in resected HCC specimens was associated with resistance to adjuvant sorafenib therapy. In cultured HCC cells that expressed p-MET, cabozantinib inhibited the activity of MET and its downstream effectors, leading to G1 phase arrest. Cabozantinib inhibited tumor growth in p-MET-positive and p-MET-negative HCC by decreasing angiogenesis, inhibiting proliferation, and promoting apoptosis, but it exhibited more profound efficacy in p-MET-positive HCC xenografts. Cabozantinib blocked HGF-stimulated MET pathway and inhibited the migration and invasion of the HCC cells. Notably, cabozantinib reduced the number of metastatic lesions in the lungs and liver in the experimental metastatic mouse model. Conclusions: HCC patients with high level of p-MET are associated with resistance to adjuvant sorafenib treatment. The dual blockade of VEGFR2 and MET by cabozantinib has significant anti-tumor activities in HCC, and the activation of MET in HCC may be a promising efficacy-predicting biomarker."
    It seems Chinese oncology is increasingly interested in the synergies of MET/VEGFR2 inhibition. This ongoing study is taking place with nationalized funding at Sun-Yat-Sen Hospital in Beijing.

  • Reply to

    When is the next big calalyst on this one?

    by smithts777 Jul 5, 2014 12:36 PM
    wilderguide wilderguide Jul 5, 2014 12:55 PM Flag

    Any day. We are overdue for EXAM overall survival data.
    If the assumptions utilized to design Comet 1 were appropriate, that trial could report a data-locking event at anytime. Roche's CoBrim could also deliver top line data at any time, and it expect those data releases to be quickly followed by an NDA filing. Lots about to happen.Take your pick...
    I expect we'll hear something substantial this month, maybe next...

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    At this juncture, it is entirely possible that we see Meteor P3 data before we see any new Comet data, and I am adjusting my trading position to accommodate EXEL taking off like a rocket on the strength of early response in advanced mRCC. If we get data in-line with the P2 RDT results, there should be a great pop to play into ASCO. If we get positive OS data on any front at ASCO, this stock could go absolutely tropospheric.
    Good luck all & have a great weekend!

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    Europe Pubmed Central June 2014, Drs Samore & Gondi...
    More juice for the European campaign. Very little has been as yet published on Cabo in PDAC, with exception that cabozantinib has shown to overcome treatment-induced resistance to gemcitabine (Gemzar).

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    Published July 15, 2014 in the Journal of Cellular Biochemistry Drs Stern & Alvares
    "....cabozantinib inhibited cell proliferation and decreased MTT activity. Effects on alkaline phosphatase activity were biphasic, with small stimulatory effects at concentrations below 3 μM. When RAW 264.7 osteoclast precursor cells differentiated with 20 ng/ml RANKL were co-treated for 24 hr with 3 μM cabozantinib, expression of RANK, TRAP, cathepsin K, alpha v or beta 3 integrin, or NFATc1 were unaffected. 5 day treatment of RANKL-treated RAW 264.7 cells with 3 μM cabozantinib decreased TRAP and MTT activity. The results suggest that the osteoblast could be the initial target, with subsequent direct and indirect effects on osteoclastogenesis leading to decreased resorption. The multiple effects of cabozantinib on the cell microenvironment of bone are consistent with its effectiveness in reducing lesions from prostate cancer metastases."

  • wilderguide by wilderguide May 7, 2014 7:15 AM Flag

    ...create a great argument for a Roche takeout. Comparing the numbers between those previously treated with Vemurafenib vs those known to be BRAFi-naive, Roche would not only stand to gain total control of the advanced-stage assets Cabo and Cobi, but would also optimally fortify their Zelboraf program in melanoma. Almost like getting three drugs for the price of two...
    EXEL looks pretty dern cheap today...

  • wilderguide by wilderguide May 20, 2014 6:30 PM Flag

    Just a heads-up...this combo trial of Cabo w/ Panitumumab in mCRC began recruiting on 5/7/14 with the following provisions for an expansion cohort once MTD is determined:
    "Cabozantinib will start at a dose of 60 mg daily with reductions to 40 and 20 mg daily possible. There will be two parts to this study: 1) the dose escalation cohort; and 2) the expansion cohort. In the dose escalation cohort, a standard 3+3 dose escalation format will be used. Once the MTD/RPTD is established, enrollment will begin in an expansion cohort to establish the safety and tolerability of the combination."
    JMO - this trial is really worth watching. Last years' 4/13 AACR reported preclinical data that supported a 12-for-12 positive DCR in 12 ex planted patient cell lines. This work up came out of the Univ of Colorado Messersmith Research Lab, and is worthy of review. GLTA

  • Reply to

    ASCO 2014 - Takeaways for PCa Cancer Patients

    by wilderguide Jul 1, 2014 9:27 PM
    wilderguide wilderguide Jul 2, 2014 2:15 AM Flag

    "Not one piece of quantifiable data other than one person's opinion..."
    You've just described every post you've ever placed on this MB. Inconsistent, insubstantial, unsubstantiated, and totally discombobulated. Go back to the comforts of your Mama's teat, where you belong. Some folks are clearly a waste of good air, and you lead that crowd, nummnutz...

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    Dr Kurt Miller, Chief Urologist Ben Franklin Medical Center, Berlin Germany
    Available at ecancerdotorg. Published 5/12/14. I think this lecture actually took place at the Asia-Pacific Prostate Cancer Conference last March. Good presentation. Dr Miller has published and co-authored extensively on Cabozantinib. My suspicion is that he expects approval. JMO

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    Peer reviewed, accepted and epublished ahead of print in the Annals of Oncology, 5/14/14, Dr T Choueiri, et al... More gearing up for the European campaign...

  • Reply to

    "Cobi is nothing notable." - usernames

    by wilderguide May 21, 2014 3:58 PM
    wilderguide wilderguide May 21, 2014 5:42 PM Flag

    For me it's about the science. For you, it's always about the shares.
    I begin to suspect you represent a huge naked short, so large in fact that you cannot find enough shares to cover your massive short. Makes me wonder who you represent...Roche would be my first guess...I've decided not to ignore you, because learning your conniving ways might be revealing.

  • Reply to

    Comet 1 mistake

    by boredincambs May 6, 2014 4:29 PM
    wilderguide wilderguide May 6, 2014 5:23 PM Flag

    Re "Comet 1 mistake"
    Boredincambs and semanresu...
    Your Moms (I'm assuming you are not related) made a felony class mistake in not flushing you turds.
    Why not just give Cabo and prednisone to everyone and hope it all works out?
    Nitwitted dunderheads...Crass, clueless and classless...

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