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Vertex Pharmaceuticals Incorporated Message Board

thirdmeinvestor 18 posts  |  Last Activity: Sep 23, 2015 4:56 PM Member since: Feb 25, 2004
  • Reply to


    by gladpick Sep 23, 2015 4:02 PM
    thirdmeinvestor thirdmeinvestor Sep 23, 2015 4:56 PM Flag

    I don't know patent laws, but know some science behind the drug. The excretion from the body after taking deuterated form will be slightly slower and the concentration in the body will be higher. Its effects can be good and bad. The side effects will be also elevated. But, people would not want to take a drug containing an isotope although it is harmless.

  • Reply to

    VRTX chart

    by papaalien2000 Sep 23, 2015 3:03 PM
    thirdmeinvestor thirdmeinvestor Sep 23, 2015 3:23 PM Flag

    IBB had been dropping, but it is bottoming out.

  • VX-371 is the new name for the Parion’s ENaC inhibitor, P-1037, which Vertex in-licensed. Below I would like to argue that both VX-371 and Orkambi would strengthen the defense against infection and inflammation by hydrating lung airway mucus.

    The chronic infection and inflammation of lung airway in cystic fibrosis (CF) patients is the primary reason for the progressive decline of lung function resulting in daily symptoms such as cough and sputum production. The primary cause for the infection is the very viscous mucus on the airway surface.

    In CF lungs chloride ions don't flow out actively [=pumped with ATP] into the mucus water volume. Positive ions such as sodium ions cannot diffuse out into the interface water because they follow anions [=chloride ions]. On top of that, the active Na+ ion pumping by hyperactive ENaC removes Na ions out of the mucus volume. Both sodium and chloride ions are kept away from the mucus. The net result is that the mucus will be short in both ions and water [water always follows the ions]. Immune cells in the mucus will be very unhappy and cannot remove bacteria in it. This weakened immune defense against bacteria such as P. a. is central to developing airway inflammation and lowered lung function.

    The total ion concentration in the mucus on the airway lining determines the water volume. If the ions flow out into the airway mucus, the airway will be hydrated and the lung will be happy. But if the ions are excessively moved into the tissue from the mucus, the airway will be dehydrated and the lung will be unhappy.

    Orkambi or Kalydeco partially restores chloride pumping into the airways water volume, and VX-371 would block sodium pumping out of the mucus. So, plenty of both ions will be there and water volume will increase.
    Visit the Parion website and learn more about P-1071 (=VX-371).

  • Reply to


    by gladpick Sep 18, 2015 11:27 AM
    thirdmeinvestor thirdmeinvestor Sep 18, 2015 1:00 PM Flag

    You are right, Glad.

  • thirdmeinvestor by thirdmeinvestor Sep 7, 2015 8:24 PM Flag

    A good amount of the last earnings call was devoted to this collaboration. Without the background of EDITAS’ technology it is difficult to understand the CC substance. I am trying to fill in some gaps so that when you read the transcript second time, you can understand better.

    EDITAS founders and workers are employees or associates of MIT’s Broad Inst.. They engage in clinical translation of gene editing using CRISPR/Cas9 technology for which EDITAS has the original patents. Juno paid upfront fee of $25 M to EDITAS’ technology and another 20M for their research. CRISPR/Cas9 technology is essentially the immunology of bacteria against pervasive viruses that try to incorporate their genome into the bacterial DNA for virus’ gene replication. CRISPR/Cas9 technology can literally dig out the viral DNA hiding in their own to degrade them. In higher animal applications of this technology the removed sequence is replaced with another to change the genome and the expression (proteins). The technology is well known for high reproducibility and precision.

    Then, what CRISPR/Cas9 technology can do to CAR-T? It can use the technology’s ability to eliminate, substitute, or improve on genome sequences in human cells (it cannot yet be used in cells in the body, but cells taken out of the body can be worked on). It is quite clear that JUNO’s goal is to develop the next generation CAR T cells which proliferate faster AND more durable in the body. However, the ultimate objective is, as the CFO put it, to overcome the challenges of tumor micro environment to be able to treat solid tumors. The Juno officers indicated that EDITAS was working well and the collaboration is progressing rapidly. We'll hear about early results of collaboration throughout 2016, but may get some early results in the beginning part of next year.

