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Vertex Pharmaceuticals Incorporated Message Board

thirdmeinvestor 14 posts  |  Last Activity: Nov 23, 2014 12:30 PM Member since: Feb 25, 2004
  • Reply to

    Resurrection of Incivek

    by thirdmeinvestor Nov 23, 2014 1:04 AM
    thirdmeinvestor thirdmeinvestor Nov 23, 2014 12:30 PM Flag

    Right. Both Santaris and Regulus have been working on this miRNA-122 targeting drugs for several years. Santaris tested Telaprevir with Miravirsen. However, both development face a formidable challenge of all-oral drugs. Santaris has to come up with a drug better than 3 log reduction at 5 injections of 7 mg/kg dose. They better use the GalNAc delivery system of Alnylam as Regulus does. It will be difficult to compete against Harvoni if it takes 5 injections. Even 2 injections will be too many. The CEO of Regulus said the company may report the results from 2nd cohort, who takes a single 4 mg/kg dose, in January. I would not be surprised if the dose brings down viral load by 5 log.

  • thirdmeinvestor by thirdmeinvestor Nov 23, 2014 1:04 AM Flag

    A month ago, Regulus, a biotech specializing in drugs targeting micro-RNA, announced a surprising clinical results. Their second drug in development RG-101 knocked down HCV by 4.1 log with a single 1 ml subcu injection of a low 2mg/kg dose. Four weeks after this single dose, 6 out of 14 treatment naive and experienced patients treated with this low dose did not have any detectable virus in their blood. Several years ago Jopling and Sarnow showed that a human factor called mir-122 is essential for the survival of HCV genome in human body. Mir-122 is abundant only in hepatocytes and HCV can survive only in the liver for this reason. Very recently this year Sarnow showed that mir-122 forms a protective shield for HCV RNA against the host ribonuclease called XRN2. Without mir-122 HCV RNA will be degraded by the nuclease. Regulus is testing this drug with J&J's Simeprevir (OLYSIO) to study the effectiveness of the combination. The idea underlying the combination treatment is that 2 - 4 week OLYSIO regimen sandwiched between only two injections of RG-101 could destroy any genotype of HCV in patients.

    So, Regulus has opened the potential to revolutionize hep C treatment. It has also opened the possibility that Vertex can once again market Telaprevir in combination with RG-101. The side effects plaguing Telaprevir+IFN+RIBA do not appear in the first 2-4 weeks of dosing in the majority of hep C patients and Telaprevir is as effective as Simeprevir. RG-101 is very very safe. Vertex management should consider testing Telaprevir in combination with RG-101. Simeprevir (OLYSIO) is absolutely useless by itself because of Gilead's Harvoni and Abbott's combo, and RG-101 may turn out to be its savior.

  • thirdmeinvestor thirdmeinvestor Nov 20, 2014 12:54 PM Flag

    Economy sensitive areas are up in this early going. Biotech sector has been bearish since Friday.
    Also, they are trying to increase the trading volume. They sweep up and down to catch trading interest. Buy below 110 if you can.

  • thirdmeinvestor by thirdmeinvestor Nov 13, 2014 5:16 PM Flag

    Kleanthis, the CEO, said in the Credit Suisse CC that the data from the second cohort (4mg/kg) will be ready in January. I predict that the a single shot of this 1 ml subcutaneous dose will reduce the viral load by 5 log in 4 wks on average. Many will achieve the SVR without oral combination.

    Be careful how you trade.

  • thirdmeinvestor by thirdmeinvestor Nov 10, 2014 8:03 PM Flag

    I see a 4-way bidding war for the control of marketing RG-101.

    AbbVie cannot afford to lose this anti-miR drug because their oral DAA combo is cumbersome to take for 12 weeks for treatment (two pills in the morning and one in the evening). By combining RG-101 with any one of their DAA (excl. Riba) would cut the treatment time to one third.

    J & J has a protease inhibitor in Olysio which would be absolutely useless unless it is combined with RG-101. It is no wonder Regulus is tesing this combo.

    Merck today announced that their trial to test a 4 wk regimen practically failed to see the market. Just adding RG-101 to any one of their drug can make a 4-wk regimen a possibility.

    The company which would lose most from the success of RG-101 is Gilead. The sales of Harvoni will be cut by 50% or more. They may have to buyout for the survival of the company. They paid 11 B for Sovaldi. How much would they pay for RG-101?

