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Vertex Pharmaceuticals Incorporated Message Board

thirdmeinvestor 35 posts  |  Last Activity: Jul 17, 2015 7:45 PM Member since: Feb 25, 2004
  • Reply to


    by trangy Jul 17, 2015 4:14 PM
    thirdmeinvestor thirdmeinvestor Jul 17, 2015 7:45 PM Flag

    Try to read and understand the data coming out of clinical trials! Go to the Alnylam website and read about the data for Patisiran (TTR02) for FAP, Revusiran (TTRsc) for FAC and SSA, ALN-AT3 for hemophiliac, ALN-CC5 for PNH, ALN-PCS for hypercholesterolemia, ALN-HBV for Hep B and others. Each one of the above drugs has a block buster potential.

  • Reply to

    VX 661

    by iamhowsweetitis Jul 10, 2015 12:54 PM
    thirdmeinvestor thirdmeinvestor Jul 11, 2015 10:46 AM Flag

    The Clinicaltrial website gives for the approximate data collection date to be May of 2016.
    Both efficacy and safety for homozygous 508 mutation would be as good as, or better than, Orkambi, and the efficacy for heterozygotes with 508 in one allele and Ivacaftor-responsive mutation on the other allele will be better than Ivacaftor alone. I am expecting for the latter a 3-4% FEV1 increase over that of Ivacaftor monotherapy. This is something one should look forward to.

  • Reply to


    by windtime24 Jul 6, 2015 3:22 PM
    thirdmeinvestor thirdmeinvestor Jul 6, 2015 6:55 PM Flag

    The VRTX target share price was raised earlier to $160 from 130 at Robert W. Baird, also to $161 from $146 at Piper Jaffray.

    We'll get there one way or another. There might be a surprise at the earnings' conf call.

  • thirdmeinvestor by thirdmeinvestor Jun 29, 2015 6:31 PM Flag

    Juno is a ten bagger stock. Wait 5 years.

  • thirdmeinvestor by thirdmeinvestor Jun 25, 2015 5:47 PM Flag

    The shares are being traded at 133.95 right now.

  • Reply to

    Why the jump on Friday?

    by junnkmail Jun 13, 2015 10:02 PM
    thirdmeinvestor thirdmeinvestor Jun 20, 2015 1:42 AM Flag

    The high % short positions is a good bullish sign. Look up today's chart for ALNY.

  • thirdmeinvestor by thirdmeinvestor Jun 16, 2015 11:27 PM Flag

    Boulder, CO-based N30 Pharma debuts as Nivalis Therapeutics tomorrow with its IPO. Its lead product candidate is N91115, a small molecule that addresses a defect in CFTR, the underlying cause of CF. N91115 modulates CFTR activity through a novel mechanism of action that stabilizes CFTR inside the cell and at the cell surface. An added benefit is that N91115 is expected to be complementary to existing and future CFTR modulators. A Phase 1b trial is close to completion. A Phase 2 will follow that will evaluate N91115 in a triple therapy with two other CFTR modulators: lumacaftor (Vertex Pharmaceuticals' (NASDAQ:VRTX) investigational VX-809) with ivacaftor (Vertex's Kalydeco) or lumacaftor/ivacaftor (Vertex's Orkambi).

    It is interesting to learn that Vertex chose Parion, not Nivalis for financial help.

  • Reply to

    Why the jump on Friday?

    by junnkmail Jun 13, 2015 10:02 PM
    thirdmeinvestor thirdmeinvestor Jun 14, 2015 12:57 PM Flag

    The bears' case was weak and emotional. The bulls like good science and good medicine.

    The combo of oral DAAs with RG-101 will be a huge success. A single RG-101 shot cuts the viral load by 4 log. This reduces the duration of DAA dosing to cure HCV infection regardless of genotypes. DAA combos fail many high viral load, cirrhotic, or co-infected patients. The success rate for the patients with Genotype 3 is as low as 60%. Patients who fail oral DAA treatment has no other recourse but injecting the old Interferon and taking dreadful Ribavirin for 48 weeks minimum.

