 Okay, so while we're looking for my slides, I just say thank you very much to Larry for inviting me to be here today. Janssen and Johnson & Johnson are very pleased to sponsor this exhibit and also to have a chance to address with you how we're actually applying this revolution that you've heard about over the last few speakers to the science of drug discovery and development and to the evolving science of developing co-diagnostics, companion diagnostics for our products. Do you? I am the second one. Okay, thank you very much. Not showing on the screen. Is that control F7? Oh, it is, good, great, okay, thank you. All right, so I just kick it off by framing for you our vision at Janssen Pharmaceuticals, which is to eliminate disease through developing highly innovative medical solutions for people around the world. So clearly a very high-reaching vision and one that we believe the whole platform of genomics and genomic sciences is absolutely critical to helping us achieve. At a very high level, the strategy that we have for research is firstly to focus on those areas where we believe that there are extreme unmet medical needs and compelling science that will allow us to address those needs. We have a very strong platform in integrating internal research with external research, and I think that it's obvious listening to all the discussion this morning why that is so important. Companion diagnostics are a key part of our programs for most diseases. As well are the notion of disease interception approaches. In other words, trying to intervene earlier and earlier in a disease in order to have a more effective treatment and stop the progression which can lead to significant morbidity and mortality. And also starting to think about solutions for patients as opposed to simply drugs. So the idea of this is packaging together drugs and companion diagnostics or drugs and devices or simply ways that patients can interact more facially with information. And we've heard a lot about that also this morning. So we're focused on five therapeutic areas as shown here. And in each of these we've selected a series of diseases that we believe have the most compelling science coupled with significant unmet medical need. And underpinning all of our efforts are significant platforms that we've invested in and that we collaborate with others on genomics, informatics and biomarker discovery. Now all of that is great but the basic science itself will not ultimately lead to products that are really useful for patients unless we at the same time invest in developing code diagnostics from those biomarker discoveries. And to ensure that we can do that in the most efficient and effective way we've formed Janssen companion diagnostics with exists within the pharmaceutical companies and supports all of these therapeutic areas in their work. So we've heard a lot this morning about how the genomics platforms will impact oncology and I'm gonna talk a little bit about that. And also give you a few examples from my own area of interest immunology where I think that we are a little bit behind because of the nature of the disease but still we can start to see the implication of some of these platforms changing the paradigm for treatment. So let's start with oncology. And just to frame things, there are about 14 or so companion diagnostics that have been approved by the FDA for use with various drugs in cancer. And what's very important to note about all of these is that they depend upon recognizing a mutation in a specific gene or expression in a specific gene which is frequently the target of the therapy itself and the best example of that of course would be Herceptin or Trastuzumab. Or they recognize a mutation in the signal transduction pathway that's downstream of the target but in all cases they're looking at a single marker. And it's very clear because of the complexity of cancer and the heterogeneity and the progression of the disease that this is not going to suffice for all companion diagnostics and we need to get beyond the single marker era and to be able to develop tests that will rely upon much more complex molecular profiles. And so far none of these have made it to the market or though there's clearly a lot of work going on. And some of the barriers here that firstly you need a very, very large sample size in your clinical trials at the efficacious dose in order to detect and reproduce a profile. Second, there have been challenges with obtaining sufficient tumor samples. Tumor samples are hard to get in most non-blood cancers. There have been challenges with the sensitivity of the assays that are available and their robustness and reproducibility. And also we live with the challenges at the end points that are studied in phase two trials or mid-stage trials are typically looking at shrinkage of tumors or tumor burden but these don't always translate to those markers that are looked at in phase three and that are ultimately required for approvals that relate more to survival. So I'd like to tell you about one of the platforms that we've been working on at Janssen which we think is probably the most exciting thing that will help us address some of these questions in oncology leading to a new era where we will see more companion diagnostics for a broader array of medicines. So what I would like to review is the circulating tumor cell technology or CTC technology that we've been working on within our Veridex unit for some years now and which we're now collaborating with the Massachusetts General Hospital and Harvard School of Medicine on in terms of bringing forward next generation devices. So CTCs are tumor cells that can be found in the blood and it's already been demonstrated that in some cancers these are prognostic for both disease outcomes and certain treatment outcomes and there is a test on the market called Cell Search which was approved almost 10 years ago now as the pioneer in this field originally for prostate and now for several other cancers. The next generation device that we are working on which is shown here on the right will enable not only the enumeration of CTCs but also their capture and characterization. And the way that this device works is basically by applying very sophisticated microfluidics