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Vertex Pharmaceuticals Incorporated Message Board

thirdmeinvestor 13 posts  |  Last Activity: Apr 25, 2015 11:51 PM Member since: Feb 25, 2004
  • Gilead's newest triple (Sovaldi + Ledi + PI) given for 4 wks achieved 27% for the 12 wk SVR for GT1 where RG-101 achieved 32% SVR only with a single shot. When multiple doses are given and each dose knock out 4 log, it does not take many doses to cut down to the level where immune response alone can mop out the remaining HCV. Gilead's drug (Sovaldi) cannot cure GT 3 without Ribavirin and pegIFN, and even with the latter it takes 16-24 weeks of dosing. GT 3 is one of the most prevalent HCV GT worldwide. RG-101 is a pan-GT and prior-treatment-independent drug. Gilead has to acquire RG-101 if it is going to survive as a company.

  • Reply to

    Possible scenario

    by thirdmeinvestor Nov 10, 2014 8:03 PM
    thirdmeinvestor thirdmeinvestor Apr 25, 2015 7:07 PM Flag

    Kleanthis indicated in the video presentation that the upcoming trial will have three combo arms sandwiched between two injections of RG-101: (1) 4 week dosing with NS5A inhibitors (he may be thinking of BMY's or Gilead's), (2) 4 week protease inhibitor (has to be Olysio for which DI has been tested), and (3) 4 week combination with NS5B and NS5A inhibitors (Harvoni of Gilead is the only candidate). To sum up, he is not committing to any single company to partner with. This may be wise. However, I think that the SVR outcome would be very similar no matter which DAA is used.

  • About 500 patients with homozygous F508del mutation (two copies) are being enrolled in a six month Ph 3 study. Response to VX-661+Iva will not be the same across the treatment group. In real world some will respond far better with this combo than with Luma+Iva combo. The Phase II trials were relatively small to detect who respond better than others. Variables are degree of disease progression, age, weight and other drugs taken.
    True value of VX-661 will be enhanced when it is combined with a 2nd generation corrector along with Iva to treat homozygous F508del CFers. There will be a quantum jump if the in vitro study is a good guide as it has been. Vertex will nominate a 2nd gen corrector this year and will test its potential to increase FEV1 (the change could be as much as 10% almost like Kalydeco on 551 mutation). For this triple combo VX-661 is essential.

    Another 500 CFers with F508del in one allele and Kalydeco-responsive mutation in the other allele will be treated with VX-661+Iva duo for 8 weeks. Because this portion of trial is short the results may be available for presentation in this year's NACFC meeting in early October. Nearly ¾ of CFers with G551D, other gating mutations and with residual function mutations will enjoy the benefit beyond the benefit Kalydeco alone can provide because the other allele has 508 mutation which can be repaired by VX-661. The commercial value of the duo combo will greatly exceed that of Iva given alone, and could reach the 1.5 – 2.0 Bln range. There are 7000 CFers in this group in major markets.

  • thirdmeinvestor by thirdmeinvestor Apr 1, 2015 11:27 PM Flag

    It is easy for a blog writer to underestimate the clinical power of Lumacafter+Ivacator combination if he does not appreciate the seriousness of Pulmonary Exacerbations CF patients have to suffer every year. The combo (400mg Luma) reduced the rate of PE by 39%. This means that less frequent hospital visits for IV antibiotic infusion and a lower loss of lung function. The FDA will approve the combo marketing for the homozygous 508 suffers in a few months.

    If you invest 100K in VRTX shares at 116 now, you will have a good chance to sell shares at above 150 when the FDA panel recommends approval in 1.3 months, and a good chance to make a 50% gain on your investment when the FDA approves Lumacaftor marketing and Vertex announces 300K pricing. Do not sell here. If you sell you are throwing away 50,000 dollars (on 100K investment). I do not know any other big-cap biotech which can appreciate so much in a few months.

  • thirdmeinvestor thirdmeinvestor Mar 31, 2015 1:03 PM Flag

    Thank you, Q. Today, Celgene and Gilead are leading big cap biotechs to go lower. Celgene has a patent issue with Revlimid in the EU.

  • Reply to


    by gladpick Mar 23, 2015 6:15 PM
    thirdmeinvestor thirdmeinvestor Mar 23, 2015 11:24 PM Flag

    I agree with Robyn Karnauskas. VX-661 will succeed. A PE of 35 is modest when compared with Alexion, which earned only 3+ dollars in the past year. The Alexion's PE is 57 right now and its market cap is greater than the Vertex' by more than 20% where it will face a great competition from Alnylam in a few years.