  • Reply to

    Why ENaC? And why is it synergistic??

    by verityvoila Jun 5, 2015 9:24 AM
    thirdmeinvestor thirdmeinvestor Jun 6, 2015 11:53 AM Flag

    The total ion concentration in the water layer on the airways lining determines the water volume. If the ions flow out into the lining interface water, the airways will be hydrated and the lung will be happy. But if the ions are excessively moved into the tissue from the interface water volume, the airways will be dehydrated and the lung will be unhappy. Remember water always follow the ions. In CF lungs chloride ions don't flow out actively into the interface water volume. Positive ions such as sodium ions cannot diffuse out into the interface water because they follow anions such as chloride ions. On top of that, in CF lungs the active Na+ ion pumping by ENaC removes Na ions out of the interface volume. Both sodium and chloride ions are kept away from the interface. The net result is that the interface will lack both ions and water. Immune cells in the interface will be very unhappy and cannot remove bacteria in it.

    Now Orkambi partially restores chloride pumping into the interface, and an ENaC inhibitor would block sodium pumping out of the interface. So, plenty of both ions will be there and water volume will increase. I hope this answers your question.

  • thirdmeinvestor thirdmeinvestor Jun 4, 2015 5:09 PM Flag

    There should be synergy btw ENaC inhibition and chloride transport enhanced by Kalydeco or by Orkambi. Lung function should improve more as a result.

  • thirdmeinvestor thirdmeinvestor May 27, 2015 2:48 PM Flag

    I should work for VX-661 as well. I'll see how much Van Goor knows about it, or how much he wants to reveal. I have Van Goor's email address.

  • thirdmeinvestor thirdmeinvestor May 27, 2015 11:56 AM Flag

    I'll send the link to the journal paper to van Goor and Altshuler. It is likely that van Goor was one of the reviewers for the paper.

  • A week ago, Science Signaling, a sister publication of Science, reported a striking finding. It is stated that activation of a molecule could improve the performance of VX-809 (Lumacaftor) by threefold. The authors obtained VX-809 presumably from Vertex, and Vertex should be aware of their work and findings. This research group in Portugal has published the basic findings underlying the new results in earlier papers.
    Their new finding will be summarized below.
    In human cells there is a checkpoint pathway that removes improperly folded proteins from the plasma membrane through a mechanism called CHIP. Because this checkpoint degrades misfolded CFTR, it could also degrade some of VX-809-rescued F508del-CFTR, and limits its efficacy. They found that activation of the cytoskeletal regulator Rac1 resulted in bypassing the checkpoint. So that the exposure of airway cells to Rac1 activator together with VX-809 nearly tripled the efficacy of VX-809. They also found that by blocking an intermediate step VX-809 and Rac1 activation could not reproduce the gain seen without the blocker.

    If this VX-809 performance can be replicated in human body, who needs second-generation correctors because 508del heterozygotes can achieve a 4% FEV1 improvement.

  • Reply to

    Earnings power from Orkambi and Kalydeco

    by thirdmeinvestor May 16, 2015 10:53 PM
    thirdmeinvestor thirdmeinvestor May 17, 2015 11:27 PM Flag

    Verity, I only meant using one's own 508 CFTR as a template to replace the other CFTR on the other allele. They could do this kind in animals, but not for CFTR. They could also deliver normal pieces by attaching them to modified lentivirus. The compound has to be inhaled, I suppose.

  • Reply to

    Earnings power from Orkambi and Kalydeco

    by thirdmeinvestor May 16, 2015 10:53 PM
    thirdmeinvestor thirdmeinvestor May 17, 2015 4:15 PM Flag

    Verity, thank you for pointing out that it may take more than 1 year for EU countries to reimburse for Orkambi use, and also that I did not include the likely participation by younger 508 homozygotes in the US. These two mistakes for the year 2016 roughly cancel each other, and in two years we may see substantial share price rise. Today's report that the New England Journal of Medicine published the results from Traffic and Transport studies is very encouraging.
    I hope that Vertex has started some attempt to use CRISPR technology to put the missing phenylalanine base in the CFTR gene. It should be easier to convert heterozygous 508del into a homozygous 508del because existing DNA in the other allele can be used as template. Ultimately, exogenous CFTR DNA had to be delivered into the lung lining cells and other cells.

