If this is a repeat - my apologies - but this was new to me, and it generates some interesting perspective on the synergistic potential of Cabo w/ checkpoint inhibition or vaccine-based combinations. This excerpt is from AACR abstract 5497 dated 4/22/15. I suspect these data came from one (or more) of the Univ of Mich sponsored studies...but the author list is very long and multi-institutional.
"...cytokine array profiling of supernatant from bone marrow metastases from castrate-resistant prostate cancer patients showed increased neutrophil markers and decreased IL-6 levels within the bone microenvironment following 6 weeks of cabozantinib treatment., thus polarizing the neutrophils into" N1" effector cells. Collectively, these results shed light on a novel anti-tumor immunogenic mechanism for cabozantinib within the tumor microenvironment of PTEN/p53 deficient tumors, which unleashes a profound innate anti-tumor immune response. These findings suggest the possibility of combination therapies of cabozantinib with T-cell checkpoint blockade or vaccine-based approaches, to augment immunologic responses in advanced cancers."
Thanks for the response, there's a lot to consider in that study - and as Nomad insists on pointing out on a regular basis - I may not be the sharpest tool in the shed. And - ya know what? I've discovered that when it comes to the really convoluted cell signaling processes, feedback loops, crosstalk mechanisms, acquired resistances, and discerning short motive - he might be right. Last note I have from yer way is 4/8. If there's something more recent, best hit resend. We've been pretty busy. Glad to see you up and about...
I had an unintended discussion of this nature earlier today. My wife is looking to get us into a large, used truck while gas prices are down. We've looked at quite a few, and today test drove a late model Ford - big diesel, beautiful, clean...by all appearances meticulously maintained. My wife drove it a few miles & loved it. I asked to drive the return leg. Permission granted. My wife chatted with the owner, and grew suspicious as his answers were inconsistent with her observations. As they chatted, I drove. I decided to try out the tow/haul auto drive feature, and saw immediately that the overdrive code light did not illuminate - nor was there any change in RPM despite repetitive cycling of the switch.Red flag warning. I returned to the parking spot, and turned the truck off. I asked when last the tranny codes were downloaded, and his response blew my mind. Never been downloaded. No need...truck runs great. The moral of the story: if you don't consider the possibility of a downside, you can easily convince yourself that none exists. We left him shaking his head... We're still looking...
Very interesting work-up being conducted by Genentech:
"MET suppresses epithelial VEGFR2 via intracrine VEGF-induced endoplasmic reticulum-associated degradation" T Chen et al. Published May 2015 Science Direct. All listed authors are Genentech employees, and the MEK inhibitor being utilized in this study is cobimetinib.
The rationale is not only compelling, but it's not too great a stretch of the imagine to consider a combination of Cabo and Cobi. There are simply too many targets addressed by Cabo for me to intelligibly elucidate upon this combo but I'd really enjoy any commentary wrt to this publication. Joeflow, Ernie, Bif, onco...share a few thoughts here as you can...
"Time for everyone to get out of the pool..."
History is not on your side here. Take a look at the multiple successes of BOD chair Stelios Papadopoulos. How many BKs can you count under his watch? Look at the remainder of the BOD - a veritable "Who's Who" of oncological research endeavor and therapeutic success. The CEO owns over 2M shares...George Scangos holds over 3M shares... Institutional holdings are huge. The fact that they are heavily traded speaks only to the willfulness to trade the volitility. It's not just about the risk. It's also about the day-to-day profit. The converts made the short position way too viable. The best thing that could happen to EXEL would be a partnered renegotiation of the debt. If the converts went away, my contention is that the huge short position would also evaporate...and pretty darn quick. The long-term "ace-in-the-hole" dividend would vanish, and EXEL would resume trading with a modicum of normalcy - rather than a lunatic poster child of profit-driven volatility.
How could anyone but an idiot suggest this stock is not a manipulator's plaything? Up 100% over 3 months on no news...then up 10% on GREAT news - left to languish and bleed on the vine. It's a minefield of manipulation - but it sure is a fun trade. This last bounce you could read for months in advance.
It's not about revenue. It's not about risk. It's about profiteering...
"...there is no conventionally recognized baseline that Value investors can look at and pass judgement on over/under said baseline."
This is precisely my argument for trading in biotech to the lowest attainable cost basis, while preserving a core account. This strategy has worked well for me, especially where dilution potential exists, inadequate management lurks, debt persists, and a persistent short element lingers.
Given the data...short side analytics going into Q3 are doomed. Cobi will not only get approved, but the V&C combination will be readily absorbed into clinical use. Cabo's potential to enable broad spectrum PFS is apparent, and not not only in treatment refractory mRCC. JMO, but my opinion is that it's a fool's bet against top-line METEOR.
Given those two potential successes - is EXEL worth $1B?
My answer...at least that, and quite likely much more - given the extent of the far-reaching IP...the potential of CS-3150...and the sleeper potential of XL-888. Financing won't be an issue beyond Q3. I just hope for sensible financing, not like we were dealt by the Karbe/Goldman fiasco.
A success story for CS-3150 would put us in the diabetes space, and a whole new set of binary catalysts - a dream machine for a momo trader.
"There is little doubt that Cabo and Cobi are active..."
...and anyone that tries to sell you a different story is either poorly informed, or guilty of a self-absorbed agenda. They might as well be hyping that Nixon was not a #$%$, Oliver North didn't sell guns to the Contras, and Bruce Jenner didn't recently transform into Caitlyn...
The facts best represent the truth, and those facts are irrefutable.
"There is no baseline value."
