From the EMA website: Seems like an appropriate day to announce the marketing authorization of another orphan drug, doesn't it?
"About Rare Disease Day"
The European Medicines Agency supports Rare Disease Day, which takes place on Friday 28 February 2014.
Rare Disease Day is held every year on the last day of February. Launched in 2008, it seeks to raise awareness of rare diseases, and to improve access to treatment and medical representation for individuals with rare diseases and their families. It is coordinated by the European Organisation for Rare Diseases (EURORDIS).
This year, the theme of Rare Disease Day is care. The goal is to encourage everyone in the rare disease community to join together for better care. "
Hey Ernie...this thread got me to thinking of the impact on future trial structure, should we get negative return on OS from the EXAM trial. The post marketing mandate for a P4 trial is still in planning stage with a proposed upper dose cohort at 140mg. The lower dose has yet to be elucidated, but it's apparent the 140mg trial dose has essentially become extinct.
If reported OS from EXAM is less than statsig (or marginal), how could the P4 trial possibly recruit that high dose -.particularly given the obvious probability of higher dose off-target toxicity compromising the OS signal?
I figure that-if we should see the lower P4 dose published prior to the announcement of EXAM OS results - it could give us a fair insight as to what to expect. I don't believe it's coincidental that the P4 start-up is not scheduled till July 2014. It appears intentional that we not see that lower dose value until after we get existing trial reporting from EXAM and the Comets.
Think this is an intentional withholding, or is this just the way the game is played?
E-pubIished ahead of print 2/21/14 PubMed, L Thomas et al.
High tox profile, 4% non-PD AE5's...not much competition here. Cabo rocks!
"Drug (sorafenib) was discontinued in 16% of patients because of toxicities or intolerance, and the dose was reduced in a further 56%. Side effects with an incidence ≥50% were hand-foot syndrome (74%), diarrhea (70%), skin rash (67%), fatigue (61%), and weight loss (57%). Deaths not related to progressive disease occurred in nearly 4% of patients.Conclusion.Treatment with sorafenib in patients with progressive DTC and MTC is a promising strategy, but the adverse event rate is high, leading to a high rate of dose reduction or discontinuation. Consequently, sorafenib use in patients with metastatic thyroid cancer requires careful selection of patients and careful management of side effects."
Interesting JCO early release 2/24/14 Dr David Jonson, et al:
"Recent Clinical Advances in Lung Cancer Management"
Some interesting findings from the US Lung Cancer Mutation Consortium...for those looking to expand on the Cabo/ Erlotinib combo rationale. In addition, the document speaks to many avenues of targeted therapy rationale in LC.
"Unfortunately, TKI-treated patients with EGFR mutations are not cured by the EGFR TKI therapy, and progress after a median of 9 to 10 months. The mechanisms of resistance reported to date include secondary gatekeeper mutations in the EGFR gene at T790M, the outgrowth of small-cell lung cancer cells, and acti- vation of other pathways such as MET, FGFR and AXL, HER2 amplification and epithelial to mesenchymal transition. New TKIs that bind to T790M and activating EGFR mutations but not to wild-type EGFR receptors have been developed and hold promise for improved results."
Sure...Old uncle Wilderthorpe...
..my favored uncle that hangs out, grows the spleef...
Rolls the bajoom...quaffs a little 'Lude...
And invents little truisms like the one above.
I am not certain that uncertainty exists, but I do know that everything is more like it is now...
than it it ever was before. And, if this should change - the balance of all that ever was, ever will be, or ever could be -will, in turn- be defined by the perception of all that ever was or ever could have been.
- Wilderthorpe's wager
"But then in January 2014, they went to market again and raised $75 million. The did a better job of it at least (by dumping Goldman Sachs), but never the less, their burn rate clearly is scaring management as well."
I agree with this sentiment. I'm hopeful that we see some asset potential out of either Cobimetinib,Foretinib, or XL-888 (their HSP90 inhibitor). I'd rather see another partnering - or an outright asset sale - than yet another dilution. Foretinib's recent unveiling of it's potential in ROS1 inhibition should prove valuable...and XL-888 is still recruiting in that Moffitt CC melanoma trial. They must like what they are seeing. Wrt dilution: enough is enough.
"Does it really matter whether a patient is receiving 60mg or 20mg, when the cost to develop cabo over the last 10 years is the denominator used to determine the cost..."
Undeniably, but we're talking "wiggle room", not dramatic price reduction. If you
take your statement at face value, enabler, should Cabo never get approval in any other indication, they could jack up the pricing to $100k per month and never recover development costs. MTC alone can never pay for itself, but as other indications and dosages come on-line, I can see negotiation space for reimbursors to parley...particularly should Cabo witness success in 20mg every other day dosing. How could you compare that to 100mg per day and not see room for negotiation? At that point, it becomes a bit like apples at airport prices of $1/apiece vs. road stand pricing of $3/ 10lbs.
Lots of margin for profit...
Bif, doesn't it seem reasonable that Exelixis has bit of "wiggle room" wrt pricing?
After all the findings in lower dose efficacy, many of the currently proposed treatment regimens are far below the initial dosing when compared to that of EXAM. As yet, the dosing for the P4 post marketing MTC trial has not been elucidated, but I'm expecting to see half dosing of EXAM start-up, and perhaps lower. I realize IP valuation is relatively unaffected by dose halving, but production costs can only be downwardly bound as lower doses prove effective.