  • Reply to


    by gladpick Mar 23, 2015 6:15 PM
    thirdmeinvestor thirdmeinvestor Mar 23, 2015 8:22 PM Flag

    In my earlier estimates (Bullish Case) I made an algebraic error and the target price came out to be ridiculously high. I corrected that below, and used very conservative values for revenues from Lumacaftor and Ivacaftor. The combo will be approved to treat homozygous F508del mutation by the FDA within a month or two, and also by the EU counterpart soon after. The net the company gets for the Lum/Iva combo pill twice daily over a year per person would be assumed conservatively to be around 180 K.
    There are about 20,500 homozygous 508 mutation holders (12 years old or older) in US and major EU markets. 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 75% of 20,500 homozygotes take the combo within 2 years of launch. You get a revenue of 20.5 K x 0.75 x 180 K = 2767.5 Mln. This figure is at the low end of revenue analysts have been predicting for the combo. Add to that the sales for the Ivacaftor mono.-responsive mutation holders 3.7 K x 180 K x 0.9 = 600 M,
    assuming that Ivacaftor is taken by 90% of them and the revenue from each person is again 180 K. The annual company expenditure will not exceed 1.5 Bln, and the tax for orphan drug sales is zero. By the end of 2017 latest the gross from CF drug sales would be (2767 Mln + 600 Mln - 1500 Mln) = 1867 Bln.
    Dividing this figure with the number of shares in 2017 which will be about 260 Mln, the earnings per share will be 1867Mln/260 Mln = $ 7.18 per share. After paying the 10% royalty to CF Foundation, we get a net of $ 6.46 per share. If VX-661 and second generation correctors are successful, we have to give a PE of at least 35 because heterozygous 508 CFers will be treated. So you may expect 6.46 x 35 =$ 226 /share by then.

  • Reply to

    Concert Pharma Competition?

    by mary27705 Mar 12, 2015 9:05 AM
    thirdmeinvestor thirdmeinvestor Mar 15, 2015 9:10 PM Flag

    The zinc-finger nuclease (ZFN) technology used by Crane et al. is a very old technology. Vertex is focused on gene editing technologies that are specific to the target gene (CFTR) and efficient unlike ZFN. But both technologies have to overcome huge problems of delivering to human cells in the body.

  • Reply to

    Q, Glad, Others

    by mary27705 Mar 11, 2015 10:11 AM
    thirdmeinvestor thirdmeinvestor Mar 11, 2015 10:59 PM Flag

    You may want to look at Alnylam (ALNY), a RNAi company.

  • thirdmeinvestor by thirdmeinvestor Feb 16, 2015 10:38 PM Flag

    Gene editing using CRISPR technology in higher animals and plants is very new, and potentially allows fixing genetic problems at the very root. Today people are talking about an exact CRISPR procedure to repair the sickle cell anemia gene. It can delete sections of the genome with precision. And a gene engineering could refill the void with normal codes in the future.
    It is amusing to think about CRISPR/Cas9 techniques as new technology because bacteria have been using the method for a billion years to fight off bacteriophage infection. About ten years ago, researchers found that the bacteria carried CRISPR [Clustered Regularly Interspaced Short Palindromic Repeats] sequence in their DNA body. It took a few more years to figure out the reason. It turned out that the repeated genetic codes contained the code of phage which had attacked the bacteria before, and when attacked again by the same phage, the code sequence would be transcribed into RNA, then chopped into small pieces, each containing phage gene codes. Then Cas9 nuclease goes into action by cleaving the bonds holding the phage DNA double strands where the chopped RNA recognizes as the phage gene. Next Cas9 shreds the phage DNA and kills the phage. So, CRISPR/Cas9 is an immune system for the bacteria.
    Only less than two years ago, a few groups reported that they can cut to produce a DNA double-strand break in human or mouse embryonic cells, and some reported that they repaired the cut with another gene segment to produce a new organism. They say that the technique is simple, fast, and reliable that any graduate student in biology can master it to apply to different model systems. If so, could this system be used to treat genetic abnormalities in human? Some challenges are still remaining, but those too may be overcome in future.

  • thirdmeinvestor thirdmeinvestor Jan 31, 2015 7:42 PM Flag

    Glad, the full trial results are apparently not known to the sponsor of the trial. They may know the number of dropout rate for example. Should they disclose such events without knowing the full circumstances? They have to have a consistent picture of the results before reporting them. The most important fact reported for us is that the FDA approved the huge (1120 people altogether) Phase 3 trial for the 661 combo. If there were a possibility of serious safety issues, the FDA would not have allowed the trial. The efficacy is concerned, it should be better than that of 809 combo.

    Glad, I am certain that the share price will reach 200 in two years. The market is mad right now. Most Wall Street analyst assume that the 809 drug combo will cost 150K per year per person. What Karnauskas found out by talking to the management is that 150K is too low a value. She told this in CNBC several weeks ago.

    Good luck to you.

  • thirdmeinvestor thirdmeinvestor Jan 30, 2015 7:17 PM Flag

    Robyn Karnauskas at Deutsche Bank has been bullish with the Vertex CF program. She or other members of the bank raised the target price to 155 after the Q4 earnings report because they don't see much risk for this year's clinical trial or regulatory approval.

    However, I think that the interim VX-661 Ph 2b trial reading was inconsistent with previous results. This was a tiny trial with only 20 people receiving the drug combo. It should not weigh on the share price one way or another.

    I am optimistic on the future of Vertex because the new CSO, Dr. Altshuler is not only a first rate scholar, but also came from the Broad Institute. Remember CRISPR/Cas9 ? A company called EDITAS is dedicated to clinical applications of this revolutionary technology. Founders of EDITAS did their work at the Broad Inst.. I guess that the name came from gene EDITing with RNASE. In vitro, they can edit DNA codes by replacing mutated sequences with normal ones. Some says that gene editing using a CRISPR technology can enter clinic in a few years. That may be too optimistic. I would be surprised if one of very first attack is not CF. Vertex pulled off a coup in being able to recruit Altshuler. I promise to post more about the gene therapy applied to CF.

  • Robin is the smartest of all analysts.

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