Mark J. Schoenebaum - Evercore ISI
Analyst · Mark Schoenebaum from Evercore ISI. Your line is open
Sorry. Thank you very much for taking my question – not plural. Paul, congrats again on great P&L management. We all appreciate it, and your investors appreciate it. So many questions to ask. Maybe, Al, just because this is the one I get the most, just going back to the Eisai collaboration, and the A-beta antibody that may or may not have data shortly, the question that I've been getting – I'd just love to hear your thoughts – are, you emphasized a lot when looking at these competing A-beta antibodies, really understanding what the imaging data show post-therapy. That is, does it drain plaque from the brain? And if the answer to that's no, then the clinical outcome is perhaps less important because it doesn't do what your a-mab does, so to speak. But there's been some questions about specifically where the Eisai BAN antibody binds, which type of fibrils, and whether or not – given its specific binding affinities – whether or not you would expect necessarily to see changes on PET scan. So I was just wondering if you could talk us through that. Thanks so much.
Alfred W. Sandrock, Jr. - Executive Vice President, Neurology Discovery & Development Center, Neurodegeneration Therapeutic Area and Chief Medical Officer: Yeah, Mark. The BAN2401, to my understanding, binds the protofibrils as well as oligomers, and I would expect it to reduce amyloid plaque burden. The question for me is does it do that, first of all, and second, to what degree? The thing that was remarkable about aducanumab was that we had a very substantial reduction in the course of one year, arguably 85% or so. Competitor antibodies have not done that, and I don't know where 2401 will land, but that's an important piece. And then we can then start to understand that the relationship between reduction in plaque burden and cognitive outcome. In our hands, in the aducanumab program, only the patients who reduced plaque burden by greater than one standard deviation changed relative to what the placebo patients did – in other words, beyond the noise. Those are the people who got cognitive benefit. The people who did not do that did not have any benefit that we could detect. So we think that's an important piece to look at.