"From mechanic to..."
Yeah...it's been a real disappointment even for me, not finding work I truly enjoyed in transition to civilian life. My MOS was LRPS along the Cambodian border during the early '70's. Sure wish we'd met back then...
You & me - We mighta been very, very close acquaintances...
But not for very long, and that woulda been unfortunate for you.
Most very unfortunate...
Christina Izzo, Onclive 9/22/14
“Instead of only looking for the most resistant population of ALL cells at the end of this selection process, we monitored for drug sensitivity of the cells at each stage of the dose escalation,” Lauffenburger said. “This led us to discover the vulnerabilities of a tumor at different stages of clonal evolution, a phenomenon we would have missed if we only analyzed for drug sensitivity at the last stage of this process, which is equivalent to when a patient has relapsed.”
Cell lines treated with frontline dasatinib followed by a single dose escalation were more sensitive to crizotinib and foretinib, as a result of tumor heterogeneity. However, continued dose escalations of dasatinib cancelled this added sensitivity, suggesting distinct stages of tumor evolution when specific drugs might be more effective."
"Why would this E thing be any different?"
Just stopped in to commend Fezz on his consistent DD, and laughed like hell when I saw this post.
Bottomline is that folks oughta just pay attention...
Keep up the great work, Fezz...don't get too dang diverted keeping the dummies in line...
NCT02243605 NCI P2 study Cabo in relapsed osteosarcoma posted 9/16/14. Will be recruiting primarily in France currently 10 sites listed as not yet recruiting. Also Cabo CRC study published in International Journal of Cancer 9/20/14 JJ Arcoroli, et al.
Interesting uptick in European interest in cabozantinib of late with ESMO pending.
"Brain Pharmacodynamic Activity of Cobimetinib"
Published in Molecular Pharmaceuticals 9/22/14 EF Choo, et al.
Thanks for the positivity, Salty...
This study undoubtedly provides the rationale for the coBRIM-B melanoma brain mets clinical trial that has only recently been announced. GL
Here's Dr Vin's bio from the EXEL website:
"Vincent T. Marchesi, M.D., Ph.D. has been a director since May 2001. Since 1973, Dr. Marchesi has been a Professor of Pathology and Cell Biology at Yale University and, since 1991, the Director of the Boyer Center for Molecular Medicine at Yale University. In 1982, Dr. Marchesi co-founded Molecular Diagnostics, Inc., a diagnostic development company. Dr. Marchesi was formerly Chair of Pathology at the Yale-New Haven Hospital. Dr. Marchesi holds an M.D. from Yale University and a Ph.D. from Oxford University, and is a member of the National Academy of Sciences and the Institute of Medicine."
This hardly seems like the bio of a lunatic that would mindlessly throw 40K out the window.
Think about it. Look at the stock action. Compare it to charts from past controlled takeovers at HGSI & INBX.
There is a strategic purpose to the short element here. Think about all the short activity on this board in recent months trying to convince you to sell your shares. Why would these people care how you invest? Why have they worked so tirelessly to part you from your shares? Why have they contrived so many smarmy, know-it-all aliases insistent that you sell? Sell, sell, sell... Why could they possibly care?
Think about it... Just think about it...
Thanks for making my point.
You cannot reference any post from me that has EVER made any attempt to induce anyone to buy anything. I present the news both good and bad. I'm not here on a mission to convince anyone of anything, and could really care less what anyone else does with their investment money. You, on the other hand - and all your aliases - are here at a moment's notice to harass any effort to pass along current information. The nature of my posts is apparent to all that care to actually read them, while yours are obviously a contrivance of misguiding, misinforming will. Take your self-proclaimed philanthropy and shove it, Bozo.
"...and feels guilty about taking the company's money..."
You're kidding, right? This is your argument? Another #$%$ feeling the guilt of having too much dough...??? You are a freekin fruitcake...
"What is it to the hard working Joe that is trying to invest...??"
Right. I got an extra 30 seconds or so...tell me everything you know about work.
You are a living, breathing scam if ever one existed. Nothing more.
"...it seems unlikely that the EXEL board was privy to the data."
I thought of this as well, and have concluded that the risk of the appearance of gainful collusion is simply too great. Doc Marchesi is a cellular biologist, and his insight just might prove invaluable here. Of course, I too, am just another zany YMB pumper.
What do I know?
"...Roche has this data locked down pretty tight."
If Roche is actually contemplating a takeout based on Cobi potentials, it'd be most wise to divulge as little as is possible, dictated by partnering guidance. I know I've beaten this path deeply, but I still believe Roche has a major short interest in this play - simply because they might need EXEL to keep Vemurafenib competitive. In the world of BRAF inhibition, inadvertent MAPK activation is one of the largest current concerns, and Cobi has proven very adept at managing iMAPKact with an acceptable AE signature. There's still a lot we don't know, and the Pres Symposium covering PD-1i integration with the heavily competitive space of BRAF/MEK inhibition may raise many questions as to how this will all best work for patients going forward. Suddenly the space is very crowded w/ new choices...