that allows the sorting of cells at an extremely high rate about 10 million cells per second and very importantly allows the capture of tumor cells that are not labeled or not, you don't need to know the specific tumor antigen in order to collect the cells. That means that the platform can ultimately be agnostic to whatever type of tumor you're looking at and also that you can collect these cells in a very unperturbed manner which is very important for their analysis. One of the critical things that this device we think will allow is molecular profiling of the tumor in a very facile and quick way meaning that you can take multiple samples over the course of disease, baseline, post-treatment and start to understand what the tumor looks like at the molecular level not only at diagnoses but also at relapse and have an idea of what the metastatic profile is as well as the original tumor when it's detected. So we're talking here about seven and a half mils of blood, a single blood sample and now being able to do many different types of sophisticated analyses as shown here at the cellular and molecular level as well as hopefully in the future even doing cell-based assays to understand more about the biological function of these cells. And here taken from this recent paper in science and translational medicine which I would encourage everybody to look at really shows some of the power of this technique and in this particular example that was taken from a patient with prostate cancer you can see that in 15 different cells that were analyzed if you look over to the right each of these cells which are shown on the top each column represents a different circulating tumor cell from the same patient has a different gene expression profile. So this is really powerful information it allows you to look at the molecular level at single circulating tumor cells and it also shows you again the complexity of cancer and that within a single patient tumor at a one single moment in time that there is this tremendous heterogeneity. So we're extremely excited about this one of the applications of genomics and genomic platforms to really move forward the whole field of codiagnostic platforms in cancer. Switching now to my own area of expertise immunology we've been looking at several different diseases notably rheumatoid arthritis and inflammatory bowel diseases which are very complex immunologically mediated diseases that really rely not only on genetics multiple gene mutations but also a very strong effect of environmental factors in driving the disease not all of which are very well understood. But what is clear is that there is basically unchecked inflammation in rheumatoid arthritis that initially leads to swelling and severe pain and disability and ultimately leads to joint destruction, loss of function, decreased quality of life, et cetera permanent disabilities and a number of comorbidities that go along with the disease including various types of cancer including lymphomas and cardiovascular disease. So our goal being one of the leading companies in developing new medicines for rheumatoid arthritis is to move beyond where we are today which are basically anti-inflammatories that block this inflammatory cascade to being able to intervene earlier in the disease and the whole genomics platform is gonna be very important for that. If we look at the incidence of this disease it's about four and a half million patients in the G7 countries but interestingly a very small number of them are treated with the most powerful disease modifying medicines today which are biologics and even in that small subset that do receive biologic treatments a very small number of those achieve complete remission so clearly we need a better approach. What we're envisioning here through the impact of both genomic sequencing and molecular profiling is firstly to have better prognostic markers for this disease allow early disease identification, routine screening tests even before the disease presents itself with overt symptoms which is how it's now diagnosed. Predictive biomarkers that will help us understand which of the many mechanisms that are now available are appropriate for which patient. Monitoring through your iPhone of what your response is to treatment and how your disease is doing is it flaring, is it in remission and also the disease interception platform which really requires a very deep understanding of the disease and which is also being driven by the advances in molecular profiling. Just a couple of examples of the types of things that we're working on within our group. Firstly, if I could just direct your attention to the right side of this slide which shows the standard type of measures that are used in clinical trials to determine if a drug is working in rheumatoid arthritis. And on the x-axis you have these markers called ACR 20, 50 and 70 that's basically a composite clinical score which indicates that a patient has had a 20%, 50 or 70% improvement versus their own baseline. And today the most effective medicines which are the anti-TNFs and other biologics will give you roughly 40% of patients getting a 50% improvement which is not terribly satisfying. What we would like to do is drive that response way up. And one of the ways that we think that we can do it is to understand who responds to which mechanism of action. So we are co-leading a consortia called the Batterup Consortia with Biogen Ilan. And the goal of this is to validate a predictive signature which has been published on but only in very small trials. So this is a trial involving 500 RA patients that have been treated with various different anti-TNF antibodies manufactured by different companies. Their clinical response is monitored according to these ACR scores but at the same time we're looking both at baseline and then post-treatment at these messenger RNA signatures to understand if there really is a signature that can predict response. And the power of that would be that when a patient is first treated if they are in that responder pool we hope that we would be able to then have 80% of patients responding at an ACR 50 and maybe half of the patients responding with an ACR 70 score. The other approach that we're taking which is newer and reflects the