 Thanks, Teri. It's a pleasure to start off today post-lunch and tell you a little bit about the PAPI-2 study and also potentially other collaborative opportunities that we have ongoing or planned at the University of Maryland. So the PAPI-2 study stands for Pharmacogenomics of Anti-Platelet Intervention, and of course two means that there was a PAPI-1, and I'll describe that in just a few words in the interest of time. Before I get there, I thought I would just give a wider angle of view of the programs that are planned or that have been initiated at the University of Maryland's program in personalized medicine, and of course I'm not going to go through all of these initiatives here, but they basically involve building infrastructure to move from discovery into clinical and translational research ultimately to develop the evidence base for translation and changing practice. And in the interest of this particular group, I'll bring your attention to the left hand of the slide, the translational initiatives, and I'm not going to go through each of these individually. Just to point out, though, that we do have institutional funding to perform a number of translational demonstration projects, several of which are well underway, others that are planned. Like other institutions, we're going to make these demonstration projects clinician champion driven. We believe that those are the ones that are going to matter, and those are the ones that are going to be successful. CYP2C19 and Clopridic Rel is what we'll talk a fair bit about today, but we also are very excited about projects that will be initiated in cancer, ID, transplant, in diabetes. So the PAPI2 trial, all of you know the CYP2C19, Clopridic Rel story, the fact that a large number of publications, all of them retrospective in nature, have identified this very common store to loss of function allele as a major predictor of Clopridic Rel response. And really, the burden of evidence here in the literature is quite compelling. More than 20 studies performed, and multiple levels have all converged on the same observation, whether you looked at active metabolite levels by genotype, ex vivo platelet aggregation by genotype, and in a number of studies also cardiovascular events and outcomes. And of course, one of the first things that happens when you get a number of studies over 10 is that the first meta-analysis publication is performed, and again, compelling evidence that this is a variant that matters and that is potentially clinically implementable to save lives in patients who have coronary artery disease and who are at a higher risk of recurrent events. And I guess this all culminates with a change in the label by the FDA now about a year and a half ago. This boxed warning alerts physicians to the fact that there are poor metabolizers of CYP2C19, maybe more accurately poor activators of Clopridic Rel, since Clopridic Rel is a pro-drug that requires activation in the liver, and CYP2C19 seems to be the predominant enzyme that does that relatively easy. Genetic tests can be done since this particular SNP is quite common in the population. There are other loss of function variants, but those are much rarer in most populations. So in essence, a single SNP can be used for an implementable test to predict Clopridic Rel response and ultimately preempt recurrent cardiovascular events in genetically predicted non-responders. Now many people have better slides and more comprehensive slides than this with regard to defining what the barriers are to implementation, even with a compelling evidence base as there is for the Clopridic Rel CYP2C19 story, but really when you get 100 cardiologists into a room and you present them all of the data and you have discussions with them and then you go around the room and ask each one of them whether they're going to implement CYP2C19 genetic testing in their clinics, every one of them will say no, of course not, we're not going to do this, because there have not been any prospective randomized clinical trials demonstrating that pharmacogenomics improves outcomes, saves costs, et cetera, and really having gone to a number of these meetings and having spoken to many cardiologists at my own institution as well as others, we were completely convinced that this is really the single major barrier to implementation. And this realization actually came to us around a year and a half ago around the time of our renewal application for the Pharmacogenomics Research Network and actually was the purpose of our renewal major aim to initiate the PAPI2 study, a prospective randomized clinical trial of genotype-directed anti-platelet therapy. Our thinking at the time of the application was also driven by Jeff Dresen who actually was on the Scientific Advisory Board of the panel of the Pharmacogenomics Research Consortium, and he would say not uncommonly that prospective randomized clinical trials, at least in the early going, were a good idea, and I think one of the things that I remember well is that he would suggest that we just get over with it in terms of doing these prospective clinical trials if we really did believe that genotype mattered. And even recently, Jeff has written this editorial actually in response to Scott's paper in the New England Journal of Medicine not more than a month or six weeks ago. And Jeff here goes on record as saying, the next step must be to mount clinical trials in which patients are stratified according to their biological signature to determine whether knowledge of this information leads to better clinical outcomes. And finally, if personalized medicine is going to become a reality, we need to design and execute these critical trials. Now, I'd be the first to say that we can't do, and you've heard in this room, often we can't do prospective randomized clinical trials on all genotypes, pharmacogenomic and other that we want to implement into clinical medicine. But it's my firm belief that at this juncture in time in this particular field, with this particular application, a prospective randomized clinical trial is warranted. So this is the background of the birth of the PAPI-2 trial. You can see here the design. This design actually went through multiple alterations. The first one that we proposed to the FDA was considered unethical actually because of arguments that Gail had put forth earlier before lunch. And we've hopefully came up with this protocol that we believe will satisfy, actually, that we know satisfies the FDA and also will answer the question. And to walk you