  • Reply to

    Why down

    by rlowin10 Aug 31, 2015 3:56 PM
    thirdmeinvestor thirdmeinvestor Aug 31, 2015 6:32 PM Flag

    Typo: ALN-CCR should read ALN-CC5.

  • Reply to

    Why down

    by rlowin10 Aug 31, 2015 3:56 PM
    thirdmeinvestor thirdmeinvestor Aug 31, 2015 6:22 PM Flag

    ALNY was a victim of its own success. ALN-PCSsc is so potent and durable that mAb drugs of REGN and AMGN will become obsolete in several years. REGN fell 23 points today. AMGN fell too. They pushed down IBB. Look at the Charts of REGN and IBB. ALNY is a component of IBB, and often traded like IBB.

    Don't worry about the share price. It will more than double next year. Catalysts: ALN-AT3 for hemophilia A and B and RBD, ALN-CCR for PNH, Patisiran, and Revusiran for FAP and FAC. All reporting data this year.

    The data of ALN-PCSsc have demonstrated the power of ESC-GalNAc platform.

  • thirdmeinvestor thirdmeinvestor Aug 29, 2015 3:50 PM Flag

    Investors are anticipating a very good news from the Ph I trial of ALN-PCSsc. If the news and morning CC tomorrow announce a reduction of LDL-c is around 60%, MDCO may jump to 40 or above provided there is no safety issue. Regeneron and Amgen have mAb version of inhibitors to PCSK9. Absence or loss-of-function mutation of this gene PCSK9 have been shown to reduce the risk of cardiovascular events.

  • thirdmeinvestor by thirdmeinvestor Aug 29, 2015 3:11 PM Flag

    A portion of an abstract of an article in the September issue of J. Clin. Virology:

    "--- People who inject drugs (PWID) are the most important risk group for incident Hepatitis C virus (HCV) infection. In PWID in Europe HCV genotype 3a is highly prevalent. Unfortunately, many of the recently developed directly acting antiviral drugs against HCV (DAAs) are suboptimal for treatment of this genotype. Detection of resistance-associated variants (RAV) in genotype 3a may help to optimize treatment decisions, however, robust protocols for amplification and sequencing of HCV NS5A as an important target for treatment of genotype 3a are currently lacking. ---"

  • thirdmeinvestor by thirdmeinvestor Aug 22, 2015 12:33 PM Flag

    There is a good reason to believe that the effect of two drugs in combo is the sum of effects of each type (logarithmically additive synergy). Oral drugs such as Sovaldi, Olysio, or Daklinza can reduce the viral count by a factor of 100,000; they individually kill 99999 out of 100K HCV RNA. A single shot of 2mg RG-101 degrades all but 1 out of 10K HCV RNA. Does this mean that when both are given together the combo can kill all but only 1 out of 1 billion HCV RNA (-5 log + (-4 log) = - 9 log)? This can be true only the two actions are completely independent; RNA that survives an oral drug has the 1 in 10K chance to survive RG-101. If there is an overlap between the two mechanisms of killing, then the effect is less than the direct sum of the parts. All of all-oral drugs inhibits HCV RNA synthesis in hepatocytes. If the mode of action by RG-101 were the same action of inhibiting RNA synthesis, the effect of the combo is less than the sum of the effects of two individually.
    Sarnow who had discovered that miR-122 is essential for the survival HCV in the body found more recently that miR-122 protects HCV RNA from degradation by abundant exoribornase XRN2. The normal function of miR-122 is to control lipid metabolism in the liver, but HCV takes advantage of it by binding to it to block XRN2 attack. No evidence exists that shows synthesis inhibition by anti-miR such as RG-101, and all-oral to degrade HCV RNA. These facts suggest the two modes of actions are independent of one another, and the effect will be additive.
    I think that the 'sandwich' design of 4 wk dosing will be an overkill.

