"There is something to be said about the Rain Man, numbers and Peoples Court, but the option players will not know unless they can count cards from multiple decks..."
"Has cabo ever been combined with everolimus for mRCC?"
I don't believe it's been considered as yet. Put on everlolimus' other hat as an immuno-suppressant to prevent tissue rejection on the wake of organ transplant, and it becomes a rather awkward coupling consideration. If there are hidden rewards, I suspect they've not been considered. Interesting...
Ernie, my apologies... I should have better phrased my intro.
I meant to say I did not expect the PD class inhibitors to present with durability. As an intervention, I see near-term commercial success...but as you have pointed out - the effects are less than durable. Are you invested in HALO? I've been for a while, and am beginning to see PEGph20 as a platform drug in high HA tumor presentations. No telling as yet where the compatibilities lie, but the current IP presentation suggests that mitigating Hyaluranonic acid presence may lead to better chemo therapeutic exposure - favorable responses with lower dosing structures and optimal metabolic delivery. As PEG data matures, I consider a future in which drugs like Cabo are delivered via conjugated delivery into an optimally pre-conditioned tumor environment, ideally lowering toxic exposure times while maximizing cellular interaction - more localized than systemic. Even electro-poration has gotten my attention in this...
"Are there a particular class of medications that you view a threat to Cabo..."
Just conjecture on my part, but I don't see PD immunotherapy as a mono therapeutic success over the long term. Hormone axis manipulation - while an effective intervention - doesn't yet appear to hold all the cards. I'm still self-familiarizing with the rationale for PD/PD-L1 combinations with existing TKIs...looking for fast-acting intervention, high-end response rates, and patient tolerability that also presents with a durability of response not yet reported. I look forward to the ASCO Cabo/Abi update wrt to svAR-7 impact. I'm not a clinician, and perhaps a bit naive on the statistical uptake...but, I'm a relentless reader. My bet on Cabo is mostly based on my belief that it will find a predictive biomarker as the assay technologies mature. We'll see...
"Making Progress on Progression in Metastatic Prostate Cancer"
Armstrong & Halabi, JCO April 2015
Though this editorial doesn't specifically mention Cabo (nor the Comet trials), I felt its importance in understanding the changing perspective on defining progressive disease in CRPC should not go un-noticed. The use of BSR in making treatment determinations appears to be evolving, and JMO - I think research and investigative work with Cabo has played to inform this evolution of perspective. Good read...
"To conclude at this juncture that there are significant safety concerns is simply ludicrous..."
I prefer to look at it this way. As investors, we will always be looking to minimize downside risk vs the prospect of maximizing upside potential. In the clinic, minimizing patient risk vs measurable health benefit is not only a relative goal - relative to type of cancer, oncogenic origins, known drivers, etc - but also relative to the evolution of the treatment landscape and the introduction of newer (and possibly less toxic) treatments.
In a nutshell, treatments deemed to possess an acceptable toxicity today may not maintain that acceptability in the future. I think that is the greatest uncertainty here - that Cabo may prove too toxic to withstand the test of commercial success over time. Cabo's activity profile as a therapeutic intervention is not so much at question as is its prospective tenure as a commercially successful, revenue-generating enterprise in a quickly evolving treatment theater.
No FUD. No BS - just a little recommended reading from the ASCO Post:
"Expert Point of View: Eric J. Small, MD
By Alice Goodman
April 10, 2015, Volume 6, Issue 6"
To a degree, I share Dr Small's opinion. Also my opinion - Cabo needs a biomarker that best defines it's optimal use in a genetically defined target group...that group being best defined not only in terms of response rates and variables of efficacy, but also in terms of overall tolerability. Nothing new here. I've been saying this for quite some time now. My past posts bear this out consistently, while also acknowledging that TKI use - in general - brings with it a host of undesirable...yet clinically manageable...side effects. If you are aware of an orally bio available TKI that has no history of toxic profile, please share that info. Hope this helps.
Surely all those thumbs-downs came from a bunch of whiny, humorless, Democrats.
Be sure to get yer Mommies to powder yer behinds before you go night-night...