Speculating on biotech is definitely not for the meek. Interpreting data, results, and clinical intent can be a daunting endeavor. Contrarian indicators can be a very healthy thing. Back in winter 2010, nomad carpet bombed this MB from the $3s to over $12/share while the potential of the Cabo bone phenom was highly discussed. Going on 5 years later - the Cabo BSR is still recognized - it's importance as yet poorly understood. One thing is certain - bone mets kill. I would add the word "recognized" to your phrase...
"There is no (recognized) baseline value." The jury's still out on that one...
The failed Comet-1 trial met some important endpoints, despite losing wrt OS. BSR, pain relief, CTC normalization, PFS, and statsig OS in visceral mets and post-cabazitaxel subset patient groups is still some pretty compelling stuff - particularly when the heavily pre-treated enrollment group is held in consideration. I you cannot see the potential for unrecognized value, I can't help you. Check out the recent posting regarding sequencing of new therapies in mCRPC issued the the French National Cancer Society. They are still trying to sequence Cabo into utility in the prostate space. The only one that sees no potential value is apparently you... Good luck with that...
Yer about a useless fruitcake...
I think yer gonna Meep! Meep! us all the way back to $12, just like you did a few years back...
Seymour, you've completely missed the point of my post. Let me politely explain the significance of Dr Apolo's research, and perhaps I can solicit a little goodwill along the path to your enlightenment.
Cabozantinib is an active agent across a broad spectrum of cancers. It's risk/benefit profile will not likely lend to it a broad, encompassing prescription. However, prescription behind the directed discretion of a predictive assay - such as that being developed by Apolo (with NCI funding, I might add) may define the patient pool to best optimize Cabo benefit. This - in turn - could lead to a broad spectrum assay that may apply in other cancer indications. It's a win-win for everyone.
This study is one of many being published in conjunction with ASCO, yet not being formally presented. This is a CTC platform evaluation being conducted alongside Andrea Apolo's Cabo work in UC. Very interesting stuff here, particularly given that we get a clue as to another combo trial putting Cabo in bed with Nivolumab in mUC. JMO - Dr Apolo's work is worth following...
"Conclusions: Using this flow cytometry-based platform, baseline CTC count predicted response and survival in pts with metastatic UC receiving cabo. This new platform places CTC analysis within the clinical investigator’s institution to promote precision medicine in drug development. The CTC assay has been modified to incorporate quantification of PD-L1 expression for an ongoing phase 1 trial of cabo + nivolumab +/- ipilimumab in this population."
Dude...grow a sense of humor, and flex it once in a while.
Stop mediating the masses. The MB can self-arbitrate...
Life's too short to be so serious all the time.
Lest yer liable to find yerself in my screenplay too...
...and you may not like whom I've chosen to portray you.
"Underwater" by Seymour Duckweed - a short tale of short investment gone wrong.
I've agreed to co-write the screenplay, but only with the proviso that Seth Rogen, Jay Baruchel, James Franco, Molly Shannon, and Paul Giamatti play the EXEL management team....and PeeWee Herman has just got to be Seymour. Bob Redford offered me 7 figures for the project, but I told him I'd do it for giggles.
Sometimes I just lose control...
"I bet I have traded this more in the past year than you have in your life."
O, you very brave adventurous soul. May the Saints be with you...
You bold spirit...
"So, what are the chances of a fastrack..."
Of course, we're all armchair quarterbacks here...but if the decision were mine, I'd consider applying for a category 2 NCCN listing without delay. It's likely to get a go, and payors would respect it till the treatment algorithm caught its breath. It might generate near-term revenue to carry on without a dilutive offering, and I don't see a downside to the strategy. Amongst the trials that have been carried since 2009 - and with optimum consideration to the recent NCI update - there's a good chance for at least a 2b rating. The company needs revenue, and the current level of evidence might carry the justification. Some authors of E-1512 are on the lung cancer committee, others familiar with Cabo are on the steering committee. It might just fly. They couldn't advertise the indication, but I think the #'s speak for themselves.
Seymour, you are certainly a " Much Ado About Nothing" type...
Keep in mind, all the while you've been LOLOLOLing on YMBs, other folks have actually been leading constructive, creative, adventuresome lives. Don't ever begin to compare your own fruitless endeavors to those of others. You are obviously useless beyond comparison. Just an honest observation...but you are in desperate need of a group hug - and might even be better served by a public spanking to replace all those you deserved as a child...but never received.
Sorry, but I don't think you'll find those kindnesses here...
No one here really cares about what you think...what you say....or what you need.
Better get used to it...
Snowflake - add coconut oil to your diet. Cook with it. Add it to your tea. I bake with it, adding sweetness with applesauce. Butter your toast with it, substitute it liberally for all all your butter and veggie oil needs. I use it for frying dishes, sometimes mixing it with olive oil. It liquifies at 70F, and is very easy to work with... And downright flavorful to boot. It'll help.
"The only thing straight is the bridge..."
A few years back, my wife plugged into a few courses at "Oaksterdam University" to acclimate to the changing legal, ethical, and botanical infrastructures involved in legally growing and possessing "da spleef". We have visited SF on occasion, and I always enjoy the seacoast access...but it's sure a boatload of city for a country boy. JMO - but there's simply too much turmoil intrinsic to the city. Traffic is highest on my personal list, though I've been known to play the risk if the musical venue so warrants. As a part of my early investment in EXEL, we visited SF just to see Zheng Cao perform with the SF opera company. She was an early success story for sequenced Tarceva & Cabo in NSCLC. It was an embracing experience, particularly knowing her challenges. I'll never forget that visit...
Doesn't hurt to be social. Try it sometime...
Might even make someone wanna correspond with you.
Contribute, don't criticize. Share what you find...
Instead of conducting all your DD...
...mooching on the efforts of others on a YMB.