"So then you're just stalking me?"
And just how is it you ended up on the NVIV mb?
"... I can go into MegaBash mode and make this place unreadable."
"You want to threaten me now."
It's amazing. You alternate between bluster and self-victimization. What is it you want, respect, pity, admiration?
"Didn't the Baker Brothers have a big position in EXEL ?"
It looks like they sold after the Comets.
"... I can go into MegaBash mode and make this place unreadable."
By all means, please do whatever you think best.
"Anyone know how it all dispersed?"
FMR LLC, the parent company of Fidelity, picked up the lions share. They went from 16 million to 33 million shares and own 15% of the company.
"It's like a royalty payment.,, It's positive income."
It's not a royalty and it's not income. From investopedia:
"DEFINITION of 'Paid In Capital"
The amount of capital "paid in" by investors during common or preferred stock issuances, including the par value of the shares themselves. Paid in capital represents the funds raised by the business from equity, and not from ongoing operations.
In January 2014 EXEL raised $75 million in a stock offering. It was not treated as revenue or earnings in the first quarter 2014 financial results. That press release was 5/1/2014, please read it and you will see for yourself.
"Clovis, Genentech to test lung cancer combo"
It's Roceletinib. an improved EGFR inhibitor and the same PDL1 antibody Roche is testing with Cobi in 2 trials. The trial I'd like to see someone do is Cabo in combination with a PD1 inhibitor in EDFR wild type NSCLC.
"Other than cabo in CRPC, the only other trial that has shown clearance of metastatic lesions in large percentage of patients was Vemurafenib (ZELBORAF) in melanoma patients - we all know that story."
Hey Joe Factually correct if you assume that the bone scan response was an actual clearance of disease. I think it is, but there are problems. Remember the first data showed 17/20 with PR's and CR's. The RDT with a 100mg dose had a 60+% rate and eventually Comet 1 had a 42% BSR, but 28% were not evaluable so the actual rate may have been closer to 50%, certainly respectable. Duration of response was also good at 5.8 months. Problematic is that little of this apparent benefit seemed to flow through to survival, 11.0 mos vs 9.8 mos HR=.90 and a look at the KM shows that the medians overstate the benefit. One thing we've never been told is the nature of the progression once it occurs in BSR patients. Does it return to the previous sites or form new lesions?
Here's another thing to think about. 191 of the approx. 1000 patients had visceral mets. Those 191 had a 2.7 month PFS advantage and 2.3 months of that was preserved as a survival advantage with HR=.65. The overall ITT HR was .90. If you pull the 191 out of the ITT and look at bone only disease, those 800+ are going still have a survival advantage, but now it will be somewhere around HR= .92 or .93. So if we are going to find an indication in CRPC based on Cabo's activity in bone, my thinking is that you will have a tough time of it. CRPC is pretty much a survival endpoint only disease and the further you move up the treatment paradigm, the larger, longer and more expensive the trials become.
If they really want to relive the CRPC experience, I think the obvious place to look is end stage with visceral mets. Smallish indication, but also a shorter 400 patient trial would be overkill if the RDT and Comet subgroup data for this indication is repeatable.
"Next quarter, we're looking at a gain due to the stock offering."
Nice try, but no. It's not treated as revenue and doesn't flow to the bottom line. I'm sure we have at least one accountant here to correct me, but I believe it is considered paid in capital. It is an asset and does positively affect cash flow and cash balance.
"Also, we might expect "higer than expected" earnings form off label usage as a result of trial data;"
Most major insurance and government reimbursement agencies use the NCCN guidelines to determine what off label drugs are reimbursable under insurance coverage. Right now, the only approved off label use for Cometriq is RET positive NSCLC. It is an infrequent condition, comprising about 1-2% of new cases. Eventually newly presenting NSCLC patients will be given a single panel test up front that will look for all known genetic mutations and a handful of the major cancer treatment centers use the Foundation test for this purpose, but most do not. They do their genetic testing in a serial fashion eliminating possibilities one at a time with cheaper FISH tests and at the tail end of this process may be a test for RET, if the oncologist is aware of it and willing to perform the test. Most don't.
At $10K+ per month, Cometriq off label use will be driven by the reimbursement issue and by the means to identify the pool of patients who are eligible and would benefit.
."I'd still like to see the potentials of frontline AR modulation in combo w low dose Cabo fully explored in the prostate space. It seems increasingly clear that COMET design was flawed. "
I still don't know what to think about the bone scan response phenomenon. Cabo did not have any more efficacy in CRPC than sunitinib or avastin. The best CRPC data it had was from the RDT trial in which patients were required to be evaluable (ie measurable soft tissue lesions) and a similar subgroup from Comet 1. Comet 2 indicated that the pain response was probably attributable to placebo effect. Patients saw better bone scans so they thought they felt better. Cabo's best results are in highly refractory indications, especially patients with prior VEGF treatment. Even 1512 was in end stage chemo refractory patients.
"Given the dynamics of METEOR data that we have been already seen - and the rather large clinical potential - my personal suspicion is that an oral presentation in a plenary setting is warranted."
I agree and I wonder if BMS will present their Nivo data.
" Any prospective partner will fully explore for potential weakness in METEOR, and I think any deal favoring EXEL will correlate with the weight of those OS benefits."