Regulatory action is inevitable wrt reducing healthcare costs, but if the market finds productive clinical enterprise in 20mg dosing, should that pricing be equated to 100mg pricing?
"Next capital call around June 30..."
Actualy, Jonesy...I think you may be somewhat close to correct here.
By the late June date you suggest, we will have seen European marketing approval, statsig OS data in MTC, reasonably satisfying interim data from Comet 1, perhaps a preview of positive data return from Comet 2, an SNDA filing in mCRPC, and a host of supportive ASCO presentation data from the many NCI trials that support Cabo MOA. An offering with the strength of approvable data behind it might fetch a tidy $9 - $10/ share. That won't bother too many that frequent this MB. Question is...will it bother you, drizzle britches?
"...but the really big bucks,I humbly suggest, are just ahead."
I agree, but I pulled some off the table at $8...and bought some back on this weeks's rundown. The risk/reward I see here is too appreciable to consider bailing out completely, but this whole process has taken much longer than I initially surmised, and EXEL no longer looks like the asset play that I had first bought into. To me - it's looks as though these guys want to enter the global marketplace
In addition, the treatment landscape has changed dramatically...and the untested introduction of Obama's AHCA is worth watching out for. I've still got a boatload of shares.
No worries, I've always been on board for the science - and near as I can tell - that story's only gotten better. In addition, if every indication that has shown promise actually flies, the NCI/CTEP program will have picked up much the tab. That, in itself, has a lot of intrinsic value.
Bif...just an FYI. I recently decided that before I made a decision wrt bailing out of EXEL, I would purchase the last publication from the McDonald lab at UCSF:
"Controlling Escape from Angiogenesis Inhibitors" Sennino, et al 10/12/12.
Doc McDonald is listed as second author, and has been cited many times in MET/VEGF combo synergy research. I feel it'd be wise to acknowledge leading edge pre-clinical data before shifting gears outta here. I've been guilty of premature departure too many times in the past. Visit Doc M's website...he's still a very busy guy. GL
Don't get me wrong, I'm not pessimistic about the science. I am not...Not at all.
Let me put it this way. Recognizing the limitations of associating patient response with overall survival is a perspective normally left to clinicians, not investors. This stock has taken me five times the amount of analysis, study, and learning process that I put into my other biotech investments. In that regard, it's been more of a learning process than a stock play.
Ernie has commented that many of the early Cabo clinicians have "softened" and perhaps begun to lose theIr supportive participatory "spirit". I feel that many simply tired of banging their heads against the regulatory wall that must necessarily be climbed to get Cabo approved (short of producing statsig OS). Fact is, many premier oncologists in the prostate space are still on board...Doc Scher's ASCO 2013 CRPC biomarker assay presentation - if taken at face value - supports Cabo treatment in CRPC, though it's not directed at Cabo. Doc Celestia Higano has begun her third clinical trial with Cabo - why in God's name would she waste her time if not for patient benefit? Doc Vogelzang is a SWOG participant in the Comets...Ethan Basch is still top-dog in the realm of patient-reported outcomes, and PRO's are thriving. Doc Dan George is still stumping for non-narcotic pain relief as a surrogate endpoint for OS in clinical trials. The list of past players is long, and those apples have not fallen far from the tree. Am I optimistic??? Hell yes...
It's simply difficult to see past the painful apocalypse of yet another EXEL secondary...
This is certainly a stock play that fosters ambivalence.
In the absence of statsig OS, you must be willing to accept the future direction of the supporting science to a most unusual degree. You've essentially got to believe that the Cabo BSR not only suggests patient benefit - but actually predicts improved OS. Same-same for CTC reduction, bone turnover biomarkers, modified LDH levels, bone pain relief, and narcotic use reduction. All great patient concerns, none of which carry any regulatory weight whatever wrt approvability. Proven PFS is really all Cabo's got going for it...
How can the average investor accept these study endpoints as anything other than experimental when even the FDA does not? It's a dilemma...
I'm still of the opinion that you get more information in darkened parking lots with pull-over ski masks and baseball bats than you can by trying to interpret an endless ream of SEC filings.
No wonder these guys hired a new mouthpiece.
I think they wore the old one out. LOL
"Special Notes regarding Forward-Looking Statements"
"The foregoing provisions make it difficult for holders of our common stock to replace our board of directors. In addition, the authorization of undesignated preferred stock makes it possible for our board of directors to issue preferred stock with voting or other rights or preferences that could impede the success of any attempt to change control of our company."
This prospectus filing has all the hallmarks of changing EXEL to a higher risk investment than has been previously portrayed. Could this filing be our new lawyer's first contribution? All commentary invited.
Of course there's no verifiable truth to the matter, as Karbe is on record for refusing to comment, but the article appeared 4/12/14 in Bloomberg:
" Exelixisseattle Said to Hire GS for Takeover Offers"
Bloomberg wouldn't reveal their source, the company would not corroborate the release. Welcome to America...
"Exelixis hired Goldman in anticipation of possible bids after preliminary data on the treatment, XL184, was published Nov. 17, said one of the people, who asked not to be identified because the situation is private. Some large pharmaceutical companies have shown interest, the person said.
“We don’t comment on those types of reports which have been around the company for a long time,” Charles Butler, Exelixis’s vice president for investor relations, said yesterday in a telephone interview. “We have a long standing relationship with Goldman Sachs, we just did a public offering with them.”
Why should Bloomberg lie?