At the end of the day, the NIH/IST-sponsored studies exploring a patient-defining biomarker for Cabo will prove invaluable. I don't think this point can be overemphasized. We are only at the threshold of biomarker-driven cancer care, and there exists an undeniably optimal Cabo treatment group. When Cabo works well - it works really, really well in patients that apparently also tolerate it's toxicities quite well. Once that patient group can be isolated with a simple predictive assay, Cabo will find its way into every treatment algorithm in which it has displayed efficacy, plus several that are as yet unexplored. Watch the short thesis evaporate when that future presentation takes place...
JMO - but I would look to the NCCN to recognize such a biomarker before the FDA.
Published 9/1/14 in Molecular Imaging, Doran et al...
"Cabozantinib Resolves Bone Scans in Tumor-Naive Mice Harboring Skeletal Injuries"
"In summary, although the mechanism by which cabozantinib suppresses radionuclide incorporation into foci undergoing bone remodeling remains unknown, that this phenomenon occurs in tumor-naïve models indicates that caution should be exercised in interpreting the clinical significance of this event."
Advising caution in interpreting Cabo bone scan significance...
Here's the balance of that abstract. I encourage the read for all longs..
"...Cabozantinib (XL-184, BMS-907351 Cometriq) has displayed impressive clinical activity against several indications, culminating in its recent approval for medullary thyroid cancer. Among malignancies with tropism for the bone (prostate, breast), one striking feature of early clinical reports about this drug has been the rapid and complete resolution of bone scans, a phenomenon almost never observed even among therapies already shown to confer survival benefit. In castration-resistant prostate cancer, not all conventional response indicators change as dramatically posttreatment, raising the possibility that cabozantinib may impair the ability of bone-seeking radionuclides to integrate within the remodeling bone. To test this hypothesis, we surgically induced bone remodeling via physical insult in non-tumor-bearing mice and performed 18F-sodium fluoride (18F-NaF) positron emission tomographic (PET) and technetium 99m-methylene diphosphonate (99mTc-MDP) single-photon emission computed tomographic (SPECT) scans pre- and posttreatment with cabozantinib and related inhibitors. A consistent reduction in the accumulation of either radiotracer at the site of bone remodeling was observed in animals treated with cabozantinib. Given that cabozantinib is known to inhibit several receptor tyrosine kinases, we drugged animals with various permutations of more selective inhibitors to attempt to refine the molecular basis of bone scan resolution. Neither the vascular endothelial growth factor receptor (VEGFR) inhibitor axitinib, the MET inhibitor crizotinib, nor the combination was capable of inhibiting 18F-NaF accumulation at known bioactive doses."
"More regurgitation of old news."
Hush up and learn something, dummy.
You've no frickin clue what you are talking about here. You are so intent on attacking me that you have no idea what is being stated. More useless dooshwaddle junk from a useless Bozo...
Get a clue. Get a life. Get a job.
"...there is now compelling evidence in preclinical models that cabozantinib has direct anti tumor, which reintroduces theossibility that some portion of the bone scan resolution OS attributable to prostate cancer ablation."
I found it interesting that a coauthor of this study was Dr Charles Sawyers. This lends a credibility to the prospect of a future presentation on this topic as a veritable world-class PR event. Earlier publications by JS DeBono have suggested tumor-specific necrosis, and the Dave Smith UM trial has given us a positive aspect on the Cabo effect within the trabecular environ. Tying these implications to adjunct studies of bone remodeling, bone biomarker effects, and bone mets prevention should be given the highest priority IMO. I have to admit, this article shocked me at first, the positivity of it is taking some time to fully assimilate.
Something potentially remarkable is being witnessed at the molecular level, and the science is struggling to grasp it's significance.
There aren't any...why not?
Look at biotechs that have run the same course as EXEL in terms of PPS...
There are litigations up the Royal Bazoo - law firms seeking lead clients...
Something quite extraordinary is taking place here, and legal counsel is not being sought.
Hasn't even yet been suggested on this YMB, where folks really oughta be free to vent...
Why? What is about to happen here? Is semanresu's head gonna explode...?
"Let's back up because..."
Your self-proclaimed alter ego "Offsitehelp" has endlessly referred to Cobi as Voodoo therapy without value. Now own up or be the frick gone, loser boy....you can't own up to multiple aliases and not own up every piece of junk that y'all spout. Pack of frickin dipshizzles...
"...any chance of listening to the presentations...?"
I suspect they'll become available following the conference, and YouTube or oncologyTV would be good guesses for googling. Madrid is on CEST - a full 9 hours ahead of me on PDST - so I expect there'll be an early Monday morning (likely premarket) PR with the presentation highlights.
I'm hopeful for some productive discussion on the results. Nivolumab will be the entry level player in the mix, and I expect some good results. It will take some time, poring over all 3 presentations, to gather any sense of how the treatment sequencing might be perceived by Mr Market. I anticipate good results from CoBRIM, but will they be good enough to guarantee durable commercial success in advanced melanoma? Unanswerable at this time...GL