Mark J. Schoenebaum - Evercore ISI
Analyst · therapy, and we see that with therapies in RA and in immunology in general. So when I compare the two, I feel very encouraged by the results that we've seen with ABT-494. We've seen very strong efficacy, not just at the ACR20 level, but at much higher levels of response, ACR50, ACR70, DAS remission, et cetera. And we've seen that across two large Phase IIb studies, including a TNF-inadequate responder study, and those are the results that I mentioned in our opening comments. And there, we see a level of response in TNF-inadequate responders that we believe has the potential to be best-in-class. And so if you link that up with what I said about how RA dynamics play out, those data can be very important, and we believe that that is a big opportunity for this molecule. We do believe over time that 494 will certainly have use in earlier lines of therapy. But when you look at the balanced profile of 494, we feel very good about it. So moving on to ABT-122 and Ablynx, those are in mid-stage trials, and we'll see data from ABT-122 mid-year, and from Ablynx towards the back end of the year. And once we have those data, then that'll be the time to make decisions about next steps, so we'll be sharing those data as soon as it's reasonable to do so after we get them
What are the hurdles for success in those trials?
Michael E. Severino - Executive Vice President, Research & Development and Chief Scientific Officer: Well, our general approach has been that we believe we need to raise the standard of care. So what we're going to want to see is something that is over and above the level of efficacy that can be achieved with comparable agents, if you will. So ABT-122 combines 17 in TNF, so you're going to want to see something in the disease populations we've studied in RA and in psoriatic arthritis. It's better than one can get with those mechanisms alone. And Ablynx is another approach at IL-6, you'll see something that's better than the existing therapies that are out there. Now, obviously, these aren't comparative studies, but we'll have the data, we believe, to make those assessments and to determine whether we will advance those programs this year, as I've said. So, with Acerta, there certainly has been a lot of talk about Acerta given its relatively early stage of development. What I would say, first and foremost, is we've set a very high bar with IMBRUVICA. We've set a very high bar with efficacy and also with safety. I quoted some of the numbers from RESONATE-2. We don't believe we've left any room on the table for there to be a story of improved efficacy. And we feel very good about the safety profile of IMBRUVICA. With Acerta, we're looking at much earlier data. We're looking at Phase Ib, Phase IIa studies. I think the study that's garnered the most attention is about a 61-patient dose rising study with an expansion. And it's really just not possible to compare those very early trials to a molecule like IMBRUVICA which has multiple phases of readouts and has been on the market now for a considerable period of time. So we'll see as their programs continues to progress, what they're able to demonstrate. They have comparative studies, so a readout in a couple of years' time, and I think that's really the first time we'll be able to make any sort of comparative assessment. Those are open-label studies, and that's a limitation of them. And I'll also add that Acerta's comparative studies are in relapsed/refractory patients, and IMBRUVICA is moving to the front-line over time. And that momentum is going to keep up. So we feel very confident in our position with IMBRUVICA.