And you, danq - best stock up on Dydees...yer gonna need 'em.
Lots of high-comedy drama on this MB...over-exuberant pumpers, anxious longs, over-confident shorts, hyper-critical analysts, a CEO as obviously nervous as a prom queen at homecoming. Some feller even created an ID just to tell Clem he was "full of it" for quoting IR. Add Wrong-Way Willie and you've got the Keystone Cops.
You can't buy this kind of entertainment...
Not to worry. After both Comet's failed to produce, AF quoted Klein in a Street article giving Cabo a dim future:"We believe that RCC represents cabozantinib's last hope and expect that negative results will scuttle any further cabozantinib development, including the Phase 3 CELESTIAL trial in HCC. Recall the METEOR trial in RCC is 90% powered to detect a hazard ratio (HR) of 0.667 with a two-sided alpha of 0.05, employing a PFS assumption of 5.0 months for everolimus versus 7.5 months for cabozantinib. While PFS may be the primary endpoint of the trial and the company expects to file an NDA on positive data, given the myriad of approved therapies for RCC, we anticipate this trial will need to demonstrate at least a trend toward improved survival in order to gain approval and market adoption. In addition, we note that the safety/tolerability profile for cabozantinib will need to be compelling for commercial usage, and we believe cabozantinib's fatigue side effect may make it unappealing to patients"
My response: ya can't suffer fatigue if yer dead. Cabo can save the lives of some patients. We've all seen this. Ask those patients their opinion. My bet is each one prefers tired to the boneyard - hands down.
Your cheerleading, your commentary on strategy, and your very presence lend new meaning to the phrase deep, dark, and danq...
Forgive my back door inference...
As Cabo has shown to overcome Crizo resistance in ROS1 rearrangements, I see Cabo as potential follow-on therapy in any indication where Crizo may be prescribed. Jury's still out...but good to see Cabo gaining respect.
There are also a couple of new publications in Cancer Discovery regarding METex14 skipping and durable responses by MET inhibitors. One is authored by Alexander Drilon, same author of the RET fusion Cabo study presenting at this years' ASCO. I begin to suspect his work with Cabo may lead us to an additional compendium listing in METex14 deleted disease...
There's also a worthwhile presentation by Dr Steven Dubinett, UCLA Lung Cancer Program Directior, entitled "New Frontiers in Lung Cancer Biology" that addresses the most recent breakdown stats on driver mutations and the high need for patient selectivity in targeted treatment. Check it out @ namdrcdotorg
16:41 hrs 1 share traded at $3.46
16:52 hrs 200 shares traded at 3.45
16:52 hrs 1 share traded at 3.40
No doubt about it, Wall Street thugs rule...
Looks like an easy exit, shorty.
I'd take full advantage, were I in your shoes...
By all considerations of prior financial agreements - whether with Deerfield or Goldman - this play has all the ingredients of a Faustian bargain. I encourage you to look that up, if that phrase is outside your realm of awareness.This is turning into either the play of the decade...or the bust of the century.
I'm the most credible guy around...
Just ask my Mom...
She'll tell ya...
Agreed. Cabozantinib has a history of toxicity - but that history includes dose reduction vs efficacy studies, all of which maintain a TP consistent with other TKIs. Cabo has been studied in NSCLC clinical trials since 2008. Now - suddenly...6 years later - in the wake of compelling PFS data that threatens competition with SOC - suddenly those TP issues reappear? Utter nonsense... Nice try Kevin Riley...
The quote comes from a Benzinga staff writer named Kevin Riley, who claims to be a healthcare analyst. If you check his recent reviews, he has also written stock reviews on Pepsi & Tillys...
"What do you think is gonna happen?"
I think it's important to distinguish between validating the science...
...and validating the investment potential. Importantly - since J Scott Garland moved on to Relypsa, who has taken responsibility for monetizing these assets? I really surprised that this question has not posed at the handful of Q&A sessions that have taken place since JSG's Oct 14 departure...
Now that we've got all this validated science, how in the heck do we monetize it?
How high in regard does MMM hold the concept of shareholder value?
Are these fair questions to pose at the annual meeting?