We don't need to worry about the maturity of the survival benefit. It was only immature from the perspective that it failed to meet the requisite p value that would have allowed the trial to end early. That interim analysis was not there because anyone contemplated the possibility of an early stoppage, it was there to simply confirm that Cabo patients did not enjoy extended PFS with zero or a negative survival impact. That the OS analysis came so close to achieving significance that early is very surprising. The final analysis is now just a formality.
"The multi-targeted verbiage, secular phraseology, and unique nomenclatures attached to the CT process can be a huge obstacle to truly understanding your bio-investment."
It can be daunting. I have a great deal of respect for the poster kahn boonie who wasn't willing to take what I said at face value and challenged it with cites of 2 articles he found. The problem with the articles though is that they assumed an initial level of understanding that made interpretation difficult if you that level is lacking. You mentioned that I am self taught and one of the initial sites I relied on is very good at taking someone with a basic understanding of plain algebra and unraveling the math behind p values, Kaplan Meier curves, confidence intervals, censored data, log rank analysis and essentially turning it into a short online course.
To start I suggest searching Cancerguide, The Median isn't the Message and read the article by Stephen Jay Gould. Then follow the links on the left side of the page and it will take you through the entire clinical trial process using lay terms and understandable explanations. When they explain the math, get a legal pad and a pencil and work though the examples long hand. The fog will clear and it will all make more sense.
"Is the Kaplan -Meier curve as predictable when there is unexpected patient survival in a small subset?"
I don't think the most people fully appreciate just how good the topline result is. A majority of the patients enjoyed unexpected good survival. The PFS and OS HR's speak for themselves at .58 and .67 respectively. These are very impressive improvements over the standard of care. It is generally recognized that HR's are more comprehensive measures of efficacy than Median comparisons but median comparisons are easier to explain and understand.
"I am not an expert, but I don't believe that the PFS results as reported (hazard ratio) contains information about median PFS benefit. It could be modest, or it could be very large."
You're wondering how one can infer median PFS with only HR as a guide. There is no exact relationship, but the ratios are frequented equated as a "rule of thumb." EXEL did it in posting the powering statistics for both Meteor and Celestial. Celestial is powered at 90% to show an HR of ,67 which they equate to a median comparison of 7,5 months to 5 months. One divided by .67 times 5.0 is 7.5. The OS assumption for Celestial is 80% power to show an HR of .75 which they equate to 15 months vs 20 months. Do the math. The ratio of the medians is the same as the HR and the same relationship is true for the assumptions for Celestial and Comet 1. All those stats are in EXEL press releases or presentations.
Again, this is a rule of thumb, not a hard and solid relationship, but it holds pretty true for oncology PFS comparisons, although exceptions can be found in cases where the KM curves have unusual shapes that either minimize or maximize the spread of the curves right at the 50% line from the Y axis.
"An optimistic interpretation of this would be that median PFS (duration) has not been reached for the cabozantinib arm and therefore no median PFS extension benefit is yet calculable."
Kaplan Meier curves are used to calculate medians. These curves have an almost magical aspect in that they are predictive in nature. Even before an arm has a 50% event rate, the curves can show a predicted median. As mature as this data set is, the KM curve for the Cabo arm will dip below the 50% level even if the event total is shy of 50% of the Cabo arm patients. This is because each step down on the curve represents an event, but the step downs are not of equal magnitude. As the curve moves to the right, the step downs increase in size as fewer and fewer participants are at risk.
"FMR LLC has recently increased ownership in EXEL to 33,153,128 SHARES or 14.999%. Nearly DOUBLE THE SHARES from their last report."
I guess that's why I only got 500 shares in the offering.
"will bring $8 then kaboom to double digit .. ya warned!"
I hope you are correct, but history would argue otherwise. One characteristic of EXEL is that they reveal very little about developments that are not fully mature. Enrolment updates, status of negotiations, preliminary results prior to formal publication, are just things they have been reluctant to discuss during quarterly updates. Typically major announcements are done in a separate venue and preceded with a press release and followed by a conf call. Quarterly conferences have more often than not been rather disappointing for those with outsized expectations. There are near term catalysts which will have material impact on the company and those are the developments I optimistically await, but tomorrow might be a bit long on redirect and short on important news. We'll see soon enough.
"I had looked at that after the spike, Valuation still cheap, but they have a ways to go to get to market. What time frame are you expecting related to P3 and would you not expect a capital raise?"
One tendency I have had in biotech investing is to jump on the bandwagon too early. I'm learning to temper my initial enthusiasm. Some things I now consider is to wait for the inevitable dilution, to leverage in with several buys rather than a single purchase and just be more patient. I also prefer statistically relevant sample sizes, randomized data and I give extra consideration to the validation that breakthrough status gives.
"Question: What are the differences between the criteria for breakthrough therapy designation and fast track designation?"
Both are for serious diseases with an unmet need. The difference is that for fast track any efficacy need only be theoretical. For Breakthrough some degree of promising efficacy needs to have been demonstrated. Fast track is not a big deal. Breakthrough is.
"If cabo doubled PFS, it could happen...? From the data, it's possible it did 4.5 months to 8-10 months."
Very, very unlikely with a hazaed ratio of .58. The exact ratio of medians depends on the shape of the Kaplan Meier curves and where the point of greatest separation falls, but with that HR, a more likely outcome is 8 months vs 5 months, or thereabouts.
"It would be a 60 day review on BTS."
Just so everyone understands, it's a 60 day review to award breakthrough not a 60 day review for approval of the NDA.