Dovepress, June 2014...Smyth, Sclafani, & Cunningham
Excellent comparative analysis of MET inhibitors. Table 1 has a comparator review of MET biomarker trial results as applicable. Both Cabo and foretinib are reviewed in many indications, and Cabo seems highly regarded by these authors. Well written...well organized...
"Ciaran Devane, chief executive at Macmillan Cancer Support, said: "Shockingly, the most common form of skin cancer, malignant melanoma, has shot up by 78% among men and 48% among women in the last 10 years. This makes it now the fifth most common cancer in England."
"The number of people diagnosed with liver cancer has risen sharply. An Office for National Statistics study shows the incidence of liver cancer in England increased by 70% for males and 60% for females between 2003 and 2012."
I saw this coming. I've been adding sunscreen to my beer for years.
From "CTCs in Prostate Cancer" by Hu, Rochefort, and Goldkorn NCBI December 2013. Well researched update on CTC gathering and enumeration modalities with statistical breakdowns in various stages of disease. It appears likely that CTC count & genomic characterization will provide future treatment guidance in many stages of metastatic disease.
From subsection 5 titled "CTCs in Advanced Prostate Cancer", these excerpted data are attributed to JS DeBono:
"Changes in a patient’s CTC count after treatment were also associated with survival. Patients who experienced a change from favorable (≤5) to unfavorable ( 5) CTC count had a significantly worse survival when compared to those with continuously favorable CTC counts ( 26 vs. 9.3 months, p
I am particularly intrigued by the following excerpt from the " Materials & Methods" section of the poster:
"The development of osteolytic lesions was detected by radiography at the end of the study. The mice were sacrificed 5 weeks after inoculation, examined macroscopically, and their bones were collected for histomorphometric analysis. 4/15 mice were euthanized before the end of the experiment due to paraplegia in control and bortezomib groups, but none in cabozantinib groups.Animals euthanized within 4 days of the end of the experiments were included in the analysis."
"...but none in cabozantinib groups..."
Reading into this might suggest that Cabo treatment has a dynamic therapeutic impact on disease progression in it's most advanced stage, perhaps even when compared to treatment with bortezomib. I like the direction this is taking.
I think we are overdue an update on the Cabo MM trial, as it has been recruiting for nearly two years - which isn't necessarily an indication of how far advanced that enrollment may be...re: Comet 2.
But the preclinical data presented here seem compelling. I can't seem to find much published information on the Pharmatest murine model, but there is a lot of research suggesting problematic data and response translation from murine to human studies. Immunoglobulin G2b (ilG2b) is thought to be a metric of tumor burden, and the initial elevation observed in this study may be a very favorable sign...of course, only if the observation bears out in patient pops. Still, I am optimistic. The earlier clinical observations that Cabo may only prove effective in mitigating osteoblastic lesions seems to have been dispelled and replaced with early data that suggests the effect on the bone micro environment may provide improved homeostasis to enable management of MM lytic lesions as well. Hbomb, you've been good at interpreting these types of data...got time for the nickel tour?
Some interesting observations here, many of which are beyond my qualifications to adequately interpret, but the therapeutic benefit of cabozantinib on osteolytic lesions in this model of Multiple Myeloma appears superior to that of Bortezomib treatment with obviously better soft tumor response. This preclinical work up is worth a look. Commentary invited. This poster appears to have presented at the AACR, Feb 2014.
...for Men With Bone Metastases Resulting From Castration-Resistant Prostate Cancer"
Good treatise on SOC, new, and emerging treatment options.
NCBI Feb 2014 by Jack McCain
"Perhaps one of these days you'll make a bit of money..."
Already done did all that, drizzle britches.
I've traded EXEL for nearly four years, and accumulated a good pile of shares, currently at a bragging ACB level? The short thesis doesn't impress me, nor do you.
I know who you are. Bring it.
Ain't it funny how ol' offsite gets outtasite when his thesis is denied...
Miyamoto, Sequist, and RJ Lee May 13, 2014..Nature Reviews Clinical Oncology.
Pay for article that surfaces with an open search of cabozantinib. Of considerable note is that RJ Lee has published extensively on CTC response to cabozantinib and was also a co-author of the Mass General dose-ranging study with Matt Smith.
"...there is an unmet clinical need for reliable biomarkers that can be used to guide therapy. Circulating tumour cells (CTCs) are rare cells that are shed from primary and metastatic tumour deposits into the peripheral circulation, and represent a means of performing noninvasive tumour sampling. Indeed, enumeration of CTCs before and after therapy has shown that CTC burden correlates with prognosis in patients with mCRPC. Moreover, studies have demonstrated the potential of molecular analysis of CTCs in monitoring and predicting response to therapy in patients. This Review describes the challenges associated with monitoring treatment response in mCRPC, and the advancements in CTC-analysis technologies applied to such assessments and, ultimately, guiding prostate cancer treatment."
"I'm going abroad for 2 weeks..."
I'm getting old...remind me...
Is going abroad better than getting a broad?