  • thirdmeinvestor by thirdmeinvestor May 17, 2015 12:03 AM Flag

    Other trial results which could raise PE would be Phase I dose optimization study for VX-970 and VX-803. These molecules are inhibitors of ATR and possibly ATM as well. ATR and ATM are cell cycle checkpoint initiators. Tumor cells damaged by radiation, cisplatin, gemcitabine, or etoposide can be rescued by DNA repair, which cannot happen if the cell cycle is allowed to proceed. If DNA damaged cells enter the mitosis phase, irreparable chromosomal break would occur. VX-970 and VX-803 inhibit the checkpoint initiator so that damaged tumor cells are not stopped before the entry into mitosis phase where the tumor cells would be mortally wounded.

  • Reply to

    Earnings power from Orkambi and Kalydeco

    by thirdmeinvestor May 16, 2015 10:53 PM
    thirdmeinvestor thirdmeinvestor May 16, 2015 11:13 PM Flag

    VX-661 will achieve an absolute FEV1 change of 3 - 4%, and we have to give a minimum PE of at least 30. So you may expect 5.76 x 30 =$ 173/share by then. If the second generation correctors in the [oven] are really good in treating 508del heterozygotes, a PE of 75 is possible.

  • thirdmeinvestor by thirdmeinvestor May 16, 2015 10:53 PM Flag

    The net the company will be reimbursed for Orkambi pill would be assumed conservatively to be 200 K per year. The list price will be much higher, and cannot be much lower than the price of Kalydeco. If the price of Orkambi were much lower than that of Kalydeco, the 70% Kalydeco taking patients who have 508del mutation would switch to Orkambi because Orkambi can improve the FEV1 change by another 4% for people with 508del in one allele and Kalydeco responsive mutation in the other allele.

    There are about 20,500 homozygous 508del persons (12 years old or older) in US and major EU markets. For this year, we can count on 8500 persons in the US. In the Lum+Iva rollover study, greater than 90% of Phase III participants joined the trial. Uptake of this combo will be slower than the speed of adoption by 551 CFers, and let us assume that an average of 75 % of 8500 homozygotes take the combo within 6 months of launch (by the end of the year). You get a revenue of 8500 x 0.75 x 200 K x 0.5 year = 638 Mln. Vertex projects to receive 570 Mln from Kalydeco responsive CFers. The annual company expenditure will not exceed 1.1 Bln (source: Vertex), and the tax for orphan drug sales is zero. Then, by the end of 2015 the net will be 108 Mln (= 638 Mln + 570 Mln - 1100 Mln). This corresponds to $ 0.39 per share.

    For 2016, 200 Kalydeco taking CFer will be freed from the VX-661 Phase III trial to raise the sales to 600 Mln, the US sales from Orkambi will be 1.4 Bln, and the EU sales will be 800 Mln. Adding all three, we get 2.8 Bln. If R&D and SG&A amount to 1.2 Bln then, we have 1.6 Bln. Subtracting 10 % royalty payment to CF Foundation, we get 1.44 Bln. Dividing this figure with the number of shares which will be about 250 Mln, the earnings per share will be 1440 Mln/250 Mln = $ 5.76 per share.

  • My rather conservative calculation shows that Vertex will have positive earnings for the whole year of 2015, and can earn at least $ 5.5 per shr next year from the sales of Kalydeco and Orkambi. VX-661 and second correctors will be successful, and we have to give a P/E of 30 at least. Even if the earnings for the next year is only $5.5, the share price should be 165 at the end of 2016.

    RBC notes says:

    Orkambi helps VRTX get to $5B peak CF sales and visibility on $10 in
    earnings power over next few years - using peer multiples of 15-20x gets the
    stock to $150-200 with that math. Plus - there's pipeline that could further
    expand on that with '661 (2-drug combo) or dual correctors (triplet combo)
    for 30% more pts called heterozygous; Outperform

  • Reply to

    500 million shares?

    by rojospan May 11, 2015 7:21 PM
    thirdmeinvestor thirdmeinvestor May 11, 2015 9:59 PM Flag

    Thank you for posting the 770 on 508 trial result. The FDA does not have any basis for objection.

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