  • thirdmeinvestor by thirdmeinvestor Nov 9, 2014 2:10 PM Flag

    A few years back I assumed a fast action such as the speed of ribonucleases to explain the rapid decrease of HCV counts immediately following the oral Hep C drug dosing in human patients. These drugs, such as incevek, sovaldi, and NS5A inhibitors, were designed to inhibit viral RNA replication, not to destroy existing HCV. The immunological destruction of HCV, I thought, would take much longer to observe the action. My assumption turned out to be right. Sarnow, the Father of mir-122 identification and HCV link, published a latest result to shed light on the connection between mir-122 and HCV survival. Oral DAAs also may act to interrupt mir-122 protection of HCV RNA from the nuclease attack. But, the direct action by anti-mir-122 on mir-122 eliminates the protection HCV RNA sought to find by binding to mir-122. With reduced mir-122 the exoribonuclease XRN2 simply degrades the viral RNA. I wonder a combination therapy is needed here. See below.

    http://www.ncbi.nlm.nih.gov/pubmed/25121753

    The abundant, liver-specific microRNA miR-122 forms extensive base-pairing interactions with the 5' noncoding region of the hepatitis C virus (HCV) RNA genome, protecting the viral RNA from degradation. We discovered that the 5'-3' exoribonuclease Xrn2, which plays a crucial role in the transcription termination of RNA polymerase II, modulates HCV RNA abundance in the cytoplasm, but is counteracted by miR-122-mediated protection. Specifically, Xrn2 depletion results in increased accumulation of viral RNA, while Xrn2 overexpression diminishes viral RNA abundance. Depletion of Xrn2 did not alter translation or replication rates of HCV RNA, but affected viral RNA stability. Importantly, during sequestration of miR-122, Xrn2 depletion restored HCV RNA abundance, arguing that Xrn2 depletion eliminates the miR-122 requirement for viral RNA stability. Thus, Xrn2 has a cytoplasmic, antiviral function against HCV that is counteracted by HCV's subversion of miR-122 to form a protective oligomeric complex at the 5' end of the viral genome.

  • thirdmeinvestor thirdmeinvestor Oct 24, 2014 11:08 PM Flag

    There are a lot to look forward to. They should disclose their plan to use gene editing for CFTR repair in future. CFO Smith already mentioned it as their direction. Until the new CSO is appointed they may not decide how to explore this area. Whether or not they plan to buy a technology or to partner with a well-advanced company, they would need an internal expertise in gene editinng.

  • thirdmeinvestor thirdmeinvestor Oct 21, 2014 5:28 PM Flag

    Q, the strong endorsement by the Committee for the label expansion bodes well for the approval of more important treatment for 508del homozygotes next year. The very likely approval by the FDA to include R117H CFers of 6 to 18 year old would indicate that the FDA is very positive on the Vertex CF program.

  • thirdmeinvestor thirdmeinvestor Oct 21, 2014 4:39 PM Flag

    The Advisory Committee recommends 13 to 2 in favor of the label expansion for Kalydeco to include 6 years or older R117H mutation holders.

  • Reply to

    New analyst coverage with Price target $147

    by qdelfan Oct 2, 2014 8:58 AM
    thirdmeinvestor thirdmeinvestor Oct 6, 2014 9:36 PM Flag

    Verity, have you seen articles about Dr. Jennifer A. Doudna, or about CRISPR/Cas9? Google them if you have not.

  • thirdmeinvestor thirdmeinvestor Oct 4, 2014 4:26 PM Flag

    That is a great find, Q. Along with non-gating-mutations Ivacaftor-monotherapy addressable group will increase by more than 50% when it is approved. Even if the label restricts Iva use to 18 or older R117H CFers, the revenue will jump more than 50%.

  • Reply to

    New analyst coverage with Price target $147

    by qdelfan Oct 2, 2014 8:58 AM
    thirdmeinvestor thirdmeinvestor Oct 2, 2014 9:29 PM Flag

    Verity, at the last MS conf. CFO Smith mentioned that Vertex is looking into RNA interference and gene editing technologies to repair CF mutations. This might be a more systematic approach than ProQR is hoping to offer. There are much to look forward to in the future.

  • Reply to

    New analyst coverage with Price target $147

    by qdelfan Oct 2, 2014 8:58 AM
    thirdmeinvestor thirdmeinvestor Oct 2, 2014 7:52 PM Flag

    This price 147 must be a 12 month target. What is clear to analysts now is that Lumacaftor is safe and effective for long term dosing. For that the average drug price all treatable CF mutations would be around 200K. If you assume this, the target for 2 to 3 years out is 200 or greater. If VX-661 + Ivacaftor combo is successful for treating heterozygous 508 CF, the share price would go much higher.

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