See "Exelixis - Down but not Out" by Ohad Hammer, posted March 30, 2014. Ohad's breakdown is conservative, and does not address possibilities of successful low-dose Cabo synergy in pre-Chemo prostate combination with Abiraterone, which I expect to play well. The devil is in the details, and though indications may prove fickle, I expect clinical adoption of cabozantinib beyond MTC in prostate, mRCC, and HCC by late 2016. I also expect Cabo to pick up refractory late stage indications in NSCLC, mCRC, and at least one additional thyroid indication. Cobimetinib will find reasonable success in BRAF-resistant melanoma, and the rationale for co-development with PDL1i will prove fruitful. MEK inhibition is enjoying an upswing in research endeavor, and I expect cobimetinib trial expansions to better reflect it's potential in the coming year. Biomarker-driven treatment guidelines will change the treatment paradigm dramatically in the next two years, and all TKI's will be compelled toward CDX. I see an EXEL market cap of 3.5 - 4 B by mid-2017, perhaps sooner.
"We really need to square that away before we have any more meaningful discussion....Fair enough?"
You've lost your mind. This is not a debate. This is a forum where like-minded investors can share thoughts. My agenda is my own, and I post EXEL-related information as I can find it in an easily verifiable fashion. I occasionally supplement my postings with opinion, and make every attempt to ensure that it is openly displayed as my opinion. I'm a fan of the science, and am motivated to enjoin others similarly motivated.
All you want folks to do here is sell quickly. Sell, sell, sell...
You harp on debt endlessly. Most experienced biotech investors expect to see debt attached to late stage development drugs. It's an inherently expensive and enduring process. Here we find two Phase 3 drugs delivering pivotal data, likely this year, and you are insisting that folks listen to your incessant pleas to sell before it's too late. Guess what, Sherlock?
It ain't gonna happen for most, regardless of how often you claim the sky is falling. It accounts for low volume days like today - no sellers, no buyers. Everyone with a clue is waiting for data. Give it a break.
"You just rag anyone with a differing opinion."
Never...not if that person can substantiate their differing opinion. Your refusal to address IP valuation only to maintain a daily fixation on tangible financials is inappropriate to the biotech sector, where virtually all companies' valuations are in limbo till trial results reach maturity. You talk about EXEL earnings reports as if anyone here actually expects to see viable income from an orphan subset thyroid indication. Give it up. We all know it ain't gonna happen. You babble on day after day about zero shareholder equity. Welcome to biotech. No biggie. This is biotech, where If they ain't broke now, wait a month and they might be.
The data suggests a successful outcome in Comet 1. We're all aware of the risks...thank-you-very-much for your concerns. Quit being a pest. Act responsibly. Stop annoying for the sake of continued annoyance. Quit being a troll, and perhaps you'll find that you are no longer addressed as such.
Your suggestions that EXEL has no promising data behind it's IP only displays your ignorance, your lack of DD, and your stubborn short perspective. You obviously have an agenda beyond your transparent lack of a personal trade. The folks that have done their homework look at you for the smiling butt-clown that you make yourself out to be. To them (and me), it's obvious that you have no skin in the game. Straighten up and fly right, and maybe we'll let you continue to hang out into double digits.
Duckduffer, what you are proposing is next to impossible. It's a bit like soliciting a credible representative of the short thesis on EXEL, and getting stuck with the dipstick shorts that post on this MB. They are about as cluelessly and underwhelmingly misinformed as the editorialist/interviewer/puddpullers at Seeking Alpha.
This is out of character for me, but I decided to take this issue one step further for the sake of covering the bases, and sent the following e-mail to Dr Bridgette Widemann, PI of NCT01709435...the Cabo "younger patients" solid tumors trial:
"Good day Dr Widemann,
Please forgive my intrusiveness, I will make every effort to be brief.
This note is draw your attention to the plight of a 6-year old Australian girl named Eva Wheatley. She is a victim of RMS, and has drawn recent global attention for the fund-raising efforts of her parents to enable their daughter's treatment on the multi-targeted TKI cabozantinib. The young girl is apparently at the end of her treatment options, and has already lost an arm to this disease.
At this stage in the development of Cabo, it is likely that no one - except you, yourself - has any real knowledge of the potential this compound may have in children. I see that your "younger patients" cabozantinib trial is still in recruitment phase, though some treatment centers have fully accrued.
I ask you this...
Would it not be possible to qualify this young Australian girl for cabozantinib treatment under the clinical auspices of your NCI-funded program? I really have no idea as to whether she meets the inclusion criteria of your trial, and I also realize that RMS is not specifically addressed in the trial protocol. But, I encourage you to look within your own best judgment...and also within the research aspects of what might best serve the science...and determine if there may be any way your trial might help this youngster and her parents in their desperate need.
Thanks in advance for any consideration."
"Do you know if they are donating the drug?"
Hi Bif - I didn't ask that question. I'd already presumed that the fund-raising effort as reported by the Sun-Herald precluded the possibility of a compassionate use freebie. My pointed question to Susan was whether or not Eva could be qualified for the pediatric trial. She replied that it simply wasn't available in Australia. The cabozantinib "younger patients" trial is sponsored by the NCI with locations mostly limited to the US..with one additional recruiting site in Canada. My thinking is that if EXEL were donating the drug to Eva, they'd let it be known for the PR. I'd like nothing more than to see that little girl get Cabo for free, but I don't think that is going to happen.
Actually, I just got off the phone with Susan. She invited me to call via e-mail. The conversation was informative and enjoyable. She assured me that Exelixis was well aware of Eva's fight with RMS, and was working with the attending oncologist thru the Aussie NPU to assist in dosing regimen, response rate monitoring, and recommendations for AE prophylaxis. There was much she would not address for the sake of patient confidentiality. Susan seems very bright, and very motivated. She introduced herself in depth, and I nearly laughed out loud when she asked if I'd ever heard of her former employer - Gilead.
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...