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Vertex Pharmaceuticals Incorporated Message Board

  • rojospan rojospan Dec 19, 2013 8:52 PM Flag

    VX 765 and AIDS. Huge upside


    It is good to be hard working and smart but if you can get lucky too, that's what one needs in Wall Street. VX 765 is a caspase -1 inhibitor which has been struggling to find an indication and going through rare disorders as published by NIH papers, Psoriasis and Treatment resistance partial epilepsy but no real luck. I was hopping to see if some one could do a pilot study for Cardiac arrest patients with anoxic brain injury to see if this could be supplemental to hypothermia to reverse or prevent anoxic brain injury, but didn't see much. Today, I read Science and Nature and my jaw dropped. Baby this is BIGGGGGGGGG!!!!!!!!!! VX 765 could be a potential candidate to prevent AIDS. Jeff Laiden will be talking about this in JP Morgan conference for sure.

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    • The online version of the research article related to AIDS and VX-765 is published, and the printed version will appear in the tomorrow's(January 23, 2014) edition of NATURE. I post here only the abstract of the article. It is a serious report to show that VX-765 will block progression of HIV into AIDS, and it may also be possible to treat HIV and AIDS patients for a cure. It is the time for Vertex to disclose their intentions on the use of VX-765 for anti-AIDS therapy.

      [[The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood although apoptosis has been proposed as a key mechanism. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of CD4 T cells corresponding to those that are both activated and productively infected. The remaining over 95% of quiescent lymphoid CD4 Tcells die by caspase-1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis corresponds to an intensely inflammatory form of programmed cell death in which cytoplasmic contents and pro-inflammatory cytokines, including IL-1b, are released. This death pathway thus links the two signature events in HIV infection—CD4T-cell depletion and chronic inflammation—and creates a pathogenic vicious cycle in which dying CD4 T cells release inflammatory signals that attract more cells to die. This cycle can be broken by caspase1 inhibitors shown to be safe in humans, raising the possibility of a new class of ‘anti-AIDS’ therapeutics targeting the host rather than the virus.]]

    • I was hoping to hear the opinions of Third regarding the articles in Nature and Science that demonstrate the therapeutic potential to use VX 765 to treat HIV infection. Any comments Third?

      • 1 Reply to qdelfan
      • Q, I just found your message. I read the Nature article, but it is taking time to read the Science article. The science appears to be good. Greene and his associates have shown that caspase-1 inhibitors can block the transition from HIV infection into full-blown AIDS. However, the latest antiretroviral therapy can do the same. South Africa which has 21% of worldwide HIV infected individuals successfully negotiated to buy a single triple pill at a price of $10/pill. Caspase-1 inhibitor alone is not as effective as the triple anti-HIV drug ex-vivo as shown by Greene. So, I would say there is little commercial value to VX-765 if dosed alone to prevent AIDS because it has to be sold at much below $10/daily dose. Nevertheless, if it can be shown clinically that infection-related dementia, cancer, and others can be prevented by a cocktail of antiretrovirals + VX-765, the drug may have a commercial value. Moreover, IF proliferation of memory T cells (reservoir of HIV) is driven by inflammation and VX-765 can suppress the growth of this reservoir of HIV, then it might be possible to eliminate all remaining HIV with 765 following triple ARV drug therapy. No wonder, Fauchi called the goals theoretical.

    • What a great surprise for the holidays. Monetizing vx 765 would be a huge unexpected revenue stream on top of CF. It may have greater commercial potential to treat HIV worldwide than vx 509 has in autoimmune disease, given the current competition in the RA/autoimmune market. Hopefully Vertex will retain majority control of the commercial potential of this asset as it develops a collaboration agreement.

      • 1 Reply to qdelfan
      • i'm not sure what this means. sounds like it "could" be positive for vertex if someone else runs with any trials required and vertex simply gets a piece of the pie if and when it becomes something. my only concern is their ongoing challenges in making "deals". the promised partnerships for RA and Flu have stumbled and if 765 is reborn, can they make a deal that will monetize it?

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