advances in whole genome sequencing more recently is we're sponsoring the first, I should say the largest study that we are aware of of sequencing the whole genomes of RA patients. And of course we run many clinical trials in RA patients and we're able to obtain large numbers of samples from those trials and we have developed a consortia of collaborators shown here to bring to this first of all the power of next gen sequencing through BGI and also to bring together the informatics skill and the computational biology skill that's required in order to understand the raw data that we'll get. So we think from this first experiment we'll first be able to get an idea of what the number of patients really is, what's the power of the experiment that we would need to do in order to get meaningful information out of whole genome sequencing in rheumatoid arthritis. And ultimately we think that this will lead to new targets for drug discovery as well as potentially to better understanding of the disease, companion diagnostics, et cetera. Just moving quickly then to inflammatory bowel diseases which are Crohn's disease and ulcerative colitis. So these are diseases of the gut which result from uncontrolled inflammation and a whole host of clinical symptoms and effects to the tissues that are shown here which are not only extremely unpleasant for the folks that have this disease but also have very significant and severe consequences. Most patients with inflammatory bowel diseases will have some type of intestinal resection surgery in their lives because the inflammation just cannot be controlled with the medicines that are available today. So again, this is an area where we're trying to understand better what drives this disease and to come up with treatments where we can intervene earlier. And one of the most exciting areas for research that was mentioned briefly earlier is understanding and profiling the role of the microbiome or the bacteria that live in the gut on the immune system and also on this disease. It's clear from many studies that in IBD there is a dysfunctional microbiome host interaction and we have embarked on several programs both in collaboration with biotech companies such as second genome as well as through our own clinical trials and a network of academic collaborators in order to sequence samples from patients with IBD at baseline, after treatment with various drugs, and to try to understand whether there are predictive markers in there for disease progression or drug response. And also to understand more at the molecular level what exactly is the nature of the interaction between the microbiome and the immune system that seems to be important in driving ulcerative colitis or Crohn's disease. Another very exciting area is developing co-diagnostics for anti-TNFs. We've done several studies now dating back quite some years with both Remicade which is also known as Infleximab and Sympony in company-sponsored trials for ulcerative colitis. Both of these are now approved medicines for UC and in the treatment of UC, the collection of both doing endoscopies and the collection of biopsies is something that we have done and that is done in clinical medicine. So we've leveraged that in order to look at the gene signatures of patients with the disease and also to identify putative signatures, biomarker signatures based on mRNAs that exist in the responders or the non-responders as shown here. And we now have, we're embarking on a large prospective validation trial in order to determine if these response signatures hold up. So just to conclude, Dr. Paul Janssen who was the founder of Janssen Pharmaceuticals back in the early 50s and had an enormously productive career delivering something like 80 medicines back then is remembered amongst many things for always saying the patients are waiting. And I think today it's clear to all of us that the opportunities that are presented by the genomic platforms that we've talked about here really are an unprecedented time in medicine. I couldn't believe, I couldn't agree more that this is the time for more investment not less investment in order to understand disease and create new medicines for patients. However, as we've also heard there are still lots of things, lots of challenges in front of us. And I just mentioned a few of them here, some of them have been touched on. The first is that bioinformatics, computing, network pharmacology expertise is needed and is needed to be continually evolved in order to translate this huge amount of data so-called big data into knowledge. This is definitely something that the bits of information are coming in much faster than our ability to really use it. The second is, and this has also been touched upon in the thoughts about how physicians will be using this information, we also need new types of training programs for scientists that integrate not only genomics and bioinformatics but also how these things can be applied in the pharmaceutical sciences. It's a very, very early days for this and for the most part, people coming out of the universities don't have the constellation of all of those expertise. Obviously, the information comes from every place for this type of work and we need both new business models as well as new ways of collaborating with very broad networks of scientists working with industry in order to take these basic discoveries and make them into products that will be useful for patients. And a very important part of that process are the regulators, so nothing will come to the market without the FDA issuing clear guidelines on what's required, and just as the science evolves, the need for new regulatory guidelines is evolving and is a real challenge when you're working in a pioneering area without a real roadmap to the end goal, but nonetheless, there is progress being made in all of these areas and we're very excited at Janssen about how this is influencing our work. So I hope that this has been useful and answered the question about how a big pharmaceutical company like Janssen is applying these new techniques and with that, I'll thank you very much. Thank you very much, Dr. Dillon. For the last, is there any burning question for any of our last three speakers? If not, we're gonna move on.