 Good afternoon, and I'm really happy to be here today. I've learned a lot. I've heard about COMP because I'm in the Office of Strategic Coordination along with Trish. So it's great to see how much it's been interacting with a lot of different programs. And I'm going to tell you a little bit of, teeny bit, about its future interactions with our new somatic cell genome editing program. So this program is just launching now, and it's really designed to take advantage of the opportunities provided by incredible advances in the genome editing field, where these editing techniques are getting to be so versatile that basically they're democratizing therapeutic development. So there are a lot of people interested now in making therapies for many, many diseases. And there are, as you know, thousands of presently incurable diseases that at least theoretically could be cured, or at least treated well by genome editing approaches. And for some of these conditions, at least a single treatment could be cured. There's been a huge uptick in interest in doing these trials, and this article in New Scientist came out in May of 2017. But as of today, in the U.S., there are no clinical trials that have CRISPR tools in patients. They're being used to modify cells ex vivo outside, and then those cells are going back in the patients. There are just a couple of those. But the ones that are in trial are all from one company, Sangamo, and they're all based on zinc fingers, which have been around for quite a while. So these are actually the most advanced clinical tools right now. And you can see that they're really only being studied in two diseases, MPS1 and 2, and hemophilia A and B. So there's a lot of promise, or there's a lot of potential promise. There's a lot of hints out there that this is going to be revolutionary, but so far it hasn't happened. And so a little over a year ago, the NIH had a workshop to which we invited experts from academia, from industry, and from other federal agencies, such as the FDA, to come and talk to us about where the gaps and opportunities are in the field if there was a potential for the common fund to fill any gaps. And actually this group, as you can imagine, came up with an awful lot of gaps and a long list, and some of which are shown here. So one of the major gaps was more relevant, both human and animal models, for testing new editors and delivery methods preclinically. There's also a paucity of cell and tissue-specific delivery systems. And many of the editors are error-prone or not up to par, so people suggested that we need more editors and especially alternatives to the CRISPR type of nucleases that cut the DNA and can cause DNA damage. There was a request for standardized assays for measuring off-target effects because nobody really knows how many off-target effects are okay and how many are not and how you actually test them and prove that you have a low number, what even a low number means, and also long-term cell-tracking assays to fulfill the FDA goal of following the patients for many years after the treatment. So we got together a working group of NIH staff, which is led by Dr. Chris Austin, who you heard about from today. And we have program staff from over a dozen of the institutes and centers at NIH. And we thought about if we're going to design a common fund program, we need to fulfill the common fund criteria, which hopefully all of the common people already know. The bottom line is the common fund programs are usually five or 10 years and they need to fulfill goals in a short amount of time. And how they fulfill those goals, they should be deliverables that actually affect the way that biomedical research or clinical care is done over the next few years. And they need to be synergistic and cross-cutting with the missions of the institutes and multiple institutes. The more institutes, the better. And they should be unique, something nobody else is actually doing. You've obviously heard some about some common fund programs today. And so we looked into what the other federal agencies were doing. We made sure not to duplicate, but to try to synergize with those efforts. And we designed a program that is really based on three different types of activities. So one activity is technology development. We thought we'll have a couple of initiatives. One on creating better, safer, more accurate editors. And another one on creating better, more accurate, safer delivery technologies. And then we'll build a couple of testing systems. We'll generate testing systems in a number of animal models, because we don't know which one is the best for everything. And we did include the mouse, of course. But we also have human systems so that we can compare the efficacy of the editors and the delivery tools in human cells. And then once these new technologies pass muster, the data, the protocols, et cetera, will go into a toolkit for the community so the community can look up and say, oh, I want a delivery vehicle that goes to the kidney, but doesn't go to the liver. Is there one that this program has characterized? And they could find it, find out where to get it, find out how to use it. And so what we're hoping to do is fill this gap of safe and effective tissue-specific methods for in vivo targeting that is putting an editor in the body, having it go where we want it to go and edit specifically. So we're leaving it to others to pick up the tools and create their own pre-IND packages. So just to go quite quickly through the initiatives, the stage that we're at is this FOAs went out about nine months ago. We've had applications come in and be reviewed. And we've just now funded a large cohort of projects, about 22 projects. And the total commitment for this program over the next five to six years is around $190 million. So Initiative 1 encompasses both the small and large animal reporter strains that I told you about as well as testing centers to use those strains to test the delivery and editor reagents. And it's led by Dr. Oleg Merchenko from the Office of Research Infrastructure Program. And so this is our first major connection. Its goals are to develop both mice and large reporter animals to detect both on- and off-target genome editing. So the major goal of these within the program is to validate the delivery vehicles created in one of the technology development initiatives. But they'll also be working with the editor initiative to test new editors. And their scope includes testing in all individual cell types, including the germ cells, because we want to be able to say whether our delivery vehicles affect the germ line or not. And hopefully they do not, because we want to avoid, at this point, germ cell editing. And the timeline is right now. We just this past month made two awards, one to Dr. Jason Haney from the Baylor College of Medicine and another to Steven Murray of Jackson Lab. Very strong comp connection. So you can see how we're going to take advantage of the comp, oops, sorry, the comp pipelines and expertise. And so one theme that you'll see throughout the next few slides is that in the first two years, all the components earlier are supposed to generate the resources and develop proof of concept. And after the end of two years, they're all supposed to start collaborating with each other. And in this case of the small animal testing centers, they're really charged with validating those delivery systems. There are other things they can do. They could collaborate with the editors. They can do all sorts of things if they have time and funds or interest. But they are really charged with helping us validate them, because we thought that was an important component of the delivery vehicles is to have independent validation of where they go and what