quickly through it, we're basically going to consent patients who are coming into the cath lab. And once we know that they have stents placed and will be going on an anti-platelet agent, they will be randomized. And they'll be randomized into a genotype-directed arm where the intermediate and poor metabolizers will get the alternative drug, prosa-grille extensive and ultra metabolizers will get clopridigrel. And that arm will be compared to the standard of care arm. Those individuals who will not be genotyped and will get standard dual anti-platelet therapy based upon the clinician's best judgment. And ultimately, one year down the road, we will be monitoring for clinical events, cardiovascular outcomes, and also, of course, a number of secondary outcomes. And we also have a discovery phase in which we wish to use this cohort to discover new variants. Now, you can see that the sample size here is about 3,600 subjects in each arm that will be randomized. So this is a large study, but one in which you'll see we still have, I would say, marginal power, and for which we hope to seek additional sites. So this is where collaboration comes in to, ultimately, we hope expand the number of sites and the number of subjects we recruit into this study. You can see here that retrospectively, the standard of care group is going to be genotyped. And the primary analysis actually is going to be a composite cardiovascular endpoint in which only the intermediate and poor metabolizers from each arm are going to be compared. So that's about 1,200, 1,000 to 1,200 individuals in each arm that will be compared as the primary endpoint. And I won't go through all the details of these secondary endpoints, but you can see that we also will be looking at adverse events, such as bleeding. And with Bill Weintraub, one of our collaborators, we will be doing an intensive pharmacoeconomic analysis to see if genotyping not only improves outcomes but also saves dollars. Again, not going through the complete detail of the organizational structure of PAPI-2, but just to point out that this is a multi-center trial. We have five sites that are involved, the University of Maryland, Hopkins, Sinai Hospital of Baltimore, Geisinger, and Christiana Health Services. So we already have, I guess, three institutions that are already around the table that are part of the PAPI-2 trial, and as I'll mention, we'll welcome others. So the genotyping platform that we'll be using is a verigine system. It's a point-of-care genotyping platform. It can be done in a clear, approved environment and takes about three to four hours to turn around. These instruments will be landed in each of the five sites, and we've just completed actually a validation study in our CLIA-certified laboratory, and you can see that this is an assay that actually performs quite well, virtually 100% accuracy. There are some samples in which you get a no-call the first time around, but you take the same sample and run it back through the instrument, you then get most of these no-calls turned into calls that are quite accurate. So I told you that this is a trial that's large, but we think still is of marginal power. As I've mentioned, we're going to look at one-year cardiovascular events, and the power here shows us that with 1,000 individuals, at least the intensive intermediate and poor metabolizers arms, we have about 80% power to detect a difference in events in the standard of care versus genotype-directed arm of 7% versus about 4.1%. So that's a relative risk reduction of about 60%. I think one that is not out of the realm of possibility, but probably a bit optimistic. So in terms of a progress report, we actually have an IRB approved protocol now. Approval at the other centers is currently in progress. This trial finally was considered FDA-exempt, and the reason is that in the standard of care arm, we don't know the genotype. We're going to be retrospectively genotyping them, and that seemed to satisfy the FDA. We've convened our DSMB and recruitment we expect to begin in Maryland in February of 2012 with other sites soon to come on board, and then ultimately we expect by the spring of 2012 we'll be seeking additional sites in addition to the five, and contemporaneously looking for funding to open those additional sites. So that's the PAPI-2 trial. I have maybe two other quick projects that I thought I'd throw out for potential collaboration by the group. I told you about our new translational genomics lab. We're quite proud about our certificate of registration inspection to occur a little bit later this year for full certification, and essentially what we did at the University of Maryland is we took our genomics core, our research-grade genomics core that does everything from single-snip genotyping to next-gen sequencing, and we essentially bit the bullet and converted that entire lab into a clear, approved laboratory, which as you heard is still in progress, and we expect to be able to offer a panoply from single-snips to next-gen sequencing, and we expect that this translational genomics lab will be particularly useful for these essentially translational projects where we have clinical trials, pragmatic, prospective, whatever in which we believe we need to perform to show that implementation of genomics makes a difference. The TGL, the Translational Genomics Lab, is going to be where we will be performing our genotyping for a related project that I thought I would mention, one that's funded through the PGRN called the Translational Pharmacogenomics Project, TPP, and this involves basically six sites, PGRN sites in which we will be implementing some of the CPIC guidelines that you heard discussed earlier today, and the number of these six groups, sites are going to be utilizing various kinds of genetic testing, ultimately to figure out the science of translation. You heard a little bit about TPMT and thiopurines. Several of our groups are looking at Clopridigrel, Warfarin, and others are looking more on the preemptive arena with larger arrays, DMET chips, and custom panels. All of this done in clear, approved environments, and the six groups working together to develop decision support software for some of the commonly used EMRs, healthcare provider education programs, and also collecting metrics to see whether the implementation actually worked and whether it's going to be, whether it has changed clinician practice. Ultimately, an aim of this TPP is to disseminate knowledge, and this is where the rest of you come in and would be possible