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Exelixis, Inc. Message Board

wildbiftek 113 posts  |  Last Activity: Jul 3, 2015 4:49 PM Member since: Oct 25, 2011
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  • Reply to

    CTO

    by csanderson1805 Jul 2, 2015 3:39 PM
    wildbiftek wildbiftek Jul 3, 2015 4:49 PM Flag

    This article:

    targetedoncDOTcom/articles/fda-extends-review-period-for-cobimetinib-melanoma-nda

    indicates it was to ensure sufficient time to review the followup data released at ASCO. Since there's a competing combo with the same theoretical mechanism, there's probably less of a rush.

  • Reply to

    BRAF V600E

    by stimulustrader Jul 1, 2015 11:33 AM
    wildbiftek wildbiftek Jul 2, 2015 11:16 PM Flag

    These checkpoint inhibitors (surprisingly) don't always require specific ligand expression on tumors in order to work. At this year's ASCO, PD-1 checkpoint inhibitor Nivolumab was just as effective in improving OS as an active taxane, docetaxel for patients NOT expressing PD-L1. It was much better for those who did. Targeting that pathway also limits AEs because of the way lymphocytes infiltrate tumors and tend to act only in the region of the tumor expressing the PD-L1 ligands when there is a response.

    While it's true checkpoint inhibition doesn't work everywhere and CTLA-4 inhibitor AEs are severe, in the many indications it does work it works longer than checkpoint inhibitors for the substantial number of patients who do see a response. Responses can come after with-drawl of the drug and doesn't require continuous dosing like inhibitors and also the outcomes are more durable than with inhibitors where many more patients progress. ASCO 2015 also showed good results for nivolumab inhibitors (in addition to melanoma and NSCLC) in CRC, GBM, HCC, and RCC. Inhibitors aren't going anywhere, but I wouldn't understate the importance of checkpoint inhibition going forward.

  • Reply to

    BRAF V600E

    by stimulustrader Jul 1, 2015 11:33 AM
    wildbiftek wildbiftek Jul 2, 2015 5:28 PM Flag

    Antibodies are all related to the immune system in the sense that B-Cells produce them, so what you say about immunotherapy technically true.

    However CTLA-4 and PD-1/L1 checkpoint inhibiting antibodies are immune check-point inhibitors and their mechanism acts primarily by upregulating immune response against tumors and thwarting tumors' attempts to down regulate the immune system respectively. This is different from other antibodies which may block tumor cell pathway signaling, draw natural killer cells to consume the cell onto which it binds, or in the case of adcetris, drop a chemotherapy payload within the cell after lysosomal degradation within the cell.

    These checkpoint inhibitors are pervasively effective and utilize the immune system much more directly than a drug like ADCETRIS.

  • Reply to

    BRAF V600E

    by stimulustrader Jul 1, 2015 11:33 AM
    wildbiftek wildbiftek Jul 1, 2015 2:21 PM Flag

    I'd like to qualify that for NSCLC, results are not nearly as mature as in melanoma. You can see the combo data at:

    meetinglibraryDOTascoDOTorg/content/125736-144

  • Reply to

    BRAF V600E

    by stimulustrader Jul 1, 2015 11:33 AM
    wildbiftek wildbiftek Jul 1, 2015 2:09 PM Flag

    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.

  • Reply to

    BRAF V600E

    by stimulustrader Jul 1, 2015 11:33 AM
    wildbiftek wildbiftek Jul 1, 2015 2:08 PM Flag

    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.

  • Reply to

    BRAF V600E

    by stimulustrader Jul 1, 2015 11:33 AM
    wildbiftek wildbiftek Jul 1, 2015 12:59 PM Flag

    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.

  • Reply to

    3 month delay announced

    by drglrd1101 Jul 1, 2015 8:54 AM
    wildbiftek wildbiftek Jul 1, 2015 9:40 AM Flag

    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.

  • Reply to

    3 month delay announced

    by drglrd1101 Jul 1, 2015 8:54 AM
    wildbiftek wildbiftek Jul 1, 2015 9:27 AM Flag

    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.

  • Reply to

    Puts

    by stimulustrader Jun 26, 2015 10:33 AM
    wildbiftek wildbiftek Jun 26, 2015 10:53 AM Flag

    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.

  • Reply to

    Puts

    by stimulustrader Jun 26, 2015 10:33 AM
    wildbiftek wildbiftek Jun 26, 2015 10:37 AM Flag

    Never mind that, ~50k $2 strike August 15 puts open. Could be worthless just because EXEL announces in Sept.

  • wildbiftek wildbiftek Jun 19, 2015 9:19 PM Flag

    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.

  • wildbiftek wildbiftek Jun 19, 2015 6:58 PM Flag

    What was the orientation of Morrisey's coiffing today? (Sure sign of price move on Monday btw.)

  • wildbiftek wildbiftek Jun 19, 2015 4:43 PM Flag

    Haha, for him it was a John Nash like moment of clarity compared to his usual comments.

  • wildbiftek wildbiftek Jun 19, 2015 4:37 PM Flag

    No wonder Semanresu was pulling out all the stops last week... even semi-coherent arguments!

  • wildbiftek wildbiftek Jun 19, 2015 4:25 PM Flag

    That would explain 1.4 million shares of volume, so the rest is probably someone who smelled blood...

  • wildbiftek wildbiftek Jun 19, 2015 4:23 PM Flag

    14,000+ calls open at $3.50 expiring today. Someone was buying to deliver on exercise, so covering their unhedged short of those calls.

  • Reply to

    1 Drug Will Make or Break These 3 Biotech Stocks

    by wilderguide Jun 14, 2015 12:40 PM
    wildbiftek wildbiftek Jun 18, 2015 2:05 PM Flag

    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.

  • Reply to

    1 Drug Will Make or Break These 3 Biotech Stocks

    by wilderguide Jun 14, 2015 12:40 PM
    wildbiftek wildbiftek Jun 18, 2015 1:41 PM Flag

    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")

  • Reply to

    1 Drug Will Make or Break These 3 Biotech Stocks

    by wilderguide Jun 14, 2015 12:40 PM
    wildbiftek wildbiftek Jun 18, 2015 1:32 PM Flag

    "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.

EXEL
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