they do. And so the timeline for the large animal reporters is a little bit different. We did just make awards to a group of investigators who will make the reporter strains. We have a different FOA out for the testing centers, because we thought these might be two different types of people that would apply. And so right now, the role of this group is to generate the reporter pigs and non-human primates. And they'll submit them when the large animal testing centers come on board. And of course, because these animals take a lot longer to reach maturity, the timelines for their development is longer. So they're not going to be ready at the end of year two to collaborate with the rest. But we thought this was an important investment, and hopefully at least the pigs will have in year three or four to start testing after the delivery vehicles have been validated by the small animal testing centers. So Initiative 2 was the other testing system initiative, and that's for the human cell systems. And these are based on organoid type systems or any kind of system that tries to replicate normal human biology on a platform that's reproducible. The platform has to be amenable to sequencing basis approaches to show off target effects as genomic off-target effects as sort of a control. But really the point is to look at unintended biological effects like immunogenicity or changes in biological function or even genotoxicity or carcinogenicity. And that one, again, we have just made four awards for this. We're very excited that of this group, two of them have just lost their ESI status, so we have some young dynamic people on this group. And they will spend the first two years creating their platforms, showing proof of concept and demonstrating the capacity to identify adverse effects on biology. And then they'll start collaborating with the rest of the group really as they see fit, whether to test delivery vehicles or editors or maybe to create a different type of platform based on a target tissue from another group. The third initiative is one of the technology development initiatives to create the new delivery systems. And this is basically the focus could be on either a single cell type to deliver specifically to one cell type or to multiple cell types. But the idea was that the technologies should improve the clinical applications. And again, as I said, one of the major goals of this program is to develop delivery vehicles that have been validated independently. So it's required for this group to have their tested systems then validated at the small animal testing centers. So we've divided this initiative into two sections where the first three years are for them to develop and test, validate their systems in small animals. And then if they pass that and do that, then we'll give them a couple of more years. So this is really one of those types of projects that ends after three years if they're unsuccessful. And if they are successful in the small animal testing centers, they'll get more money to scale up the production and optimize their system so that they can then go into large animals. And we have quite a broad range of investigators here. We have nine projects that we've just funded. And you can see that they're addressing both viral and non-viral delivery methods. And we have some quite innovative technologies here too, including extracellular vesicles and peptide nucleic acid. So this is quite a broad range of delivery vehicles. And the other thing that we're happy about is that together they're addressing six or seven different organ systems in the human body with three groups trying to target the brain, their nervous system, and three trying to target the lung, a couple targeting muscle, a couple targeting the hemopoietic system, and one the inner ear. Initiative four is the technology development initiative to create new editors or improved editors. And this one really is focused on improving either the specificity, the efficiency, or the functionality of the editors. And these could be nucleases or non-nucleases. They could be epigenetic modifiers or RNA editors, really anything. And they could identify novel enzymatic activities or improve unknown activities. And we also fostered strategies for manipulating inaccessible genomes or genomic regions. And so even though we only have three awards, we're kind of covering all those bases that we had in the FOA. We have some of the leaders in the field for these editors or initiatives. And so Jennifer Doudner is going to identify novel cast proteins in DNA repair systems that could be used for editing. Stephen Ecker is generating editors for the mitochondrial genome and mitochondrial RNA. And David Lu will improve on his repertoire of base editors. And again, within the first two years, they should show proof of concept. They have a new editor or improved editor that can do something. Then they'll start sharing the editors, maybe with the delivery systems to get a package, or maybe with the biology systems to show that they can edit specific genes and specific cell types. And then last but not least, Initiative 5, the Dissemination Coordinating Center is going to be led by Colin Fletcher, who you all know, our other comp connection. And its goal is really to establish this coordinating center that's going to help the NIH pull this all together and make it happen. So they have three major roles. One is to help coordinate, providing logistical and administrative assistance, and helping exchange of information and discussion among the consortium members. They'll also be responsible for putting together the data in this toolkit and making it accessible to the community. And they'll provide collaboration support. They're going to set up a system to manage a collaborative opportunity fund that will help the investigators within the consortium share and cross-test and evaluate each other's technologies. Unfortunately, I can't tell you who the awardee for that is going to be, because this one's going to be awarded in the later in FY19. But we have gone through the review and identified a group that we would like to fund. And the funding plan is working its way up through the NIH system. But we're very happy with the awardee. And they're on a little bit shorter timeline than everybody else, because they need to get on the ground and start running. So in year one, they'll start developing the pipelines and the procedures and the policies for the consortium. And then in their year two, they'll start the collaboration, et cetera, funds. So perhaps most importantly, for this audience, there are a few additional funding opportunities on the street. The bad news is that the receipt data is in just a couple of weeks, October 18. We have reissued everybody leaves and starts diving. We've reissued the human cell platform testing system, FOA, the one to develop new delivery systems and the one to develop new editors. We've also published a new FOA called Innovative Technologies to Noninvasively Monitor Genome Edited Cells and Vivo. And that one really is to develop tools of technologies to enable long-term longitudinal monitoring of genome-edited cells in people so that we can fulfill that FDA mandate to track people over time. And we think it would be great to actually be able to see what happens to those cells over time. So this is a little bit by in the sky, but we're supporting either the discovery of novel approaches to label and track these cells or improvements or adaptations over pre-existing technologies. And we're really interested to see what we're going to get for this one. So the only other thing that's planned is very soon. In December, we will have a kickoff meeting for everyone to meet and start talking and collaborating. So thank you.