  • Reply to

    RG-101 for hep c cirrhosis

    by thirdmeinvestor Aug 15, 2015 11:07 AM
    thirdmeinvestor thirdmeinvestor Aug 15, 2015 11:19 AM Flag

    Ribavirin was spelled wrong in the above post.

  • thirdmeinvestor by thirdmeinvestor Aug 15, 2015 11:07 AM Flag

    Treatment outcomes for genotype 3 and cirrhotic HCV patients of all genotypes are poor using all-oral drugs or in combination with interferon and rivabirin. If Phase II trial gives the SVR24 of around 95% or so, there is a good chance that the above hard-to-treat groups can benefit from the "sandwich" regimens.

    There are more than 7 million HCV patients in major markets (US and EU). 15% of these is cirrhotic. So, there are more than 1 million patients who can benefit from RG-101 + oral drugs in the major markets. Suppose that only 50 K of 1 M (5%) treats a year with this combo, and the drug is priced around 10 K (this is a bargain). This can generate a revenue of 500 M. If this can be achieved, the market cap for Regulus would be around few billions. The share price would be around 70 without the help from other drugs in the pipeline.

  • Reply to

    news release

    by bdmd51 Aug 12, 2015 11:17 PM
    thirdmeinvestor thirdmeinvestor Aug 13, 2015 10:54 PM Flag

    August 30 is the date of a ESC Congress presentation of ALN-PCSsc Phase I trial results.

  • thirdmeinvestor by thirdmeinvestor Aug 9, 2015 5:14 PM Flag

    Dr. Alan Carr of Needham would never overstate his case. He attended the ER CC and asked about the injection site reaction and rash observed with Revusiran. Needham sent out a message indicating the following.

    Mgmt noted 3 pts discontinued revusiran due to rash in Phase 2 OLE trial. The Phase 3 trial is continuing without notable safety issues. All drugs at Alnylam other than patisiran and revusiran incorporate ESC-GalNAc and are not associated w/injection site reactions.

    Several important milestones are expected from clinical programs in 2H15, including initial ALN-PCSsc Phase 1 data in hypercholesterolemia, additional data from patisiran and revusiran Phase 2 OLE trials, initial data
    from ALN-AS1 Phase 1/2 trial in porphyria, and additional data from Phase ½ trials of ALN-CC5 in complement-mediated disease and ALN-AT3 in hemophilia.

    Needham remains confident in platform and reiterate BUY. They see ample opportunity for upside in 2H15.

    If you listened to the CC, you’ll find that only 3 out of 25 who received relatively longer term had rash. The rash disappeared spontaneously upon discontinuation without intervention.

  • Reply to

    Buyout by Gilead is possible

    by thirdmeinvestor Aug 2, 2015 8:08 AM
    thirdmeinvestor thirdmeinvestor Aug 2, 2015 12:42 PM Flag

    It does not matter. Gilead has more cash than they know what to do with. Any takeover will be friendly and the Juno board will agree with.

  • thirdmeinvestor by thirdmeinvestor Aug 2, 2015 8:08 AM Flag

    Gilead's COO, John Milligan at the recent earnings call said that while immuno-oncology is extremely crowded, he wouldn't rule out an investment in that area if the approach was novel or the benefit to patients great. The PD-1 and PD-L1 inhibitor space is crowded and dominated by Merck, Bristol, and Roche, but CAR-T space is novel but low in buyout price.

    Gilead has cash from sales of Harvoni et al.. Celgene's equity position would not prevent Gilead from buying Juno. They could offer 150 dollars per share; 15 B is not too high for Gilead. They paid 11B for one drug, Sovaldi. Potentially, CAR-T offers a lot more.

  • 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.

110.00+0.97(+0.89%)Oct 9 4:00 PMEDT