I'd like to qualify that for NSCLC, results are not nearly as mature as in melanoma. You can see the combo data at:
Your very same words can be applied to Vem + Cobi. You have to ignore expert opinion and trial results to dismiss the real shift in sentiment due to very good efficacy by PD-1/L1 inhibitors.
Best of luck to you. I'm just an investor so I am trying my best to keep all the options for an indication in perspective. Exelixis is a great company but it has its warts and there are other equally compelling names if one looks deeply enough.
I think immunotherapy will be tried first in the future because of very real possibility of a durable remission in some patients as well as a response after with-drawl of treatment.; more patients on inhibitors need to take it continuously and ultimately relapse it seems. The ORR is more modest for immunotherapy because they change the equilibrium between the body's own immune vigilance and tumors rather than inhibitors which squeeze the tumors signaling pathways hard. This can be a much longer lasting effect though. See Sznol's opinion in "Relative Roles of Targeted Therapies and Immunotherapies in Melanoma"
The AEs for nivo + ipi are horrible, but I would personally give that about 4 months then switch to an inhibitor combo.
Checkmate 067 showed the Nivolumab Ipilimumab combo work independent of BRAF status. Although ORR is modest, long term OS looks better too. Early data shows two year survival rates for Vemu + Cobi are 61% at 2 years compared to 88% Nivo + Ipi. I think it's unclear where BRAF+MEK combos will come (before or after immunotherapies) but immunotherapies will be the backbone of future treatments in melanoma and beyond, as central as chemotherapy.
The press release specifically mentioned that the FDA requested additional supplementary materials. The language used makes it seem like it's specific to this combo's application, and not for the general supplemental indication for vemurafenib. It would be nice if they said something about the nature of these materials but I couldn't see anything.
The published results for the drug are good and there doesn't seem to be anything in terms of efficacy or adverse reaction that should prevent it from being ultimately approved for advanced BRAF positive melanoma. I didn't expect a delay, and I'm not sure exactly what the FDA requested. It's frustrating how opaque the FDA communications with companies can be, but nothing I've seen makes me think it should be material to the ultimate (positive) outcome. It does chop off 3 months of (discounted) revenue from the period up to patent expiration when Exelixis can profitably sell the drug.
That's not unreasonable if you think METEOR fails. They stumble hard if METEOR fails because they won't make it to CELESTIAL readout without raising more cash.
A large short of June calls would be consistent betting on the thesis that METEOR fails. In such an event, median PFS would be below 7.5 months and it would be likely that we'd have known by now after accounting for data cleaning and analysis.
What was the orientation of Morrisey's coiffing today? (Sure sign of price move on Monday btw.)
No wonder Semanresu was pulling out all the stops last week... even semi-coherent arguments!
That would explain 1.4 million shares of volume, so the rest is probably someone who smelled blood...
14,000+ calls open at $3.50 expiring today. Someone was buying to deliver on exercise, so covering their unhedged short of those calls.
The expenses don't worry me much. There is a concern and that's how much Roche will charge for Cobimetinib in light of existing and new competition in melanoma. Cobimetinib alone only #$%$ growth whereas in combination w/ other drugs, it induces cell death. I also don't believe it has any indications where it's being tested in monotherapy. In that sense, it is something of a sweetener for other compounds and Roche may price it as such... In all likelihood though, it will be priced competitively against the Dabrafenib + Trametinib combo depending on the AE profile and of the efficacy drug. Vemurafenib already has an established price and Cobi will fill out the difference.
From the 10K:
"After MTD was determined, we granted to Genentech an exclusive worldwide revenue-bearing license to cobimetinib in March 2009, at which point Genentech became responsible for completing the phase 1 clinical trial and subsequent clinical development. We received an additional $7.0 million payment in March 2010."
Interest in buying these cash flows have been demonstrated by hedge funds searching for yield. (See: "ImmunoGen, Inc. Announces $200 Million Non-Dilutive Royalty Transaction")
"About the Cobimetinib Development Collaboration
Exelixis discovered cobimetinib internally and advanced the compound to investigational new drug (IND) status. In late 2006, Exelixis entered into a worldwide co-development agreement with Genentech, under which Exelixis received initial upfront and milestone payments in connection with signing the agreement and submitting the IND. Exelixis was responsible for development of cobimetinib through the determination of the maximum tolerated dose in phase 1, at which point Genentech exercised its option to further develop the compound.
In November 2013, Exelixis exercised its option to co-promote cobimetinib, if approved, in the United States. Exelixis is entitled to an initial equal share of U.S. profits and losses, which will decrease as sales increase, and will share equally in the U.S. marketing and commercialization costs. Exelixis is eligible to receive royalties on any sales of the product outside the United States."
The agreement for Exelixis doesn't include development costs past Phase 1.
Joe, didn't mean for my words to get carried away. Sorry about that and see you on around the board.
... and here I thought we were finally being civil and talking about some actual ideas in an informed context instead of resorting to name / credential dropping and assuming the conclusions we want to prove. Whenever you're ready Joe; I've failed punks smarter than you but I've no ill will toward them and I'm always ready to talk about the actual ideas.
An appeal to his greatness, Ernie's authority in your arguments or wagging your purported top-secret biotech credentials around won't make your actual argument any more or less valid. (Btw, Ernie you're great.)
Your reasoning assumes a 12 month figure for the Cabo arm and after using a "fancy" weighted average with 5 months for the Everolimus arm, concludes that it's very close to "where we are with PFS, to date, for total patients" whatever that means. You still need to rule out other consistent scenarios for both arms (the best you can do is show they're unlikely under some more assumptions) and furthermore, explain in a coherent way what it even is that you're approximating with those "complicated" Math terms you're dropping.
It's about the likely shape of the Cabo arm's distribution after 1) making an assumption about the Everolimus distribution based on historical performance along with 2) knowing roughly the count of total events after a median of 12 months of follow up. I assume progression events bunch up around the historical 5-6 month median for Everolimus and mostly tail off by 12 months. If at 12 months fewer than 3/4 of total events have occurred, and it's likely most of the events have occurred in the Everolimus arm, it leaves about half the events yet to occur in the Cabo arm at around 12 months of followup.