to involve various non-PGRN groups in this effort, similar to how the CPIC has actually evolved. So in terms of a progress report for TPP, we have our monthly teleconferences, working groups. FarmGKB is the site for sharing documents and other information. We've begun to standardize definitions of specific gene drug pairs, taking actual diplotypes into metabolizer or likely metabolizer phenotypes. We're populating various tables that provide information with regard to institution-specific suggested actions that will be useful, we believe, to share and to implement more broadly. And we're developing common outcomes tracking tools that can be used across institutions, tools that will look at the implementation process, changes in prescribing practices, user satisfaction surveys, et cetera, and sharing of educational materials, which we believe is quite important. The last thing I'll mention in the last slide is yet another opportunity for collaboration, and that is the formation of a relatively new consortium, the International Clopridigrel Pharmacogenomics Consortium, ICPC for short. The goal here is to contribute to the evidence base for this particular drug gene pair. And to be able to muster larger, more diverse sample sizes so that we can begin to get a more granular picture of the implications of genetic variation in clopridigrel response. There's more to be learned about CYP2C19, particularly the role of rare variants, which indications are important, ethnic differences, roles of interactions with other drugs, smoking, et cetera. In addition, the group would like to study in a larger way less well-documented candidate genes, particularly ones that might have smaller effect sizes for which larger samples are required. And ultimately, we wish to move this into a discovery format using genome-wide association studies, and we expect probably next-gen sequencing as well. So this international consortium is quite young, but we do have some momentum, and this is a good time to advertise the consortium for potential collaborations. The consortium will be coordinated through FarmGKB, an honest, relatively impartial broker of these kinds of consortia. We've actually convened our executive committee and have met a couple of times via teleconference. We've begun to have some of those tough decisions about phenotype definitions, genotype validation, DNA availability, data management, and analyses. An MOU is now being drafted, and we will be e-mailing and inviting individuals into the consortium, initially beginning with clinicaltrials.gov, in which there are 365 listed clopridigrel studies. And we welcome these trials, but also other investigators who have interest in participating in the consortium. So I think I'll end there and happy to answer questions. Just before we get to Mark. There was another. So, Alan, a couple of questions about the randomized trial. So first of all, couldn't you get a false negative trial if the positions are prescribing crasigrel in your control group? Yeah, this is a moving target, Mark, and we've talked about this a lot. And in fact, over the course of the next couple of three or four years, standard of care practices may very well change. We're just going to continue to monitor that. And in addition, as a secondary analysis, we will analyze only clopridigrel users in the standard of care arm. And second of all, is there any disadvantaged crasigrel other than cost? I mean, is this, are we really just talking about the cost of genotyping versus the cost of crasigrel versus clopridigrel? Well, there's a cost, but also crasigrel is associated with higher bleeding rates. And this is, I think, talking to cardiologists, the primary reason why, at least in the U.S., it's not being used very broadly. Thank you. So Alan, the question I had related to the last slide where you mentioned a little bit about phenotype definitions. At Intermountain Healthcare, the cardiologists elected to do routine platelet aggregation studies on the patients, which is a phenotypic measure and in some ways is closer to the actual, if you will, physiologic mechanism than the genotype where we're inferring phenotype. Now, they made this decision prior to some of the more recent data about the reproducibility of that testing, and they may well have changed their mind. But I think it is a salient question across a lot of these activities that if we have the opportunity to measure a phenotype as opposed to a genotype, how do we design studies to determine which is best, and is that something that you're going to build into this? Right. So it's a great question, and this is one of the reasons why this field is so charged with regard to any kind of testing, whether it be platelet aggregation or genotype or whatever, you really need to demonstrate that it matters because there is such controversy over platelet function testing. So I think the short answer is that probably platelet aggregation testing and genotype will be complementary to each other, maybe sequentially, and in fact that was something that we, one of the study designs that we tried to build into this study but had to cut arms somewhere as we realized the costs were escalating, so we do have an optional visit for platelet aggregation testing at day 10, and so we will be able to go back and do retrospective forms of analysis to try to compare the two. Yeah, just about the logistics, you mentioned that only patients who actually receive a stent will then be going forward with genotyping, and then you add your turnaround time, et cetera, et cetera, so can you just talk briefly through the expected timeframe after the event of a stent being placed? Yeah. That fits with common clinical practice of these patients being discharged if there's no complication quite early. Yes. So we hope to have all patients randomized by the time of their discharge, which is usually the following morning, and we believe we'll be able to do that in virtually all cases. The protocol actually specifies that we can randomize as many as four days out, but of course we'd have to go and chase the patient and potentially change their drug. My cardiology friends tell me that if you're going to change medications they actually want to reload with Prostagril if they've gotten Clopridigrel, and so certainly that would have to be done in the hospital before discharge. So the answer is that we hope to do the randomization before discharge. In most cases the following morning. Okay, comments for Alan? Super. Thank you very much. Now you can eat your lunch.