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    July 20, 2011

    Noel Southall – Drug Repositioning Panel Discussion Transcript

    So actually in the interest of time, I might actually skip my slide overview and actually turn this more back into a panel discussion just by referencing some of the points from the previous talks.  I think Chris really gave an excellent presentation that raised some really interesting points. But first to go back to the first talk where David was talking about differentiation and the opportunities from the academic sector…

    I work at NIH, the opportunities for doing repurposing are not limited necessarily by commercialization requirements. However, the best path to a marketed product is through a commercialization partner, and that is definitely something that we recognize. But that said, if you’re truly interested in doing repurposing from a disease perspective, we recognize that there are excellent partners out there to move projects forward and that also sort of brings up the point… And, Barry, in your talk, you mentioned the Thalidomide example, which I think is an excellent example, from the perspective of what Cellgene decided to do with Thalidomide and the multilple myeloma opportunity, which was they realized that Thalidomide was having an action on TNF-alpha levels but instead of actually pursuing – – and they were – – they did eventually pursue marketing of Thalidomide, but first they used it as an opportunity to really push an NCE to the clinic which was Revlimid, which had a potency several thousand times better than Thalidomide.  So once the off target… Once the opportunity was really characterized with Thalidomide, they then took that back to discovery and to development to really design a drug that really targeted specifically the action that they were interested in, instead of just making do with the off target activity that did exist.

    And then I think Chris’s point about whether or not repurposing projects in general are going to suffer from the same efficacy failures that we see in late stage clinical trials, I think that’s a great open question and I would love to hear others’ feedback on that.  So in a couple minutes, I think that’s some of the high levels points that were raised today and really excellent presentations.

    Barry Bunin

    So if we can make this a little bit interactive, I guess my question to you, Noel, would be: The initiatives at the NIH, the molecular libraries, TRND, NCGC, what sort of advice would you give for others that would be interested in partnering or complementing NIH’s efforts?

    Noel Southall

    Well I mean we work basically through an open grant process and basically what we’ve seen come in, I would say that about a third of our portfolio are repurposing opportunities. So when repurposing applications come in on par with a novel target and chemotype, about a third of those rise up to the top on par with the best new projects that are just starting off.  And then in terms of commercialization, I mean I really think that a repurposing – – the key is what you do with the repurposing opportunity and to turning into a commercialization opportunity.

    Barry Bunin

    Well another question just with the NPC Browser and that new set of drugs we’ve uploaded into a private CDD Vault, I know you’re iterating and Chris alluded to the challenge of the content duration, just I’m curious because that would be a great resource …

    Noel Southall

    Yes.

    Barry Bunin

    …when the Version 1.1 would be available; we’d want to make that available.

    Noel Southall

    So, yeah, the Version 1.1 I think was released about a week ago. I can say that the goal there was to physically construct a screening collection that is publicly accessible by collaboration with the sensor. The browser itself I think in the first month it’s been available, we’ve had several thousand downloads of it and actually a thousand user curations have come back to us in terms of cast number of structures, and really it’s a neat little tool that gives you quick access to the relevant information, the product insert packages, I and N original registration, et cetera.  So it’s available. I think the URL is tripod.nih.gov. So thanks for bringing that up.

    Barry Bunin

    Chris, any questions from you or others?

    Christopher Lipinski

    Well…  So I’m wondering sort of with the – – Noel has the expertise on this, but the NCATS Center, do you think the – – because I – – the material I read on the Web about it and in print suggests to me that it’s going to have a very target-centric, mechanism-centric focus, and I just wonder to what extent things like phenotypic screening or high content cell-based screening might be part of that sort of those translational initiatives.

    Noel Southall

    In the initial use of the MPC screening collection, we really have taken a focus on phenotypic assays.  That’s where the interesting insights really come from in terms of the existing biology intersecting with the disease biology in really interesting ways, in addition to discovering off target activity.  So I think your experience looking at, if you want to call it, an integrated system for looking at biology is really the way to push forward and that’s been our experience.

    Christopher Lipinski

    Thank you.

     

    Barry Bunin

    We actually are on schedule pretty much here and maybe the best way to do this is just to follow-up by email with some of the questions from folks who are remote, and just about being on schedule and being sensitive to other speakers.  So at this point, I think I’d like to just thank all the speakers and keep us more or less on schedule.  Thank you.

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